Compositions and methods for cellular immunotherapy

Abstract

The present disclosure provides polypeptide dimers and polypeptides for improving cellular immunotherapy. Disclosed embodiments include polypeptide dimers (referred-to herein as chTCRs, chimeric TCRs, or chTCRs) that can confer to a host cell (e.g. a T cell) target-specificity of a CAR while leveraging natural T cell signaling properties. chTCRs can be efficiently expressed at the surface of host cells and confer to host cells a diversified and highly sensitive signaling complex that acts with native host (e.g. T) cell signaling properties. Certain embodiments provide a chTCR that binds to a human CD22 (e.g., in an extracellular domain thereof). In certain further embodiments, the chTCR further comprises a binding domain that binds a human CD19. In other embodiments, the present disclosure provides chTCRs that bind human GPRC5D and human BCMA. In other embodiments, the present disclosure provides chTCRs that bind human SLAMF7 and human BCMA. Also provided are polynucleotides encoding the chTCRs, and vectors that comprise the polynucleotides. Also provided are host cells, such as T cells, that encode or express the chTCR. Also provided are compositions and methods for using the same the same.

Description

COMPOSITIONS AND METHODS FOR CELLULAR IMMUNOTHERAPYSTATEMENT OF GOVERNMENT INTERESTThis invention was made with government support under CAI 14536 awarded by the National Institutes of Health. The government has certain rights in the invention.REFERENCE TO AN ELECTRONIC SEQUENCE LISTINGThe contents of the electronic sequence listing (360056_511WO_SL.xml; Size: 313,909 bytes; and Date of Creation: November 2, 2024) is herein incorporated by reference in its entirety.BACKGROUNDDespite some clinical success, CAR T cells have limitations, and a large fraction of treated patients will eventually relapse. A major mechanism for tumor relapse is the emergence of tumor clones expressing low levels of, or negative for, the targeted protein. Some CAR T cells are poorly able to sense target cells expressing low levels of antigen, which is thought to be largely contributing to these relapses. Moreover, tumors can be heterogenous in antigen expression before CAR T cell therapy and / or immunoediting following CAR T cell therapy can lead to the emergence of cells presenting mutations within the epitope recognized by the CAR, or entirely devoid of target expression. Multispecific targeting is a potential approach to address these challenges. Unfortunately, CAR designs attempting to achieve multispecific targeting were shown to be largely suboptimal with often reduced ability to bind, signal and provide optimal T cell functions in response to one of the two targeted antigens compared to monospecific designs.BRIEF DESCRIPTION OF THE DRAWINGSFigures 1A-1E relate to certain embodiments of chimeric T cell receptor (chTCR) constructs of the present disclosure, with single-chain chimeric antigen receptors (CARs) as comparators. (A) Left panel: schematic of human CD22 at a cell membrane and schematics of of anti-CD22 scFv made using the VH and VL domains of antibody "9A8" or of antibody "m971". The relative positions of the scFvs vis-a-vis the CD22 protein as shown in the Figure do not necessarily reflect binding specificity or epitope. The right panel shows, from left to right, schematics of: anti-CD22 CAR comprising a m971 scFv; and "Full ChTCR" constructs comprising m971 scFv, at a cell membrane. Unless otherwise indicated, in the present figures, a “full” chTCR refers to a complete binding domain (e.g., a scFv) being disposed in a single polypeptide chain of a chTCR, whereas different portions of a complete binding domain mayalternatively be “split” across two polypeptide chains of a chTCR (e.g., a “full” scFv chTCR can comprise a scFv (e.g, comprising VH-linker-VL or VL-linker-VH) in a single polypeptide chain with one TCR constant domain of a chTCR, while a “split” scFv chTCR can comprise a VH on one polypeptide chain further comprising a TCR constant domain, and a cognate VL on another polypeptide chain further comprising a cognate TCR constant domain, i.e. the VH and VL domains that can be comprised in a scFv comprised on one polypeptide chain of a (“full” format) chTCR may instead be “split” across two polypeptide chains of a chTCR).The CAR includes m971 scFv (in VH / VL orientation), CD8 hinge and transmembrane domains, a 4-1BB co-stimulatory domain, and a CD3^ effector domain. The illustrated chTCRs include a m971 scFv (in VH / VL or VL / VH orientation) fused to a T cell receptor beta-chain constant domain (CP). The CD3 proteins ( , 8, y, 5) shown in proximity to the chTCRs are endogenously expressed (and are not part of the chTCR molecule); “ChTCR” refers to the illustrated paired Ca-containing and C -containing polypeptides. (B) Expression of CAR and the chTCRs with a m971 scFv as in (A) (top row) or with a 9A8 scFv (bottom row) in T cells. The chTCRs for this Figure IB as well as in Figures 1C-1D comprise the scFv fused to CP in VH / VL or VL / VH orientation. (C) Expression (quantified as geometric mean of binding to recombinant CD22) of CAR and chTCR constructs shown in Figure IB, in T cells. (D) Top: histograms showing CD22 expression in Nalm-6 wild-type (Nalm-6 WT) and Nalm-6 with CD22 knockout (Nalm-6 CD22ko) cell lines; an antibody isotype control (Isotype) was included. Center: concentration of IL-2 produced by T cells transduced with a m971-BBz CAR, a 9A8-BBz CAR, or a m971 or 9A8 chTCRs, after co-culture with Nalm-6 WT and Nalm-6 CD22kocell lines. Bottom: concentration of IFN-y produced by T cells transduced with a CAR or chTCRs as in the center panel of this Figure ID, after co-culture with Nalm-6 WT and Nalm-6 CD22kocell lines. (E) Proliferation of T cells transduced with the indicated CAR or chTCR, in response to CD22 -expressing Nalm6 cells. Left: histograms of proliferation using Cell Trace Violet (CTV). Right: percentage CTV-low cells of T cells transduced with CARs and ChTCRs shown in Figure IB.Figures 2A-2E relate to certain embodiments of anti-CD22 m971 chTCRs of the present disclosure, with a CAR as comparator. (A) Schematic of m971 scFv in CAR and Full ChTCR formats. The CAR is as in Figure 1A. The illustrated full ChTCR formats comprise a m971 scFv (in VH / VL or VL / VH orientation) fused to TRBC (CP) or T cell receptor alpha-chain constant (TRAC; Ca)) domains. (B) Left: Expression of the m971 CAR and chTCRs as shown in Figure 2A, in T cells. Right: Expression (quantified as geometric mean of binding to rCD22) of m971 CAR and ChTCRs as shown in Figure 2A, in T cells. (C) Left: histogram showing CD3 expression in T cells transduced with m971 CAR or indicated m971chTCR. Right: Expression (quantified as geometric mean of CD3) of CD3 in T cellstransduced with CAR and ChTCRs shown in Figure 2A. (D) Left: histogram showing TCRaP expression in T cells transduced with the indicated m971 CAR or chTCR. Right: Expression (quantified as geometric mean TCR) of TCR in T cells transduced with the indicated m971 CAR or chTCR. (E) Left: concentration of IL-2 produced by T cells transduced with the indicated m971 CAR or chTCR, after coculture with Nalm-6 WT or Nalm-6 CD22kocell lines. Right: concentration of IFN-y produced by T cells transduced with the indicated m971 CAR or chTCR, after co-culture with Nalm-6 WT or Nalm-6 CD22kocell lines.Figures 3A-3G relate to certain embodiments of bispecific (anti-CD19 x anti-CD22) ChTCR constructs of the present disclosure, with CARs as comparators. (A) Schematic of certain CARs and certain embodiments of bispecific chTCR constructs of the present disclosure. The CD19-BBz CAR comprises a scFv comprising the VL and VH of anti-CD19 antibody FMC63. The CD22-BBz CAR comprises a scFv comprising the VH and VL of anti-CD22 antibody m971. The CD19 / CD22 Loop CAR (e.g., Spiegel, J.Y., Patel, S., Muffly, L. et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med 27, 1419-1431 (2021). https: / / doi.org / 10.1038 / s41591-021-01436-0), comprises the VH and VL of FMC63 and the VH and VL of m971. The tested chTCRs comprise a scFv comprising the VH and VL (VL-linker-VH orientation) of FMC63 fused to Ca and and a scFv comprising the VH and VL of 9A8 fused to Cp (the 9A8 scFv was tested in VH-linker-VL and VL-linker-VH orientations). (B) Expression of the CAR and chTCR constructs shown in Figure 3A in T cells: CD19-BBz CAR; CD22-BBz CAR; CD19 / CD22 Loop Car; CD19 / CD22 Bispecific chTCR with the 9A8 scFv in VH / VL or VL / VH orientation. (C) Left: Expression (quantified as geometric mean of binding to rCD19) by the indicated CARs and chTCRs, in T cells. Right: Expression (quantified as geometric mean of binding to rCD22) of the indicated CARs and chTCRs, in T cells. (D) Left: histogram showing CD3 expression in T cells transduced with the indicated CAR or chTCR. Right: expression (quantified as geometric mean CD3) of CD3 in T cells transduced with the indicated CAR or chTCR. (E) Basal activation of of Jurkat NF AT reporter cells transduced with the indicated CAR or chTCR, reported as (left) NFAT-GFP expression and (right) percentage of NFAT- postive cells, with untransduced cells included as a control in the right-hand panel. (F) Histograms showing expression of CD 19 and CD22 in Nalm-6 WT, Nalm-6 with CD 19 knockout (CD19ko), Nalm-6 CD22ko, and Nalm-6 with both CD 19 and CD22 knockout (DKO) cell lines. (G) Proliferation of T cells transduced with the indicated CAR or chTCR after co-culture with Nalm-6 cell lines. Top: Proliferation as measured using CTV. Bottom: percentage of CTV-low cells in T cells transduced with the indicated CAR or chTCR.Figures 4A-4AO show amino acid sequences of certain polypeptides disclosure and short descriptions of the same, with annotations (shading in short description corresponding to shading in sequence) for certain domains or portions thereof. “STOP” or “*” indicates the presence of a stop codon in an expression construct encoding the indicated CAR or chTCR. Unless otherwise indicated, the depicted CAR and chTCR are shown as expression products; it will be understood that, for example: all or a portion of a signal peptide may be removed from a polypeptide chain prior to expression at a cell surface; alternative signal peptides (e.g., other than those shown in a given sequence) may be used; alternative scFv linker sequences (e.g., other than those shown in a given sequence) may be used, with binding function preferably being fully retained; alternative self-cleaving (e.g., 2A) peptides may be used or may be absent; alternative furin recognition sequences / sites may be used, or a furin recognition sequence / site may be absent; or any combination thereof (provided that for chTCRs, the Ca-containing and Cp-containing polypeptides can be expressed as separate polypeptides). It will also be understood that the 5’— >3’ (or N-terminal to C-terminal, for amino acid sequences) orientation of sequences in a chTCR expression construct may be different to what is depicted in the figure; for example, a sequence encoding a Cp-containing polypeptide may be disposed 5 ’ to a sequence encoding a Ca-containing polypeptide, or a sequence encoding a Ca-containing polypeptide may be disposed 5 ’ to a sequence encoding a Cp-containing polypeptide.Figure 4A: anti-CD19 scFv comprising the variable domains of FMC63. Figure 4B: anti-CD22 scFv comprising the variable domains of m971. Figure 4C: anti-CD22 scFv comprising the variable domains of 9A8. Figure 4D: anti-CD22 CAR comprising a m971 scFv and 4-lBBz intracellular signaling domain. Figure 4E: anti-CD22 CAR comprising a 9A8 scFv and 4-lBBz intracellular signaling domain. Figure 4F: Full chTCR comprising a m971 scFv (VH / VL orientation) fused to TRAC. Figure 4G: Full chTCR comprising a m971 scFv (VL / VH orientation) fused to TRAC. Figure 4H: Full chTCR comprising a m971 scFv (VH / VL orientation) fused to TRBC. Figure 41: Full chTCR comprising a m971 scFv (VL / VH orientation) fused to TRBC. Figure 4J: Full ChTCR comprising a 9A8 scFv (VH / VL orientation) fused to TRAC. Figure 4K: Full ChTCR comprising a 9A8 scFv (VL / VH orientation) fused to TRAC. Figure 4L: Full ChTCR comprising a 9A8 scFv (VH / VL orientation) fused to TRBC. Figure 4M: Full chTCR comprising a 9A8 scFv (VL / VH orientation) fused to TRBC. Figure 4N: Split chTCR comprising m971 VH fused to TRAC and m971 VL fused to TRBC. Figure 40: Split chTCR comprising m971 VL fused to TRAC and m971 VH fused to TRBC. Figure 4P: Split chTCR comprising 9A8 VH fused to TRAC and 9A8 VL fused to TRBC. Figure 4Q Split chTCR comprising 9A8 VL fused to TRAC and 9A8 VH fused to TRBC. Figure 4R: Loop CAR comprising FMC63 and m971 scFvs. Figure 4S: Loop CAR comprising FMC63 and 9A8 scFvs. Figure 4T: Bispecific chTCR comprising a FMC63 scFv(VH / VL)_TRAC + a 9A8 scFv (VH / VL) TRBC. Figure 4U: Bispecific chTCR comprising a FMC63 scFv (VLZVH) TRAC + a 9A8 scFv (VH / VL)_TRBC. Figure 4V: Bispecific chTCR comprising a FMC63 scFv (VH / VL)_TRAC + a 9A8 scFv (VL / VH) TRBC. Figure 4W: Bispecific chTCR comprising a FMC63 scFv (VL / VH)_TRAC + a 9A8 scFv (VL / VH)_TRBC. Figure 4X: Bispecific chTCR comprising a FMC63 (VH / VL)_TRAC + a m971 scFv (VH / VL) TRBC. Figure 4Y shows: Bispecific chTCR comprising a FMC63 scFv ( VL / VH )_TR AC + a m971 scFv (VH / VL)_TRBC. Figure 4Z: Bispecific chTCR comprising a FMC63 scFv (VH / VL)_TRAC + a m971 scFv (VL / VH) TRBC. Figure 4AA: Bispecific chTCR comprising a FMC63 scFv (VL / VH)_TRAC + a m971 scFv (VL / VH)_TRBC. Figure 4AB: A SLAMF7-specific scFv (comprising VH and VL of anti-SLAMF7 antibody HuLuc63). Figure 4AC: Bispecific CAR from Zah, E., Nam, E., Bhuvan, V. et al. Systematically optimized BCMA / CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. Nat Commun 11, 2283 (2020). https: / / doi.org / 10.1038 / s41467-020-16160-5. Figure 4AD: Bispecific chTCR BCMA / SLAMF7 “format #1” (VH / VL SLAMF7 (HuLuc63)_TRBC + VH / VL BCMA (Cl 1D5.3)_TRAC). Figure 4AE: Bispecific chTCR BCMA / SLAMF7 “format #2” (VH / VL BCMA TRBC + VH / VL SLAMF7 TRAC). Figure 4AF: Bispecific chTCR BCMA / SLAMF7 “format #3” (VL / VH SLAMF7 TRBC + VL / VH BCMA TRAC). Figure 4AG: Bispecific chTCR BCMA / SLAMF7 “format #4” (VL / VH BCMA TRBC + VL / VH SLAMF7 TRAC). Figure 4AH Bispecific chTCR BCMA / SLAMF7 “format #5” (VL / VH SLAMF7 TRBC + VH / VL BCMA TRAC). Figure 4AI: Bispecific chTCR BCMA / SLAMF7 “format #6” (VH / VL SLAMF7 TRBC + VL / VH BCMA TRAC). Figure 4AJ: a GPRC5D-specific scFv (VL-linker-VH orientation). Figure 4AK: a GPRC5D-specific CAR. Figure 4AL: Bispecific chTCR BCMA / GPRC5D “format #1” (VH / VL GPRC5D TRBC + VH / VL BCMA TRAC). Figure 4AM: Bispecific chTCR BCMA / GPRC5D “format #2” (VH / VL BCMA TRBC + VH / VL GPRC5D TRAC). Figure 4AN: Bispecific chTCR BCMA / GPRC5D “format #3” (VL / VH GPRC5D TRBC + VL / VH BCMA TRAC). Figure 4AO: Bispecific chTCR BCMA / GPRC5D “format #4” (VL / VH GPRC5D TRBC + VH / VL BCMA TRAC) .Figures 5A-12D relate to certain bispecific (BCMA / SLAMF7) chTCRs of the present disclosure. In some experiments, CARs were tested as comparators. Several “formats” of the chTCRs were expressed in Jurkat TPR cells (Figures 5A and 5B) and expression was assayed in a number of ways. “Format 1” (see also Figure 4AD) was selected for further studies. Figure 6 shows that the tested bispecific (BCMA / SLAMF7) chTCR expresses in primary T cells. BCMA-specific and SLAMF7- specific reference CARs are shown for comparison. chTCR and CAR constructs were expressed in Jurkat TPR cells expressing a reporter gene under control of the NF AT promoter; chTCR-T cells did notevidence tonic signaling, with lower levels of NF AT expression than a CD19-28z CAR and a SLAMF7- BBz CAR (Figure 7).SLAMF7 can be expressed by T cells and SLAMF7-CAR T cells have been reported to confer selective fratricide of SLAMF7+ normal lymphocytes while also having anti-myeloma activity (see Tea Gogishvili, Sophia Danhof, Sabrina Prommersberger, Julian Rydzek, Martin Schreder, Christian Brede, Hermann Einsele, Michael Hudecek; SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes. Blood 2017; 130 (26): 2838-2847. doi: doi.org / 10.1182 / blood-2017-04-778423). Cytidine base editing (CBE) was performed to knock-out SLAMF7 and CD229 in chTCR- or CAR-expressing T cells. Figures 8A and 8B show that SLAMF7 can be knocked-out, such as along with endogenous TCR chains, in T cells. In certain embodiments, a cell (e.g., a T cell) encoding or expressing an anti-SLAMF7 chTCR of the present disclosure comprises a chromosomal gene knockout of a SLAMF7, of an endogenous TCR chain, or both. Figures 9A-9D show that bispecific chTCRs demonstrate true bispecificity. In Figures 9B-9D, BCMA-specific and SLAMF7- specific CARs are shown as comparators. Figures 10A-10E show that bispecific chTCRs demonstrate superior antigen sensitivity as compared to reference CARs. Figures 11A-11B show that bispecific chTCRs demonstrate superior signaling as compared to a published bispecific BCMA / SLAMF7 CAR (see Figure 4AC). Figures 12A-12D show that bispecific chTCRs demonstrate potent anti-tumor efficacy in vivo in an antigen heterogeneity model (injected Nalm-6 cells: 33% BCMA+; 33% SLAMF7+; 33% BCMA+SLAMF7+).Figures 13A-14D relate to certain bispecific (BCMA / GPRC5D) chTCRs of the present disclosure. In some experiments, a BCMA-specific 4-lBBz-containing CAR and a GPRC5D-specific 4- IBBz-containing CAR were tested as references. “Formats” 1-4 of BCMA / GPRC5D bispecific chTCRs (see also Figures 4AL-4AO) were tested for expression in T cells, and of these, “formats” 1-3 expressed better than “format” 4. “Format” 3 (Figure 4AN) was selected for functional studies. This chTCR expressed in T cells, demonstrated bispecificity, and did not show evidence of tonic signaling.Figures 15A-15H relate to certain embodiments of anti-CD19 chTCRs of the present disclosure, with anti-CD19 CARs as comparators. (A) Schematic of CD19-specific ChTCRs and CARs: Left to right - Split ChTCR VHCa: FMC63 heavy chain variable domain-TCR alpha constant chain, VLCP: FMC63 light chain variable domain-TCR beta constant chain; Full ChTCR: FMC63VL-linker-VH-Ca:Cp. Both ChTCRs are shown in association with endogenous CD3so. CD3 and CD3ya subunits. CD28^CAR with FMC63 VL-linker-VH scFv, CD28 hinge / transmembrane and co-stimulatory domain, and CD3^ effector domain; BBz CAR with FMC63 VL-linker-VH scFv, IgG4 hinge, CD28 transmembrane domain, 4-1BB co-stimulatory domain and CD3z effector domain. (B) Representative flow plots of primary CD8 T cellsstained with anti -TCRaP antibody and recombinant CD 19 protein after lentiviral transduction of chTCR or CAR and base editing to knock-out endogenous TCRa expression. (C) Geometric mean of rCD19- APC binding to primary T cells transduced with Split or Full ChTCR and with and without base editing of the constant domain-encoding locuses (or loci) for TCRa, TCR or both (TCRa, TCR ) chains (n=5 biological independent samples). *P<0.05, **P< 0.01 using two-way ANOVA. (D) Left: representative TCRa expression by mock unedited and TCRaP gene edited ChTCR+ and CAR+ T cells. Center: Representative CD3s expression by mock unedited and TCRaP gene edited ChTCR+ and CAR+ T cells. Right: geometric mean ± SD of CD3e-BUV395 fluorescence (n=4 independent donors). *** P< 0.001, **** p< 0.0001 by two-way ANOVA. (E) Left: Representative TIRF microscopy images of ChTCR+ and CAR+ T cells interacting with a soluble lipid bilayer functionalized with ICAM- 1 extracellular domain, CD19 extracellular domain and stained with an anti-CD45-AF555 antibody. Scale bars = 10pm. Right: Normalized mean intensity of ICAM-1-AF488 and CD19-AF647 staining across cell radiuses in synapses; dots represent mean at each position with solid trend line, n=100 cells. (F) Left: Representative calcium flux measured after antigen crosslinking of T cells expressing the indicated receptor. The y-axis shows the ratio of calcium bound to unbound Indo-1 dye overtime on the x-axis. Arrows indicate crosslinking of receptors and addition of PMA / ionomycin. Right: Area under the curve of calcium flux measurements over 300 seconds after antigen cross-linking, (n=4 independent experiments). *** P< 0.001, **** P< 0.0001 by two-way ANOVA. (G) Left: Representative western blot of LAT pTyr220, Actin and LAT after antigen activation of T cells expressing the indicated receptor. Right: heat map of mean band intensity of LAT pTyr220 normalized to actin loading control (n=3 independent experiments). (H) Left: Representative Western Blot analysis of Zap70 pTyr319, Actin and Zap70 after antigen activation of T cells expressing the indicated receptor. Right: Heat map of mean band intensity of Zap70 pTyr319 normalized to actin loading control (n=3 independent experiments).Figures 16A-16H relate to certain embodiments of anti-CD19 chTCRs of the present disclosure, with CARs as comparators. (A) Flow histograms of CD 19 expression in Nalm-6 cells with varying levels of CD19. (B) Top: Concentration of IL-2 in culture supernatant after overnight co-culture of T cells expressing the indicated receptor with Nalm-6 CD19High, CD19Mid, and CD19Low cells at an effector to target ratio (E:T) of 1: 1. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 by two-way ANOVA. Bottom: Concentration of IFN-y in culture supernatant for each experimental group shown at the top of the figure. Data is shown as the mean + / SD for 3 independent experiments. *P<0.05, **P<0.01, ***P<0.001 by two-way ANOVA. (C) Representative histograms of CellTrace Violet (CTV) dye dilution in T cells expressing the indicated receptor measured after 3 days of co-culture with Nalm-6 CD19Mid (left) and Nalm-6 CD19Low (right)tumor cells. Percent of divided cells (mean ± SD) for 3 independent experiments, *P<0.05, **P<0.01, ****P<0.0001 by two-way ANOVA also shown, corresponding to each representative histogram. (D) Left: Representative western blot of LAT pTyr220, Actin and LAT after antigen activation of T cells expressing the indicated receptor. Right: heat map of mean band intensity of LAT pTyr220 normalized to actin loading control. (E) Left: Schematic of a Raji GFP-ffluc+ NSG mouse model for testing antitumor activity of T cells expressing the indicated receptor as shown at right. Right: Representative bioluminescence images of Raji-ffluc tumor burden in NSG mice treated with 2xl06T cells expressing the indicated receptor. (F) Top: Tumor burden (mean ± SD radiance (photons / sec / cm2 / steradian) of Raji GFP-ffluc+ bearing NSG mice treated as described for Figure 16E. (n=4 or 5 mice per group; 3 independent experiments). Bottom: Kaplan-Meier survival of Raji GFP-ffluc+-bearing NSG mice treated as described for 16E (n=14 mice per treatment group). *P <0.05, **P<0.01, ***P<0.001. (G) Left: Schematic of a Nalm-6 CD191ow GFP-ffluc+ NSG mouse model for testing antitumor activity of T cells expressing the indicated receptor as shown at right. Right: Representative bioluminescence images of NSG mice inoculated with Nalm-6 CD191ow GFP-ffluc+ tumor cells and treated with T cells expressing the indicated receptor. (H) Top: Tumor burden (mean ± SD radiance (photons / sec / cm2 / steradian)) of Nalm-6 CD191ow GFP-ffluc+-bearing NSG mice 18 days after treatment with T cells expressing the indicated receptor (n=5 mice per group). *P <0.05, **P<0.01 by two-tailed unpaired t-test. Bottom: Kaplan-Meier survival of Nalm-6 CD191ow GFP-ffluc+-bearing NSG mice treated as described for Figure 16G.Figures 17A-17G relate to certain embodiments of anti-CD22 chTCRs of the present disclosure, with a CAR as a comparator. (A) Left: Schematic of the human CD22 protein with m971 and 9A8 scFvs, respectively. Right: Structure of CD22-specific receptors: CD22-BBz CAR: anti-CD22 scFV VH-linker- VL (m971 or 9A8), CD8 hinge and transmembrane domain, 4-1BB co-stimulatory domain, and CD3z effector domain; CD22 Full ChTCRs: m971 or 9A8 in VH-linker-VL or VL-linker-VH orientations with TRBC and shown associated with endogenous CD3 subunits. (B) Left: Representative flow plots of primary CD8 T cells stained with anti-TCR antibody and recombinant CD22 protein after lentiviral transduction and base editing to knock-out TCRap. Top row of flow plots: T cells expressing CAR and ChTCRs constructed with the m971 scFv; Bottom row of flow plots: T cells expressing CAR and ChTCRs constructed with the 9A8 scFv. Right: Geometric mean ±SD of recombinant CD22-APC binding to CAR and ChTCR T cells constructed with either m971 or 9A8 scFv. Data is shown for T cells from 3 independent donors. *P< 0.05, **P< 0.01, ***p< 0.001 by two-way ANOVA. (C) Concentration of IFN- y (left) and IL-2 (right) in culture supernatant after overnight co-culture of T cells expressing the indicated receptor with Nalm-6WT or Nalm-6CD22ko cells. Data is shown as the mean ±SD for T cells from 3independent healthy donors. *P< 0.05, **P< 0.01, 0.0001 by two-way ANOVA. (D) Left:Representative histograms of CellTrace Violet (CTV) dilution measured after 72h cocultures of T cells expressing the indicated receptor with Nalm-6 cells. Right: Frequency of divided cells. Data is shown as the mean ± SD for 3 independent healthy donors. *P< 0.05, **P< 0.01,0.0001 by two-wayANOVA. (E) Left: Representative TIRF microscopy images of anti-CD22 ChTCR T cells constructed with the m971 scFv (top) or 9A8 scFv (bottom) interacting with a soluble lipid bilayer functionalized with ICAM-1 extracellular domain and CD22 extracellular domain, or brightfield. Scale bars = 5 pm. Center: Normalized mean intensity of ICAM-1-AF488 and CD22-AF647 staining across cell radiuses in synapses; dots represent mean at each position, with trend line (n=100 cells). Right: Mean intensity of CD22-AF647 staining within the synapse of 100 T cells expressing ChTCRs constructed with the m971 scFv or 9A8 scFv. **** P<0.0001 by two-tailed t-test. (F) Top: Representative flow histograms of CellTrace Violet (CTV) dilution measured after 72h co-culture of T cells expressing the indicated receptor with Nalm-6 cells expressing different levels of CD22 or CD22 knockout. Bottom: Frequency of divided cells in each group. Data is shown as the mean ± SD for 3 independent healthy donors. *P< 0.05, **P< 0.01, ****p< 0.0001 by two-way ANOVA. (G) Concentration of IL-2 (left) and IFN-y (right) in culture supernatant after overnight co-culture with Nalm-6 CD221ow cells. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05 and **P< 0.01 by 2-way ANOVA test.Figures 18A-18H relate to an embodiment of a bispecific (CD19 / CD22) chTCR of the present disclosure, with CARs included as comparators. (A) Schematic of bispecific CD19 / CD22 ChTCR, monospecific CD19 and CD22 4-lBB / CD3^ CARs, and bispecific CD19 / CD22 Loop CAR [Kokalaki, E., et al., Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR. Mol Ther, 2023. 31(7): p. 2089-2104], CD19-specific FMC63 scFv and CD22-specific 9A8 scFv were used in the Bi-ChTCR construct; FMC63 and / or m971 scFvs were used in all CAR constructs. (B) Left: Representative flow plots of transduced and TCRaP base-edited primary CD8 T cells stained with anti- TCR antibody and recombinant CD 19 (top) or CD22 proteins (bottom). Right: Geometric mean ± SD of CD19-PE or CD22-APC, as shown, binding to T cells expressing the indicated receptor (n=3 independent experiments). *P< 0.05, **P< 0.01,0.0001 by two-way ANOVA. (C) Left: Representative TIRF microscopy image of CD19 / CD22 Bi-ChTCR T cells interacting with a soluble lipid bilayer functionalized with ICAM-1 extracellular domain, CD 19 and CD22 extracellular domains. Scale bars = 10pm. Right: Normalized mean intensity of ICAM-1-AF488, CD19-AF647 and CD22-AF555 staining across the cell radiuses in synapses. Dots represent mean at each position, with trend line (n=100 cells). (D) Concentration of IL-2 in culture supernatants after overnight co-culture of T cells expressing the indicated receptor with Nalm-6WT, Nalm-6CD22ko, Nalm-6CD19ko and Nalm-6DK0 cells. Data isshown as the mean ± SD for T cells from 3 independent healthy donors. *P< 0.05, **P< 0.01, ***p< 0.001 by two-way ANOVA. (E) Left: Representative flow histograms of CellTrace Violet (CTV) dilution measured after 72h co-culture of T cells expressing the indicated receptor with Nalm-6 cells expressing CD 19 and CD22 or knocked out for one or both targets. Right: Frequency of divided cells (% CTVlow cells) measured after 72h co-culture of T cells expressing the indicated receptor with Nalm-6 cells. Data is shown as the mean ± SD from 3 independent healthy donors. *P< 0.05, ***p< 0.001,0.0001 by two-way ANOVA. (F) Left: Schematic of a Nalm-6 GFP-FfLuc mouse model for testing antitumor activity of T cells expressing the indicated receptor as shown at right. Right: Representative bioluminescence images of mice inoculated with Nalm-6 GFP-FfLuc tumor cells (as shown in the schematic to the left) and treated with T cells expressing the indicated receptor. (G) Left: Tumor burden (mean ± SD radiance) of Nalm-6 GFP-FfLuc-bearing mice treated as described for 18F. Right: Kaplan- Meier survival of Nalm-6 GFP-FfLuc-bearing mice as described for 18F. (H) Representative flow plots (top) and pie graphs (bottom) of CD 19 and CD22 expression on Nalm-6 GFP-ffluc+ tumor cells harvested from the bone marrow at the time of euthanasia for each of the treatment groups (n=3-4 mice per group).Figures 19A-19G relate to certain embodiments of chTCRs (a CD19-specific Full ChTCR and a CD19 / CD22 bispecific ChTCR) of the present disclosure, with a CAR included as a comparator. At left in both (A) and (B): Representative western blots for LAT pTyr220, Actin and LAT in lysates from T cells expressing the indicated receptor after stimulation with Nalm-6 CD19+CD22ko cells (A) or Nalm-6 CD19koCD22+ cells (B) for the indicated times. At right in both (A) and (B) are heat maps of mean band intensity of LAT pTyr220 normalized to actin loading control (n=3 independent experiments), as shown. (C) Flow plots depicting CD 19 and CD22 expression levels on Nalm-6 cells after gene knockout. (D) Left: Representative flow histograms of CellTrace Violet (CTV) dilution measured after 72h co-culture with Nalm-6 cell CD19koCD22ko (DKO, control) or Nalm-6 CD19LowCD22ko cells. Left-center: Frequency of divided cells (CTVlow cells) measured after 72h co-culture with Nalm-6 CD19LowCD22ko cells (mean ± SD) (n=3 independent healthy donors). P values from two-way ANOVA test, **P< 0.01, ***P< 0.001. Right-center and right: Concentration of IL-2 and IFN-y in culture supernatant after overnight co-culture with Nalm-6 CD19LowCD22ko cells (mean ± SD) (n=3 independent healthy donors). P values from two-way ANOVA statistical test, *P< 0.05. (E). Left: Representative flow histograms of CellTrace Violet (CTV) dilution measured after 72h co-culture with Nalm-6 DKO cells or Nalm-6 CD19koCD22Low cells. Left-center: Frequency of divided cells (CTVlow cells) measured after 72h coculture with Nalm-6 CD19koCD22Low cells (mean ± SD) (n=3 independent healthy donors). P values from two-way ANOVA statistical test, **P< 0.01, ***p< 0.001. Right-center and right:Concentration of IL-2 and IFN-y in culture supernatant after overnight co-culture with Nalm-6 CD19koCD22Low cells (mean ± SD) (n=3 independent healthy donors). P values from two-way ANOVA test, *P< 0.05. (F) Left: Schematic of NSG mice engrafted with Nalm-6 GFP-ffluc+ cells that are heterogeneous for CD 19 and CD22 expression. Right: Representative bioluminescence images of Nalm-6 GFP-ffluc+ tumor burden in mice treated with 2x106T cells expressing the indicated CARs or the Bi-ChTCR. (G) Top-left: Tumor burden (mean ± SD radiance) of tumor-bearing NSG mice treated with T cells expressing the indicated CARs or the Bi-ChTCR (n=5 to 8 mice per group). *P<0.05, **P<0.01, ***P< 0.001 by two-way ANOVA. Bottom-left: Kaplan-Meier survival of Nalm-6 GFPffluc+-bearing NSG mice treated with CARs or Bi-ChTCRs (n=5-8). *P <0.05, **P<0.01, ***P<0.001. Top-right and bottom right, as shown.Figures 20A-20H relate to an embodiment of a bispecific (BCMA / SLAMF7) chTCR of the present disclosure, with CARs included as comparators. (A) Schematic of CARs (anti-BCMA or anti- SLAMF7) and a Bi-ChTCR specific for BCMA and SLAMF7. The BCMA BB^ CAR was constructed with the Cl 1D5.3 scFv (VH-linker-VL), IgG4 hinge, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. The SLAMF7 BB^ CAR was constructed with HuLuc63 scFv (VH-linker-VL), a “long” (IgG4 4 / 2NQ) hinge, CD28 transmembrane domain, and 4-1BB and CD3z signaling domains; The BCMA / SLAMF7 Bi-ChTCR was constructed with the C11D5.3 scFv (VH-linker-VL) in fusion with TRAC and the HuLuc63 scFv (VH-linker-VL) in fusion with TRBC. (B) Left: Representative flow plots of transduced and TCRaP- and SLAMF7-base-edited primary CD8 T cells stained with recombinant SLAMF7-PE and BCMA-APC. Right: Normalized geometric mean ± SD of binding of BCMA-APC or SLAMF7-PE to CD8 T cells expressing the indicated CAR or the Bi-ChTCR. Data is shown for 6 independent experiments. **P< 0.01 by paired t-test. (C) Top-left and bottom-left: Representative western blot analysis of lysates from BCMA CAR and Bi-ChTCR or SLAMF7 CAR and Bi-ChTCR for pZap70 pTyr319 and Zap70 after crosslinking the receptor with antigen -coated beads. Top-right and bottom-right: Fold-change in mean intensity of pZap70 pTyr319 normalized to actin per stimulation timepoints. (D) Flow histograms of BCMA (left) and SLAMF7 (right) expression in INA-6 WT, INA-6 SLAMF7KO and INA-6 BCMAKO myeloma cells. (E) Left: Cytotoxic activity of CAR or Bi-ChTCR T cells against the indicated INA-6 cells measured by chromium release assay. Data is shown as the mean ± SD for 3 independent experiments. Right: Concentration of IFN-y in culture supernatant after overnight coculture of T cells expressing the indicated receptor with wild -type and single antigen knock-out INA-6 cells. Data is shown as the mean ± SD for 3 independent experiments. P< 0.05, **P< 0.01, ***p< 0.001 by two-way ANOVA. (F) Left: Schematic of NSG mice engrafted with Nalm-6 cells that are heterogeneous for BCMA and SLAMF7 antigen expression and treated with 2xl06CAR or Bi-ChTCR Tcells. Right: Bioluminescence imaging of Nalm6-ffluc tumor burden in mice after treatment with T cells expressing the indicated receptor. (G). Top: Mean ± SD radiance (photons / sec / cm2 / steradian) of Nalm-6 GFP-ffluc tumor burden for each treatment group (n=3-5 mice per group). Middle: Kaplan-Meier survival of Nalm-6 GFP-ffLuc-bearing mice in each treatment group (n=3-5 mice per group). *P<0.05, ** P <0.01. Bottom: Frequency of CAR+ and Bi-ChTCR+ T cells in the blood at indicated timepoints (% of Live+Lymphocyte+). (H) Left: Bioluminescence images of tumor burden in mice rechallenged with a mixture of BCMA+SLAMF7+, BCMA-SLAMF7+ and BCMA+SLAMF7- Nalm-6 GFP-ffluc cells 45 days after initial tumor infusion. Right: Mean of Nalm-6 GFP-ffluc tumor burden in new control group or mice previously treated with Bi-ChTCR T cells and rechallenged (mean radiance ± SD) (photons / sec / cm2 / steradian) (n=3-5 mice per group). ****P<0.0001 by two-way ANOVA.Figures 21A-21D: (A) Schematic of certain CD19-specific ChTCR and CAR constructs. (B) Schematic showing process for CAR or ChTCR transduction and cytosine base editing of TCRaP genes in primary T cells, followed by T cell expansion. (C) Representative flow cytometry plots of ChTCR T cells stained with anti TCR antibody-BV421 and recombinant CD 19 protein-APC without TCR knockout, after single (TRAC) KO, single (TRBC) KO or double (TRAC and TRBC) KO. (D) Frequency of ChTCR+ T cells without and with knockout of TRAC, TRBC or both. Data is shown as the mean ± SD for 5 independent experiments. *P<0.05, **P<0.01, ***P<0.001 and ****P<0.0001 by two-way ANOVA.Figure 22 shows western blot analysis of TCRa, TCRP and CD3^, 5, a and y subunits following immunoprecipitation of HA -tagged CAR and ChTCR receptors from transduced and gene-edited primary T cells using an anti-HA tag antibody. Cell expressing a TCR without an HA tag was used as a negative control. Proteins co -immunoprecipitated with the receptors were detected by western blot with antibodies specific to TCRa, TCRP and each of the CD3 subunits. Blotting with anti-HA was performed as a loading / immunoprecipitation control .Figures 23A-23C relate to signaling studies conducted using Jurkat reporter cells. (A) Representative flow plots showing expression of CD19-specific ChTCRs and CARs (TCR antibody- BV421 and recombinant CD19-APC) and NY-ESO-1 -specific TCR 1G4 (anti-TCR antibody-BV421 and NY-ESO-1157-165 / A2 tetramer-APC) in Jurkat J76 TPR cells. (B) Left: Representative histogram of NFATeGFP reporter expression in J76 TPR Jurkat cells expressing the indicated receptors, and mean frequency ± SD of NFAT-eGFP positive cells (n=3 independent experiments). ****P<0.0001 by two-way ANOVA. Right: Representative histogram ofNFkB-CFP reporter expression in J76 TPR Jurkat cells expressing the indicated receptors and mean frequency ± SD ofNFkB-CFP positive cells (n=3 independent experiments). ****P<0.0001 by two-way ANOVA. (C). Left: Representative western blotanalysis for LAT pTyrl71, Actin and LAT. Right: Heat map of mean band intensity of LAT pTyrl71 normalized to actin loading control (n=2 independent experiments).Figures 24A-24C show results from studies related to certain chTCRs expressed in CD4+ T cells. (A) Left: Representative flow plots of primary CD4+ T cells stained with anti-TCR antibody and recombinant CD 19 protein 7 days after lentiviral transduction and base editing to knock-out endogenous TCRaP expression. Right: Geometric mean of rCD19-APC binding to primary T cells transduced with CARs or ChTCRs (n=3 biological independent samples). (B) Left: Representative TCRaP expression by mock unedited and TCRaP gene-edited split and full ChTCR+ T cells. Right: Representative CD3s expression by mock unedited and TCRaP gene edited split- and full- ChTCR+ T cells. (C) Concentration of IL-2 (top) and IFN-y (bottom) in culture supernatant after overnight coculture of T cells expressing the indicated receptor with Nalm-6 CD19High (top-left and bottom-left) cells or Nalm-6 CD19Low cells (top-right and bottom-right) at an effector to target ratiio (E:T) of 1: 1. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.01, ***P<0.001 by two-way ANOVA.Figures 25A-25E relate to expression of certain constructs with knockout of endogenous TCR. (A) (bottom) Schematic of CD19-specific mutSTAR, split ChTCR and full ChTCR lentiviral constructs and (top) the receptors assembled at the cell surface, in association with endogenous CD3 subunits. (B) Representative flow cytometry plots of mutSTAR and ChTCR T cells stained with TCR antibody-BV421 and recombinant CD 19 protein-APC without TCR knockout, after single (TRAC) KO, single (TRBC) KO or double (TRAC and TRBC) KO. (C) Left: Frequency of mutSTAR+ T cells and of ChTCR+ T cells without TCR KO or with knockout of both TRAC and TRBC. Data is shown as the mean ± SD for 4 independent experiments. *P<0.05 by two-way ANOVA. Right: Geometric mean of rCD19-APC binding to primary T cells transduced with mutSTAR or the indicated ChTCR without TCR KO or with knockout of both TRAC and TRBC. Data is shown as the mean ± SD for 4 independent experiments. ***P<0.001 and ****P<0.0001 by two-way ANOVA. (D) Left: Representative flow cytometry plots of mutSTAR T cells stained with mouse TCRb-BV421 antibody and recombinant CD 19 protein-APC without TCR knockout, after single (TRAC) KO, single (TRBC) KO or double (TRAC and TRBC) KO. Right: Geometric mean of mouse TCRb-BV421 in primary T cells transduced with mutSTAR without TCR KO, after single (TRAC) KO, single (TRBC) KO or double (TRAC and TRBC) KO. Data is shown as the mean ± SD for 4 independent experiments. *P<0.05 and **P<0.01 by two-way ANOVA. (E) Left: Representative flow cytometry histogram of TCR KO T cells expressing mutSTAR, split chTCR, or full ChTCR stained with CD3a-BUV395 antibody. Left-center: Geometric mean of CD3a-BUV395 on TCR KO T cells expressing mutSTAR, split ChTCR, or full ChTCR. Data is shown as the mean ± SD for 3 independent experiments. **P<0.01 by two-way ANOVA. Right-center and right: Concentration of IL-2and IFN-y in culture supernatant after overnight co-culture of T cells expressing the indicated receptor (and for one mutSTAR experimental group, with TCRKO) with Nalm-6 CD19Low target cells at an effector to target ratio (E:T) of 1 : 1. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.01, ***P<0.001 by two-way ANOVA.Figures 26A-26F: (A) Schematic of construct encoding a CD19-specific HLA-independent T cell receptor (“HIT receptor”) and its targeted knock-in within the TRAC locus. (B) Left and left-center: Representative flow cytometry plots of TRAC-knocked-in HIT T cells stained with TCRab-BV421 and recombinant CD 19 protein-APC with or without TRBC KO. Right-center: Frequency of HIT+ T cells with or without TRBC KO. Data is shown as the mean ± SD for 3 independent experiments. Right: Geometric mean of rCD19-APC binding to primary T cells expressing the HIT receptor with or without TRBC KO. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05 by two-way ANOVA. (C) Left and left-center: Concentration of IFN-y and IL-2 in culture supernatant afer overnight co-culture of T cells expressing the HIT receptor with or without TRBC KO with Nalm-6 CD19Low target cells at an effector to target ratio (E:T) of 1 : 1. Data is shown as the mean for 3 independent experiments. *P<0.05 by two-way ANOVA. Right-center and right: Representative histograms of CellTrace Violet (CTV) dye dilution in T cells expressing the indicated receptor measured after 3 days of co-culture with Nalm-6 CD19Low tumor cells. Right: Percent of divided cells (mean) for 3 independent experiments. (D) Representative flow cytometry plots of primary T cells expressing HIT receptor, split ChTCR, or full ChTCR stained with TCRab-BV421 and recombinant CD19 protein-APC with TCR KO. (E) Left: Representative flow cytometry histogram of TCR KO T cells expressing the indicated receptor and stained with TCRab-BV241 antibody. Right: Geometric mean of TCRab-BV421 in TCR KO T cells expressing HIT receptor, split ChTCR, or full ChTCR. Data is shown as the mean ± SD for 3 independent experiments. **P<0.0I, ***P<0.001 by two-way ANOVA. (F) Left: Representative flow cytometry histogram of TCR KO T cells expressing the indicated receptor and stained with CD3s-BUV395 antibody. Left-center: Geometric mean of CD3a-BUV395 in TCR KO T cells expressing HIT receptor, split ChTCR, or full ChTCR. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.01 by two-way ANOVA. Right-center and right: Concentration of IFN-y and IL-2 in culture supernatant after overnight co-culture of TCR KO T cells expressing HIT receptor, split ChTCR or full ChTCR with Nalm-6 CD 19Low target cells at an effector to target ratio (E:T) of 1: 1. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.0I, ***P<0.001 by two-way ANOVA.Figures 27A-27C relate to certain embodiments of the present disclosure. (A) Left: CD22 expression measured by flow cytometry on Nalm-6 WT or CD22ko cells. Right: Schematic of anti-CD22 CAR and Full ChTCRs (CAR and ChTCRs using m971 scFvs; ChTCRs using scFv in VH-linker-VL orVL-linker-VH orientation with TRAC. (B) Left: Representative flow plots showing expression of CD22- specific CAR and Full ChTCRs in primary CD8+ T cells (TCRa / b-BV421 and rCD22-APC). Right: Geometric mean ± SD of rCD22-protein-APC bound to receptors (n=2 independent experiments). *P<0.05 by two-way ANOVA. (C) Concentration of IL-2 (left) or IFN-y (right) in culture supernatant after overnight co-culture of CAR and ChTCR T cells with the indicated Nalm-6 cells (mean ± SD, n=2 independent experiments).Figures 28A-28E: (A) Schematic of CD22-specific CAR, Split ChTCR and Full ChTCRs using 9A8 scFvs. (B) Representative flow plots of CAR and ChTCR expression on primary CD8 T cells stained with TCRab-BV421 and recombinant CD22-protein-APC. (C) Left: Geometric mean ± SD of recombinant CD22-protein-APC bound to CD22-specific receptors (n=3 independent experiments). *P<0.05 by two-way ANOVA. Right: Geometric mean ± SD of TCRab-BV421 expression by CD22- specific ChTCRs (n=3 independent experiments). **P<0.01 by two-way ANOVA. (D) CD22 expression by Nalm-6 WT, CD22ko and CD22Low target cells measured by flow cytometry. (E) Left: Schematic of CD22-specific 28^ and 4-lBB^ CARs, Split ChTCR, and Full ChTCRs using 9A8 scFvs (or VH and VL for the Split ChTCR) as indicated. Center and right: Concentration of IFN- and IL-2 in culture supernatant afer overnight co-culture of T cells expressing the indicated CD22-specific receptor with Nalm-6 CD22Low target cells at an effector to target ratio (E:T) of 1 : 1. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 by two-way ANOVA.Figures 29A-29F: (A) Schematic of CD 19- and CD22- mono- and bispecific receptor constructs. (B). Left: Representative histogram of NFAT-GFP reporter expression in J76 TPR Jurkat cells expressing the indicated receptor. Center: Frequency of NFAT-GFP positive cells. Right: Geometric mean ± SD of NFAT-GFP reporter gene (n=3 independent experiments). *P<0.5, **P<0.01, *** PO.OOl, ****PO .0001 by two-way ANOVA. (C) Left: Representative histogram ofNFkB-CFP reporter expression in J76 TPR Jurkat cells expressing the indicated receptor. Center: Frequency ofNFkB-CFP positive cells. Right: Geometric mean ± SD ofNFkB-CFP reporter gene (n=3 independent experiments). *P<0.5, **P<0.01, *** PO.OOl, ****P<0.0001 by two-way ANOVA. (D) Left: Representative histograms of AP-l-m Cherry reporter expression in J76 TPR Jurkat cells expressing the indicated receptor. Center: Frequency of AP-l-m Cherry positive cells. Right: Geometric mean ± SD of AP-1- mCherry reporter gene (n=3 independent experiments). *P<0.5, **P<0.01, *** PO.OOl, ****P0.0001 by two-way ANOVA. (E) Left: CD 19 and CD22 expression by Nalm-6 WT, CD19+CD22ko, CD19koCD22+ and CD19koCD22ko target cells measured by flow cytometry. Right: Concentration of IFN-y in culture supernatant after overnight co-culture of T cells expressing the indicated CARs and Bi- ChTCRs with indicated Nalm-6 cell lines. Data is shown as the mean ± SD for 3 independentexperiments. *P<0.05 and **P<0.01 by two-way AN OVA. (F) Cytotoxicity of the indicated Nalm-6 cell lines by CAR and Bi-ChTCR T cells at varying E:T ratios.Figures 30A-30E: (A) Left: Representative flow histograms of SLAMF7 expression on primary CD8 T cells KO for SLAMF7 using cytodine base editing (CBE) and one of 5 different SLAMF-7 specific sgRNAs. Right: Frequency of SLAMF7+ cells after gene editing (n=2 independent experiments). (B) Left: Representative flow plots of CD8 primary T cells edited or not for TRAC and TRBC and / or SLAMF7. Right: Frequency ± SD of TCRab and SLAMF7+ cells after TRAC and TRBC KO with or without concomitant SLAMF7 KO (n=3 independent experiments). ***P<0.001 and ****P<0.0001 by two-way ANOVA. (C) Left: Schematic of SLAMF7-specific split and full ChTCRs. Right: Representative flow cytometry plots of split and full ChTCR T cells stained with TCRab-BV421 and recombinant SLAMF7 protein -APC. (D) Left: Geometric mean of rSLAMF7-APC binding to primary T cells transduced with split or full ChTCR as indicated. Data is shown as the mean ± SD for 2 independent experiments. Center: Geometric mean of CD3a-BUV395 in primary T cells transduced with split or full ChTCRs. Data is shown as the mean ± SD for 2 independent experiments. **P<0.01 by two-way ANOVA. Right: Percent of divided cells after co-culture of SLAMF7-specific split or full ChTCR T cells on plate-bound antigen for 3 days (mean ± SD for 2 independent experiments). *P<0.05 by two-way ANOVA. (E) Left: Schematic of BCMA-specific split and full ChTCRs. Left-center: Representative flow cytometry plots of split and full ChTCR T cells stained with TCRab-BV421 and recombinant BCMA protein-APC. Center-right: Geometric mean of rBCMA-APC binding to primary T cells transduced with split or full ChTCR. Data is shown as the mean ± SD for 2 independent experiments. ****P<0.0001 by two-way ANOVA. Right: Geometric mean of CD3s-BUV395 in primary T cells transduced with split or full ChTCR. Data is shown as the mean ± SD for 2 independent experiments. **P<0.01 by two-way ANOVA. Bottom: Percent of divided cells after co-culture of BCMA-specific split or full ChTCR T cells on plate-bound antigen for 3 days (mean ± SD for 2 independent experiments). *P<0.05 by two-way ANOVA.Figures 31A-31D: (A) Schematic of BCMA / SLAMF7 Bi-ChTCRs with different configurations of scFv and connection to TCR constant domain. (B) Representative flow plots of Jurkat 76 TPR cells expressing the indicated Bi-ChTCR after staining with recombinant SLAMF7 and BCMA protein. (C) Geometric mean ± SD of rBCMA-PE (left) and rSLAMF7-APC (right) bound to receptors (gated on Bi- ChTCR+ cells; n=3 independent experiments). (D) Right: Representative histogram of CD3s expression in Bi-ChTCR+ and Jurkat TPR cells. Right: Geometric mean ± SD of CD3a expression (gated on Bi- ChTCR+ cells; n=3 independent experiments).Figures 32A-32D relate to certain embodiments of bispecific (BCMA / SLAMF7) ChTCRs of the present disclosure, with CARs included as comparators. (A) Schematic of SLAMF7- and BCMA- mono- or bispecific receptor constructs. (B) Left: Absolute numbers ± SD of BCMA-specific CAR, SLAMF7- specific CAR, and Bi-ChTCR (BCMA / SLAMF7) T cells. Right: Viability ± SD of BCMA and SLAMF7 CAR T cells and Bi-ChTCR T cells (n=3 independent experiments). (C) Left: Cytotoxicity assay of CAR T cells and Bi-ChTCR T cells using different ratios of Nalm-6 SLAMF7+BCMAko and SLAMF7koBCMA+ tumor cells to mimic antigen heterogeneity (Data is shown as the mean ± SD at an E:T of 10: 1, n=3 independent experiments). Center and right: IFN-y production (pg / mL) of CAR T cells and Bi-ChTCR T cells to various concentrations of plate bound recombinant BCMA protein or recombinant SLAMF7 protein (n=3 independent experiments). (D) Left: Flow cytometry histogram of MOLP8 and H929 multiple myeloma cell lines stained with BCMA -PE (absolute number of BCMA molecules shown). Center and right: Concentration of IFN-y in culture supernatant afer overnight coculture of T cells expressing indicated BCMA-specific receptor with H929 (h) and MOLP8 (i) target cells at an effector to target ratio (E:T) of 1 : 1. Data is shown as the mean ± SD for 3 independent experiments. *P<0.05, **P<0.01 by two-way ANOVA.Figures 33A-33C: (A) Left: Representative flow plots showing binding of recombinant BCMA- APC and SLAMF7-PE to primary CD8 T cells transduced with the BCMA / SLAMF7 bispecific CAR or Bi-ChTCR. Center and right: Geometric mean ± SD of rBCMA-APC (center) and rSLAMF7-PE binding to bispecific CAR and bi-ChTCR T cells (right) (gated on receptor positive cells; n=2 independent experiments). (B) Representative western blot analysis for pZap70 pTyr319 and Zap70 for Bi-ChTCR or bispecific CAR stimulated with 0.5M of rBCMA (1), 0.5M of rSLAMF7 (2), 0.25M of rBCMA + 0.25M rSLAMF7 (3) or .05M rBCMA + 0.5M rSLAMF7 (4) coated-beads for indicated time. (C) Mean band intensity ± SD for pZap70 pTyr319 normalized to standard (n=2 independent experiments).DETAILED DESCRIPTIONThe present disclosure provides compositions and methods for improving cellular immunotherapy, such as against cancer, infection, autoimmune disease, or neurodegenerative disease.Disclosed embodiments include polypeptide dimers (referred to herein as “chimeric TCRs” or “chTCRs”, also referred to as “TCR / CARs”) that confer to a host cell (e.g. a T cell) target-specificity (including, in some contexts, high binding affinity and / or non-MHC-restricted binding) of a CAR while leveraging natural T cell signaling properties. ChTCRs can be efficiently expressed at the surface of, for example, host T cells and confer to host T cells a diversified and highly sensitive signaling complex that acts with native T cell signaling properties. In some embodiments, a T cell expressing a chTCR has oneor more of the following properties as compared to a T cell expressing a CAR that binds the same target(s): increased sensitivity to antigen; increased production of one or more cytokine (e.g., IFN-y, IL- 2); increased killing against cells expressing the target(s); increased proliferation when in the presence of the target(s); reduced basal or non-specific activation; increased survival of a model mammal comprising cells expressing the target(s) (e.g, target-expressing cancer cells); increased antitumor activity against tumor cells expressing the target(s); lower target EC50 for production of IL-2 and / or IFN-y; higher avidity (e.g., a greater amount of chTCR-expressing cells bound to target); and association of the chTCR with one or more CD3 proteins.In some embodiments, a T cell expressing a chTCR has one or more of the following properties as compared to a T cell expressing a STAR, mutSTAR, or HIT receptor (see herein) that binds the same target: improved expression of the antigen-binding receptor; increased sensitivity to antigen; increased production of one or more cytokine (e.g., IFN-y, IL-2); increased killing against cells expressing the target; increased proliferation when in the presence of the target; reduced basal or non-specific activation; increased survival of a model mammal comprising cells expressing the target (e.g., target-expressing cancer cells); increased antitumor activity against tumor cells expressing the target; lower target EC50 for production of IL-2 and / or IFN-y; higher avidity (e.g., a greater amount of chTCR-expressing cells bound to target); and association of the chTCR with one or more CD3 proteins (CD3g CD3s. CD3y, and / or CD35).Certain embodiments provide a chTCR that binds to a human CD22 (e.g. , in an extracellular domain thereof). In some embodiments, a chTCR comprises a binding domain that binds to a membrane - proximal epitope in human CD22. In some embodiments, a chTCR comprises a binding domain that binds to a membrane-distal epitope in human CD22. In some embodiments, a chTCR comprises a binding domain that competes with antibody 9A8 for binding to human CD22. In some embodiments, the chTCR comprises a CD22-binding domain (e.g., a scFv) derived from antibody 9A8 or antibody m971, or from another CD22-specific antibody. In certain further embodiments, the chTCR further comprises a binding domain (e.g, a scFv) that binds a human CD19. In some embodiments, the CD19-binding domain is derived from antibody FMC63. In certain preferred embodiments, a chTCR comprises a CD22 -binding domain derived from antibody 9A8 and a CD19-binding domain (e.g., a scFv) derived from FMC63. In some embodiments, a chTCR comprises a CD22-binding domain (e.g., a scFv) comprising the six CDRs, and optionally the VH and VL, of antibody 9A8 or of antibody m971, and a CD 19 -binding domain (e.g, a scFv) comprising the six CDRs, and optionally the VH and VL, of antibody FMC63.In some embodiments, the CD19-binding domain is fused to a TCR a-chain constant domain of the chTCR and the CD22-binding domain is fused to a TCR P-chain constant domain of the chTCR. In other embodiments, the CD22-binding domain is fused to a TCR a-chain constant domain of the chTCR and the CD19-binding domain is fused to a TCR P-chain constant domain of the chTCR.In other embodiments, the present disclosure provides chTCRs that bind human GPRC5D and human BCMA. In other embodiments, the present disclosure provides chTCRs that bind human SLAMF7 and human BCMA.In some embodiments, a chTCR that binds human BCMA comprises a binding domain (e.g., a scFv) comprising the six CDRs, and optionally the VH and VL, of antibody Cl 1D5.3. In some embodiments, a chTCR that binds human SLAMF7 comprises a binding domain (e.g., a scFv) comprising the six CDRs, and optionally the VH and VL, of antibody huLuc63.In some embodiments, a host cell, e.g. a human T cell such as a CD8+ T cell or a CD4+ T cell, encodes or expresses a chTCR and comprises a chromosomal knockout (e.g., an introduced splicing site or stop codon that disrupts expression of a gene product) at a genomic locus encoding a TRAC, a TRBC, a SLAMF7, a TIGIT, or any combination thereof. Introducing a chromosomal (e.g., gene) knockout may comprise, for example, inducing a double-strand DNA break, base editing, or the like. In some embodiments, a polynucleotide sequence encoding the chTCR is not integrated into an endogenous TRAC, TRBC, SLAMF7, or TIGIT locus, or is not integrated into a chromosome of the host cell.In some embodiments, a host cell comprises a mutation (e.g. , a point mutation) resulting in a stop codon, a splice site mutation, or a missense mutation, in an endogenous TRAC locus and in an endogenous TRBC locus, and a polynucleotide encoding the chTCR is not disposed within or integrated into the endogenous TRAC locus or the endogenous TRBC locus. Introduction of a splicing site or stop codon that disrupts expression of the encoded gene product can be performed using any suitable means, such as base editing (e.g., cytodine base editing) as described herein. Introduction of a chromosomal splice site mutation that disrupts expression of the encoded gene product can be performed using any suitable means, such as base editing (e.g., cytodine base editing) as described herein. Introduction of a missense mutation that disrupts expression of the encoded gene product, or that disrupts expression of the functional encoded gene product, can be performed using any suitable means, such as base editing (e.g., cytodine base editing) as described herein. In some embodiments, the host cell comprises an introduced splicing site or stop codon in an endogenous TRAC locus. In some embodiments, the host cell comprises an introduced missense mutation in an endogenous TRAC locus. In some embodiments, the host cell comprises a chromosomal splice site mutation in an endogenous TRAC locus. In some embodiments, the host cell comprises an introduced splicing site or stop codon in an endogenous TRBC locus. In someembodiments, the host cell comprises a splice acceptor mutation in an endogenous TRAC locus, in an endogenous TRBC locus, or both. In some embodiments, a host cell comprises a splice donor mutation in an endogenous TRAC locus, in an endogenous TRBC locus, or both. In some embodiments, the host cell comprises an introduced splicing site or stop codon in an endogenous TRAC locus and in an endogenous TRBC locus. In some embodiments, the host cell comprises an introduced missense mutation or chromosomal splice site mutation in an endogenous TRAC locus and in an endogenous TRBC locus. In some embodiments, the host cell comprises or further comprises an introduced splicing site or stop codon in an endogenous SLAMF7 locus. In some embodiments, the host cell comprises an introduced missense mutation or chromosomal splice site mutation in an endogenous SLAMF7 locus. In some embodiments, the host cell comprises or further comprises an introduced splicing site or stop codon in an endogenous TIGIT locus. In some embodiments, the host cell comprises an introduced missense mutation or chromosomal splice site mutation in an endogenous TIGIT locus.Certain embodiments provide host cells, such as T cells, e.g., human T cells, e.g., CD8+ T cells and / or CD4+ T cells, that (i) comprise chromosomal knockout (e.g., an introduced splicing site or stop codon that disruptes expression of the gene product) at a genomic locus encoding a TRAC, at a genomic locus encoding a TRBC, at a genomic locus encoding a SLAMF7, at a genomic locus encoding a TIGIT, or any combination thereof, and (ii) an introduced polynucleotide or expression cassette or construct (e.g., delivered into the cell using a viral vector such as for example a lentiviral vector, and / or introduced into the cell using a lipid nanoparticle composition, and / or integrated into the genome of the cell) that encodes (1) a chTCR (e.g, as described herein and / or as described in PCT / US2023 / 066466 which published as WO2023215725), (2) a TCR, (3) a single-chain TCR, (4) a STAR or mutSTAR receptor (see, e.g., Liu et al., Sci. Trans I. Med. 13, eabb5191 (2021)) (5) a HIT receptor (see, e.g., Mansilla-Soto, J., et al.. HLA- independent T cell receptors for targeting tumors with low antigen density. Nature Medicine, 2022) and / or (6) a Co-STAR receptor (see, e.g., Mog et al. Sci Transl Med. 16(155) 2024, DOI:10.1126 / scitranslmed.adg7123. In some embodiments, a chromosomal (e.g., gene) knockout comprises an introduced splicing site or stop codon that disrupts expression of the encoded TRAC, TRBC, SLAMF7, or TIGIT. A splicing site or stop codon can be introduced into a host cell (e.g., T cell) chromosomal position (e.g., gene locus) using, for example, base editing as described herein. A missense mutation or chromosomal splice site mutation can be introduced into a host cell (e.g., T cell) chromosomal position (e.g., gene locus) using, for example, base editing as described herein. Base editing can be performed, for example, using a Cas9-based (NGG PAM) cytosine base editing enzyme, which can be introduced into a cell as mRNA. CBE4max (available from TriLink or Aldevron as mRNA), AncBE4max, or the like may be used. Cytidine and adenine base editors useful in accordance with thepresent disclosure include those described in, for example, Koblan et al. , Nat Biotechnol. 2018 October; 36(9): 843-846. doi: 10.1038 / nbt.4172, the base editors, related methods, and amino acid and nucleic acid sequences of which (including in the supplemental materials thereof) are incorporated herein by reference. Base editing can be performed on T cells, for example, beginning at about 2 days following activation of the T cells with anti-CD3 / anti-CD28-coated beads. In some embodiments, the host cell does not comprise an introduced double-strand break in a genomic TRAC, TRBC, SLAMF7, and / or TIGIT locus. In some embodiments, a sequence encoding the chTCR, STAR, mutSTAR, TCR, scTCR, Co- STAR, or HIT receptor is integrated into a host cell chromosomal TRAC locus and the host cell comprises a chromosomal knockout (e.g., an introduced splicing site or stop codon) in a host cell chromosomal TRBC locus. In some embodiments, a sequence encoding the chTCR, STAR, mutSTAR, TCR, scTCR, Co-STAR, or HIT receptor is integrated into a host cell chromosomal TRBC locus and the host cell comprises a chromosomal gene knockout (e.g., an introduced splicing site or stop codon) in a host cell chromosomal TRAC locus.In some embodiments, a method is provided that comprises: introducing a chromosomal (e.g., gene) knockout into a TRAC locus, into a TRBC locus, or into both, of a host cell (e.g., a human T cell), wherein the host cell comprises an introduced polynucleotide or expression cassette or construct encoding, or wherein the host cell exogenously expresses, a chTCR, a STAR, a mutSTAR, a TCR, a Co- STAR, a scTCR, or a HIT receptor.In some embodiments, a method is provided that comprises: introducing into a host cell (e.g., a human T cell) a polynucleotide or expression cassette or construct encoding a chTCR, a STAR, a mutSTAR, a TCR, a scTCR, a Co-STAR, and / or a HIT receptor, and introducing into the host cell a chromosomal gene knockout in a TRAC locus, in a TRBC locus, or in both.In some embodiments, a method is provided that comprises the following steps: (1) obtaining a plurality of T cells from a donor (e.g. , a healthy human donor or a human donor with a diagnosed disease or condition), or thawing a plurality of cryopreserved T cells from a donor (e.g., a healthy human donor or a human donor with a diagnosed disease or condition); (2) about one day after (1), activating T cells of the plurality, e.g. using anti-CD3 / anti-CD28 beads; introducing (e.g., using a lentivirus) into T cells of the plurality a polynucleotide encoding a chTCR, STAR or mutSTAR, TCR, scTCR, Co-STAR, or HIT receptor; and about one day after (2), introducing into a chromosomal TRAC locus, a chromosomal TRBC locus, or into an endogenous TRAC locus and into an endogenous TRBC locus of T cells of the plurality, a splicing site or stop codon that disrupts expression of the encoded TRAC or TRBC. In certain embodiments, the introducing a splicing site or stop codon comprises base editing. In certain embodiments, the method further comprises expanding T cells of the plurality (e.g., having confirmedexpression of the chTCR, STAR, mutSTAR, TCR, scTCR, Co-STAR, or HIT receptor and / or having a confirmed introduced splicing site or stop codon).Presently disclosed chTCRs demonstrate advantages over CARs that bind to the same target(s), and in some cases that comprise a binding domain (e.g. , scFv) derived from the same antibody as a targetbinding domain of a chTCR. In some embodiments, a chTCR (or host cell expressing the same) has reduced tonic signaling, reduced NF AT expression, increased antigen-sensitivity, increased expression, improved bispecificity (e.g., is more resistant to loss of one antigen), improved cytokine production, improved antitumor activity, improved signaling in response to antigen, or any combination of the foregoing, as compared to a reference single-chain CAR. In some embodiments, host cells (e.g., T cells) express a chTCR more efficiently and / or more robustly than reference host cells express a CAR that binds the same target(s) as the chTCR.In some embodiments, a chTCR comprises (1) a first polypeptide comprising a first TCR constant domain and (2) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another. The association can comprise native interactions between cognate TCR constant domains (e.g. a native disulfide bond), engineered interactions between the TCR constant domains (e.g. one or more disulfide bonds introduced by protein engineering, knob-into-hole-type interactions, and / or charge-pair interactions), or both. In some embodiments, one or both of the first polypeptide and the second polypeptide further comprises a target-binding domain disposed N-terminal to the TCR constant domain, and the target-binding domain does not comprise one or more TCR variable regions. In certain embodiments, one or both of the first polypeptide and the second polypeptide comprises a target-binding domain disposed N-terminal to the TCR constant domain, wherein the target binding domain is selected from the target binding domains described herein. In certain embodiments, one or both of the first polypeptide and the second polypeptide comprises a target-binding domain disposed N-terminal to the TCR constant domain, wherein the target binding domain is selected from the target binding domains described herein and one or both of the first polypeptide and the second polypeptide may further comprise a TCR variable domain, provided that one or both of the first polypeptide and the second polypeptide comprise a target-binding domain that is not, or does not comprise, a TCR variable domain.ChTCRs are preferably heterodimers (z.e., at least the TCR constant domains of the two polypeptides are different to one another), though chTCRs wherein the TCR constant domains of the two polypeptides are the same or substantially the same (e.g. are homodimeric with respect to the constant domains; see e.g. Groettrup et al. EMBO J 77(7):2735-2745 (1992)) are also contemplated. In some embodiments, the first TCR constant domain comprises a TCR alpha-chain constant domain (Ca) and thesecond TCR constant domain comprises a TCR beta-chain constant domain (CP). In other embodiments, the first TCR constant domain comprises a C and the second TCR constant domain comprises a Ca.In some embodiments, the first TCR constant domain and the second TCR constant domain each comprise a human TCR constant domain or an engineered variant thereof.In some embodiments, the first polypeptide and / or the second polypeptide of a chTCR comprises an intracellular portion that consists essentially of or that consists of the intracellular portion of the respective TCR constant domain. In some embodiments, the first polypeptide and / or the second polypeptide (preferably, both) does not comprise an intracellular signaling component (e.g. effector domain) from a CD3 protein, such as CD3g In some embodiments, the first polypeptide and / or the second polypeptide (preferably, both) does not comprise an intracellular costimulatory domain from a costimulatory protein, such as CD28, 4-1BB, ICOS, CD27, 0X40, DAP10, or any combination thereof. In some embodiments, the first polypeptide and / or the second polypeptide (preferably, both) does not comprise an immunoglobulin CHI, an immunoglobulin CH2, an immunoglobulin CH3, and / or an immunoglobulin CL (light chain constant domain). In some embodiments, the first polypeptide and / or the second polypeptide (preferably, both) does not comprise an immunoglobulin CHI, an immunoglobulin CH2, an immunoglobulin CH3, and / or an immunoglobulin CL (light chain constant domain) disposed C-terminal of the TCR constant domain(s). In some embodiments, a chTCR does not comprise an immunoglobulin hinge disposed between a TCR constant domain and a target-binding domain. In some embodiments, a chTCR does not comprise a spacer domain (e.g., an IgG CH3 or CH2- CH3 spacer) disposed between a TCR constant domain and a target-binding domain. In some embodiments, a chTCR does not comprise a linker disposed between a TCR constant domain and a target-binding domain. In some embodiments, a CHTCR comprises a linker or spacer of at most 15, at most 14, at most 13, at most 12, at most 11, at most 10, at most 9, at most 8, at most 7, at most 6, at most 5, at most 4, at most 3, at most 2, or 1, amino acid(s) disposed between a TCR constant domain and a target-binding domain. In some embodiments, a target-binding domain is fused directly to a N-terminal end of a TCR constant domain. In some embodiments, a (one) TCR constant domain of a chTCR does not comprise a binding domain or a portion or fragment thereof linked or fused thereto.The target-binding domain can comprise any naturally occurring or engineered binding domain suitable for binding a target of interest, such as, for example, an antibody heavy chain variable domain (VH), an antibody light chain variable domain (VL), a VH and a VL, a single-chain variable fragment (scFv) comprising VH-linker-VL or VL-linker-VH, a fragment antigen-binding region (Fab), a singlechain Fab, an antigen-binding fragment of a heavy chain-only antibody (VHH, also referred-to as a nanobody), a killer immunoreceptor from aNK cell, a designed ankyrin repeat protein (DARPin (Binz etal., J. Mol. Biol. 332:489, 2003 and Binz et al., Nat. Biotechnol. 22:515, 2004)), a10FNIII domain such as an Adnectin™ or monobody ((Richards et al., J. Mol. Biol. 326'. 1475, 2003; Parker et al. , Protein Eng.Des. Selec. 7 <3:435, 2005 and Hackel et al. (2008) J. Mol. Biol. 381: 1238-1252)), a lectin binding domain, a receptor ectodomain or functional portion or fragment thereof, provided that the receptor ectodomain does not comprise a TCR variable domain, a ligand such as e.g. a cytokine, a fully synthetic polypeptide (e.g. designed in silico, such as using the AlphaFold modeling program), a fibrinogen domain (see, e.g., Weisel et al., Science 230: 1388, 1985), Kunitz domains (see, e.g., US Patent No. 6,423,498), a cysteine- knot miniprotein (Vita et al. (1995) Proc. Nat'l. Acad. Sci. (USA) 92:6404-6408; Martin et al. (2002) Nat. Biotechnol. 21 :1\, 2002 and Huang et al. (2005) Structure 13:155, 2005; Lui et al. Nature Communications 11:295 (2020)), a tetratricopeptide repeat domain (Main et al., Structure 11A91, 2003 and Cortajarena et al., ACS Chem. Biol. 3: 161, 2008), a leucine-rich repeat domain (Stumpp et al., J. Mol. Biol. 332A1 , 2003), a lipocalin domain (see, e.g., NlO 2006 / 095164, Beste et al., Proc. Nat'l. Acad. Sci. (USA) 96: 1898, 1999 and Scheinfeld et al., Proc. Nat'l. Acad. Sci. (USA) 706:8198, 2009), an armadillo repeat protein (see, e.g., Madhurantakam et al., Protein Sci. 21: 1015, 2012; PCT Patent Application Publication No. WO 2009 / 040338), an affilin (Ebersbach et al., J. Mol. Biol. 372: 172, 2007), an affibody, an avimer, a knottin, a fynomer, an atrimer, cytotoxic T-lymphocyte associated protein-4 (Weidle et al., Cancer Gen. Proteo. 70: 155, 2013) orthe like (Nord et al. , Protein Eng. <3:601, 1995; Nord et al., Nat. Biotechnol. 15:112, 1997; Nord et al., Euro. J. Biochem. 268A269, 2001; Binz et al., Nat. Biotechnol. 23: 1257, 2005; Boersma and Pltickthun, Curr. Opin. Biotechnol.22A 9, 2011), a centyrin, or the like, or any combination thereof.In some embodiments, a target-binding domain is “split” across the first polypeptide and the second polypeptide of a chTCR, meaning that the component parts of a target-binding domain are dispersed between the first polypeptide and the second polypeptide; for example, where a VH and a VL together function to bind to a target, the VH may be comprised in the first polypeptide and the VL is comprised in the second polypeptide, or vice versa. In some embodiments, a target-binding domain is fully comprised in one TCR constant domain-containing polypeptide. For example, a scFv (VH-linker- VL or VL-linker-VH) may be comprised in the first polypeptide or the second polypeptide of a chTCR; such an arrangement can be described as “full-scFv”. As another example of a “full” format, a scFab (e.g., VH-CH1 -linker- VL-CL or VL-CL-linker-VH-CHl) may be comprised in the first polypeptide or the second polypeptide of a chTCR. As another example of a “full” format, a VHH or antibody variable domain (VH or VL) that is itself capable of binding the target (i. e. , does not require the presence of the cognate variable domain) may be comprised in the first polypeptide or the second polypeptide of a chTCR.In some embodiments, both of the first polypeptide and the second polypeptide fully comprise a target-binding domain. For example, the first polypeptide can comprise a Ca linked or fused to a first scFv and the second polypeptide can comprise a Cp linked or fused to a second scFv. A target binding domain can be fused directly to a TCR constant domain or can be linked thereto by a linker, such as, for example, a hinge sequence.In some embodiments, a target binding domain or a portion thereof is fused directly to a TCR constant domain.In some embodiments, a scFv is fused directly to a TCR constant domain. In some embodiments, first a scFv is fused directly to a Ca and a second scFv is fused directly to a C . In some embodiments, a VH or a VL of an antibody is sufficient to confer specific binding to a target (e.g. , binding interactions between the antibody and its target occur, or can occur, through only VH and the target or through only VL and the target); accordingly, in certain embodiments, a chTCR, or a first polypeptide and / or a second polypeptide of a chTCR, comprises only a VH or a VL as a binding domain.Certain embodiments provide multispecific (e.g. bispecific) chTCRs. In some contexts, a multispecific chTCR binds to two or more antigens that are expressed by a cancer; for example, to target multiple myeloma, a multispecific chTCR may target any two or more of: BCMA, GPRC5D, SLAMF7, CD 19, CD229, and CD22. In some embodiments, a multispecific chTCR binds to CD 19 and CD22, or binds to or binds to BCMA and SLAMF7, or binds to BCMA and GPRC5D. In certain embodiments, a target comprises a protein ligand and a binding domain is from a receptor for the ligand. For example, a binding domain can comprise a receptor ectodomain from Bcl2 and a target comprises BIM.Also provided are chimeric co-stimulatory receptor polypeptides (CCRs) that are capable of improving host cell (e.g. T cell) function when the host cell encounters PVR aka CD 155. PVR aka CD 155 is often overexpressed by tumor cells and is a shared ligand for two T cell proteins, CD226 and TIGIT. CD226 can be gradually lost following chronic antigen stimulation, while TIGIT is expressed following T cell activation and becomes constitutively expressed during T cell exhaustion. TIGIT has a higher affinity for PVR (approximately 100-fold) than does CD226. Disclosed CCRs modulate PVR / TIGIT / CD226 signaling and improve one or more function of a host (e.g. T) cell in the presence of PVR (e.g. in the presence of tumor cells).In some embodiments, a CCR comprises an extracellular binding domain from CD226 (e.g. can comprise a CD226 ectodomain (also referred-to as extracellular domain)), or a portion or variant thereof that is functional to bind PVR. The CCR can further comprise a transmembrane domain from CD226. In other embodiments, a CCR comprises an extracellular binding domain from TIGIT (e.g. can comprise a TIGIT ectodomain), or a portion or variant thereof that is functional to bind PVR. The CCR can furthercomprise a transmembrane domain from TIGIT. A CCR further comprises an intracellular component designed to preserve normal CD226 signaling or disrupt or abrogate normal TIGIT signaling, such as by abrogating this signaling and / or by converting this signaling into an activating or co-stimulatory signal. A CCR may comprise a signaling (e.g. costimulatory) domain from, for example, CD2, CD28, 4- IBB, 0X40, CD27, CD3e, CD35, CD3y, CD3^, CD79A, CD79B, SLAMF1, ICOS, DAP10, CD25, CARD11, FcRa, FcRp, FcRy, Fyn, HVEM, LIGHT, CD30, Lek, LAG3, LAT, LRP, NKG2D, NOTCH1, NOTCH2, NOTCH3, NOTCH4, ROR2, Ryk, Slp76, pTa, TCRa, TCRp, TRIM, Zap70, PTCH2, or the like. Any of these signaling domains or any combination of these signaling domains may be present in a CCR.Thus, a CCR may comprise a CD226 ectodomain and a signaling (e.g. costimulatory) domain from, for example, CD2, CD28, 4-1BB, 0X40, CD27, CD3e, CD35, CD3y, CD3^, CD79A, CD79B, SLAMF1, ICOS, DAP10, GITR, CD25, CARD11, FcRa, FcRp, FcRy, Fyn, HVEM, LIGHT, CD30, Lek, LAG3, LAT, LRP, NKG2D, NOTCH 1, NOTCH2, NOTCH3, NOTCH4, ROR2, Ryk, Slp76, pTa, TCRa, TCRp, TRIM, Zap70, or PTCH2. A CCR may comprise a TIGIT ectodomain and a signaling (e.g. costimulatory) domain from, for example, CD2, CD28, 4-1BB, 0X40, CD27, CD3e, CD35, CD3y, CD3^, CD79A, CD79B, SLAMF1, ICOS, DAP10, GITR, CD25, CARD11, FcRa, FcRp, FcRy, Fyn, HVEM, LIGHT, CD30, Lek, LAG3, LAT, LRP, NKG2D, NOTCH1, NOTCH2, NOTCH3, NOTCH4, ROR2, Ryk, Slp76, pTa, TCRa, TCRp, TRIM, Zap70, or PTCH2.For example, a CCR can comprise: (i) a CD226 ectodomain and a mutated CD226 endodomain (also called intracellular domain) sequence (e.g. comprising a K295A mutation, a K333A mutation, or both; see Braun et al. , Immunity 53(4):805-823.el5 (2020)); (ii) a CD226 ectodomain and a CD2 intracellular domain; (iii) a CD226 ectodomain and a truncated CD2 intracellular domain; (iv) a CD226 ectodomain and a CD28 co-stimulatory domain; (v) a CD226 ectodomain and a 4- IBB co-stimulatory domain; (vi) a TIGIT ectodomain and a CD2 intracellular domain; (vii) a TIGIT ectodomain and a truncated CD2 intracellular domain; (viii) a TIGIT ectodomain and a CD28 co-stimulatory domain; (ix) a TIGIT ectodomain and a 4-1BB co-stimulatory domain; (x) a CD226 ectodomain and a CD27 co- stimulatory domain; (xi) a CD226 ectodomain and an 0X40 costimulatory domain; (xii) a CD226 ectodomain and an ICOS costimulatory domain; (xiii) a CD226 ectodomain and a DAP 10 costimulatory domain; (xiv) a CD226 ectodomain and a HVEM costimulatory domain; (xv) a CD226 ectodomain and a LIGHT costimulatory domain; (xvi) a CD226 ectodomain and CD30 costimulatory domain; (xvii) a CD226 ectodomain and SLAM1 costimulatory domain; (xviii) a TIGIT ectodomain and a CD27 co- stimulatory domain; (xix) a TIGIT ectodomain and an 0X40 costimulatory domain; (xx) a TIGIT ectodomain and an ICOS costimulatory domain; (xxi) a TIGIT ectodomain and a DAP 10 costimulatory domain; (xxii) a TIGIT ectodomain and a HVEM costimulatory domain; (xxiii) a TIGIT ectodomain anda LIGHT costimulatory domain; (xiv) a TIGIT ectodomain and CD30 costimulatory domain; (xv) a TIGIT ectodomain and SLAM1 costimulatory domain; (xvi) a TIGIT ectodomain and a GITR costimulatory domain; or (xvii) a CD226 ectodomain and a GITR costimulatory domain. It will be appreciated that embodiments comprising a portion or variant of a CD226 or TIGIT ectodomain that is functional to bind PVR are contemplated.A CCR comprising a TIGIT ectodomain can comprise a TIGIT transmembrane domain. A CCR comprising a CD226 ectodomain can comprise a CD226 transmembrane domain.Any CCR of the present disclosure can be expressed in a host cell (e.g. T cell) with any chTCR of the present disclosure (or with a TCR, or a CAR) and can provide an activating and / or co-stimulatory signal to the host cell; for example, a host T cell encounters a tumor cell that expresses an antigen and PVR binds to the antigen through the chTCR, thus providing an antigen-binding signal to the T cell, and binds to PVR through the CCR, thus preventing a normal PVR-binding signal via endogenous CD226 or TIGIT and optionally converting the PVR-binding signal into an activating and / or co-stimulatory signal.Also provided are polynucleotides that encode a disclosed chTCR, a disclosed CCR, or both. A polynucleotide can be codon -optimized for expression in a host cell. A polynucleotide can be comprised in a vector, such as, for example, a viral vector, such as a lentiviral vector or a retroviral vector. A polynucleotide or vector can include one or more additional features to facilitate desired expression of the encoded polypeptide(s), such as one or more promoter, one or more sequence encoding a signal peptide (also known as a leader peptide or leader sequence or transit peptide), one or more sequence encoding a furin cleavage sequence, one or more sequence encoding a self-cleaving peptide, or any combination thereof.Also provided are fusion polypeptides that comprise a binding-domain-containing chTCR polypeptide of the present disclosure. Any of the presently disclosed first or second chTCR polypeptides may be provided as an isolated polypeptide, provided that the polypeptide comprises a binding domain, and not accompanied by a cognate chTCR polypeptide. Polynucleotides and vectors that encode the fusion polypeptides are also provided.Any of the presently disclosed polypeptide dimers, polypeptides, or fusion polypeptides can be expressed as membrane -bound molecule or dimer at a cell surface. In some embodiments, a polypeptide dimer associates with one or more CD3 proteins of a host T cell expressing the polypeptide dimer, e.g. when the polypeptide dimer binds to its target(s) .Also provided are host cells that express a presently disclosed chTCR and optionally a presently disclosed CCR. A chTCR (polypeptide dimer) and / or a CCR can be expressed as a membrane -bound protein (CCR) or protein dimer (chTCR) at a cell surface of a host cell. Also provided are host cells thatcomprise a polynucleotide or vector encoding a a presently disclosed chTCR, a presently disclosed CCR, or both. In certain embodiments, a host cell comprises a hematopoietic progenitor cell, a hematopoeitic stem cell, or an immune system cell, such as a human immune system cell. In certain embodiments, an immune system cell comprises a T cell, a NK-T cell, or a macrophage. In certain embodiments, a T cell comprises a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, an aP+ T cell, a y5+ T cell, or any combination thereof. In certain embodiments, a T cell comprises a naive T cell, a central memory T cell, a stem cell memory T cell, an effector memory T cell, or any combination thereof. In certain embodiments, a host cell comprises an induced pluripotent stem cell, an embryonic stem cell, or a peripheral blood mononuclear cell.In some embodiments, a host cell comprises a chromosomal knockout of TIGIT, of a TCR locus (e.g. TRAC, TRBC, or both), of a CD8 locus, of a CD4 locus, of a PD-1 locus, of a LAG-3 locus, of a TIMS locus, of an HLA locus (e.g. a gene that encodes an al macroglobulin, an al macroglobulin, an a3 macroglobulin, a pi microglobulin, or a P2 microglobulin), of a TGF / 3R1 locus, of a TGF / 3R2 locus, of a LAT locus, of an A2AR locus, of a Fas locus, of a FasL locus, of a B7-H3 locus, of a B7-H4 locus, of an IDO locus, of a VISTA locus, of a SIGLEC7 locus, of a SIGLEC9 locus, of a CBLB locus, of aRASAl locus, of a UBASH3A locus, of a CISH locus, or of any combination thereof. In some embodiments, a host cell comprises a chromosomal knockout of TRAC and a chromosomal knockout of TRBC. In some embodiments, a host cell comprises an introduced splicing site or stop codon in a TRAC locus that disrupts expression of the TRAC and comprises an introduced splicing site or stop codon in a TRBC locus that disrupts expression of the TRBC.In some embodiments, a host cell expresses a chTCR and comprises a chromosomal knockout of one or more genes expressing a protein that is recognized by the chTCR. For example, in some embodiments, a host cell expresses a chTCR that binds SLAMF7 and comprises a chromosomal knockout of a SLAMF7 locus. In some embodiments, a host cell expresses a chTCR that binds CD229 and comprises a chromosomal knockout of a CD229 locus. Adminstering a plurality of such host cells to a subject may reduce fratricidal lysis as between the host cells. In certain further embodiments, the host cell is a T cell. The T cell can further comprise a chromosomal (e.g., gene) knockout of a CD4 gene locus and / or of a CD8 gene locus.Compositions that comprise the host cells (e.g. T cells) (including any combination thereof), polynucleotides, chTCRs, fusion polypepties, or vectors, and optionally a pharmaceutically acceptable carrier, excipient, or diluent, are also provided. Also provided are methods of making a host cell, wherein the methods comprise introducing a polynucleotide or vector encoding (i) a chTCR of the present disclosure and / or (ii) a CCR of the present disclosure.Also provided are methods of using any of the presently disclosed chTCRs, CCRs, fusion polypeptides, polynucleotides, vectors, host cells, and compositions to treat a disease or disorder, such as, for example, a cancer, such as, for example, a solid cancer or a hematological malignancy.Also provided are methods of using any of the presently disclosed chTCRs, CCRs, fusion polypeptides, polynucleotides, vectors, host cells, and compositions in the preparation of a medicament to treat a disease or disorder, such as, for example, a cancer, such as, for example, a solid cancer or a hematological malignancy.Also provided are methods of using any of the presently disclosed chTCRs, CCRs, fusion polypeptides, polynucleotides, vectors, host cells, and compositions for use as a medicament to treat a disease or disorder, such as, for example, a cancer, such as, for example, a solid cancer or a hematological malignancy.Prior to setting forth this disclosure in more detail, it may be helpful to an understanding thereof to provide additional definitions of certain terms to be used herein. Still more definitions are set forth throughout this disclosure.In the present description, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated. Also, any number range recited herein relating to any physical feature, such as polymer subunits, size or thickness, is to be understood to include any integer within the recited range, unless otherwise indicated. As used herein, the term "about" means ± 20% of the indicated range, value, or structure, unless otherwise indicated. "About" includes ±15%, ±10%, and ±5%. It should be understood that the terms "a" and "an" as used herein refer to "one or more" of the enumerated components. The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination of the alternatives. As used herein, the terms "include," "have," and "comprise" are used synonymously, which terms and variants thereof are intended to be construed as non -limiting."Optional" or "optionally" means that the subsequently described element, component, event, or circumstance may or may not occur, and that the description includes instances in which the element, component, event, or circumstance occurs and instances in which they do not.In addition, it should be understood that the individual constructs, or groups of constructs, derived from the various combinations of the structures and subunits described herein, are disclosed by the present application to the same extent as if each construct or group of constructs was set forth individually. Thus, selection of particular structures or particular subunits is within the scope of the present disclosure.The term "consisting essentially of is not equivalent to "comprising" and refers to the specified materials or steps of a claim, or to those that do not materially affect the basic characteristics of a claimed subject matter. For example, a protein domain, region, or module (e.g. , a protein domain, linker, signal peptide) or a protein (which may have one or more domains, regions, or modules) "consists essentially of a particular amino acid sequence when the amino acid sequence of a domain, region, module, or protein includes extensions, deletions, mutations, or a combination thereof (e.g., amino acids at the amino- or carboxy-terminus or between domains) that, in combination, contribute to at most 20% (e.g. , at most 15%, 10%, 8%, 6%, 5%, 4%, 3%, 2% or 1%) of the length of a domain, region, module, or protein and do not substantially affect (z.e., do not reduce the activity by more than 50%, such as no more than 40%, 30%, 25%, 20%, 15%, 10%, 5%, or 1%) the activity of the domain(s), region(s), module(s), or protein (e.g. , the target binding affinity of a binding protein).As used herein, "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g, hydroxyproline, y-carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds that have the same basic chemical structure as a naturally occurring amino acid, z.e., an a-carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refer to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that function in a manner similar to a naturally occurring amino acid.As used herein, "mutation" refers to a change in the sequence of a nucleic acid molecule or polypeptide molecule as compared to a reference or wild-type nucleic acid molecule or polypeptide molecule, respectively. A mutation can result in several different types of change in sequence, including substitution, insertion or deletion of nucleotide(s) or amino acid(s).A "conservative substitution" refers to amino acid substitutions that do not significantly affect or alter binding characteristics of a particular protein. Generally, conservative substitutions are ones in which a substituted amino acid residue is replaced with an amino acid residue having a similar side chain. Conservative substitutions include a substitution found in one of the following groups: Group 1: Alanine (Ala or A), Glycine (Gly or G), Serine (Ser or S), Threonine (Thr or T); Group 2: Aspartic acid (Asp or D), Glutamic acid (Glu or Z); Group 3: Asparagine (Asn or N), Glutamine (Gin or Q); Group 4: Arginine (Arg or R), Lysine (Lys or K), Histidine (His or H); Group 5: Isoleucine (lie or I), Leucine (Leu or L),Methionine (Met or M), Valine (Vai or V); and Group 6: Phenylalanine (Phe or F), Tyrosine (Tyr or Y), Tryptophan (Trp or W). Additionally or alternatively, amino acids can be grouped into conservative substitution groups by similar function, chemical structure, or composition (e.g., acidic, basic, aliphatic, aromatic, or sulfur-containing). For example, an aliphatic grouping may include, for purposes of substitution, Gly, Ala, Vai, Leu, and He. Other conservative substitutions groups include: sulfur- containing: Met and Cysteine (Cys or C); acidic: Asp, Glu, Asn, and Gin; small aliphatic, nonpolar or slightly polar residues: Ala, Ser, Thr, Pro, and Gly; polar, negatively charged residues and their amides: Asp, Asn, Glu, and Gin; polar, positively charged residues: His, Arg, and Lys; large aliphatic, nonpolar residues: Met, Leu, He, Vai, and Cys; and large aromatic residues: Phe, Tyr, and Trp. Additional information can be found in Creighton (1984) Proteins. W.H. Freeman and Company. Variant proteins, peptides, polypeptides, and amino acid sequences of the present disclosure can, in certain embodiments, comprise one or more conservative substitutions relative to a reference amino acid sequence.As used herein, "protein" or "polypeptide" refers to a polymer of amino acid residues. Proteins apply to naturally occurring amino acid polymers, as well as to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid and non -naturally occurring amino acid polymers.As used herein, "fusion protein" or "fusion polypeptide" refers to a protein that, in a single chain, has at least two distinct domains and / or motifs, wherein the domains or motifs are not naturally found together (e.g., in the given arrangement, order, or number, or at all) in a protein. In certain embodiments, a fusion protein comprises at least two distinct domains and / or motifs that are not found together in a single naturally occurring peptide or polypeptide. In certain embodiments, a fusion protein comprises amino acid sequences from two or more distinct polypeptides. chTCRs include one or more fusion polypeptides. CCRs comprise a fusion polypeptide. A polynucleotide encoding a fusion protein may be constructed using PCR, recombinantly engineered, or the like, or such fusion proteins can be synthesized. A fusion protein may further contain other components, such as a tag, a linker, or a transduction marker. In certain embodiments, a fusion protein expressed or produced by a host cell (e.g., a T cell) locates to the cell surface, where the fusion protein can be anchored to the cell membrane."Nucleic acid molecule" or "polynucleotide" refers to a polymeric compound including covalently linked nucleotides, which can be made up of natural subunits (e.g., purine or pyrimidine bases) or non-natural subunits (e.g., morpholine ring). Purine bases include adenine, guanine, hypoxanthine, and xanthine, and pyrimidine bases include uracil, thymine, and cytosine. Nucleic acid molecules include polyribonucleic acid (RNA), polydeoxyribonucleic acid (DNA), which includes cDNA, genomic DNA, and synthetic DNA, either of which may be single or double-stranded. If single -stranded, the nucleic acidmolecule may be the coding strand or non-coding (anti-sense strand). A nucleic acid molecule encoding an amino acid sequence includes all nucleotide sequences that encode the same amino acid sequence. Some versions of the nucleotide sequences may also include intron(s) to the extent that the intron(s) would be removed through co- or post-transcriptional mechanisms. In other words, different nucleotide sequences may encode the same amino acid sequence as the result of the redundancy or degeneracy of the genetic code, or by splicing.In some embodiments, a polynucleotide or expression construct of the present disclosure comprises DNA. In some embodiments, a polynucleotide or expression construct of the present disclosure comprises RNA. In some embodiments, a polynucleotide or expression construct of the present disclosure comprises mRNA. In some embodiments, a polynucleotide or expression construct of the present disclsoure comprises circRNA, saRNA, or both. A polynucleotide or expression construct can, for example, be comprised, contained, and / or delivered to a subject or a host cell in a carrier, wherein the carrier comprises a lipid, a lipid-derived delivery vehicle, such as a liposome, a solid lipid nanoparticle, an oily suspension, a submicron lipid emulsion, a lipid microbubble, an inverse lipid micelle, a cochlear liposome, a lipid microtubule, a lipid microcylinder, lipid nanoparticle (LNP), a lipopolyplex (LPP), a cationic polypeptide, a polymeric nanoparticle, or a nanoscale platform, such as a nanoemulsion.Variants of nucleic acid molecules of this disclosure are also contemplated. Variant nucleic acid molecules are at least 70%, 75%, 80%, 85%, 90%, and are preferably 95%, 96%, 97%, 98%, 99%, or 99.9% identical a nucleic acid molecule of a defined or reference polynucleotide as described herein, or that hybridize to a polynucleotide under stringent hybridization conditions of 0.015M sodium chloride, 0.0015M sodium citrate at about 65-68°C or 0.015M sodium chloride, 0.0015M sodium citrate, and 50% formamide at about 42°C. Nucleic acid molecule variants retain the capacity to encode a fusion protein or a binding domain thereof having a functionality described herein, such as specifically binding a target molecule."Percent sequence identity" refers to a relationship between two or more sequences, as determined by comparing the sequences. Preferred methods to determine sequence identity are designed to give the best match between the sequences being compared. For example, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment). Further, non-homologous sequences may be disregarded for comparison purposes. The percent sequence identity referenced herein is calculated over the length of the reference sequence, unless indicated otherwise. Methods to determine sequence identity and similarity can be found in publicly available computer programs. Sequence alignments and percent identity calculations may be performed using a BLAST program (e.g., BLAST 2.0, BLASTP, BLASTN,or BLASTX). The mathematical algorithm used in the BLAST programs can be found in Altschul et al., Nucleic Acids Res. 25:3389-3402, 1997. Within the context of this disclosure, it will be understood that where sequence analysis software is used for analysis, the results of the analysis are based on the "default values" of the program referenced. "Default values" mean any set of values or parameters which originally load with the software when first initialized. In some embodiments, an amino acid sequence and a reference amino acid sequence are of the same length (number of amino acids) and sequence differences therebetween reflected in the two amino acid sequences having less than 100% identity to one another are due solely to the presence of one or more differences in the amino acid present at a given position.The term "isolated" means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally occurring nucleic acid or polypeptide present in a living animal is not isolated, but the same nucleic acid or polypeptide, separated from some or all of the co-existing materials in the natural system, is isolated. Such nucleic acid could be part of a vector and / or such nucleic acid or polypeptide could be part of a composition (e.g., a cell lysate), and still be isolated in that such vector or composition is not part of the natural environment for the nucleic acid or polypeptide. In some embodiments, a composition of the present disclosure can be "isolated" in the sense that it is physically separated from and not comprised within a subject to whom the composition can be, was, or is to be administered.The term "gene" means the segment of DNA involved in producing a polypeptide chain; it includes regions preceding and following the coding region ("leader and trailer") as well as intervening sequences (introns) between individual coding segments (exons).A "functional variant" refers to a polypeptide or polynucleotide that is structurally similar or substantially structurally similar to a parent or reference compound of this disclosure, but differs, in some contexts slightly, in composition (e.g., one base, atom or functional group is different, added, or removed), such that the polypeptide or encoded polypeptide is capable of performing at least one function of the encoded parent polypeptide with at least 50% efficiency, preferably at least 55%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.9%, or 100% level of activity of the parent polypeptide. In other words, a functional variant of a polypeptide or encoded polypeptide of this disclosure has "similar binding," "similar affinity" or "similar activity" when the functional variant displays no more than a 50% reduction in performance in a selected assay as compared to the parent or reference polypeptide, such as an assay for measuring binding affinity (e.g, Biacore® or tetramer staining measuring an association (Ka) or a dissociation (KD) constant) or avidity; or an assay measuring TCR signaling or an activity stimulatedthereby (e.g. as exemplified herein, such as measuring IFN-g production, IL-2 production, intracellular calcium flux, cellular avidity as determined by the percentage of cells in a sample that bind to antigen, proliferation, specific cytotoxicity against a target cell, NF AT expression, NFkB expression, AP-1 expression, Nur77 expression) optionally in the presence of PVR or PVR-expressing cells.))As used herein, a "functional portion" or "functional fragment" refers to a polypeptide or polynucleotide that comprises only a domain, portion or fragment of a parent or reference compound, and the polypeptide or encoded polypeptide retains at least 50% activity associated with the domain, portion or fragment of the parent or reference compound, preferably at least 55%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.9%, or 100% level of activity of the parent polypeptide, or provides a biological benefit (e.g., T cell signaling and / or activity following binding to antigen). A "functional portion" or "functional fragment" of a polypeptide or encoded polypeptide of this disclosure has "similar binding" or "similar activity" when the functional portion or fragment displays no more than a 50% reduction in performance in a selected assay as compared to the parent or reference polypeptide (preferably no more than 20% or 10%, or no more than a log difference as compared to the parent or reference with regard to affinity), such as an assay for measuring binding affinity or measuring effector function (e.g., cytokine release).As used herein, "heterologous" or "non-endogenous" or "exogenous" refers to any gene, protein, compound, nucleic acid molecule, or activity that is not native to a host cell or a subject, or any gene, protein, compound, nucleic acid molecule, or activity native to a host cell or a subject that has been altered. Heterologous, non-endogenous, or exogenous includes genes, proteins, compounds, or nucleic acid molecules that have been mutated or otherwise altered such that the structure, activity, or both is different as between the native and altered genes, proteins, compounds, or nucleic acid molecules. In certain embodiments, heterologous, non-endogenous, or exogenous genes, proteins, or nucleic acid molecules (e.g. , receptors, ligands, etc.) may not be endogenous to a host cell or a subject, but instead nucleic acids encoding such genes, proteins, or nucleic acid molecules may have been added to a host cell by conjugation, transformation, transfection, electroporation, or the like, wherein the added nucleic acid molecule may integrate into a host cell genome or can exist as extra-chromosomal genetic material (e.g., as a plasmid or other self-replicating vector). It will be appreciated that in the case of a host cell that comprises a heterologous polynucleotide, the polynucleotide is "heterologous" to progeny of the host cell, whether or not the progeny were themselves manipulated to, for example, introduce the polynucleotide.The term "homologous" or "homolog" refers to a gene, protein, compound, nucleic acid molecule, or activity found in or derived from a host cell, species, or strain. For example, a heterologous orexogenous polynucleotide or gene encoding a polypeptide may be homologous to a native polynucleotide or gene and encode a homologous polypeptide or activity, but the polynucleotide or polypeptide may have an altered structure, sequence, expression level, or any combination thereof. A non-endogenous polynucleotide or gene, as well as the encoded polypeptide or activity, may be from the same species, a different species, or a combination thereof.As used herein, the term "endogenous" or "native" refers to a polynucleotide, gene, protein, compound, molecule, or activity that is normally present in a host cell or a subject.The term "expression", as used herein, refers to the process by which a polypeptide is produced based on the encoding sequence of a nucleic acid molecule, such as a gene. The process may include transcription, post-transcriptional control, post-transcriptional modification, translation, post-translational control, post-translational modification, or any combination thereof. An expressed nucleic acid molecule is typically operably linked to an expression control sequence (e.g., a promoter).The term "operably linked" refers to the association of two or more nucleic acid molecules on a single nucleic acid fragment so that the function of one is affected by the other. For example, a promoter is operably linked with a coding sequence when it is capable of affecting the expression of that coding sequence (z.e., the coding sequence is under the transcriptional control of the promoter). "Unlinked" means that the associated genetic elements are not closely associated with one another and the function of one does not affect the other.As used herein, "expression vector" refers to a DNA construct containing a nucleic acid molecule that is operably linked to a suitable control sequence capable of effecting the expression of the nucleic acid molecule in a suitable host. Such control sequences include a promoter to effect transcription, an optional operator sequence to control such transcription, a sequence encoding suitable mRNA ribosome binding sites, and sequences which control termination of transcription and translation. The vector may be a plasmid, a phage particle, a virus, or simply a potential genomic insert. Once transformed into a suitable host, the vector may replicate and function independently of the host genome, or may, in some instances, integrate into the genome itself. In the present specification, "plasmid," "expression plasmid," "virus" and "vector" are often used interchangeably.The term "introduced" in the context of inserting a nucleic acid molecule into a cell, means "transfection", or "transformation" or "transduction" and includes reference to the incorporation of a nucleic acid molecule into a eukaryotic or prokaryotic cell wherein the nucleic acid molecule may be incorporated into the genome of a cell (e.g., chromosome, plasmid, plastid, or mitochondrial DNA), converted into an autonomous replicon, or transiently expressed (e.g., transfected mRNA). As used herein, the term "engineered," "recombinant" or "non-natural" refers to an organism, microorganism, cell,nucleic acid molecule, or vector that includes at least one genetic alteration or has been modified by introduction of an exogenous nucleic acid molecule, wherein such alterations or modifications are introduced by genetic engineering (i.e., human intervention). Genetic alterations include, for example, modifications introducing expressible nucleic acid molecules encoding proteins, fusion proteins or enzymes, or other nucleic acid molecule additions, deletions, substitutions or other functional disruption of a cell’s genetic material. Additional modifications include, for example, non-coding regulatory regions in which the modifications alter expression of a polynucleotide, gene or operon.As described herein, more than one heterologous nucleic acid molecule can be introduced into a host cell as separate nucleic acid molecules, as a plurality of individually controlled genes, as a polycistronic nucleic acid molecule, as a single nucleic acid molecule encoding a fusion protein, or any combination thereof. When two or more heterologous nucleic acid molecules are introduced into a host cell, it is understood that the two or more heterologous nucleic acid molecules can be introduced as a single nucleic acid molecule (e.g., on a single vector), on separate vectors, integrated into the host chromosome at a single site or multiple sites, or any combination thereof. The number of referenced heterologous nucleic acid molecules or protein activities refers to the number of encoding nucleic acid molecules or the number of protein activities, not the number of separate nucleic acid molecules introduced into a host cell.The term "construct" refers to any polynucleotide that contains a recombinant nucleic acid molecule. A construct may be present in a vector (e.g., a bacterial vector, a viral vector) or may be integrated into a genome. A "vector" is a nucleic acid molecule that is capable of transporting another nucleic acid molecule. Vectors may be, for example, plasmids, cosmids, viruses, a RNA vector or a linear or circular DNA or RNA molecule that may include chromosomal, non-chromosomal, semisynthetic or synthetic nucleic acid molecules. Vectors of the present disclosure also include transposon systems (e.g, Sleeping Beauty, see, e.g., Geurts etal.,Mol. Ther. 8: 108, 2003: Mates et al., Nat. Genet. 4T.15 , 2009). Exemplary vectors are those capable of autonomous replication (episomal vector), capable of delivering a polynucleotide to a cell genome (e.g., viral vector), or capable of expressing nucleic acid molecules to which they are linked (expression vectors).As used herein, the term "host" refers to a cell (e.g., T cell) or microorganism targeted for genetic modification with a heterologous nucleic acid molecule to produce a polypeptide of interest (e.g., a fusion protein of the present disclosure). In certain embodiments, a host cell may optionally possess or be modified to include other genetic modifications that confer desired properties related or unrelated to, e.g., biosynthesis of the heterologous protein (e.g, inclusion of a detectable marker; deleted, altered or truncated endogenous host cell protein; expression of an antigen-binding protein).As used herein, "enriched" or "depleted" with respect to amounts of cell types in a mixture refers to an increase in the number of the "enriched" type, a decrease in the number of the "depleted" cells, or both, in a mixture of cells resulting from one or more enriching or depleting processes or steps. Thus, depending upon the source of an original population of cells subjected to an enriching process, a mixture or composition may contain 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or more (in number or count) of the "enriched" cells. Cells subjected to a depleting process can result in a mixture or composition containing 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% percent or less (in number or count) of the "depleted" cells. In certain embodiments, amounts of a certain cell type in a mixture will be enriched and amounts of a different cell type will be depleted, such as enriching for CD4+cells while depleting CD8+cells, or enriching for CD62L+cells while depleting CD62L cells, or combinations thereof."T cell receptor" (TCR) refers to a multi-protein complex (each component protein having a variable binding domain, a constant domain, a transmembrane region, and a short cytoplasmic tail; see, e.g., Janeway et al., Immunobiology: The Immune System in Health and Disease, 3rdEd., Current Biology Publications, p. 4:33, 1997) capable of binding to an antigen peptide bound to a MHC receptor. A TCR can be found on the surface of a cell or in soluble form and generally is comprised of a heterodimer having a and P chains (also known as TCRa and TCR , respectively), or y and 5 chains (also known as TCRy and TCR8. respectively). The extracellular portion of TCR chains (e.g., a-chain, -chain) contain two immunoglobulin domains, a variable domain (e.g., a-chain variable domain or Va, P-chain variable domain or Vp; typically amino acids 1 to 116 based on Kabat numbering (Kabat et al., "Sequences of Proteins of Immunological Interest, US Dept. Health and Human Services, Public Health Service National Institutes of Health, 1991, 5thed.) at the N-terminus, and one constant domain (e.g., a-chain constant domain or Ca, typically amino acids 117 to 259 based on Kabat, P-chain constant domain or Cp, typically amino acids 117 to 295 based on Kabat) adjacent to the cell membrane. Non-limiting examples of TCR constant domain amino acid sequences are provided herein. The variable domains contain complementary determining regions (CDRs) separated by framework regions (FRs) (see, e.g., Jores et al., Proc. Nat'lAcad. Sci. U.S.A. 87:9138, 1990; Chothia et al., EMBO J. 7:3745, 1988; see also Lefranc et al., Dev. Comp. Immunol. 27:55, 2003). The source of a TCR or TCR binding domain as used in the present disclosure may be from various animal species, such as a human, mouse, rat, rabbit, non-human primate, or other mammal. chTCRs of the present disclosure are structurally distinct from TCRs."CD3" is a multi-protein complex of six chains (see, Abbas and Lichtman, 2003; Janeway et al.. p. 172 and 178, 1999). In mammals, the complex generally comprises a CD3y chain, a CD35 chain, two CD3a chains, and a homodimer of CD3^ chains. The CD3y, CD35, and CD3a chains are related cell surface proteins of the immunoglobulin superfamily containing a single immunoglobulin domain. The transmembrane regions of the CD3y, CD35, and CD3s chains are negatively charged, which is thought to allow these chains to associate with positively charged regions of T cell receptor chains. The intracellular tails of the CD3 complex proteins contain immunoreceptor tyrosine-based activation motifs or ITAMs, which are thought to be important for T cell signaling in response to antigen binding.CD3, as well as the protein subunits, domains, and sequences therefrom, may be from various animal species, including human, mouse, rat, or other mammals.In certain embodiments, a TCR or chTCR is found on the surface of T cells (also referred to as T lymphocytes) and associates with the CD3 complex. In certain embodiments, a TCR complex comprises a TCR or a functional portion thereof; a dimer comprising two CD3^ chains, or functional portions or variants thereof; a dimer comprising a CD35 chain and a CDe chain, or functional portions or variants thereof; and a dimer comprising a CD3y chain and a CD3e chain, or functional portions or variants thereof, any one or more of which may be endogenous or heterologous to the T cell. Certain embodiments of chTCRs of the present disclosure can associate with the CD3 complex. In certain embodiments, a chTCR complex comprises a chTCR; a dimer comprising two CD3^ chains, or functional portions or variants thereof; a dimer comprising a CD35 chain and a CD3e chain, or functional portions or variants thereof; and a dimer comprising a CD3y chain and a CD3e chain, or functional portions or variants thereof, any one or more of which may be endogenous or heterologous to the T cell."Major histocompatibility complex molecules" (MHC molecules) refer to glycoproteins that deliver peptide antigens to a cell surface. MHC class I molecules are heterodimers consisting of a membrane spanning a chain (with three a domains) and a non-covalently associated P2 microglobulin. MHC class II molecules are composed of two transmembrane glycoproteins, a and P, both of which span the membrane. Each chain has two domains. MHC class I molecules deliver peptides originating in the cytosol to the cell surface, where a peptide:MHC complex is recognized by CD8+T cells. MHC class II molecules deliver peptides originating in the vesicular system to the cell surface, where they are recognized by CD4+T cells. An MHC molecule may be from various animal species, including human, mouse, rat, cat, dog, goat, horse, or other mammals."CD4" refers to an immunoglobulin co-receptor glycoprotein that can assist the TCR in binding to antigemMHC and communicating with antigen-presenting cells (see, Campbell & Reece, Biology 909 (Benjamin Cummings, Sixth Ed., 2002); UniProtKB P01730). CD4 is found on the surface of immunecells such as T helper cells, monocytes, macrophages, and dendritic cells, and includes four immunoglobulin domains (DI to D4) that are expressed at the cell surface. During antigen recognition, CD4 is recruited, along with the TCR complex, to bind to different regions of the MHCII molecule (CD4 binds MHCII 2, while the TCR complex binds antigemMHCII a 1 / 1).As used herein, the term "CD8 co-receptor" or "CD8" means the cell surface glycoprotein CD8, either as an alpha-alpha homodimer or an alpha-beta heterodimer. The CD8 co-receptor can assist in the function of cytotoxic T cells (CD8+) and functions through signaling via its cytoplasmic tyrosine phosphorylation pathway (Gao and Jakobsen, Immunol. Today 27:630-636, 2000; Cole and Gao, Cell. Mol. Immunol. 7 :81-88, 2004). In humans, there are five (5) different CD8 beta chains (see UniProtKB identifier Pl 0966) and a single CD8 alpha chain (see UniProtKB identifier P01732)."Chimeric antigen receptor" (CAR) refers to a fusion protein engineered to contain two or more amino acid sequences (which may be naturally occurring amino acid sequences) linked together in a way that does not occur naturally or does not occur naturally in a host cell, which fusion protein can function as an antigen-specific receptor when present on a surface of a cell. CARs of the present disclosure are single -chain fusion proteins that include an extracellular portion comprising an antigen-binding domain (e.g., obtained or derived from an immunoglobulin or immunoglobulin-like molecule, such as a scFv or scTCR derived from an antibody or TCR (respectively) specific for a cancer antigen, or an antigenbinding domain derived or obtained from a killer immunoreceptor from an NK cell, a designed ankyrin repeat protein (DARPin), an engineered fibronectin type three domain (also referred-to as a monobody) such as an Adnectin™, a ligand (e.g, a cytokine, if the target is a cytokine receptor), a receptor ectodomain (e.g. , a cytokine receptor, if the target is a cytokine) or the like) linked to a transmembrane domain and one or more intracellular signaling domains (optionally containing co -stimulatory domain(s)) (see, e.g., Sadelain et al., Cancer Discov., J(4):388 (2013); see also Harris and Kranz, Trends Pharmacol. Sci., 37(3):220 (2016); Stone et al., Cancer Immunol. Immunother., 63(11): 1163 (2014)). In certain embodiments, a CAR comprises an antigen-specific TCR binding domain (see, e.g., Walseng et al., Scientific Reports 7: 10713, 2017; it will be understood that chTCRs of the present disclosure possess a distinct structure to CARs).The term "variable region" or "variable domain" refers to the domain an antibody heavy or light chain (or, for TCRs, of a TCR of a TCR a-chain or P-chain (or y-chain and 5-chain for y5 TCRs)), that is involved in binding to antigen (i.e., contains amino acids and / or other structures that contact antigen and result in binding). The variable domains of cognate chains generally have similar structures, with each domain comprising four generally conserved framework regions (FRs) and three CDRs. In both TCRs and antibodies, framework regions separate CDRs and CDRs are situated between framework regions(i.e., in primary structure). It will be understood that some binding domains (e.g., IgNARs, VNARs) have alternative structures to TCRs and CARs.The terms "complementarity determining region," and "CDR," are synonymous with "hypervariable region" or "HVR," and refer to sequences of amino acids within TCR or antibody variable regions, which, in general, confer antigen specificity and / or binding affinity and are separated from one another in primary structure by framework sequence. In some cases, framework amino acids can also contribute to binding, e.g. , may also contact the antigen or antigen -containing molecule. In general, there are three CDRs in each variable region (e.g. , three CDRs in each of the antibody heavy chain and light chain variable regions). Variable domain sequences can be aligned to a numbering scheme (e.g., Kabat, EU, International Immunogenetics Information System (IMGT), AbM, North, Chothia, and Aho), which can allow equivalent residue positions to be annotated and for different molecules to be compared using Antigen receptor Numbering And Receptor Classification (ANARCI) software tool (2016, Bioinformatics 15:298-300)."Antigen" or "Ag" as used herein refers to an immunogenic molecule that can provoke an immune response. This immune response may involve antibody production, activation of specific immunologically competent cells (e.g., T cells), secretion of cytokines, or any combination thereof. An antigen (immunogenic molecule) may be, for example, a peptide, glycopeptide, polypeptide, glycopolypeptide, polynucleotide, polysaccharide, lipid or the like. It is readily apparent that an antigen can be synthesized, produced recombinantly, or derived from a biological sample. Exemplary biological samples that can contain one or more antigens include tissue samples, tumor samples, cells, biological fluids, or combinations thereof. Antigens can be produced by cells that have been modified or genetically engineered to express an antigen. In any of the presently disclosed embodiments, a target can be, or can comprise, an antigen.The term "epitope" or "antigenic epitope" includes any molecule, structure, amino acid sequence or protein determinant that is recognized and specifically bound by a cognate binding molecule, such as an immunoglobulin, T cell receptor (TCR), chimeric antigen receptor, or other binding molecule, domain or protein (e.g., chTCR). Epitopic determinants generally contain chemically active surface groupings of molecules, such as amino acids or sugar side chains, and can have specific three-dimensional structural characteristics, as well as specific charge characteristics."Treat" or "treatment" or "ameliorate" refers to medical management of a disease, disorder, or condition of a subject (e.g. , a human or non-human mammal, such as a primate, horse, cat, dog, goat, mouse, or rat). In general, an appropriate dose or treatment regimen comprising a host cell expressing a fusion protein of the present disclosure, and optionally an adjuvant, is administered in an amountsufficient to elicit a therapeutic or prophylactic benefit. Therapeutic or prophylactic / preventive benefit includes improved clinical outcome; lessening or alleviation of symptoms associated with a disease; decreased occurrence of symptoms; improved quality of life; longer disease-free status; diminishment of extent of disease; stabilization of disease state; delay of disease progression; remission; survival; prolonged survival; or any combination thereof. In some embodiments, a benefit of a cellular immunotherapy of this disclosure can further include a reduction (e.g. , in number or severity) or absence of a cytokine -related toxicity, such as a cytokine release syndrome.In some embodiments, treatment of a cancer or a tumor comprises killing cancer or tumor cells.In some embodiments, treatment of a cancer or a tumor comprises delaying onset of, or slowing a rate of growth of, or preventing growth of, cancer or tumor cells.In some embodiments, treatment of a cancer or a tumor comprises extending survival, preventing weight loss, or both, in a subject having the cancer or tumor relative to a reference subject having the cancer or tumor and not receiving the therapy.In some embodiments, treatment of a cancer or a tumor comprises a reduced number of tumors, a reduced volume of one or more tumor, or both, in a subject having a tumor relative to a reference subject having the tumor and not receiving the therapy.A "therapeutically effective amount" or "effective amount" of a composition (fusion protein, host cell expressing a fusion protein, polynucleotide, vector, polypeptide dimer, or the like) of this disclosure, refers to an amount of the composition sufficient to result in a therapeutic effect, including improved clinical outcome; lessening or alleviation of symptoms associated with a disease; decreased occurrence of symptoms; improved quality of life; longer disease-free status; diminishment of extent of disease, stabilization of disease state; delay of disease progression; remission; survival; or prolonged survival in a statistically significant manner. In the case of cancers, benefits can include, for example, a reduction in the size, area, volume, and / or density of a tumor, and / or a reduction or reversal in the rate of tumor growth or spread of cancer,When referring to an individual active ingredient, administered alone, a therapeutically effective amount refers to the effects of that ingredient alone. When referring to a combination, a therapeutically effective amount refers to the combined amounts of active ingredients or combined adjunctive active ingredient with a cell expressing an active ingredient that results in a therapeutic effect, whether administered serially or simultaneously. A combination may also be a cell expressing more than one active ingredient.The term "pharmaceutically acceptable excipient or carrier" or "physiologically acceptable excipient or carrier" refer to biologically compatible vehicles, e.g., physiological saline, which aredescribed in greater detail herein, that are suitable for administration to a human or other non-human mammalian subject and generally recognized as safe or not causing a serious adverse event.As used herein, "statistically significant" refers to a p-value of 0.050 or less when calculated using the Student’s t-test and indicates that it is unlikely that a particular event or result being measured has arisen by chance.As used herein, the term "adoptive immune therapy" or "adoptive immunotherapy" refers to administration of naturally occurring or genetically engineered, disease -antigen-specific immune cells (e.g., T cells). Adoptive cellular immunotherapy may be autologous (immune cells are from the recipient), allogeneic (immune cells are from a donor of the same species) or syngeneic (immune cells are from a donor genetically identical to the recipient). Adoptive cell therapy can comprise administration of (optionally genetically engineered) hematopoietic stem cells, induced pluripotent stem cells, embryonic stem cells, peripheral blood mononuclear cells, or the like.Chimeric TCRs (also called TCR / CARs or chTCRs), Polypeptides, and CCRsCertain disclosed embodiments include hybrid receptor polypeptides (referred to herein as “chimeric TCRs” or “chTCRs”, also referred to as “TCR / CARs”) that confer to a host cell (e.g. a T cell) target-specificity (including, in some contexts, high binding affinity and / or non-MHC-restricted binding) of a CAR while leveraging natural T cell signaling properties. “Chimeric TCR”, “chTCR”, and “TCR / CAR” are used interchangeably herein. ChTCRs can be efficiently expressed at the surface of host cells and confer to host cells a diversified and highly sensitive signaling complex that acts with native T cell signaling properties. ChTCRs can function as a receptor when expressed at a host cell surface. In some embodiments, a chTCR comprises (1) a first polypeptide comprising a first TCR constant domain and (2) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate to form a dimer. The association can comprise one or more native interaction between cognate TCR constant domains (e.g. a native disulfide bond), one or more engineered interaction between the TCR constant domains (e.g. one or more disulfide bonds introduced by protein engineering), or both. One or both of the first polypeptide and the second polypeptide further comprises a target-binding domain N-terminal to the TCR constant domain(s).In some embodiments, the first TCR constant domain comprises a TCR alpha-chain constant domain (Ca) and the second TCR constant domain comprises a TCR beta-chain constant domain (CP). In other embodiments, the first TCR constant domain comprises a C and the second TCR constant domain comprises a Ca.In other embodiments, the first TCR constant domain comprises a TCR gamma-chain constant domain (Cy) and the second TCR constant domain comprises a TCR delta-chain constant domain (C5). In other embodiments, the first TCR constant domain comprises a C5 and the second TCR constant domain comprises a Cy.It will be understood that the terms “TRAC” and “TRBC”, when referring to a chTCR, may be used interchangeably with the terms TCR Ca and TCR Cp, respectively, and include embodiments comprising the variant sequences and modifications described herein. A TRAC or TRBC may, but need not necessarily, comprise the native amino acid sequence encoded by a(n e.g. human) TRAC or TRBC, respectively. When describing an endogenous gene locus encoding a TCR alpha chain constant domain or beta chain constant domain, the term TRAC or TRBC, respectively, may be used.TCR constant domain sequences may be from, for example, human, mouse, marsupial (e.g. opossum, bandicoot, wallaby), shark, or non -human primate. In certain preferred embodiments, TCR constant domain sequences are human or comprise engineered variants of human sequences. TCR constant domains may be engineered to improve pairing, expression, stability, or any combination of these. See, e.g., Cohen et al., Cancer Res, 2007; Kuball et al., Blood 2007: and Haga-Friedman et al., Journal of Immunology 2009. Examples of engineering in TCR Ca and C are illustrated in Figure 7; these can include mutation of a native amino acid to a cysteine so that a disulfide bond forms between the introduced cysteine of one TCR constant domain and a native cysteine of the other TCR constant domain. Such mutations can include T48C in Ca, T57C in Cp, or both. Mutations to improve stability can include a mutation in the Ca transmembrane domain from the sequence LSVIGF (SEQ ID NO.:62) to the sequence LLVIVL (SEQ ID NO.:63) (“L-V-L” mutation; see Haga-Friedman et al. , J Immunol 188:5538- 5546 (2012), the TCR mutations and mutant TCR constant domain sequences of which are incorporated herein by reference). Also contemplated are embodiments wherein cognate TCR constant domains comprise mutations so that, for example, one TCR constant domain (e.g., one of Ca and CP) comprises an introduced “cavity” (e.g., obtainable by replacing one or more native amino acid with one or more amino acids having smaller side chains) and the other (e.g., the other of Ca and CP) comprises a compensatory “protuberance” (e.g., obtainable by replacing one or more native amino acid with one or more amino acids having larger side chains), similar to a “knob-into-hole” configuration used to promote preferential pairing of antibody heavy chains. Also contemplated are embodiments wherein TCR constant domain amino acids are mutated to introduce charge properties that favor pairing of the mutated constant domains. Examples of mutations that may be made in Ca and Cp to promote specific pairing by a knobs- into-holes-type mechanism or by a charge -pairing mechanism are provided in Voss et al. , J. Immunol 7S0(l):391-401 (2008) doi.org / 10.4049 / jimmunol.180T.391; see also US Patent No. 9,062,127. TheTCR constant domain mutations, mutated TCR constant domains, and methods used to identify sites for mutation, described in these documents, are incorporated herein by reference.An example of a TCR Ca amino acid sequence is provided in UniProt KB P01848 (human TRAC): IQNPDPAVYQ LRDSKSSDKS VCLFTDFDSQ TNVSQSKDSD VYITDKTVLD MRSMDFKSNS AVAWSNKSDF ACANAFNNSI IPEDTFFPSP ESSCDVKLVE KSFETDTNLN FQNLSVIGFR ILLLKVAGFN LLMTLRLWSS (SEQ ID NO.:56)An example of a TCR Ca amino acid sequence engineered to include threonine-to-cysteine and LVL mutations as described herein is provided in SEQ ID NO.:57: IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAW SNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS.Two human TCR CP isoforms are TRBC1 and TRBC2. An example of a TRBC1 amino acid sequence is provided in UniProt KB P01850:DLNKVFPPEV AVFEPSEAEI SHTQKATLVC LATGFFPDHV ELSWWVNGKE VHSGVSTDPQ PLKEQPALND SRYCLSSRLR VSATFWQNPR NHFRCQVQFY GLSENDEWTQ DRAKPVTQIV SAEAWGRADC GFTSVSYQQG VLSATILYEI LLGKATLYAV LVSALVLMAM VKRKDF (SEQ ID NO.:58).An example of a TRBC1 amino acid sequence engineered to include a serine-to-cysteine mutation is provided in SEQ ID NO.: 59:DLNKVFPPEV AVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF.An example of a TRBC2 amino acid sequence is provided in UniProt KB A0A5B9: DLKNVFPPKV AVFEPSEAEI SHTQKATLVC LATGFYPDHV ELSWWVNGKE VHSGVSTDPQ PLKEQPALND SRYCLSSRLR VSATFWQNPR NHFRCQVQFY GLSENDEWTQ DRAKPVTQIV SAEAWGRADC GFTSESYQQG VLSATILYEI LLGKATLYAV LVSALVLMAM VKRKDSRG (SEQ ID NO.: 60).An example of a TRBC2 amino acid sequence engineered to include a serine-to-cysteine mutation is provided in SEQ ID NO : 61: DLKNVFPPKV AVFEPSEAEI SHTQKATLVC LATGFYPDHV ELSWWVNGKE VHSGVCTDPQ PLKEQPALND SRYCLSSRLR VSATFWQNPR NHFRCQVQFY GLSENDEWTQ DRAKPVTQIV SAEAWGRADC GFTSESYQQG VLSATILYEI LLGKATLYAV LVSALVLMAM VKRKDSRG.In any of the presently disclosed embodiments, a chTCR can comprise a TCR Ca having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:56-57, and a TCR Cp having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:58-61. In certain embodiments, a chTCR comprises a TCR Ca and a TCR C having at least least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% to, or comprising or consisting of, the amino acid sequences set forth in SEQ ID NOs.: (i) 56 and 58, respectively; (ii) 56 and 59, respectively; (iii) 56 and 60, respectively; (iv) 56 and 61, respectively; (v) 57 and 58, respectively; (vi) 57 and 59, respectively; (vii) 57 and 60, respectively; or (viii) 57 and 61, respectively.In preferred embodiments, a variant TCR Ca or Cp maintains the same or substantially the same length and / or number of amino acids as compared to a native TCR Ca or Cp, respectively, such that, in certain embodiments, the variation does not comprise a truncation in the length thereof as compared to a native TCR Ca or Cp, respectively. In certain embodiments, a variant of a TCR Cp (TRBC1) maintains the intracellular sequence VKRKDF (SEQ ID NO.:64). In certain embodiments, a variant of a TCR Cp (TRBC1) maintains the intracellular sequence MAMVKRKDSRG (SEQ ID NO.:65). In some embodiments, variant TCR constant domains of the present disclosure are capable of associating with a cognate TCR constant domain and with one or more CD3 proteins. In other words, in certain embodiments, chTCRs can be assimilated into a TCR complex on a host (e.g. T) cell surface that comprises the chTCR and CD3 proteins. In particular, chTCRs of the present disclosure, including those that comprise variant TCR constant domains, are capable of producing a TCR-CD3 complex signal in a host (e.g. T) cell when the chTCR expressed by the host cell binds to its target(s).In some embodiments, the first polypeptide and / or the second polypeptide (preferably both) of a chTCR comprises an intracellular portion that consists essentially of or that consists of the intracellular portion of the respective TCR constant domain. In some embodiments, the first polypeptide and / or the second polypeptide (preferably both) does not comprise an intracellular signaling component (e.g. effector domain) from a CD3 protein, such as CD3g In some embodiments, the first polypeptide and / or the second polypeptide (preferably both) does not comprise an intracellular costimulatory domain from a costimulatory protein, such as CD28, 4-1BB, ICOS, CD27, 0X40, DAP10, or any combination thereof.In some embodiments, the first polypeptide and / or the second polypeptide (preferably both) of a chTCR does not comprise an immunoglobulin CH2 domain and / or an immunoglobulin CH3 domain and / or an immunoglobulin light chain constant domain. In some embodiments, the first polypeptide and / or the second polypeptide (preferably both) of a chTCR does not comprise an immunoglobulin CH2domain and / or an immunoglobulin CH3 domain and / or an immunoglobulin light chain constant domain disposed C-terminal to the TCR constant domain. In some embodiments, the polypeptide dimer does not comprise an immunoglobulin CH2-CH3 or an immunoglobulin CH2-CH3:CH2-CH3 dimer.In some embodiments, a polypeptide dimer comprises a target-binding domain comprising (i) a VH comprised in the first polypeptide or the second polypeptide and (ii) a cognate VL comprised in the other of the first and the second polypeptide, wherein the target is not 2,4,6 -trinitrophenyl (TNP), digoxin, or phosphorylcholine.A "binding domain" (also referred to as a "binding region" or "binding moiety"), as used herein, refers to a molecule or portion thereof (e.g., peptide, oligopeptide, polypeptide) that possesses the ability to specifically and non -covalently associate, unite, or combine with a target (e.g. antigen). A binding domain includes any naturally occurring, synthetic, semi-synthetic, or recombinantly produced binding partner for a biological molecule, a molecular complex (z.e., complex comprising two or more biological molecules), or other target of interest.Herein, a “binding domain” also includes a subunit of a complete binding domain; e.g., if VH and VL together are required for binding to a target, VH alone or VL alone may be referred-to as a “binding domain”. It will be understood that chTCRs are capable of binding to a target. Exemplary binding domains useful in chTCRs include single chain immunoglobulin variable regions (e.g., scFv, scFab), Fabs, Fv, sdAbs such as nanobodies / VHH, VNAR, receptor ectodomains, ligands (e.g., cytokines, chemokines), or (other) synthetic polypeptides selected for their specific ability to bind to a biological molecule, a molecular complex or other target of interest (e.g. , DARPins,10FNIII domains). In certain embodiments, the binding domain comprises a scFv, or ligand. In certain embodiments, the binding domain is chimeric, human, or humanized.The target-binding domain can comprise any naturally occurring or engineered binding domain suitable for binding a target of interest, such as, for example, an antibody heavy chain variable domain (VH), an antibody light chain variable domain (VL), a VH and a VL, a single-chain variable fragment (scFv) comprising VH-linker-VL or VL-linker-VH, a fragment antigen-binding region (Fab), a singlechain Fab, an antigen-binding fragment of a heavy chain-only antibody (VHH, also referred-to as a nanobody), a killer immunoreceptor from a NK cell, a designed ankyrin repeat protein (DARPin (Binz et al., J. Mol. Biol. 332:489, 2003 and Binz et al., Nat. Biotechnol. 22 525, 2004)), a10FNIII domain such as an Adnectin™ or monobody ((Richards et al., J. Mol. Biol. 326: 1475, 2003; Parker et al. , Protein Eng. Des. Selec. 18:435, 2005 and Hackel et al. (2008) J. Mol. Biol. 381: 1238-1252)), a lectin binding domain, a receptor ectodomain or functional portion or fragment thereof, provided that the receptor ectodomain does not comprise a TCR variable domain, a ligand such as e.g. a cytokine, a fully synthetic polypeptide(e.g. designed in silico, such as using the AlphaFold modeling program), a fibrinogen domain (see, e.g., Weisel et al., Science 230: 1388, 1985), Kunitz domains (see, e.g., US Patent No. 6,423,498), a cysteine- knot miniprotein (Vita et al. (1995) Proc. Nat'l. Acad. Sci. (USA) 92:6404-6408; Martin et al. (2002) Nat. Biotechnol. 21 :11, 2002 and Huang et al. (2005) Structure 13:155, 2005; Lui et al. Nature Communications 77:295 (2020)), a tetratricopeptide repeat domain (Main et al., Structure 77:497, 2003 and Cortajarena et al., ACS Chem. Biol. 3: 161, 2008), a leucine-rich repeat domains (Stumpp et al., J.Mol. Biol. 332:411, 2003), a lipocalin domain (see, e.g., NlO 2006 / 095164, Beste et al., Proc. Nat'l. Acad. Sci. (USA) 96: 1898, 1999 and Schonfeld et al., Proc. Nat'l. Acad. Sci. (USA) 706:8198, 2009), an armadillo repeat protein (see, e.g., Madhurantakam et al., Protein Sci. 21: 1015, 2012; PCT Patent Application Publication No. WO 2009 / 040338), an affilin (Ebersbach et al., J. Mol. Biol. 372'. 172, 2007), an affibody, an avimer, a knottin, a fynomer, an atrimer, cytotoxic T-lymphocyte associated protein-4 (Weidle et al., Cancer Gen. Proteo. 70: 155, 2013) orthe like (Nord et al. , Protein Eng. <3:601, 1995; Nord et al., Nat. Biotechnol. 15:112, 1997; Nord et al., Euro. J. Biochem. 26<3:4269, 2001; Binz et al., Nat. Biotechnol. 23: 1257, 2005; Boersma and Pltickthun, Curr. Opin. Biotechnol.22.'M9, 2011), a receptor ectodomain or functional portion or fragment thereof, provided that the receptor ectodomain does not comprise a TCR variable domain, a centyrin, or the like, or any combination thereof.Binding domains of this disclosure can be generated as described herein or by a variety of methods known in the art (see, e.g., U.S. Patent Nos. 6,291,161 and 6,291,158). For example, binding domains of this disclosure may be identified by screening a Fab phage library for Fab fragments that specifically bind to atarget of interest (see Hoet et al., Nat. Biotechnol. 23:344, 2005). Additionally, traditional strategies for hybridoma development using atarget of interest as an immunogen in convenient systems (e.g., mice, HuMAb mouse®, TC mouse™, KM-mouse®, llamas, chicken, rats, hamsters, rabbits, etc.) can be used to develop binding domains of this disclosure. Binding domains can be isolated from a human protein (see e.g. Traggiai et al., Nature Medicine 10(^>):^>ll-^>15 (2004)), designed in silico (e.g. using AlphaFold or a like program), isolated or derived a rat, a mouse, a hamster, or other rodent, can be from an avian source, can be from a bovine source, can be from a canine source, can be from a camelid (e.g. from camels, dromedaries, or llamas; Ghahroudi et al., FEBS Lett. 414:521, 1997; Vincke et al., J. Biol. Chem. 284:3213, 2009; Hamers-Casterman et al., Nature 363:446, 1993 and Nguyen et al., J. Mol. Biol. 275:413, 1998), a shark such as a nurse shark (Roux et al., Proc. Nat'l. Acad. Sci. (USA) 95: 11804, 1998), spotted ratfish (Nguyen et al ., Immunogen. 54:39, 2002), or lamprey (Herrin et al., Proc. Nat'l. Acad. Sci. (USA) 705:2040, 2008 and Alder et al. Nat. Immunol. 9:319, 2008). A binding domain can include sequences from a library that encodes random peptides or sequences from a library that encodes an engineered diversity of amino acids in loop regions of alternative non-antibody scaffolds.In some contexts, a VH alone is sufficient to confer binding (i.e. a target-binding domain can comprise a VH and need not comprise a VL). In some contexts, a VL alone is sufficient to confer binding (i.e. a target-binding domain can comprise a VL and need not comprise a VH).In some embodiments, a target-binding domain is “split” across the first polypeptide and the second polypeptide; for example, where a VH and a VL together function to bind to a target, the VH is comprised in the first polypeptide and the VL is comprised in the second polypeptide, or vice versa. The same may be the case, for example, with an antibody Fab; VH-CH1 may be comprised in the first polypeptide, and VL-CL may be comprised in the second polypeptide, or vice versa. Regarding Fab-type molecules that function as binding domains in the presently disclosed chTCRs, it will be understood that CHI and CL may be swapped (i.e. VH-CL, VL-CH1), and that other immunoglobulin constant domains can be utilized in place of CHI and CL (e.g., CH2-CH2 or CH3-CH3 may replace CH1-CL; see e.g. Wozniak -Knopp et al. PLoS One 73(4):e0195442 (2018)).Accordingly, certain embodiments refer to a “split” format. It will be understood that in a “split - scFv” design, “scFv” refers to the VH and VL components that would form a scFv if linked by a linker; however, “split-scFv” designs typically do not include a peptide linker disposed between and connecting the VH and the VL. Thus, “split-scFv” refers to an arrangement wherein VH is comprised in a first polypeptide of a chTCR and VL is comprised in a second polypeptide of a chTCR, and VH and VL function to form a target-binding domain. In “split” formats, VH and VL can be engineered to introduce one or more disulfide bond therebetween; see e.g. Reiter et al. Biochemistry 33:5451-5459 (1994), Brinkmann Antibody Engineering (2012) doi.org / 10.1007 / 978-3-642-01147-4_14: Weatherill et al. PEDS 25(7):321-329 (2012), and Metz et al. 7WDS 25(10):571-580 (2012)). Such disulfide bonds may be introduced in “full” scFv for full scFab formats, as well.In some embodiments, a target-binding domain is fully comprised in one TCR constant domaincontaining polypeptide. For example, a scFv (VH-linker-VL or VL-linker-VH) may be comprised in the first polypeptide or the second polypeptide of a chTCR; such an arrangement can be described as “full- scFv”.In some embodiments, both the first polypeptide and the second polypeptide fully comprise a target-binding domain. For example, the first polypeptide can comprise a Ca linked or fused to a first scFv and the second polypeptide can comprise a Cp linked or fused to a second scFv. In other embodiments, the first polypeptide can comprise a Ca linked or fused to a first VHH and the second polypeptide can comprise a C linked or fused to a second VHH. In other embodiments, the first polypeptide can comprise a Ca linked or fused to a first Fab or scFab and the second polypeptide can comprise a Cp linked or fused to a second Fab or scFab, respectively. In other embodiments, the firstpolypeptide can comprise a Ca linked or fused to a first ligand and the second polypeptide can comprise a Cp linked or fused to a second ligand. For example, the first polypeptide can comprise a Ca linked or fused to a first receptor ectodomain and the second polypeptide can comprise a C linked or fused to a second receptor ectodomain.When present, two target-binding domains (it will be understood that any arrangement and combination of binding domains is contemplated; for example, one polypeptide can comprise a scFv and the other polypeptide can comprise a VHH, or one polypeptide can comprise a Fab and the other polypeptide can comprise a scFv, or one polypeptide can comprise a receptor ectodomain and the other polypeptide can comprise a DARPin, or the like) may be the same (e.g. two copies of a same VHH may be present, one comprised in each of the first and the second polypeptide) or different. If different, the two binding domains may target different epitopes on the same target (e.g. two epitopes present within a tumor antigen), or may target different targets altogether (e.g. , may target two different tumor antigens, or may target a tumor antigen and a cytokine). Accordingly, certain embodiments provide multispecific (e.g. bispecific) chTCRs. In some contexts, a multispecific chTCR binds to two or more antigens that are expressed by a cancer; for example, to target multiple myeloma, a multispecific chTCR may target any two or more of: BCMA, GPRC5D, SLAMF7, and CD229. In some contexts, a multispecific chTCR binds to two or more antigens that are expressed by a cancer; for example, to target multiple myeloma, a multispecific chTCR may target any two or more of: BCMA, GPRC5D, SLAMF7, CD229, CD 19, and CD22.Contemplated embodiments include those wherein a polypeptide chain comprises two or more binding domains (e.g., scFv-linker-scFv-TCR constant domain; VHH-linker-VHH-TCR constant domain; or the like).A target can be a synthetic molecule or a biological antigen or other biomolecule. In some embodiments, a target is expressed on or by a cancer cell, a cell infected with a pathogen (e.g. virus, fungus, parasite, bacteria) or is otherwise associated with an an infection, or is associated with an autoimmune disease or a neurodegenerative disease (e.g, tau, amyloid-beta, alpha-synuclein), or is a cytokine (e.g. TNFa, IL- 13, IL- 10) or a chemokine. In some embodiments, a target is or comprises a cancer antigen selected from CD22, CD 19, BCMA, SLAMF7, GPRC5D, ROR1, CD229, PNE, EGFR, EGFRvIII, EGP-2, EGP-40, GD2, GD3, HPV E6, HPV E7, Her2, LI -CAM, Lewis A, Lewis Y, MUC1, MUC16, PSCA, PSMA, CD20, CD56, CD23, CD24, CD30, CD33, CD37, CD44v7 / 8, CD38, CD56, CD123, CA125, c-MET, FcRH5, WT1, folate receptor a, VEGF-a, VEGFR1, VEGFR2, IL-13Ra2, IL- 1 IRa, MAGE-A1, PSA, ephrin A2, ephrin B2, NKG2D, NY-ESO-1, TAG-72, mesothelin, NY-ESO, 5T4, BCMA, FAP, Carbonic anhydrase 9, BRAF, a-fetoprotein, MAGE-A3, MAGE-A4, SSX-2,PRAME, HA-1, P2M, ETA, tyrosinase, KRAS, NRAS, a peptide:MHC complex, and CEA. In some embodiments, a chTCR comprises a Bcl-2 ectodomain or portion or variant thereof and a target is a Bcl-2 ligand.In some embodiments, the binding domain is capable of specifically binding to the target. As used herein, "specifically binds" or "specific for" refers to an association or union of an target-binding protein or a binding domain (or fusion protein comprising the same) to a target molecule with an affinity or Ka(i.e., an equilibrium association constant of a particular binding interaction with units of 1 / M) equal to or greater than 105M1(which equals the ratio of the on -rate [Kon] to the off rate [K0fr] for this association reaction), while not significantly associating or uniting with any other molecules or components in a sample. Target-binding proteins or binding domains may be classified as "high -affinity" binding proteins or binding domains or as "low-affinity" binding proteins or binding domains. "High- affinity" binding proteins or binding domains refer to those binding proteins or binding domains having a Kaof at least IO7M1, at least IO8M1, at least IO9M1, at least IO10M1, at least 1011M1, at least 1012M-1, or at least IO13M1. "Low-affinity" binding proteins or binding domains refer to those binding proteins or binding domains having a Kaof up to IO7M1, up to IO6M1, or up to IO5M1. Alternatively, affinity may be defined as an equilibrium dissociation constant (KD) of a particular binding interaction with units of M (e.g., 10'5M to 1013M).In some embodiments, a binding domain is engineered have a preferred affinity for the target. For example, without wishing to be bound by theory, higher binding affinities (e.g., picomolar or femtomolar Kd) may in some contexts initiate or contribute to a more intense signal than is desired upon binding to antigen (e.g. , binding by a chTCR comprising such a binding domain may contribute to T cell signaling that is more intense, longer, or both, than may be desired, and may contribute to tonic signaling and / or cell exhaustion). Accordingly, certain embodiments provide binding domains which are selected for or are modified to have affinity in a preferred range, such as in the range of about InM to about lOOnM Kd, as determined by surface plasmon resonance, which may be comparable to physiological affinity of a native TCR for antigemMHC. By way of illustration, if a binding domain from an antibody with picomolar or femtomolar Kd for its antigen is selected for use in a chTCR, the binding domain may first be engineered to decrease affinity for antigen to a range of about InM to about lOOnM Kd, such as by rational mutagenesis in one or more CDRs (e.g, by mutation from an amino acid with a larger sidechain (e.g. tryptophan or phenylalanine) to an amino acid with a smaller side -chain (e.g. alanine or serine)).A variety of assays are known for identifying binding domains that specifically bind a particular target, as well as determining binding domain or antigen-binding protein affinities, such as Western blot,ELISA, analytical ultracentrifugation, spectroscopy, isothermal titration calorimetry (ITC), and surface plasmon resonance (Biacore®) analysis (see, e.g., Scatchard et al., Ann. N.Y. Acad. Sci. 51 :660, 1949; Wilson, Science 295:2103, 2002; Wolff et al., Cancer Res. 53:2560, 1993; and U.S. Patent Nos.5,283, 173, 5,468,614, or the equivalent). Assays for apparent affinity or relative affinity are also known. In certain examples, apparent affinity for a target-binding protein is measured by assessing binding to various concentrations of tetramers, for example, by flow cytometry using labeled tetramers. In some examples, apparent KD of a binding protein or binding domain is measured using 2-fold dilutions of labeled tetramers at a range of concentrations, followed by determination of binding curves by non-linear regression, apparent KDbeing determined as the concentration of ligand that yielded half-maximal binding.Non-limiting examples of binding domain amino acid sequences are provided in SEQ ID NOs.:97-109. In some embodiments, a chTCR comprises a binding domain comprising: (i) SEQ ID NO.:97 and SEQ ID NO.:98, optionally comprised in a scFv, such as having the sequence of SEQ ID NO.:99 or SEQ ID NO.: 100; (ii) SEQ ID NO.: 101 and 102, optionally in a scFv, such as having the sequence of SEQ ID NO.: 103; (iii) SEQ ID NO.: 104 and SEQ ID NO.: 105, optionally in a scFv, such as having the sequence of SEQ ID NO.: 106; (iv) SEQ ID NO.: 107, optionally comprised in SEQ ID NO.: 108; or (v) SEQ ID NO.: 109. In certain further embodiments, the binding domain comprising (i), (ii), (iii), (iv), and / or (v) above is fused or linked to a TCR Ca, to a TCR Cp, or to both of a TCRa and a TCR (e.g., where a VH and a VL are present, in a “split” format or in a “full format”). In some embodiments, the TCR Ca has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO.:56. In some embodiments, the TCR Ca has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO.:57. In some embodiments, the TCR C has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO.:58. In some embodiments, the TCR Cp has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO.:59. In some embodiments, the TCR Cp has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO.:60. In some embodiments, the TCR Cp has at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO.:61 .The target-binding domain or a component thereof may be directly fused to a TCR constant domain (i.e., there is no intervening amino acid or amino acid sequence between the target-bindingdomain or component thereof and the TCR constant domain) or may be linked to a TCR constant domain by a linker, which may function as a hinge. Accordingly, in some embodiments, a hinge sequence is disposed between and connects the target-binding domain or portion thereof and a TCR constant domain. A hinge sequence may be from an immunoglobulin superfamily molecule (e.g. an antibody hinge or a CD8 hinge, or an engineered variant hinge based thereon, or a synthetic flexible linker such as a glycineserine linker) and can confer desired structure and flexibility for binding to the target. A hinge sequence can be selected and / or engineered for preferred characteristics, such as, for example, a desired length, a desired flexibility, a desired reduced interaction or lack of interaction of interaction with a Fc receptor (e.g. a FcyR).Non-limiting examples of hinge sequences are provided in SEQ ID NOs.:42-55. These include a (648)3 linker (SEQ ID NO.:54); it will be understood that this linker and other synthetic linkers may function as a hinge, or may be present elsewhere in a chTCR or CCR of the present disclosure (e.g. , between adjacent domains of a polypeptide, such as between VH and VL in a scFv). Linkers include an (A)nlinker, wherein n is 1 or more, a GS linker, a GSG linker, a GPP linker, a (GlyxSery)nlinker wherein X, Y, and N are not zero, and may each independently be from 1-10, a Townsend linker (GSGGSGGSGGTG; SEQ ID NO. :68), a Whitlow linker aka linker 218 (GSTSGSGKPGSGEGSTKG; SEQ ID NO.:69), or a linker comprising or consisting of any one of the following amino acid sequences: GSGKPGSGEG (SEQ ID NO.:70); GKPGSGEG (SEQ ID NO.:71); SGKPGSGE (SEQ ID NO.:72); EGKSSGSGSESKVD (SEQ ID NO.:73), or BPXXXZ, wherein each X is independently a glycine (G) or serine (S), B is a positively charged amino acid and Z is glycine (G) or a negatively charged amino acid (SEQ ID NO.:74), or the like).Table 1 provides non-limiting examples of certain chTCR designs. It will be understood that a scFv can be in VH-linker-VL or VL-linker-VH orientation. It will be understood that a scFab can be in VH-CH1 -linker- VL-CL orientation or VL-CL-linker-VH-CHl orientation (or, alternatively, that CHI and CL can be exchanged or CH3 can replace CHI and CL; e.g., VH-CL-linker-VL-CHl, VL-CHl-linker- VH-CL, VH-CH3 -linker- VL-CH3, VL-CH3-linker-VH-VH3). It will be understood that any chTCR can comprise a hinge disposed between a binding domain and a TCR constant domain. It will be understood that where two or more binding domains are present, they may be the same or different. If different, they may comprise a different amino acid sequence to one another but still bind a same (or overlapping) epitope or a same target, or they may bind different epitopes on a same target or may bind different targets. It will be understood that in Table 1, “none” refers to the absence of a target or antigen-binding domain; the absence of an antigen-binding domain does not exclude the presence of amino acid sequence N-terminal to the TCR constant domain. For example, in some embodiments of the present disclosure,one of the first polypeptide and the second polypeptide comprises, N-terminal to the TCR constant domain thereof, one or more tag and optionally one or more linker. A tag can include, for example, any tag or combinations of tags known in the art, including those tags and combinations of tags described herein. It will be understood that a polypeptide dimer (chTCR) can comprise one or more additional binding domain further to the binding domain(s) specified in Table 1 ; for example, a polypeptide of a polypeptide dimer may comprise two, three, four, or more binding domains, e.g. linked in a series.Table 1Additionally or alternatively, any first and / or second polypeptide of a chTCR as in Table 1 can comprise, as a binding domain: a cytokine; a chemokine; a synthetic polypeptide selected for its specific ability to bind to a biological molecule, a molecular complex or other target of interest (e.g. , DARPins,10FNIII domains); a killer immunoreceptor from a NK cell; a designed ankyrin repeat protein (DARPin); a10FNIII domain such as an Adnectin™ or monobody; a lectin binding domain; a fibrinogen domain; a cysteine-knot miniprotein; a tetratricopeptide repeat domain; a lipocalin domain; an armadillo repeatprotein; an affibody; an avimer; a knottin; a fynomer; an atrimer; cytotoxic T-lymphocyte associated protein-4; a centyrin; or any combination thereof.In some embodiments, a first and a second polypeptide of a chTCR each comprise a scFv.Also provided are embodiments wherein a first polypeptide of a chTCR and a second polypeptide of a chTCR comprise, as a binding domain: (i) a VNAR and a VNAR, respectively (wherein the VNARs can be the same or different); (ii) a VNAR and no binding domain, respectively; (iii) no binding domain and a VNAR, respectively; (iv) a VNAR and scFv, respectively; (v) a scFv and a VNAR, respectively; (vi) a VNAR and a scFab, respectively; (vii) a scFab and a VNAR, respectively; (viii) a VNAR and a VHH or a VHH-linker-VHH, respectively; (ix) a VHH or a VHH-linker-VHHH and a VNAR, respectively; (x) a VNAR and a protein ligand-binding domain, respectively; or (xi) a protein ligandbinding domain and a VNAR, respectively.Additionally or alternatively, a chTCR can comprise a VNAR and one or more of: a cytokine; a chemokine; a synthetic polypeptide selected for its specific ability to bind to a biological molecule, a molecular complex or other target of interest (e.g., DARPins,10FNIII domains); a killer immunoreceptor from a NK cell; a designed ankyrin repeat protein (DARPin); a10FNIII domain such as an Adnectin™ or monobody; a lectin binding domain; a fibrinogen domain; a cysteine-knot miniprotein; a tetratricopeptide repeat domain; a lipocalin domain; an armadillo repeat protein; an affibody; an avimer; a knottin; a fynomer; an atrimer; cytotoxic T-lymphocyte associated protein-4; a centyrin; or any combination thereof.Also provided are embodiments wherein a VH or a VL of an antibody is sufficient for binding and a first polypeptide of a chTCR comprises the VH or VL and the second polypeptide of the chTCR does not comprise a binding domain, or comprises the cognate VL or VH of the first polypeptide, or comprises a different binding domain. In some embodiments, a first polypeptide of a chTCR and a second polypeptide of a chTCR comprise, as a binding domain: (i) an antigen-binding VH or VL and a VNAR, respectively; (ii) an antigen-binding VH or VL and no binding domain, respectively; (iii) no binding domain and an antigen-binding VH or VL, respectively; (iv) a VNAR and an antigen-binding VH or VL, respectively; (v) an antigen-binding VH or VL and an antigen-binding VH or VL, respectively; (vi) an antigen-binding VH or VL and a scFab, respectively; (vii) a scFab and an antigen-binding VH or VL, respectively; (viii) an antigen-binding VH or VL and a VHH or a VHH-linker-VHH, respectively; (ix) a VHH or a VHH-linker-VHHH and an antigen-binding VH or VL, respectively; (x) an antigenbinding VH or VL and a protein ligand-binding domain, respectively; or (xi) a protein ligand-binding domain and an antigen-binding VH or VL, respectively.Additionally or alternatively, a chTCR can comprise an antigen-binding VH or antigen-binding VL and one or more of: a cytokine; a chemokine; a synthetic polypeptide selected for its specific ability to bind to a biological molecule, a molecular complex or other target of interest (e.g., DARPins,10FNIII domains); a killer immunoreceptor from a NK cell; a designed ankyrin repeat protein (DARPin); a10FNIII domain such as an Adnectin™ or monobody; a lectin binding domain; a fibrinogen domain; a cysteine- knot miniprotein; a tetratricopeptide repeat domain; a lipocalin domain; an armadillo repeat protein; an affibody; an avimer; a knottin; a fynomer; an atrimer; cytotoxic T-lymphocyte associated protein-4; a centyrin; or any combination thereof.It will be appreciated that either or both of the first polypeptide and the second polypeptide can comprise any binding domain, such as described herein. It will be appreciated that the first polypeptide can comprise a TCR Ca and the second polypeptide can comprise a TCR Cp, or the first polypeptide can comprise a TCR C and the second polypeptide can comprise a TCR Ca.Any TCR constant domain-containing polypeptide of a chTCR can also be provided as an isolated polypeptide. For example, a Ca-containing or Cp-containing polypeptide can be provided, wherein the Ca-containing or Cp-containing polypeptide comprises a binding domain as provided herein. chTCRs (TCR / CARs) that bind human CD22In some embodiments, a chTCR is provided that comprises a target-binding domain that binds to a human CD22 (e.g. , to an epitope in an extracellular domain of a human CD22). A human CD22 amino acid sequence is provided in SEQ ID NO.:252. The UniProt KB entry corresponding to SEQ ID NO.:252 (uniprot.org / uniprotkb / P20273 / entry) teaches that SEQ ID NO.:252 comprises seven (7) extracellular immunoglobulin -like domains. These domains can be identified as in Table 2:Table 2: human CD22 (SEQ ID NO.:252) extracellular topological domainsAlternatively, the numbering of the Ig-like domains in human CD22 extracellular domain has been described in reverse order, with the N-terminal Ig-like V-type domain in Table 2 being referred to as “Ig-like domain 7”, the C-terminal Ig-like C2-type domain 6 in Table 2 being referred to as "Ig-like C2- type domain 1”, and the Ig-like C2-type domain 5 in Table 2 being referred to as “Ig-like C2-type domain 2”, and so forth.Antibodies and antibody-derived binding molecules (e.g, scFvs) that bind in the human CD22 extracelullar domain are known. Such molecules include, without limitation: 9A8 (also called 9A8-1), m971, m972, 7E1 (also called 7E1-2), 9F9-6, 9F8-2, 10C11-6, 9G11-2, 8E7-3, 7E3-5, 10C1-D9, 1G3-4, 5H4-9, 4D9-12, 1D9-3, 3B4-13, 7G6-6, 6C4-6, 15G7-2, 2B12-8, 2C4-4, 3E10-7; LT22, Inotuzumab (G5 44), HA22 and BL22 (scFvs described by Haso et al. (Blood; 2013; 121 (7)), epratuzumab, H-SCL- 1, CAT-8015 (RFB4), and HCD22.7.With reference to Table 2: HA22 and BL22 are believed to bind in Ig-like C2-type domain 2; MAB EP498Y is believed to bind in Ig-like V-type domain (wherein the peptide DSSKWVFEHP is thought to be important for this binding); H-SCL-1 and HCD22.7 are believed to bind in Ig-like V-type domain, with the peptide ESTKDGKVP believed to be important for binding by HCD22.7; inotuzumab is believed to bind in Ig-like V-type domain; epratuzumab is believed to bind in Ig-like C2-type domain 2; CAT-8015 (RFB4) is believed to bind in Ig-like C2-type domains 2 and 3; M972 is believed to bind in Ig- like C2-type domains 5 and 6; and M971 is believed to bind in Ig-like C2-type domain 6. 9F9-6, 9F8-2, and 10C11-6 are believed to bind in Ig-like C2-type domains 1 and 2; 9G11-2, 8E7-3, and 7E3-5 are believed to bind in Ig-like C2-type domain 3; and 10C1-D9, 1G3-4, 5H4-9, and 4D9-12 are believed to bind in Ig-like C2-type domain 4.Additional information for certain anti-CD22 antibodies is provided, for example, in: Kokalaki et al., Mol. Ther. 31(T . 2089-2104 (2023), including in in Figure 1A therein; and in Pre-Grant U.S. Publication US 2021 / 0113618A1 (including the antibody VH, VL, and CDR amino acid sequences in Table 1 therein, and in PCT / US2024 / 018098, which amino acid sequences are incorporated herein by reference).Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to an epitope in an extracellular domain of a humanCD22, wherein the epitope is comprised within amino acids 20-504 (i.e., the epitope is comprised within a region that includes and is bounded by amino acids 20 and 504) of SEQ ID NO.:252, preferably within amino acids 143-326 of SEQ ID NO.:252, or within amino acids 143-416 of SEQ ID NO.:252, or within amno acids 143-500 of SEQ ID NO.:252, or within amino acids 20-138 of SEQ ID NO.:252, or within amino acids 20-235 of SEQ ID NO.:252, or within amino acids 20-326 of SEQ ID NO.:252, or within amino acids 20-416 of SEQ ID NO.:252, or within amino acids 20-500 of SEQ ID NO.:252, or within amino acids 242-500 of SEQ ID NO.:252, or within amino acids 242-416 of SEQ ID NO.:252, or within amino acids 331-416 of SEQ ID NO.:252; and / or wherein the epitope comprises one or more of amino acids 139-142 of SEQ ID NO.:252, or one or more of amino acids 236-241 of SEQ ID NO.:252, or one or more of amino acids 327-330 of SEQ ID NO.:252, or one or more of amino acids 417-418 of SEQ ID NO.:252.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds an epitope in an extracellular domain of a human CD22, wherein the epitope comprises one or more amino acids of: an Ig-like V-type domain; an Ig-like C2-type domain 1; an Ig-like C2-type domain 2; an Ig-like C2-type domain 3; an Ig-like C2-type domain 4; the Ig-like V-type domain and the Ig-like C2-type domain 1; the Ig-like C2-type domain 1 and the Ig- like C2-type domain 2; the Ig-like C2-type domain 2 and the Ig-like C2-type domain 3; or the Ig-like C2- type domain 3 and the Ig-like C2-type domain 4.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds an epitope in an extracellular domain of a human CD22, wherein the epitope is comprised within amino acids 505-676 of SEQ ID NO.:252, or within amino acids SEQ ID NO.:505-582 of SEQ ID NO.:252, or within amino acids 593-676 of SEQ ID NO.:252, and / or wherein the epitope comprises one or more of amino acids 501-504 of SEQ ID NO.:252, or one more of amino acids 582-593 of SEQ ID NO.:252.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds an epitope in an extracellular domain of a human CD22, wherein the epitope comprises one or more amino acids of: the Ig-like C2-type domain 5; the Ig- like C2-type domain 6; or the Ig-like domain 5 and the Ig-like C2-type domain 6.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain competes with one or more of the following antibodies for binding to an extracellular domain of a human CD22: 9A8; 9A8-1; H-SCL-1; epratuzumab; CAT- 8015; RFB4; inotuzumab; 6C4-6; 4D9-12; 5H4-9; 10C1-D9; 15G7-2; 2B12-8; 2C4-4; 3E10-7; LT22; Inotuzumab G5_44; 1G-34; mAb EP798Y; hCD22.7; BL22 (RFB4dsFv); and HA22. Antibody competition assays (competitive binding assays) are known to those having ordinary skill in the art.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human CD22 extracellular domain and comprises the six CDRs, and optionally VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or comprising, consisting essentially of, or consisting of the VH and VL amino acid sequences (respectively) of: 9A8; H-SCL-1 ; epratuzumab; CAT-8015; RFB4; inotuzumab; 6C4-6; 4D9-12; 5H4-9; 10C1-D9; 15G7-2; 2B12-8; 2C4-4; 3E10-7; LT22; Inotuzumab G5_44; 1G-34; mAb EP798Y; hCD22.7 ; BL22 (RFB4dsFv); or HA22.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associatewith one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain competes with one or more of the following antibodies for binding to an extracellular domain of a human CD22: M971, 1D9-3; 3B4-13;and 7G6-6.Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human CD22 extracellular domain and comprises the six CDRs, and optionally comprises VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or comprising, consisting essentially of, or consisting of the VH and VL amino acid sequences (respectively) of: M971, 1D9-3; 3B4-13; or 7G6-6.In some embodiments, the target-binding domain comprises: (i) an antibody heavy chain variable domain (VH); (ii) an antibody light chain variable domain (VL); (iii) a single -chain variable fragment (scFv); (iv) a fragment antigen-binding region (Fab); (v) a single-chain Fab; (vi) an antigen-binding fragment of a heavy chain-only antibody (VHH); (vii) a designed ankyrin repeat protein (DARPin); (viii) a 10FNIII domain; (ix) a lectin binding domain; (x) a protein ligand -binding domain, such as a receptor ectodomain or a functional portion or fragment thereof; (xi) a killer immunoreceptor from aNK cell; (xii) a fibrinogen domain; (xiii) a cysteine-knot miniprotein; (xiv) a tetratricopeptide repeat domain; (xv) a leucine-rich repeat domain; (xvi) a lipocalin domain; (xvii) an armadillo repeat protein; (xviii) an affibody; (xix) an avimer; (xx) a knottin; (xxi) a fynomer; (xxii) an atrimer; (xxiii) a synthetic protein designed to bind a natural ligand or receptor; (xxiv) a ligand, such as for example comprising a glycan, a sialic acid, or aNeu5Aca2-6Gaipi-4GlcNAc; (xxv) a disulfide-stabilized antibody variable fragment; or (xxvi) any combination of (i)-(xxv), wherein, optionally, the polypeptide dimer comprises a design according to Table 1, and / or wherein the first polypeptide and the second polypeptide comprise, N- terminal to the first TCR constant domain and the second TCR constant domain, respectively: (i) a VH, and a cognate VL; (ii) a VL, and a cognate VH; (iii) a scFv, and no antigen-binding domain; (iv) no antigen-binding domain, and a scFv; (v) VH-CH1, and a cognate VL-CL; (vi) VL-CL, and a cognate VH- CH1; (vii) a scFab, and no antigen-binding domain; (viii) no antigen-binding domain, and a scFab; (ix) a scFv, and a scFv; (x) a scFab, and a scFv; (xi) a scFv, and a scFab; (xii) a VHH, and no antigen-binding domain; (xiii) no antigen-binding domain, and a VHH; (xiv) VHH-linker-VHH, and no binding domain;(xv) VHH-linker-VHH, and VHH-linker-VHH; (xvi) a scFv, and a VHH or a VHH-linker-VHH; (xvii) a VHH or a VHH-linker-VHH, and a scFv; (xvii) a scFab, and a VHH or a VHH-linker-VHH; (xviii) a VHH or a VHH-linker-VHH, and a scFab; (xix) a VHH, and a VHH; (xx) a natural or synthetic protein ligand-binding domain, and no antigen-binding domain; (xxi) no antigen-binding domain, and a natural or synthetic protein ligand-binding domain; (xxii) a scFv, and a natural or synthetic protein ligand -binding domain; (xxiii) a natural or synthetic protein ligand-binding domain, and a scFv; (xxiii) a scFab, and a natural or synthetic protein ligand-binding domain; (xxiv) a natural or synthetic protein ligand-binding domain, and a scFab; (xxv) a VHH or a VHH-linker-VHH, and a natural or synthetic protein ligandbinding domain; (xxvi) a natural or synthetic protein ligand-binding domain, and a VHH or a VHH- linker-VHH; or (xxvii) a natural or synthetic protein ligand-binding domain, and a protein ligand bindingdomain.In some embodiments, the first polypeptide, the second polypeptide, or both, does not comprise a TCR variable domain fused to the TCR constant domain.In some embodiments, the target-binding domain is or comprises a single chain variable fragment (scFv) or a single-chain Fab (scFab) or a disulfide-stabilied Fv (dsFv) or a disulfide-stabilized Fab (dsFab).In some embodiments, an scFv comprises, in a N-terminal to C-terminal direction, VH-linker-VL, or an scFab comprises, in a N-terminal to C-terminal direction, VH-CHl-linker-VL-CL.In some embodiments, an scFv comprises, in a N-terminal to C-terminal direction, VL-linker-VH, or an scFab comprises, in a N-terminal to C-terminal direction, VL-CL-linker-VH-CHl.In some embodiments, the the first polypeptide comprises the target-binding domain linked or fused to a TCR beta chain constant domain (CP) and the second polypeptide comprises, consists essentially of, or consists of a TCR alpha chain constant domain (Ca). In other embodiments, the first polypeptide comprises the target-binding domain linked or fused to a TCR alpha chain constant domain (Ca) and the second polypeptide comprises, consists essentially of, or consists of a TCR beta chain constant domain (C ).In certain embodiments, the target-binding domain comprises:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR.In some embodiments, the target-binding domain comprises:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and theCDRH3 of the VH amino acid sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTS GSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK.In some embodiments, the polypeptide dimer comprises two or more target-binding domains and is multispecific.In some embodiments, the polypeptide dimer comprises two or more target-binding domains and is bispecific.In some embodiments, the polypeptide dimer comprises a target-binding domain that binds BCMA, GPRC5D, CD 19, R0R1, SLAMF7, CD229, PNE, EGFR, EGFRvIII, EGP-2, EGP-40, GD2, GD3, HPV E6, HPV E7, Her2, Ll-CAM, Lewis A, Lewis Y, MUC1, MUC16, PSCA, PSMA, CD20, CD56, CD23, CD24, CD30, CD33, CD37, CD44v7 / 8, CD38, CD56, CD123, CA125, c-MET, FcRH5, WT1, folate receptor a, VEGF-a, VEGFR1, VEGFR2, IL-13Ra2, IL-1 IRa, MAGE-A1, PSA, ephrin A2, ephrin B2, NKG2D, NY-ESO-1, TAG-72, mesothelin, NY -ESO, 5T4, BCMA, FAP, Carbonic anhydrase 9, BRAF, a-fetoprotein, MAGE-A3, MAGE-A4, SSX-2, PRAME, HA-1, P2M, ETA, tyrosinase, KRAS, NRAS, a peptide:MHC complex, or CEA.In some embodiments, the polypeptide dimer comprises a a target-binding domain that binds CD19.In some embodiments, the target-binding domain that binds CD 19 comprises:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS , and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT ;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS , and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT .Also provided is a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide or the second polypeptide comprises a single chain variable fragment (scFv) disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the scFv binds to a human CD22 and comprises the VH amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S and the VL amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence;EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR orthe amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVES GGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTIS RDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVS.In some embodiments, the first polypeptide comprises the scFv that binds to a human CD22, the first TCR constant domain is a TCR alpha chain constant domain (Ca), and the second TCR constant domain is a TCR beta chain constant domain (CP).In some embodiments, the second polypeptide comprises a scFv that binds to a human CD 19, wherein the scFv that binds to the extracellular domain of a human CD 19 comprises the VH amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS and the VL amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, wherein, optionally, the scFv that binds to a human CD 19 comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT or the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQES GPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS.In some embodiments, the first polypeptide comprises the scFv that binds to a human CD22, the first TCR constant domain is a TCR beta chain constant domain (CP), and the second TCR constant domain is a TCR alpha chain constant domain (Ca).In some embodiments, the second polypeptide comprises a scFv that binds to a human CD 19, wherein the scFv that binds to a human CD 19 comprises the VH amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS and the VL amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, wherein, optionally, the scFv that binds to a human CD 19 comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT or the amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQES GPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS.In some embodiments, a chTCR is multispecific and binds to human CD22 extracelullar domain and at least one other target. For example, a chTCR can, in addition to a human CD22 -targeting domain, include a binding domaun such as one that comprises the VH, the VL, the HCDRs, and / or the LCDRs of: trastuzumab; pertuzumab; rituximab; erbituxumab; ublituxumab; 1.5.3; a BMCA-specific antibody such as J22.0-xi, J22.9-xi, J6M0, J6M1, J6M2, J9M0, J9M1, J9M2, CA8, A7D12.2, Cl l D5.3, C12A3.2, C13F12.1, 13C2, 17A5, 83A10, 13A4, 13D2, 14B11, 14E1, 29B11, 29F3, 13A7, CA7, SGI, S307118G03, S332121F02, S332126E04, S322110D07, S336105A07, S335115G01, S335122F05, ET140-3, ET140-24, ET140-37, ET140-40, ET140-54, TBL-CLN1, C4.E2.1, Vicky-1, pSCHLI333, pSCHLI372, pSCHLI373, and those other BCMA-specific antibodies and antigen-binding fragments disclosed in PCT Publication Nos. WO 2002 / 066516, WO 2007 / 062090, WO 2010 / 104949, WO 2011 / 108008, WO 2012 / 163805, WO 2014 / 068079, WO 2015 / 166073, WO 2014 / 122143, WO 2014 / 089335, WO 2016 / 090327, and WO 2016 / 079177; Ryan etal., Mol. Cancer. Ther. 6(l l):3009, 2007; and Abbas et al., Blood 725: 1688, 2016; a ROR1 -specific antibody such as R11, R12, Y4, Y13, Y27, or Y31; a CD19-specific antibody such as FMC63; a CD33-specific antibody such as gemtuzumab; a GPRC5D-specific antibody; a ROR1 -specific VHH; a VHH such as MB 14; 3F8; alemtuzumab; XMAB-5574; pembrolizumab; nivolumab; a PD-l-specific antibody; elotuzomab; a SLAMF-specific antibody; a CD229-specific antibody; a PD-L1 -specific antibody; a SARS-CoV-2-specific antibody, or an (e.g. cancer antigen-specific, pathogen-specific, autoimmune disease antigen-specific, or neurodegenerative-disease-specific) antibody or antigen-binding fragment approved for therapeutic and / or diagnostic use in humans by the US Food and Drug Administration, the European Medicines Agency, or both. In some embodiments, a binding domain comprises the VH, the VL, the HCDRs, and / or the LCDRs of: 3F8, 8H9, Abagovomab, Abciximab, Abituzumab, Abrilumab, Actoxumab, Adalimumab, Adecatumumab, Aducanumab, Afasevikumab, Afelimomab, Afiituzumab, Alacizumab pegol, ALD518, Alemtuzumab, Alirocumab, Altumomab pentetate, Amatuximab, Anatumomab mafenatox, Anetumab ravtansine, Anifrolumab, Anrukinzumab, Apolizumab, Arcitumomab, Ascrinvacumab, Aselizumab,Atezolizumab, Atinumab, Atlizumab, Atorolimumab, Avelumab, Bapineuzumab, Basiliximab, Bavituximab, Bectumomab, Begelomab, Belimumab, Benralizumab, Bertilimumab, Besilesomab, Bevacizumab, Bezlotoxumab,Biciromab, Bimagrumab, Bimekizumab, Bivatuzumab mertansine, Bleselumab, Blinatumomab, Blontuvetmab, Blosozumab, Bococizumab, Brazikumab, Brentuximab vedotin, Briakinumab, Brodalumab, Brolucizumab, Brontictuzumab, Burosumab, Cabiralizumab, Canakinumab, Cantuzumab mertansine, Cantuzumab ravtansine, Caplacizumab, Capromab pendetide, Carlumab, Carotuximab, Catumaxomab, cBR96- doxorubicin immunoconjugate, Cedelizumab, Cergutuzumab amunaleukin, Certolizumab pegol, Cetuximab, Citatuzumab bogatox, Cixutumumab, Clazakizumab, Clenoliximab, Clivatuzumab tetraxetan, Codrituzumab, Coltuximab ravtansine, Conatumumab, Concizumab, CR6261, Crenezumab, Crotedumab, Dacetuzumab, Daclizumab, Dalotuzumab, Dapirolizumab pegol, Daratumumab, Dectrekumab, Demcizumab, Denintuzumab mafodotin, Denosumab, Depatuxizumab mafodotin, Derlotuximab biotin, Detumomab, Dinutuximab, Donanemab, Diridavumab, Domagrozumab, Dorlimomab aritox, Drozitumab, Duligotumab, Dupilumab, Durvalumab, Dusigitumab, Ecromeximab, Eculizumab, Edobacomab, Edrecolomab, Efalizumab, Efungumab, Eldelumab, Elgemtumab, Elotuzumab, Elsilimomab, Emactuzumab, Emibetuzumab, Emicizumab, Enavatuzumab, Enfortumab vedotin, Enlimomab pegol, Enoblituzumab, Enokizumab, Enoticumab, Ensituximab, Epitumomab cituxetan, Epratuzumab, Erenumab, Erlizumab, Ertumaxomab, Etaracizumab, Etrolizumab, Evinacumab, Evolocumab, Exbivirumab, Fanolesomab, Faralimomab, Farletuzumab, Fasinumab, FBTA05, Felvizumab, Fezakinumab, Fibatuzumab, Ficlatuzumab, Figitumumab, Firivumab, Flanvotumab, Fletikumab, Fontolizumab, Foralumab, Foravirumab, Fresolimumab, Fulranumab, Futuximab, Galcanezumab, Galiximab, Ganitumab, Gantenerumab, Gavilimomab, Gemtuzumab ozogamicin, Gevokizumab, Girentuximab, Glembatumumab vedotin, Golimumab, Gomiliximab, Guselkumab, Ibalizumab, Ibritumomab tiuxetan, Icrucumab, Idarucizumab, Igovomab, IMAB362, Imalumab, Imciromab,Imgatuzumab, Inclacumab, Indatuximab ravtansine, Indusatumab vedotin, Inebilizumab, Infliximab, Inolimomab, Inotuzumab ozogamicin, Intetumumab, Ipilimumab, Iratumumab, Isatuximab, Itolizumab, Ixekizumab, Keliximab, Labetuzumab, Lampalizumab, Lanadelumab, Landogrozumab, Laprituximab emtansine, Lebrikizumab, Lemalesomab, Lendalizumab, Lenzilumab, Lerdelimumab, Lecanemab, Lexatumumab, Libivirumab, Lifastuzumab vedotin, Ligelizumab, Lilotomab satetraxetan, Lintuzumab ,Lirilumab, Lodelcizumab, Lokivetmab,Lorvotuzumab mertansine, Lucatumumab, Lulizumab pegol, Lumiliximab, Lumretuzumab, MABpl, Mapatumumab, Margetuximab, Maslimomab, Matuzumab, Mavrilimumab, Mepolizumab, Metelimumab, Milatuzumab, Minretumomab, Mirvetuximab soravtansine, Mitumomab, Mogamulizumab, Monalizumab, Morolimumab, Motavizumab, Moxetumomab pasudotox, Muromonab-CD3, Nacolomab tafenatox, Namilumab, Naptumomab estafenatox, Naratuximah emtansine, Namatumab, Natalizumab, Navicixizumab, Navivumab, Nebacumab, Necitumumab, Nemolizumab, Nerelimomab, Nesvacumab, Nimotuzumab, Nivolumab, Nofetumomab merpentan, Obiltoxaximab, Obinutuzumab, Ocaratuzumab, Ocrelizumab, Odulimomab, Ofatumumab, Olaratumab, Olokizumab, Omalizumab, Onartuzumab, Ontuxizumab, Opicinumab, Oportuzumab monatox, Oregovomab, Orticumab, Otelixizumab, Otlertuzumab, Oxelumab, Ozanezumab, Ozoralizumab, Pagibaximab, Palivizumab, Pamrevlumab, Panitumumab, Pankomab, Panobacumab, Parsatuzumab, Pascolizumab, Pasotuxizumab, Pateclizumab, Patritumab, Pembrolizumab, Pemtumomab, Perakizumab, Pertuzumab, Pexelizumab, Pidilizumab, Pinatuzumab vedotin, Pintumomab, Placulumab, Plozalizumab, Pogalizumab, Polatuzumab vedotin, Ponezumab, Prezalizumab, Priliximab, Pritoxaximab, Pritumumab, PRO 140 aka leronlimab, Quilizumab, Racotumomab, Radretumab, Rafivirumab, Ralpancizumab, Ramucirumab, Ranibizumab, Raxibacumab, Refanezumab, Regavirumab, Reslizumab, Rilotumumab, Rinucumab, Risankizumab, Rituximab,Rivabazumab pegol, Robatumumab, Roledumab, Romosozumab, Rontalizumab, Rovalpituzumab tesirine, Rovelizumab, Ruplizumab, Sacituzumab govitecan, Samalizumab, Sapelizumab, Sarilumab, Satumomab pendetide, Secukinumab, Seribantumab, Setoxaximab, Sevirumab, SGN-CD19A, SGN-CD33A, Sibrotuzumab, Sifalimumab, Siltuximab, Simtuzumab, Siplizumab, Sirukumab, Sofituzumab vedotin, Solanezumab, Solitomab, Sonepcizumab, Sontuzumab, Sotrovimab, Stamulumab, Sulesomab, Suvizumab, Tabalumab, Tacatuzumab tetraxetan, Tadocizumab, Talizumab, Tamtuvetmab, Tanezumab, Taplitumomab paptox, Tarextumab, Tefibazumab, Telimomab aritox, Tenatumomab, Teneliximab, Teplizumab, Teprotumumab, Tesidolumab, Tetulomab, Tezepelumab, TGN1412, Ticilimumab, Tigatuzumab, Tildrakizumab, Timolumab, Tisotumab vedotin, TNX-650, Tocilizumab, Toralizumab, Tosatoxumab, Tositumomab, Tovetumab, Tralokinumab, Trastuzumab, Trastuzumab emtansine, TRBS07, Tregalizumab, Tremelimumab, Trevogrumab, Tucotuzumab celmoleukin, Tuvirumab, Ublituximab, Ulocuplumab, Urelumab, Urtoxazumab, Ustekinumab, Utomilumab, Vadastuximab talirine, Vandortuzumab vedotin, Vantictumab, Vanucizumab, Vapaliximab, Varlilumab, Vatelizumab, Vedolizumab, Veltuzumab, Vepalimomab, Vesencumab, Visilizumab,Vobarilizumab, Volociximab, Vorsetuzumab mafodotin, Votumumab, Xentuzumab, Zalutumumab, Zanolimumab, Zatuximab, Ziralimumab, or Zolimomab aritox.In certain embodiments, a chTCR comprises VH, the VL, the HCDRs, and / or the LCDRs of an antibody or antigen-binding 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The above patents and published patent applications areincorporated herein by reference in their entirety for purposes of their disclosure of variable domain and CDR polypeptides, variable domain and CDR-encoding nucleic acids, host cells, vectors, methods of making the antibodies or antigen-binding fragments polypeptides encoding said variable domains, pharmaceutical compositions, and methods of treating diseases associated with the respective target of the variable domain-containing antibody or antigen-binding fragment.In certain embodiments, a chTCR that binds human CD22 extracelullar domain also comprises target-binding domain that comprises VH, the VL, the HCDRs, and / or the LCDRs of an antibody or antigen-binding fragment that is one of: Muromonab-CD3 (product marketed with the brand name Orthoclone Okt3®), Abciximab (product marketed with the brand name Reopro®.), Rituximab (product marketed with the brand name MabThera®, Rituxan®), Basiliximab (product marketed with the brand name Simulect®), Daclizumab (product marketed with the brand name Zenapax®), Palivizumab (product marketed with the brand name Synagis®), Infliximab (product marketed with the brand name Remicade®), Trastuzumab (product marketed with the brand name Herceptin®), Alemtuzumab (product marketed with the brand name MabCampath®, Campath- 1H®), Adalimumab (product marketed with the brand name Humira®), Tositumomab-1131 (product marketed with the brand name Bexxar®), Efalizumab (product marketed with the brand name Raptiva®), Cetuximab (product marketed with the brand name Erbitux®), 1'Ibritumomab tiuxetan (product marketed with the brand name Zevalin®), I'Omalizumab (product marketed with the brand name Xolair®), Bevacizumab (product marketed with the brand name Avastin®), Natalizumab (product marketed with the brand name Tysabri®), Ranibizumab (product marketed with the brand name Lucentis®), Panitumumab (product marketed with the brand name Vectibix®), 1'Eculizumab (product marketed with the brand name Soliris®), Certolizumab pegol (product marketed with the brand name Cimzia®), Golimumab (product marketed with the brand name Simponi®), Canakinumab (product marketed with the brand name Ilarise), Catumaxomab (product marketed with the brand name Removab®), Ustekinumab (product marketed with the brand name Stelara®), Tocilizumab (product marketed with the brand name RoActemra®, Actemra®), Ofatumumab (product marketed with the brand name Arzerra®), Denosumab (product marketed with the brand name Prolia®), Belimumab (product marketed with the brand name Benlysta®), Raxibacumab, Ipilimumab (product marketed with the brand name Yervoy®), and Pertuzumab (product marketed with the brand name Perjeta®). In exemplary embodiments, the antibody is one of anti-TNF alpha antibodies such as adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol; anti -IL 1. beta, antibodies such as canakinumab; anti-IL12 / 23 (p40) antibodies such as ustekinumab and briakinumab; and anti-IL2R antibodies, such as daclizumab. Examples of suitable anti-cancer antibodies include, but are not limited to, anti-BAFF antibodies such as belimumab; anti-CD20 antibodies such as rituximab; anti-CD22antibodies such as epratuzumab; anti-CD25 antibodies such as daclizumab; anti-CD30 antibodies such as iratumumab, anti-CD33 antibodies such as gemtuzumab, anti-CD52 antibodies such as alemtuzumab; anti-CD152 antibodies such as ipilimumab; anti-EGFR antibodies such as cetuximab; anti-HER2 antibodies such as trastuzumab and pertuzumab; anti-IL6 antibodies such as siltuximab; and anti-VEGF antibodies such as bevacizumab; and anti-IL6 receptor antibodies such as tocilizumab.In certain embodiments, a target comprises a protein ligand and a binding domain is from a receptor for the ligand. For example, a binding domain can comprise a receptor ectodomain from Bcl2 and a target comprises BIM.In some embodiments, a binding domain comprises a “TCR-mimic” antibody fragment (e.g. scFv or VH and VL from a TCR-mimic antibody) and a target comprises a peptide antigen in complex with a MHC (e.g. HLA) molecule. In some embodiments, the MHC molecule is a Class I MHC molecule. In other embodiments, the MHC molecule is a Class II MHC molecule. In certain further embodiments, a peptide antigemHLA complex comprises WTlne (RMFPNAPYL; SEQ ID N0.:66) / HLA-A*0201 or NY-ESO-I157 (SLLMWITQC; SEQ ID NO.:67) / HLA-A*0201. TCR-mimic antibodies may be prepared by the hybridoma methodology described by Kohler et al., Nature 256:495 (1975), or may be made using recombinant DNA methods in bacterial, eukaryotic animal, or plant cells (see, e.g., U.S. Pat. No. 4,816,567). TCR-mimic antibodies may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991), and Noy et al. Expert Rev. Anticancer Ther. 5(3):523-536 (2005); these techniques are incorporated herein in their entireties), for example. TCR-mimic antibodies may also be obtained using methods disclosed in PCT Publication No. WO 2004 / 076677A2.In some embodiments, a chTCR comprises: a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a CD22-specific scFv (e.g., a scFv comprising the variable domains of m971 in VH-linker-VL orientation or VL-linker-VH orientation, or the variable domains of 9A8 in VH-linker-VL orientation or VL-linker- VH orientation; the linker can be any suitable linker and may, for example, comprise a Whitlow linker sequence, a Gly-Ser linker sequence, or the like); and a second polypeptide comprising, consisting essentially of, or consisting of a human TCR beta chain constant domain (or an engineered variant thereof), and optionally not comprising an antigen-binding domain linked or fused to an N-terminus thereof.In some embodiments, a chTCR comprises: a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a CD22-specific scFv (e.g., a scFv comprising the variable domains of m971 in VH-linker-VL orientationor VL-linker-VH orientation, or the variable domains of 9A8 in VH-linker-VL orientation or VL-linker- VH orientation; the linker can be any suitable linker and may, for example, comprise a Whitlow linker sequence, a Gly-Ser linker sequence, or the like); and a second polypeptide comprising, consisting essentially of, or consisting of a human TCR alpha chain constant domain (or an engineered variant thereof) and optionally not comprising an antigen-binding domain linked or fused to an N-terminus thereof.In some embodiments, a chTCR comprises: a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a CD22-specific scFv (e.g., a scFv comprising the variable domains of m971 in VH-linker-VL orientation or VL-linker-VH orientation, or the variable domains of 9A8 in VH-linker-VL orientation or VL-linker- VH orientation; the linker can be any suitable linker and may, for example, comprise a Whitlow linker sequence, a Gly-Ser linker sequence, or the like); and a second polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a CD19-specific scFv (e.g, a scFv comprising the variable domains of FMC63 in VH-linker-VL orientation or VL-linker-VH orientation).In some embodiments, a chTCR comprises: a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a CD22-specific scFv (e.g., a scFv comprising the variable domains of m971 in VH-linker-VL orientation or VL-linker-VH orientation, or the variable domains of 9A8 in VH-linker-VL orientation or VL-linker- VH orientation; the linker can be any suitable linker and may, for example, comprise a Whitlow linker sequence, a Gly-Ser linker sequence, or the like); and a second polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a CD19-specific scFv (e.g, a scFv comprising the variable domains of FMC63 in VH-linker-VL orientation or VL-linker-VH orientation). chTCRs (TCR / CARs) that bind GPRC5D or SLAMF-7, and optionally also bind BCMACertain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide or the second polypeptide comprises a target-binding domain disposed amino-terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human GPRC5D and comprises an antibody variable fragment (e.g.,a disulfide-stabilized variable fragment (dsFv) or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) or a disulfide-stabilized Fab (dsFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS or the amino acid sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGS GGGGSGGGGSLEMAS SELTQDPAVSVALGQTVRITCQGD SLRSYYASWYQQKPGQAPVLVIYG KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG.In some embodiments, the first polypeptide comprises a target-binding domain binds to a human GPRC5D and the second polypeptide comprises a target-binding domain that binds to a human BCMA, wherein the target-binding domain that binds to a human BCMA comprises: an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) or a dsFab comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGS GGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK or the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETS ASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVS S .Certain embodiments provide a polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide or the second polypeptide comprises a target-binding domain disposed amino-terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human SLAMF7 and comprises an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) or a disulfide-stabilized Fab (dsFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK, wherein the CDRH1, CDRH2,CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK or the amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVES GGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISR DNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS.In some embodiments, the first polypeptide comprises a target-binding domain binds to a human SLAMF7 and the second polypeptide comprises a target-binding domain that binds to a human BCMA, wherein the target-binding domain that binds to a human BCMA comprises: an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGS GGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK or the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETS ASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVS S .In some embodiments, the first TCR constant domain is a TCR alpha chain constant domain (Ca) and the second TCR constant domain is a TCR beta chain constant domain (CP), or wherein the first TCR constant domain is a TCR beta chain constant domain (C ) and the second TCR constant domain is a Ca.In some embodiments, the first TCR constant domain, the second TCR constant domain, or both, comprises an amino acid substitution mutation that promotes pairing between the first TCR constant domain and the second TCR constant domain.In some embodiments, the amino acid substitution mutation comprises a cysteine amino acid at a non-native position and the cysteine amino acid forms a disulfide bond with an amino acid at a corresponding position in the other of the second or the first TCR constant domain, respectively.In some embodiments, the first polypeptide or the second polypeptide comprises a TCR Ca domain comprising one or more mutations to improve stability of the polypeptide dimer when expressed at a surface of a host cell, wherein, optionally, the one or more mutations comprise an L-V-L mutation.In some embodiments: (1) the first polypeptide comprises a TCR Ca having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:56-57, and the second polypeptide comprises a TCR Cp having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:58-61; or (2) the first polypeptide comprises a TCR C having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:58-61; and the second polypeptide comprises a TCR Ca having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:56-57.In some embodiments, the polypeptide dimer comprises a TCR Ca and a TCR Cp having at least least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% to, or comprising or consisting of, the amino acid sequences set forth in SEQ ID NOs.: (i) 56 and 58, respectively; (ii) 56 and 59, respectively; (iii) 56 and 60, respectively; (iv) 56 and 61, respectively; (v) 57 and 58, respectively; (vi) 57 and 59, respectively; (vii) 57 and 60, respectively; or (viii) 57 and 61, respectively.In some embodiments, the polypeptide dimer comprises a a TCR C that comprises the intracellular sequence VKRKDF (SEQ ID NO.:64) or MAMVKRKDSRG (SEQ ID NO.:65).In some embodiments, the first polypeptide, the second polypeptide, or both, comprises an intracellular portion that consists essentially of or consists of the intracellular portion of a native TCR constant domain (e.g. if the polypeptide comprises a TCR Ca, the intracellular portion of the first polypeptide consists essentially of or consists of the intracellular portion of a native TCR Ca; if the polypeptide comprises a TCR Cp, the intracellular portion of the first polypeptide consists essentially of or consists of the intracellular portion of a native TCR CP).In some embodiments, the first polypeptide, the second polypeptide, or both, does not comprise an intracellular signaling component from a CD3 protein, and / or does not comprise an intracellular costimulatory domain from a costimulatory protein.In some embodiments, the polypeptide dimer comprises a hinge sequence disposed between and connecting a target-binding domain and the first TCR constant domain or the second TCR constant domain, wherein, optionally, the hinge sequence comprises, consists essentially of, or consists of, the amino acid sequence set forth in any one of SEQ ID NOs.:42-55 and 68-74, is a (GlyxSery)nlinker wherein x, y, and n are not zero, is a (A)« linker wherein n is one or more, is a GPP linker, or any combination thereof.In some embodiments, the first polypeptide and / or the second polypeptide does not comprise an immunoglobulin CH2 domain and / or an immunoglobulin CH3 domain and / or an immunoglobulin light chain constant domain disposed C-terminal to the TCR constant domain.Also provided is a polypeptide dimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide and the second polypeptide associate with one another and wherein:(i) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence DLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the secondpolypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACAN AFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(ii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACAN AFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(iii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAW SNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(iv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVA VFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAW SNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(v) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSD FACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLR LWSS;(vi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTIS RDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSIQNPDPA VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRL WS;(vii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKV FPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALN DSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(viii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSDLNKVF PPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALND SRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(ix) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQK ATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNK SDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMT LRLWSS;(x) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLN KVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPA LNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADC GFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQK ATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFN LLMTLRLWSS;(xii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLK EQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWG RADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSSDKSVCLFT DFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xiii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKV FPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALN DSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGF TSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEmQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xiv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEmQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xvi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSDLNKVF PPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALND SRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFT SVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xvii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTS GSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEmQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xviii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTS GSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xix) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSR ITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEmQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xx) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSR ITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGS GGGGSGGGGSLEMAS SELTQDPAVSVALGQTVRITCQGD SLRSYYASWYQQKPGQAPVLVIYG KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGS GGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKDLNKVFPPEVAVFEPSE AEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRV SATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSA TILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGS GGGGSGGGGSLEMAS SELTQDPAVSVALGQTVRITCQGD SLRSYYASWYQQKPGQAPVLVIYG KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGIQNPD PAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKS DFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTL RLWSS;(xxiii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLE MAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxiv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLE MAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGV LSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxvi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxvii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxviii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxix) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxx) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRL RVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGV LSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxxi) the first polypeptide comprises, consists essentially of, or consists of the TRAC- containing polypeptide produced when the amino acid sequence shown in any one of Figures 4F-4Q, 4T- 4AA, 4AD-4AI, and 4AL-4AO is processed by a host T cell for expression at the surface of the host T cell, and the second polypeptide comprises, consists essentially of, or consists of the TRBC-containing polypeptide produced when the amino acid sequence shown in any one of Figures 4F-4Q, 4T-4AA, 4AD- 4AI, and 4AL-4AO is processed by a host T cell for expression at the surface of the host T cell; or(xxxii) the first polypeptide and the second polypeptide each comprise an amino acid sequence that remains when the amino acid sequence shown in any one of Figures 4F-4Q, 4T-4AA, 4AD-4AI, and 4AL-4AO undergoes the following in a host T cell: both signal peptides are at least partially removed, and are preferably fully removed; the self-cleaving peptide self-cleaves, and the furin site undergoes furin-mediated cleavage.44. A polynucleotide encoding, or a polypeptide comprising, consisting essentially of, or consisting of, an amino acid amino acid sequence that comprises, consists essentially of, or consists of, the amino acid sequence:(i)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGL VKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPD TSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFS GRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(ii)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHV ELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLS ENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVL MAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQS PSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTL TISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQSGPGLVKP SQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSK NQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQLRDSKSSDK SVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(iii)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWS YLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQT FGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognitionsequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(iv)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTS GSGKPGSGEGSTKGQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL GRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIW GQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(v)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVQLVESGGGL VQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDA KNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSGSTSGSGKPGS GEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGV PSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(vi)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLS ASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLE SEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSL KLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQ MDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSIQNPDPAVYQLRDSKSSD KSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIP EDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(vii)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSS QDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSI QYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGK EVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(viii)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTS GSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVA SISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGY TMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGK EVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(ix)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGD VEENPGPMLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWN WIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAR EVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETD TNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(x)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNG KEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQD RAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRK DFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVG DRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAED FATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETD TNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xi)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAW VRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQ RNYYDGSYDYEGYTMDAWGQGTSVTVSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xii)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLS ASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLE SEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xiii)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSS QDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSI QYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQS LSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKM NSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQT TSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xiv)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSS QDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSI QYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGD RVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDI ATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCT VSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQT NVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xv)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTS GSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVA SISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGY TMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQS LSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKM NSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQT TSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xvi)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTS GSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVA SISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGY TMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGD RVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDI ATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCT VSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQT NVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xvii)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWS YLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLS ASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNL EQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKS SDKS VCLFTDFD SQTNVSQ SKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xviii)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWS YLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQT FGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQ QGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLP DYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYC AKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xix)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTS GSGKPGSGEGSTKGQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIW GQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQSLSVTC TVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLS ASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNL EQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xx)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTS GSGKPGSGEGSTKGQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL GRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQ QGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLP DYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYC AKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxi)MLLLVTSLLLCELPHPAFLLIPQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGK GLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGSGGGGSGGGGSLEMASSELTQDPAVSVALGQTVRITCQGDSLRS YYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSG NPPVVFGGGTKLTVLGDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNG KEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQD RAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRK DFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGE TVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAY LQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSL AMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTL TIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxii)MLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKG LKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYW GQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWY QQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGT KLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAE AWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATN FSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQVQLVESGGGLVHPGGSLRLSCAASGFT FRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTA VYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGSGGGGSGGGGSLEMASSELTQDPAVSVAL GQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQA EDEAD YYCNSRDSSGNPPVVFGGGTKLTVLGIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNV SQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxiii)MLLLVTSLLLCELPHPAFLLIPSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQK PGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGG TKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMN WVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR SGGQWKYYDYWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELS WWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSEND EWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMA MVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSL AMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTL TIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGE TVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAY LQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDF DSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxiv)MLLLVTSLLLCELPHPAFLLIPSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQK PGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGG TKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMN WVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR SGGQWKYYDYWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELS WWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSEND EWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMA MVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPE LKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLET SASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLT QSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGS RTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTD FDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPE SSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furinrecognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxv)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWV RQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGN YWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGI AVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYP YTFGQGTKVEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVH SGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKP VTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRA KRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKI SCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQIN NLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSL GKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPV EEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxvi)MLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKR APGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYA MDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHL IHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTF GGGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGV CTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQI VSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGS GATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGGCLRLSCA ASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRA EDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVG DRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPE DVATYYCQQYSSYPYTFGQGTKVEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxvii)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKV EIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKG LEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDV WGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHS GVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPV TQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAK RGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSLAMSLGKRATIS CRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVA VYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGY TFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDT ATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxviii)MLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGT KLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKG LKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYW GQGTSVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITC KASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDF SRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAV YYCARPDGNYWYFDVWGQGTLVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxix)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQK PGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKV EIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKG LEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDV WGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHS GVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPV TQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAK RGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKIS CKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINN LKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLG KRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxx)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWV RQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGN YWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGI AVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYP YTFGQGTKVEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVH SGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKP VTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRA KRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSLAMSLGKRAT ISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDV AVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASG YTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof; or (xxxi) the amino acid sequence shown in any one of Figures 4F-4Q, 4T-4AA, 4AD-4AI, and 4AL-4AO, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative selfcleaving peptide, or any combination thereof.In some embodiments, a host cell (e.g., a human T cell) is provided that encodes or expresses a chTCR (e.g., that binds human SLAMF7), wherein the host cell comprises a chromosomal (e.g., gene) knockout (e.g., an introduced stop codon or splicing site, such as introduced by base editing) that reduces or eliminates expression by the host cell of SLAMF7, and optionally a chromosomal (e.g. , gene) knockout (e.g., an introduced stop codon or splicing site, such as introduced by base editing) that reduces or eliminates expression by the host cell of TRAC, TRBC, or both.In some embodiments, a chTCR is provided that comprises: a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N- terminus thereof, the VH of the SLAMF7-specific antibody HuLuc63; and a second polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, the VL of the SLAMF7-specific antibody HuLuc63.In some embodiments, a chTCR is provided that comprises: a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N- terminus thereof, the VH of the SLAMF7-specific antibody HuLuc63; and a second polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, the VL from the SLAMF7-specific antibody HuLuc63.In some embodiments, a chTCR is provided that comprises: a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N- terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker-VH orientation); and a second polypeptide comprising, consisting essentially of, or consisting of, a human TCR alpha chain constant domain (or an engineered variant thereof).In some embodiments, a chTCR is provided that comprises: a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N- terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker-VH orientation); and a second polypeptide comprising, consisting essentially of, or consisting of, a human TCR alpha beta constant domain (or an engineered variant thereof).In some embodiments, a chTCR is provided that comprises: a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N- terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker-VH orientation); and a second polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to a N-terminus thereof, a BCMA-specific scFv comprising the VH and VL of the BCMA-specific antibody Cl 1D5.3 (in VH-linker-VL or VL-linker-VH orientation).In some embodiments, a chTCR is provided that comprises: a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N- terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker-VH orientation); and a second polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to a N-terminus thereof, a BCMA-specific scFv comprising the VH and VL of the BCMA-specific antibody Cl 1D5.3 (in VH-linker-VL or VL-linker-VH orientation).In some embodiments, a chTCR is provided that in a “full” chTCR format as shown for Figure 31 A.In some embodiments, a chTCR comprises, or a polynucleotide encodes a chTCR comprising: a first polypeptide comprising, in N-terminal to C-terminal direction: a SLAMF7-specific scFv comprising the VH of HuLuc63, a linker (e.g., (GL^Scrf). and the VL of HuLuc63; and a human TCR beta chain constant domain (or an engineered variant thereof); and second polypeptide comprising, in N-terminal to C-terminal direction, a BCMA-specific scFv comprising: the VH of Cl 1D5.3, a linker (e.g., (Gly4Ser)s), and the VL of Cl 1D5.3; and a human TCR alpha chain constant domain (or an engineered variant thereof).In some embodiments, a polynucleotide or expression construct is provided that comprises, in 5 ’ to 3 ’ direction: an optional expression control sequence, e.g. a promoter, such as an EFla promoter;a sequence encoding a first polypeptide comprising, in N-terminal to C-terminal direction: a SLAMF7-specific scFv comprising the VH of HuLuc63, a linker (e.g., (Gly4Ser)3), and the VL of HuLuc63; and a human TCR beta chain constant domain (or an engineered variant thereof); a sequence encoding a furin cleavage site and a 2A peptide (e.g., a P2A peptide), in either order; and a sequence encoding a second polypeptide comprising, in N-terminal to C-terminal direction, a BCMA-specific scFv comprising: the VH of Cl 1D5.3, a linker (e.g., (Gly4Ser)3), and the VL of Cl 1D5.3; and a human TCR alpha chain constant domain (or an engineered variant thereof).Also provided are chimeric co -stimulatory receptor polypeptides (CCRs) that are capable of improving host cell (e.g. T cell) function when the host cell encounters PVR aka CD 155. PVR aka CD 155 is often overexpressed by tumor cells and is a shared ligand for two T cell proteins, CD226 and TIGIT. CD226 can be gradually lost following chronic antigen stimulation, while TIGIT is expressed following T cell activation and becomes constitutively expressed during T cell exhaustion. TIGIT has a higher affinity for PVR (approximately 100-fold) than does CD226. Disclosed CCRs are capable of manipulating PVR / TIGIT / CD226 signaling and improve one or more function of a host cell (e.g. peristence, anti-tumor activity, activation, proliferation, or the like) in the presence of PVR (e.g. in the presence of tumor cells). Presently disclosed CCRs are single-chain fusion polypeptides.In some embodiments, a CCR comprises an extracellular binding domain from CD226 (e.g. can comprise a CD226 ectodomain (also referred-to as extracellular domain or extracellular component)), or a portion or variant thereof that is functional to bind PVR. An example of a CD226 ectodomain amino acid sequence is provided in SEQ ID NO.:77. A portion or variant of a CD226 ectodomain that is functional to bind PVR will preferably maintain an Ig-like C2-type 1 domain and an Ig-like C2-type 2 domain of CD226. The CCR can further comprise a transmembrane domain from CD226. An example of a CD226 transmembrane domain amino acid sequence is provided in SEQ ID NO.: 78. In some embodiments, a CD226-based CCR comprises an ectodoma...

Claims

CLAIMSWhat is claimed is:

1. A polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the targetbinding domain binds to a human CD22 extracellular domain and comprises the six CDRs of, and optionally VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of, the VH and VL amino acid sequences of: 9A8; H- SCL-1; epratuzumab; CAT-8015; RFB4; inotuzumab; 6C4-6; 4D9-12; 5H4-9; 10C1-D9; 15G7-2; 2B12- 8; 2C4-4; 3E10-7; LT22; Inotuzumab G5 44; 1G-34; mAb EP798Y; hCD22.7 ; BL22 (RFB4dsFv); or HA 22.

2. The polypeptide dimer of claim 1, wherein the target-binding domain that binds to a human CD22 extracellular domain comprises the six CDRs of 9A8.

3. The polypeptide dimer of claim 2, wherein the target-binding domain that binds to a human CD22 extracellular domain comprises VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, identity to the VH (SEQ ID NO.: 156) and VL (SEQ ID NO.: 157) amino acid sequences of 9A8.

4. The polypeptide dimer of claim 3, wherein the target-binding domain that binds to a human CD22 extracellular domain comprises VH and VL amino acid sequences comprising, consisting essentially of, or consisting of the VH and VL amino acid sequences of 9A8.

5. The polypeptide dimer of any one of claims 1-4, wherein the target-binding domain that binds to a human CD22 extracellular domain comprises a single chain variable fragment or a single-chain Fab (scFab).

6. The polypeptide dimer of claim 5, wherein the target-binding domain that binds to a human CD22 extracellular domain comprises a scFv.

7. The polypeptide dimer of claim 6, wherein the scFv comprises a VL-linker-VH orientation, wherein the scFv optionally comprises the amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVES GGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTIS RDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVS (SEQ ID NO.:253).

8. The polypeptide dimer of any one of claims 1-7, wherein the second polypeptide comprises the target-binding domain that binds to a human CD22 extracellular domain, fused to a TCR beta chain constant domain (CP), and wherein the first polypeptide comprises a TCR alpha chain constant domain (Ca).

9. The polypeptide dimer of any one of claims 1-8, wherein the polypeptide dimer comprises two or more target-binding domains and is multispecific, wherein the second polypeptide comprises the target-binding domain that binds to a human CD22 extracellular domain and wherein the first polypeptide comprises a target-binding domain that binds to a human CD 19 and comprises the six CDRs of, and optionally VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of, the VH (SEQ ID NO.:98) and VL (SEQ ID NO.:97) amino acid sequences of FMC63.

10. The polypeptide dimer of claim 9, wherein the target-binding domain that binds to a human CD 19 comprises VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, identity to the VH and VL amino acid sequences of FMC63.

11. The polypeptide dimer of claim 9 or 10, wherein the target-binding domain that binds to a human CD 19 comprises VH and VL amino acid sequences comprising, consisting essentially of, or consisting of the VH and VL amino acid sequences of FMC63.

12. The polypeptide dimer of any one of claims 9-11, wherein the target-binding domain that binds to a human CD19 comprises a single chain variable fragment or a single-chain Fab (scFab).

13. The polypeptide dimer of claim 12, wherein the target-binding domain comprises a scFv.

14. The polypeptide dimer of claim 13, wherein the scFv comprises a VL-linker-VH orientation, and optionally comprises the amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQES GPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS (SEQ ID NO.:99).

15. The polypeptide dimer of any one of claims 1-8, wherein the TCR constant domain of the first polypeptide and the TCR constant domain of the second polypeptide are each a human TCR constant domain or each comprise an engineered variant of a human TCR constant domain sequence.

16. The polypeptide dimer of any one of claims 1-15, wherein the second polypeptide comprises or consists of the amino acid sequence of SEQ ID NO.: 182 or SEQ ID NO.:203.

17. The polypeptide dimer any one of of claims 9-16, wherein the first polypeptide comprises or consists of the amino acid sequence of SEQ ID NO.: 114 or SEQ ID NO.:201 or SEQ ID NO.:209.

18. The polypeptide dimer of claim 17, wherein the first polypeptide comprises or consists of the amino acid sequence of SEQ ID NO.: 114 or SEQ ID NO.:201 or SEQ ID NO.:209, and wherein the second polypeptide comprises or consists of the amino acid sequence of SEQ ID NO.: 182 or SEQ ID NO.:203.

19. A polynucleotide encoding the polypeptide dimer of any one of claims 1-18.

20. A polynucleotide encoding the amino acid sequence set forth in SEQ ID NO.:204.

21. A polypeptide dimer comprising:(1) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino-terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to an epitope in an extracellular domain of a human CD22, wherein the epitope is comprised within amino acids 20-504 of SEQ ID NO.:252, preferably within amino acids 143-326 of SEQ ID NO.:252, or within amino acids 143-416 of SEQ ID NO.:252, or within amno acids 143-500 of SEQ ID NO.:252, or within amino acids 20-138 of SEQ ID NO.:252, or within amino acids 20-235 of SEQ ID NO.:252, or within amino acids 20-326 of SEQ ID NO.:252, or within amino acids 20-416 of SEQ ID NO.:252, or within amino acids 20-500 of SEQ ID NO.:252, or within amino acids 242-500 of SEQ ID NO.:252, or within amino acids 242-416 of SEQ ID NO.:252, or within amino acids 331-416 of SEQ ID NO.:252; and / or wherein the epitope comprises one or more of amino acids 139-142 of SEQ ID NO.:252, or one or more of amino acids 236-241 of SEQ ID NO.:252, or one or more of amino acids 327-330 of SEQ ID NO.:252, or one or more of amino acids 417-418 of SEQ ID NO.:252;(2) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds an epitope in an extracellular domain of a human CD22, wherein the epitope comprises one or more amino acids of: an Ig-like V-type domain; an Ig-like C2-type domain 1; an Ig-like C2-type domain 2; an Ig-like C2-type domain 3; an Ig-like C2-type domain 4; the Ig-like V-type domain and the Ig-like C2-type domain 1; the Ig-like C2-type domain 1 and the Ig-like C2-type domain 2; the Ig-like C2-type domain 2 and the Ig-like C2-type domain 3; or the Ig-like C2-type domain 3 and the Ig-like C2-type domain 4;(3) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds an epitope in an extracellular domain of a human CD22, wherein the epitope is comprised within amino acids 505-676 of SEQ ID NO.:252, or within amino acids SEQ ID NO.:505-582 of SEQ ID NO.:252, orwithin amino acids 593-676 of SEQ ID NO.:252, and / or wherein the epitope comprises one or more of amino acids 501-504 of SEQ ID NO.:252, or one more of amino acids 582-593 of SEQ ID NO.:252;(4) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds an epitope in an extracellular domain of a human CD22, wherein the epitope comprises one or more amino acids of: the Ig-like C2-type domain 5; the Ig-like C2-type domain 6; or the Ig-like domain 5 and the Ig- like C2-type domain 6;(5) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain competes with one or more of the following antibodies for binding to an extracellular domain of a human CD22: 9A8; 9A8-1; H-SCL-1; epratuzumab; CAT-8015; RFB4; inotuzumab; 6C4-6; 4D9-12; 5H4-9; 10C1-D9; 15G7-2; 2B12-8; 2C4-4; 3E10-7; LT22; Inotuzumab G5_44; 1G-34; mAb EP798Y; hCD22.7; BL22 (RFB4dsFv); and HA22;(6) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain competes with one or more of the following antibodies for binding to an extracellular domain of a human CD22: M971, 1D9-3; 3B4-13;and 7G6-6; or(7) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide, the second polypeptide, or both, further comprises a target-binding domain disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human CD22 extracellular domain and comprises the six CDRs, and optionally comprises VH and VL amino acid sequences having at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least95%, at least 96%, at least 97%, at least 98%, at least 99%, or comprising, consisting essentially of, or consisting of the VH and VL amino acid sequences of: M971, 1D9-3; 3B4-13; or 7G6-6.

22. The polypeptide dimer of 1-21, wherein the target-binding domain comprises: (i) an antibody heavy chain variable domain (VH); (ii) an antibody light chain variable domain (VL); (iii) a single-chain variable fragment (scFv); (iv) a fragment antigen-binding region (Fab); (v) a single-chain Fab; (vi) an antigen-binding fragment of a heavy chain-only antibody (VHH); (vii) a designed ankyrin repeat protein (DARPin); (viii) a10FNIII domain; (ix) a lectin binding domain; (x) a protein ligandbinding domain, such as a receptor ectodomain or a functional portion or fragment thereof; (xi) a killer immunoreceptor from aNK cell; (xii) a fibrinogen domain; (xiii) a cysteine-knot miniprotein; (xiv) a tetratricopeptide repeat domain; (xv) a leucine-rich repeat domain; (xvi) a lipocalin domain; (xvii) an armadillo repeat protein; (xviii) an affibody; (xix) an avimer; (xx) a knottin; (xxi) a fynomer; (xxii) an atrimer; (xxiii) a synthetic protein designed to bind a natural ligand or receptor; (xxiv) a ligand, such as for example comprising a glycan, a sialic acid, or a Neu5Aca2-6Gaipi-4GlcNAc; (xxv) a disulfide- stabilized antibody variable fragment; or (xxvi) any combination of (i)-(xxv), wherein, optionally, the polypeptide dimer comprises a design according to Table 1, and / or wherein the first polypeptide and the second polypeptide comprise, N-terminal to the first TCR constant domain and the second TCR constant domain, respectively: (i) a VH, and a cognate VL; (ii) a VL, and a cognate VH; (iii) a scFv, and no antigen-binding domain; (iv) no antigen-binding domain, and a scFv; (v) VH-CH1, and a cognate VL-CL; (vi) VL-CL, and a cognate VH-CH1; (vii) a scFab, and no antigen-binding domain; (viii) no antigen-binding domain, and a scFab; (ix) a scFv, and a scFv; (x) a scFab, and a scFv; (xi) a scFv, and a scFab; (xii) a VHH, and no antigen-binding domain; (xiii) no antigen-binding domain, and a VHH; (xiv) VHH-linker-VHH, and no binding domain; (xv) VHH-linker- VHH, and VHH-linker-VHH; (xvi) a scFv, and a VHH or a VHH-linker-VHH; (xvii) a VHH or a VHH- linker-VHH, and a scFv; (xvii) a scFab, and a VHH or a VHH-linker-VHH; (xviii) a VHH or a VHH- linker-VHH, and a scFab; (xix) a VHH, and a VHH; (xx) a natural or synthetic protein ligand -binding domain, and no antigen-binding domain; (xxi) no antigen-binding domain, and a natural or synthetic protein ligand-binding domain; (xxii) a scFv, and a natural or synthetic protein ligand-binding domain; (xxiii) a natural or synthetic protein ligand-binding domain, and a scFv; (xxiii) a scFab, and a natural or synthetic protein ligand-binding domain; (xxiv) a natural or synthetic protein ligand -binding domain, and a scFab; (xxv) a VHH or a VHH-linker-VHH, and a natural or synthetic protein ligand-binding domain; (xxvi) a natural or synthetic protein ligand-binding domain, and a VHH or a VHH-linker-VHH; or (xxvii) a natural or synthetic protein ligand-binding domain, and a protein ligand binding -domain.

23. The polypeptide dimer of any one of claims 1-18, 21, and 22, wherein the first polypeptide, the second polypeptide, or both, does not comprise a TCR variable domain fused to the TCR constant domain.

24. The polypeptide dimer of any one of claims 21-23, wherein the target-binding domain is or comprises a single chain variable fragment (scFv) or a single-chain Fab (scFab), wherein, optionally,(i) the scFv comprises, in a N-terminal to C-terminal direction, VH-linker-VL, or the scFab comprises, in a N-terminal to C-terminal direction, VH-CH1 -linker- VL-CL, or(ii) the scFv comprises, in a N-terminal to C-terminal direction, VL-linker-VH, or the scFab comprises, in a N-terminal to C-terminal direction, VL-CL-linker-VH-CHl.

25. The polypeptide dimer of any one of claims 1-8 and 21-23, wherein the first polypeptide comprises the target-binding domain linked or fused to a TCR beta chain constant domain (CP) and the second polypeptide comprises, consists essentially of, or consists of a TCR alpha chain constant domain (Ca), or wherein the first polypeptide comprises the target-binding domain linked or fused to a TCR alpha chain constant domain (Ca) and the second polypeptide comprises, consists essentially of, or consists of a TCR beta chain constant domain (C ).

26. The polypeptide dimer of any one of claims 21-25, wherein:(1) the target-binding domain comprises:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, orcomprising, consisting essentially of, or consisting of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR orthe amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVES GGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTIS RDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVS; or(2) the target-binding domain comprises:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSS, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTS GSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIK or the amino acid sequence of SEQ ID NO.: 170.

27. The polypeptide dimer of any one of claims 1-8 and 21-26, wherein the polypeptide dimer comprises two or more target-binding domains and is multispecific.

28. The polypeptide dimer of any one of claims 1-27, wherein the polypeptide dimer comprises two or more target-binding domains and is bispecific.

29. The polypeptide dimer of any one of claims 1-8, 27 and 28, comprising a target-binding domain that binds BCMA, GPRC5D, CD 19, ROR1, SLAMF7, CD229, PNE, EGFR, EGFRvIII, EGP-2, EGP-40, GD2, GD3, HPV E6, HPV E7, Her2, LI -CAM, Lewis A, Lewis Y, MUC1, MUC16, PSCA, PSMA, CD20, CD56, CD23, CD24, CD30, CD33, CD37, CD44v7 / 8, CD38, CD56, CD123, CA125, c- MET, FcRH5, WT1, folate receptor a, VEGF-a, VEGFR1, VEGFR2, IL-13Ra2, IL-1 IRa, MAGE-A1, PSA, ephrin A2, ephrin B2, NKG2D, NY-ESO-1, TAG-72, mesothelin, NY-ESO, 5T4, BCMA, FAP, Carbonic anhydrase 9, BRAF, a-fetoprotein, MAGE-A3, MAGE-A4, SSX-2, PRAME, HA-1, P2M, ETA, tyrosinase, KRAS, NRAS, a peptide :MHC complex, or CEA, wherein, optionally, the polypeptide dimer comprises a target-binding domain that binds CD 19, wherein, further optionally, the target-binding domain that binds CD 19 comprises:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, or the amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQES GPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS (SEQ ID NO.:99).

30. A polypeptide dimer comprising (i) a first polypeptide comprising a first T cell receptor(TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide or the second polypeptide comprises a single chain variable fragment (scFv) disposed amino -terminal to the first or the second TCR constant domain, respectively, wherein the scFv binds to a human CD22 and comprises the VH amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV S and the VL amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence;EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKR orthe amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVES GGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTIS RDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVS, wherein, optionally,(1) the first polypeptide comprises the scFv that binds to a human CD 22, the first TCR constant domain is a TCR alpha chain constant domain (Ca), and the second TCR constant domain is a TCR beta chain constant domain (C ), and / or(2) the second polypeptide comprises a scFv that binds to a human CD 19, wherein the scFv that binds to the extracellular domain of a human CD 19 comprises the VH amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS and the VL amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, wherein, optionally, the scFv that binds to a human CD 19 comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT or the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQES GPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS, wherein, optionally,the first polypeptide comprises the scFv that binds to a human CD22, the first TCR constant domain is a TCR beta chain constant domain (CP) , and the second TCR constant domain is a TCR alpha chain constant domain (Ca), wherein, optionally, the second polypeptide comprises a scFv that binds to a human CD 19, wherein the scFv that binds to a human CD 19 comprises the VH amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS and the VL amino acid sequence DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT, wherein, optionally, the scFv that binds to a human CD 19 comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT or the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSG SGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQES GPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS.

31. A polypeptide dimer comprising:(1) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide or the second polypeptide comprises a target-binding domain disposed amino-terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human GPRC5D and comprises an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS, and thelight chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG);(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequenceQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS, and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG ; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequenceSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLE MAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSS or the amino acid sequenceQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSV KGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGSGGGGSGGGGSLEMAS SELTQDPAVSVALGQTVRITCQGD SLRSYYASWYQQKPGQAPVLVIYG KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLG; or(2) (i) a first polypeptide comprising a first T cell receptor (TCR) constant domain and (ii) a second polypeptide comprising a second TCR constant domain, wherein the first TCR constant domain and the second TCR constant domain associate with one another, and wherein the first polypeptide or the second polypeptide comprises a target-binding domain disposed amino-terminal to the first or the second TCR constant domain, respectively, wherein the target-binding domain binds to a human SLAMF7 and comprises an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, and a VLamino acid sequence comprising, consisting essentially of, or consisting of the sequenceDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIK or the amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSG SGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVES GGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISR DNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSS, wherein, optionally,(A) the first polypeptide comprises a target-binding domain binds to a human GPRC5D and the second polypeptide comprises a target-binding domain that binds to a human BCMA, wherein the target-binding domain that binds to a human BCMA comprises: an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGS GGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK or the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS, or (B) the first polypeptide comprises a target-binding domain binds to a human SLAMF7 and the second polypeptide comprises a target-binding domain that binds to a human BCMA, wherein the target-binding domain that binds to a human BCMA comprises: an antibody variable fragment (e.g., a disulfide-stabilized variable fragment or a single-chain variable fragment (scFv)) or a single chain Fab (scFab) comprising:(i) the heavy chain complementarity determining region 1 (CDRH1), the CDRH2, and the CDRH3 of the VH amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and the light chain CDR1 (CDRL1), the CDRL2, and the CDRL3 of the VL amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK, wherein the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 are optionally according to Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, or Contact, or to a combination of two or more of Kabat, IMGT, Chothia, AbM, Martin (also known as Enhanced Chothia), AHo, North, and Contact;(ii) a VH amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to, or comprising, consisting essentially of, or consisting of the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK;(iii) a VH amino acid sequence comprising, consisting essentially of, or consisting of the sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSS , and a VL amino acid sequence comprising, consisting essentially of, or consisting of the sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK; and / or(iv) a scFv comprising any one or more of (i), (ii), and (iii) above, wherein, optionally, the scFv comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDF RGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGS GGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIK or the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETS ASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVS S .

32. The polypeptide dimer of claim 31, wherein the first TCR constant domain is a TCR alpha chain constant domain (Ca) and the second TCR constant domain is a TCR beta chain constant domain (CP), or wherein the first TCR constant domain is a TCR beta chain constant domain (C ) and the second TCR constant domain is a Ca.

33. The polypeptide dimer of any one of claims 1-15 and 21-32, wherein:(1) the first TCR constant domain, the second TCR constant domain, or both, comprises an amino acid substitution mutation that promotes pairing between the first TCR constant domain and the second TCR constant domain, wherein, optionally, the amino acid substitution mutation comprises a cysteine amino acid at a non-native position and the cysteine amino acid forms a disulfide bond with an amino acid at a corresponding position in the other of the second or the first TCR constant domain, respectively; and / or(2) the first polypeptide or the second polypeptide comprises a TCR Ca domain comprising one or more mutations to improve stability of the polypeptide dimer when expressed at a surface of a host cell, wherein, optionally, the one or more mutations comprise an L-V-L mutation.

34. The polypeptide dimer of any one of claims 1-15 and 21-33, wherein: (1) the first polypeptide comprises a TCR Ca having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:56-57, and the second polypeptide comprises a TCR Cp having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:58-61; or (2) the first polypeptide comprises a TCR C having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:58-61; and the second polypeptide comprises a TCR Ca having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOs.:56-57, optionally wherein the polypeptide dimer comprises a TCR Ca and a TCR Cp having at least least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% to, or comprising or consisting of, the amino acid sequences set forth in SEQID NOs.: (i) 56 and 58, respectively; (ii) 56 and 59, respectively; (iii) 56 and 60, respectively; (iv) 56 and 61, respectively; (v) 57 and 58, respectively; (vi) 57 and 59, respectively; (vii) 57 and 60, respectively; or (viii) 57 and 61, respectively.

35. The polypeptide dimer of any one of claims 1-15 and 21-34, comprising a TCR CP that comprises the intracellular sequence VKRKDF (SEQ ID NO.:64) or MAMVKRKDSRG (SEQ ID NO.:65).

36. The polypeptide dimer of any one of claims 1-15 and 24-35, wherein:(i) the first polypeptide, the second polypeptide, or both, comprises an intracellular portion that consists essentially of or consists of the intracellular portion of a native TCR constant domain (e.g. if the polypeptide comprises a TCR Ca, the intracellular portion of the first polypeptide consists essentially of or consists of the intracellular portion of a native TCR Ca; if the polypeptide comprises a TCR Cp, the intracellular portion of the first polypeptide consists essentially of or consists of the intracellular portion of a native TCR C ); and / or(ii) the first polypeptide, the second polypeptide, or both, does not comprise an intracellular signaling component from a CD3 protein, and / or does not comprise an intracellular costimulatory domain from a costimulatory protein; and / or the polypeptide dimer further comprises a hinge sequence disposed between and connecting a target-binding domain and the first TCR constant domain or the second TCR constant domain, wherein, optionally, the hinge sequence comprises, consists essentially of, or consists of, the amino acid sequence set forth in any one of SEQ ID NOs.:42-55 and 68-74, is a (GlyxSery)nlinker wherein x, y, and n are not zero, is a (A)« linker wherein n is one or more, is a GPP linker, or any combination thereof; and / or(iv) the first polypeptide and / or the second polypeptide does not comprise an immunoglobulin CH2 domain and / or an immunoglobulin CH3 domain and / or an immunoglobulin light chain constant domain disposed C-terminal to the TCR constant domain.

37. A polypeptide dimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide and the second polypeptide associate with one another and wherein:(i) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence DLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACAN AFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(ii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACAN AFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(iii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAW SNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(iv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVA VFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAW SNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(v) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSD FACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLR LWSS;(vi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKE QPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGR ADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTIS RDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSIQNPDPA VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRL WSS;(vii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKV FPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALN DSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(viii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSDLNKVF PPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALND SRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNL LMTLRLWSS;(ix) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQK ATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDY AVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNK SDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMT LRLWSS;(x) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLN KVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPA LNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADC GFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGR GSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQK ATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFN LLMTLRLWSS;(xii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLK EQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWG RADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence DIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSR SGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSSDKSVCLFT DFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xiii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDS VKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTV SGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRR MIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKV FPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALN DSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGF TSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xiv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEmQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xvi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSDLNKVF PPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALND SRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFT SVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xvii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTS GSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xviii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTS GSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAA SSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xix) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSR ITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN SALKS RLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKP GSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHS GVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEmQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xx) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQ SGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSR ITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCL SSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQ QGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKD NSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFN NSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xxi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGS GGGGSGGGGSLEMAS SELTQDPAVSVALGQTVRITCQGD SLRSYYASWYQQKPGQAPVLVIYG KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xxii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKDLNKVFPPEVAVFEPSE AEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSA TILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGSGGGGSGGGGSLEMAS SELTQDPAVSVALGQTVRITCQGD SLRSYYASWYQQKPGQAPVLVIYG KNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGIQNPD PAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKS DFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTL RLWSS;(xxiii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequence SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSS SGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLE MAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence DIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxiv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGGTKLTVLGSRGGGGSGGGGSGGGGSLE MAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYA DSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xxv) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGV LSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xxvi) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTG VPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRV SATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNN SIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxvii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISR DNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGV LSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxviii) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence DIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxix) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequence QIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPES SCD VKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWS S ;(xxx) the first polypeptide comprises, consists essentially of, or consists of the amino acid sequenceEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSL KDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGG GGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHT GVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKVEIKDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRL RVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGV LSATILYEILLGKATLYAVLVSALVLMAMVKRKDF and the second polypeptide comprises, consists essentially of, or consists of the amino acid sequenceDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFS GSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQ SGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAF SLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS;(xxxi) the first polypeptide comprises, consists essentially of, or consists of the TRAC- containing polypeptide produced when the amino acid sequence shown in any one of Figures 4F-4Q, 4T- 4AA, 4AD-4AI, and 4AL-4AO, preferably the amin oacid sequence shown in Figure 4W, is processed by a host T cell for expression at the surface of the host T cell, and the second polypeptide comprises, consists essentially of, or consists of the TRBC-containing polypeptide produced when the amino acid sequence shown in any one of Figures 4F-4Q, 4T-4AA, 4AD-4AI, and 4AL-4AO, preferably the amin oacid sequence shown in Figure 4W, is processed by a host T cell for expression at the surface of the host T cell; or(xxxii) the first polypeptide and the second polypeptide each comprise an amino acid sequence that remains when the amino acid sequence shown in any one of Figures 4F-4Q, 4T-4AA, 4AD-4AI, and 4AL-4AO, preferably the amino acid sequence shown in Figure 4W, undergoes the following in a host T cell: both signal peptides are at least partially removed, and are preferably fully removed; the selfcleaving peptide self-cleaves, and the furin site undergoes furin -mediated cleavage.

38. A polynucleotide encoding, or a polypeptide comprising, consisting essentially of, or consisting of, an amino acid amino acid sequence that comprises, consists essentially of, or consists of, the amino acid sequence:(i)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGL VKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPD TSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSGSTSGSGKPGSGEGST KGDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFS GRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(ii)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHV ELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLS ENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVL MAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQS PSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTL TISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTSGSGKPGSGEGSTKGQVQLQQSGPGLVKP SQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSK NQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQLRDSKSSDK SVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(in)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWS YLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQT FGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(iv)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTS GSGKPGSGEGSTKGQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL GRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIW GQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSSDKSVC LFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(v)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVQLVESGGGL VQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDA KNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGV PSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(vi)MLLLVTSLLLCELPHPAFLLIPDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLS ASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLE SEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTSGSGKPGSGEGSTKGEVQLVESGGGLVQPGRSL KLSCAASGFTFSNFAMAWVRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQ MDSLRSEDTATYYCARQRNYYDGSYDYEGYTMDAWGQGTSVTVSIQNPDPAVYQLRDSKSSD KSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIP EDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(vii)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSS QDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSI QYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGK EVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furinrecognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(viii)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTS GSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVA SISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGY TMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGK EVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(ix)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGD VEENPGPMLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWN WIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAR EVTGDLEDAFDIWGQGTMVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETD TNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(x)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQD RAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRK DFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVG DRVTITCRASQTIWSYLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAED FATYYCQQSYSIPQTFGQGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xi)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRDLNK VFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCG FTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAW VRQPPTKGLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQ RNYYDGSYDYEGYTMDAWGQGTSVTVSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xii)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE WTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAM VKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLS ASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLE SEDVADYQCLQSIQYPFTFGSGTKLEIKRIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or twoalternative signal peptides, an alternative scFv linker, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xiii)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSS QDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSI QYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQS LSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKM NSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSL TISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xiv)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTK GLEWVASISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGS YDYEGYTMDAWGQGTSVTVSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASLGDRVTITCRSS QDIGNYLTWFQQKVGRSPRRMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSI QYPFTFGSGTKLEIKRDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGD RVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDI ATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCT VSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQT NVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xv)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTS GSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVA SISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGY TMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQS LSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKM NSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSL TISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xvi)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASLGDRVTITCRSSQDIGNYLTWFQQKVGRSPR RMIYGAIKLEDGVPSRFSGSRSGSDYSLTISSLESEDVADYQCLQSIQYPFTFGSGTKLEIKRGSTS GSGKPGSGEGSTKGEVQLVESGGGLVQPGRSLKLSCAASGFTFSNFAMAWVRQPPTKGLEWVA SISTGGGNTYYRDSVKGRFTISRDDAKNTQYLQMDSLRSEDTATYYCARQRNYYDGSYDYEGY TMDAWGQGTSVTVSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDR AKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKD FRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGD RVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDI ATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTD DTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xvii)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWS YLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQT FGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQSLSVTC TVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLS ASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNL EQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xviii)MLLLVTSLLLCELPHPAFLLIPQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPS RGLEWLGRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLE DAFDIWGQGTMVTVSSGSTSGSGKPGSGEGSTKGDIQMTQSPSSLSASVGDRVTITCRASQTIWS YLNWYQQRPGKAPNLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQT FGQGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISC RASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQ QGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLP DYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSF ETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xix)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTS GSGKPGSGEGSTKGQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL GRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQT DDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSSGSTSGSGKPGSGEGSTKGDIQMTQTTSSLS ASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNL EQEDIATYFCQQGNTLPYTFGGGTKLEITIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xx)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAP NLLIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEIKGSTS GSGKPGSGEGSTKGQVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWL GRTYYRSKWYNDYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQ QGNTLPYTFGGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYC AKHYYYGGSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSF ETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxi)MLLLVTSLLLCELPHPAFLLIPQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMNWVRQAPGK GLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYY DYWGQGTLVTVSSSRGGGGSGGGGSGGGGSLEMASSELTQDPAVSVALGQTVRITCQGDSLRS YYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSG NPPVVFGGGTKLTVLGDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNG KEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQD RAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRK DFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGE TVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAY LQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSL AMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTL TIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxii)MLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKG LKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYW GQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWY QQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGT KLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAE AWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATN FSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQVQLVESGGGLVHPGGSLRLSCAASGFT FRSHSMNWVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARSGGQWKYYDYWGQGTLVTVSSSRGGGGSGGGGSGGGGSLEMASSELTQDPAVSVAL GQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQA EDEAD YYCNSRDSSGNPPVVFGGGTKLTVLGIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNV SQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxiii)MLLLVTSLLLCELPHPAFLLIPSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQK PGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGG TKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMN WVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR SGGQWKYYDYWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELS WWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSEND EWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMA MVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSL AMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTL TIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGE TVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAY LQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDF DSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxiv)MLLLVTSLLLCELPHPAFLLIPSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQK PGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTASLTITGAQAEDEADYYCNSRDSSGNPPVVFGGG TKLTVLGSRGGGGSGGGGSGGGGSLEMAQVQLVESGGGLVHPGGSLRLSCAASGFTFRSHSMN WVRQAPGKGLEWVSSISSDSTYTYYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR SGGQWKYYDYWGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELS WWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSEND EWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPE LKKPGETVKISCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLET SASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLT QSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGS RTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTD FDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPE SSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxv)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWV RQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGN YWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGI AVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYP YTFGQGTKVEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVH SGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKP VTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRA KRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKI SCKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQIN NLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSL GKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPV EEDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxvi)MLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKR APGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYA MDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHL IHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTF GGGTKLEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQI VSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKRGS GATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGGCLRLSCA ASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVG DRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPE DVATYYCQQYSSYPYTFGQGTKVEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxvii)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKV EIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKG LEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDV WGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPV TQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAK RGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSLAMSLGKRATIS CRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGY TFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDT ATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxviii)MLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDVAVYYCLQSRTIPRTFGGGT KLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASGYTFTDYSINWVKRAPGKG LKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYEDTATYFCALDYSYAMDYWGQGTSVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSG VCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAKR GSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITC KASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYY CQQYSSYPYTFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDF SRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAV YYCARPDGNYWYFDVWGQGTLVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxix)MLLLVTSLLLCELPHPAFLLIPDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYPYTFGQGTKV EIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKG LEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDV WGQGTLVTVSSDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHS GVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPV TQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRAK RGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPQIQLVQSGPELKKPGETVKIS CKASGYTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINN LKYEDTATYFCALDYSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSDIVLTQSPPSLAMSLG KRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVE EDDVAVYYCLQSRTIPRTFGGGTKLEIKIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof;(xxx)MLLLVTSLLLCELPHPAFLLIPEVQLVESGGGLVQPGGCLRLSCAASGFDFSRYWMSWVRQAPGKGLEWIGEINPDSSTINYAPSLKDKFIISRDNAKNSLYLQMNSLRAEDTAVYYCARPDGNYWYFDVWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDVGIAVAWYQQKPGKVPKLLIYWASTRHTGVPDRFSGSGSGTDFTLTISSLQPEDVATYYCQQYSSYP YTFGQGTKVEIKDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVH SGVCTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKP VTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDFRA KRGSGATNFSLLKQAGDVEENPGPMLLLVTSLLLCELPHPAFLLIPDIVLTQSPPSLAMSLGKRATISCRASESVTILGSHLIHWYQQKPGQPPTLLIQLASNVQTGVPARFSGSGSRTDFTLTIDPVEEDDV AVYYCLQSRTIPRTFGGGTKLEIKGGGGSGGGGSGGGGSQIQLVQSGPELKKPGETVKISCKASG YTFTDYSINWVKRAPGKGLKWMGWINTETREPAYAYDFRGRFAFSLETSASTAYLQINNLKYED TATYFCALDYSYAMDYWGQGTSVTVSSIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLLVIVLRILLLKVAGFNLLMTLRLWSS, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof; or(xxxi) the amino acid sequence shown in any one of Figures 4F-4Q, 4T-4AA, 4AD-4AI, and 4AL-4AO, preferably Figure 4W, or a variant thereof comprising: one or two alternative signal peptides, one or two alternative scFv linkers, no furin recognition sequence or a different furin recognition sequence, an alternative self-cleaving peptide, or any combination thereof.

39. A polypeptide comprising the first polypeptide or the second polypeptide of the polypeptide dimer of any one of claims 1-18 and 21-37, provided that the polypeptide comprises a targetbinding domain disposed amino -terminal to the TCR constant domain.

40. A polynucleotide encoding the polypeptide dimer of any one of claims 1-18 and 21-38 or the polypeptide of claim 39.

41. The polynucleotide of any one of claims 19, 20, and 40, further comprising: (i) a promoter, optionally a MNDu3 promoter or a EFla promoter; (ii) one or more sequence encoding a signal peptide; (iii) one or more sequence encoding a furin cleavage sequence; (iv) one or more sequence encoding a self-cleaving peptide; (v) one or more sequence encoding a tag peptide; (vi) one or moresequence encoding a transduction marker; or (vii) any combination thereof, wherein, optionally, the polynucleotide:(a) comprises a sequence encoding a signal peptide disposed 5’ to: a sequence encoding the first polypeptide of the polypeptide dimer; a sequence encoding the second polypeptide of the polypeptide dimer; and / or a sequence encoding the polypeptide of claim 39; and / or(b) comprises (1) a sequence encoding a furin cleavage sequence site sequence and / or (2) a sequence encoding a self-cleaving peptide, disposed between: a sequence encoding the first polypeptide of the polypeptide dimer and a sequence encoding the second polypeptide of the polypeptide dimer;; a sequence encoding the first polypeptide of the polypeptide dimer and a sequence encoding the polypeptide; a sequence encoding the second polypeptide of the polypeptide dimer and a sequence encoding the polypeptide;; or any combination thereof; and / or(c) is codon optimized for expression in a host cell, wherein the host cell is optionally a human host cell, further optionally a human immune system cell, still further optionally a human T cell (e.g. a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a y5 T cell, or any combination thereof), a human NK cell, or a human NK-T cell, wherein, further optionally, the polynucleotide is codon optimized for expression in a T cell (e.g. a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a y5 T cell, or any combination thereof), a NK cell, or a NK-T cell, wherein the cell is preferably human.

42. A vector comprising the polynucleotide of claim 40 or 41, wherein, optionally: the vector is capable of delivering the polynucleotide to a hematopoietic progenitor cell or a human immune system cell, wherein, optionally, the human immune system cell comprises a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a y5 T cell, a natural killer cell, a natural killer T cell, a dendritic cell, or any combination thereof, wherein, further optionally, the T cell comprises a naive T cell, a central memory T cell, a stem cell memory T cell, an effector memory T cell, or any combination thereof, and / or the vector is a viral vector, wherein, further optionally, the viral vector is a lentiviral vector or a y-retroviral vector.

43. A host cell (1) expressing: (i) the polypeptide dimer of any one of claims 1-18 and 21-39; and / or (ii) the polypeptide of claim 39, (2) comprising the polynucleotide of claim 40 or 41, or (3) comprising the vector of claim 42.

44. The host cell of claim 43, wherein:(i) the host cell comprises a hematopoietic progenitor cell, a hematopoietic stem cell, an induced pluripotent stem cell, a peripheral blood mononuclear cell, an embryonic stem cell, or a human immune system cell; and / or(ii) the host cell comprises a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a y5 T cell, a natural killer cell, a natural killer T cell, a monocyte, or any combination thereof; and / or(iii) the host cell comprises a T cell, wherein, optionally, the T cell comprises a naive T cell, a central memory T cell, a stem cell memory T cell, an effector memory T cell, or any combination thereof; and / or(iv) the host cell comprises a chromosomal gene knockout or a mutation of: a TGFpRl gene locus, a TGFPR2 gene locus, a PD-1 gene locus, a CTLA4 gene locus, a LAT gene locus, a TIM-3 gene locus, a PD-L1 gene locus, a TIGIT gene locus, an A2AR gene locus, a Fas locus, a FasL gene locus, a B7-H3 gene locus, a B7-H4 gene locus, an IDO gene locus, a VISTA gene locus, a SIGLEC7 gene locus, a SIGLEC9 gene locus, a TRAC gene locus, a TRBC gene locus, a T cell receptor gene locus, a MHC (e.g. HLA) gene locus, a CBLB gene locus, a RASA2 gene locus, a UBASH3A gene locus, a CISH gene locus, a CD4 gene locus, a CD8 gene locus, or any combination thereof, such as a TIGIT locus, a TRAC gene locus, a TRBC gene locus, and / or one or both of a CD4 gene locus and a CD8 gene locus, preferably of a TRAC gene locus, a TRBC genelocus, or both; and / or(v) wherein the host cell is modified (e.g. , having a chromosomal knockout mutation and / or a chromosomal missense mutation and / or a chromosomal splice junction mutation; encoding an inhibitory nucleic acid such as an siRNA or an antisense oligonucleotide) to have reduced protein expression (including null expression), of an endogenous TRAC, an endogenous TRBC, an endogenous TIGIT, endogenous CD4, endogenous CD8, or any combination thereof, as compared to the unmodified host cell.

45. A composition comprising:(i) the polypeptide dimer of any one of claims 1-18 and 21-38; and / or(ii) the polypeptide of claim 39; and / or(iii) the polynucleotide of claim 19, 20, 40, or 41, optionally comprised or contained in a lipid, a lipid-derived delivery vehicle, such as a liposome, a solid lipid nanoparticle, an oily suspension, a submicron lipid emulsion, a lipid microbubble, an inverse lipid micelle, a cochlear liposome, a lipid microtubule, a lipid microcylinder, lipid nanoparticle (LNP), a lipopolyplex (LPP), a cationic polypeptide, a polymeric nanoparticle, or a nanoscale platform, such as a nanoemulsion; and / or(iv) the vector of claim 42; and / or(vi) the host cell of claim 43 or 44, and a pharmaceutically acceptable carrier, excipient, or diluent, wherein, optionally, the composition comprises (i) a composition comprising at least about 30% CD4+ T host cells, combined with (ii) a composition comprising at least about 30% CD8+ T host cells, in about a 1: 1 ratio.

46. A method of treating a disease or condition in a subject, the method comprising administering to the subject an effective amount of:(i) the polypeptide dimer of any one of claims 1-18 and 21-38; and / or(ii) the polypeptide of claim 39; and / or(iii) the polynucleotide of claim 19, 20, 40 or 41, optionally comprised or contained in a lipid, a lipid-derived delivery vehicle, such as a liposome, a solid lipid nanoparticle, an oily suspension, a submicron lipid emulsion, a lipid microbubble, an inverse lipid micelle, a cochlear liposome, a lipid microtubule, a lipid microcylinder, lipid nanoparticle (LNP), a lipopolyplex (LPP), a cationic polypeptide, a polymeric nanoparticle, or a nanoscale platform, such as a nanoemulsion; and / or(iv) the vector of claim 42; and / or(vi) the host cell of claim 43 or 44; and / or(vii) the composition of claim 45.

47. The polypeptide dimer of any one of claims 1-18 and 21-38; and / or the polypeptide of claim 39; and / or the polynucleotide of any one of claims 19, 20, 40, and 41; and / orthe vector of claim 42; and / or the host cell of claim 43 or 44; and / or the composition of claim 45, for use in a method of treating a disease or condition in a subject.

48. The polypeptide dimer of any one of claims 1-18 and 21-38; and / or the polypeptide of claim 39; and / or the polynucleotide of any one of claims 19, 20, 40, and 41; and / or the vector of claim 42; and / or the host cell of claim 43 or 44; and / or the composition of claim 45, for use in a the preparation of a medicament for treating a disease or condition in a subject.

49. The method of claim 46, or the polypeptide dimer, polypeptide, polynucleotide, vector, host cell, or composition for use of claim 47 or 48, whemein the disease or condition comprises or is ahyperproliferative disease, a proliferative disease, an autoimmune disease, a neurodegenerative disease, or an infection.

50. The method of claim 46 or 49 or the polypeptide dimer, polypeptide, polynucleotide, vector, host cell, or composition for use of any one of claims 4947-49, wherein the disease or condition is a cancer, such as a hematological cancer or a solid cancer, wherein, optionally:(1) the cancer comprises a myeloma (e.g. multiple myeloma), a carcinoma, a sarcoma, a glioma, a lymphoma, a leukemia, or any combination thereof; and / or(2) the cancer comprises a cancer of the head or neck, melanoma, pancreatic cancer, cholangiocarcinoma, hepatocellular cancer, breast cancer including triple -negative breast cancer (TNBC), gastric cancer, non-small-cell lung cancer, prostate cancer, esophageal cancer, mesothelioma, small-cell lung cancer, colorectal cancer, glioblastoma, or any combination thereof; and / or(3) the cancer comprises Askin's tumor, sarcoma botryoides, chondrosarcoma, Ewing's sarcoma, PNET, malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, alveolar soft part sarcoma, angiosarcoma, cystosarcoma phyllodes, dermatofibrosarcoma protuberans (DFSP), desmoid tumor, desmoplastic small round cell tumor, epithelioid sarcoma, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, gastrointestinal stromal tumor (GIST), hemangiopericytoma, hemangiosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphosarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor (MPNST), neurofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, linitis plastic, vipoma, cholangiocarcinoma, hepatocellular carcinoma, adenoid cystic carcinoma, renal cell carcinoma, Grawitz tumor, ependymoma, astrocytoma, oligodendroglioma, brainstem glioma, optice nerve glioma, a mixed glioma, Hodgkin’s lymphoma, a B-cell lymphoma, non-Hodgkin’s lymphoma (NHL), Burkitt's lymphoma, small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B -lymphoblastic lymphoma, and mantle cell lymphoma, Waldenstrom's macroglobulinemia, CD37+dendritic cell lymphoma, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, adult T-cell lymphoma, extranodal NK / T-cell lymphoma, nasal type, enteropathy-associated T-cell lymphoma, hepatosplenic T- cell lymphoma, blastic NK cell lymphoma, Sezary syndrome, angioimmunoblastic T cell lymphoma, anaplastic large cell lymphoma, or any combination thereof,wherein, further optionally, the cancer comprises a solid tumor, wherein, optionally, the solid tumor is a sarcoma or a carcinoma, wherein, further optionally, the solid tumor is selected from: chondrosarcoma; fibrosarcoma (fibroblastic sarcoma); Dermatofibrosarcoma protuberans (DFSP); osteosarcoma; rhabdomyosarcoma; Ewing’s sarcoma; a gastrointestinal stromal tumor; Leiomyosarcoma; angiosarcoma (vascular sarcoma); Kaposi’s sarcoma; liposarcoma; pleomorphic sarcoma; or synovial sarcoma, wherein, even further optionally, the solid tumor is selected from a lung carcinoma (e.g., Adenocarcinoma, Squamous Cell Carcinoma (Epidermoid Carcinoma); Squamous cell carcinoma; Adenocarcinoma; Adenosquamous carcinoma; anaplastic carcinoma; Large cell carcinoma; Small cell carcinoma; a breast carcinoma (e.g., Ductal Carcinoma in situ (non-invasive), Lobular carcinoma in situ (non-invasive), Invasive Ductal Carcinoma, Invasive lobular carcinoma, Non-invasive Carcinoma); a liver carcinoma (e.g., Hepatocellular Carcinoma, Cholangiocarcinomas or Bile Duct Cancer); Large-cell undifferentiated carcinoma, Bronchioalveolar carcinoma); an ovarian carcinoma (e.g., Surface epithelial-stromal tumor (Adenocarcinoma) or ovarian epithelial carcinoma (which includes serous tumor, endometrioid tumor and mucinous cystadenocarcinoma), Epidermoid (Squamous cell carcinoma), Embryonal carcinoma and choriocarcinoma (germ cell tumors)); a kidney carcinoma (e.g., Renal adenocarcinoma, hypernephroma, Transitional cell carcinoma (renal pelvis), Squamous cell carcinoma, Bellini duct carcinoma, Clear cell adenocarcinoma, Transitional cell carcinoma, Carcinoid tumor of the renal pelvis); an adrenal carcinoma (e.g., Adrenocortical carcinoma), a carcinoma of the testis (e.g., Germ cell carcinoma (Seminoma, Choriocarcinoma, Embryonal carciroma, Teratocarcinoma), Serous carcinoma); Gastric carcinoma (e.g., Adenocarcinoma); an intestinal carcinoma (e.g., Adenocarcinoma of the duodenum); a colorectal carcinoma; or a skin carcinoma (e.g., Basal cell carcinoma, Squamous cell carcinoma), and / or wherein the solid tumor is an ovarian carcinoma, an ovarian epithelial carcinoma, a cervical adenocarcinoma or small cell carcinoma, a pancreatic carcinoma, a colorectal carcinoma (e.g., an adenocarcinoma or squamous cell carcinoma), a lung carcinoma, a breast ductal carcinoma, or an adenocarcinoma of the prostate.

51. The method of claim 50 or the polypeptide dimer, polypeptide, polynucleotide, vector, host cell, or composition for use of claim 50, wherein the disease or condition is multiple myeloma.

52. The method of any one of claims 46 and 49-51, or the polypeptide dimer, polypeptide, polynucleotide, vector, host cell, or composition for use of any one of claims 47-51, wherein:(a) the host cell is an allogeneic cell, a syngeneic cell, or an autologous cell; and / or(b) the method comprises administering a plurality of doses of the fusion protein, polynucleotide, vector, host cell, or composition to the subject, wherein, optionally: (1) the plurality of doses are administered at intervals between administrations of about two, three, four, five, six, seven, eight, or more weeks; and / or (2) a dose of the host cell comprises about 105cells / m2to about 1011cells / m2; and / or(c) the subject is receiving, has received, or will receive one or more of:(i) chemotherapy;(ii) radiation therapy;(iii) an inhibitor of an immune suppression component;(iv) an agonist of a stimulatory immune checkpoint agent;(v) RNAi;(vi) a cytokine;(vii) a surgery;(viii) a monoclonal antibody and / or an antibody-drug conjugate; or(ix) any combination of (i)-(viii), in any order.

53. A method comprising introducing into a host cell (i) the polynucleotide of any one of claims 19, 20, 40, and 42 or (ii) the vector of claim 42, wherein, optionally, the host cell comprises a chromosomal gene knockout of TIGIT. ('1)226. TRAC, TRBC, ('1)8. ( '1)4. or any combination thereof, and preferably comprises a chromosomal gene knockout of TRAC, TRBC, or both, and / or wherein, optionally:(1) the host cell comprises a hematopoietic progenitor cell or an immune system cell, optionally a human immune system cell; and / or(2) the host cell comprises a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a y5 T cell, a natural killer cell, a natural killer T cell, a monocyte, or any combination thereof; and / or(3) the host cell comprises a T cell, wherein, further optionally, the T cell comprises a naive T cell, a central memory T cell, a stem cell memory T cell, an effector memory T cell, or any combination thereof wherein, further optionally, the method of claim 84, further comprises introducing to the host cell a chromosomal gene knockout of TIGIT, CD226, TRAC, TRBC, CD8, CD4, or any combination thereof, preferably introducing a chromosomal gene knockout of TRAC, TRBC, or both.

54. A host cell, e.g. a human T cell such as a CD8+ T cell or a CD4+ T cell, encoding or expressing a chTCR (e.g., a polypeptide dimer of any one of claims 1-18 and 21-38) and comprising:(i) a chromosomal knockout (e.g., an introduced splicing site or stop codon that disrupts expression of a gene product) at a genomic locus encoding a TRAC, a TRBC, a SLAMF7, a TIGIT, or any combination thereof; (ii) a chromosomal knockout (e.g., an introduced splicing site or stop codon that disrupts expression) of a TRAC, a TRBC, a SLAMF7, a TIGIT, or any combination thereof; or (iii) in its genome an introduced splicing site or stop codon that disrupts expression of an endogenous TRAC, an endogenous TRBC, an endogenous SLAMF7, an endogenous TIGIT, or any combination thereof.

55. The host cell of claim 54, having disrupted expression of an endogenous TRAC, disrupted expression of an endogenous TRBC, or disrupted expression of an endogenous TRAC and disrupted expression of an endogenous TRBC, and / or wherein the chTCR comprises a binding domain that binds SLAMF7 and the host cell comprises in its genome an introduced splicing site or stop codon that disrupts expression of endogenous SLAMF7, and / or wherein a polynucleotide sequence encoding the chTCR is not integrated into an endogenous TRAC, TRBC, SLAMF7, or TIGIT locus, or is not integrated into a chromosome of the host cell.

56. A host cell comprising:(1) (i) a chromosomal knockout (e.g. , an introduced splicing site or stop codon) that disrupts expression of a TRAC, a chromosomal knockout (e.g., an introduced splicing site or stop codon) that disrupts expression of a TRBC, or both, and (ii) a heterologous polynucleotide or expression cassette or construct or that encodes a binding protein that comprises a (1) TRAC, a TRBC, or both, and (2) a targetbinding domain or a portion thereof linked or fused to an N-terminus of the TRAC, the TRBC, or both;(2) (i) in its genome, an introduced splicing site or stop codon that disrupts expression of a TRAC, an introduced splicing site or stop codon that disrupts expression of a TRBC, or both; and (ii) a heterologous polynucleotide or expression cassette or construct that encodes a binding protein comprising (1) a TRAC, a TRBC, or both, and (2) a target-binding domain or a portion thereof linked or fused to an N-terminus of the TRAC, to an N-terminus of the TRBC, or both; or(3) (i) an introduced splicing site or stop codon in a TRAC genome locus that disrupts expression of the TRAC, an introduced splicing site or stop codon in a TRBC genome locus that disrupts expression of the TRBC, or both; and (ii) a heterologous polynucleotide or expression cassette or construct that encodes a binding protein comprising (1) a TRAC, a TRBC, or both, and (2) a target-binding domain or a portion thereof linked or fused to an N-terminus of the TRAC, to an N-terminus of the TRBC, or both.

57. The host cell of claim 56, wherein: the binding protein comprises: (1) a chTCR (e.g., as described herein and / or as described in PCT / US2023 / 066466 which published as WO2023215725), (2) a TCR, (3) a single-chain TCR, (4) a STAR or mutSTAR receptor and / or (5) a HIT receptor; and / or wherein the host cell is a mammalian cell; and / or wherein the host cell is a human cell; and / or wherein the host cell is a hematopoietic progenitor cell, an induced pluripotent stem cell, or an immune system cell, wherein, optionally, the host cell is a T cell, preferably a human T cell, wherein, further optionally, the host cell is a CD8+ T cell or the host cell is a CD4+ T cell.

58. The host cell of claim 57, wherein the host cell is a human natural killer cell or a human natural killer T cell, or wherein the T cell is a naive T cell, a central memory T cell, a stem cell memory T cell, an effector memory T cell, or any combination thereof.

59. The host cell of any one of claims 54-58, wherein the host cell does not comprise an introduced double-strand break in a genomic TRAC, TRBC, SLAMF7, and / or TIGIT locus.

60. The host cell of any one of claims 56-59, wherein: (1) a polynucleotide encoding the binding protein is integrated into a host cell chromosomal TRAC locus and the host cell comprises a chromosomal knockout (e.g., an introduced splicing site or stop codon) in a host cell chromosomal TRBC locus; or(2) a polynucleotide encoding the binding protein is integrated into a host cell chromosomal TRBC locus and the host cell comprises a chromosomal knockout (e.g., an introduced splicing site or stop codon) in a host cell chromosomal TRAC locus.

61. A method comprising introducing into the genome of a T cell: (i) a splicing site or a stop codon into a genomic TRAC locus, wherein the introduced splicing site or stop codon disrupts expression by the host cell of the TRAC; (ii) a splicing site or a stop codon into a genomic TRBC locus wherein the introduced splicing site or stop codon disrupts expression by the host cell of the TRBC; or (iii) both (i)and (ii), wherein the host cell comprises a heterologous polynucleotide or expression cassette or construct that encodes a binding protein comprising a (1) TRAC, a TRBC, or both, and (2) a target-binding domain linked or fused to an N-terminus of the TRAC, to an N-terminus of the TRBC, or both, wherein, optionally, the binding protein is a cTCR, a STAR, a mutSTAR, a TCR, a scTCR, or a HIT receptor.

62. The method of claim 61, wherein the introducing comprises base editing, optionally cytidine base editing, and / or wherein the introducing does not comprise introducing a double-strand break into chromosomal DNA.

63. A method comprising the following steps: (1) obtaining a plurality of T cells from a donor (e.g. , a healthy human donor or a human donor with a diagnosed disease or condition), or thawing a plurality of cryopreserved T cells from a donor (e.g. , a healthy human donor or a human donor with a diagnosed disease or condition); (2) about one day after (1), activating T cells of the plurality, e.g. using anti-CD3 / anti-CD28 beads; introducing (e.g, using a lentivirus) into T cells of the plurality a polynucleotide encoding a chTCR, STAR or mutSTAR, TCR, scTCR, or HIT receptor; and about one day after (2), introducing into a chromosomal TRAC locus, a chromosomal TRBC locus, or into an endogenous TRAC locus and into an endogenous TRBC locus of T cells of the plurality, a splicing site or stop codon that disrupts expression of the encoded TRAC or TRBC, wherein, optionally, the introducing a splicing site or stop codon comprises base editing.

64. The method of claim 63, further comprising expanding T cells of the plurality (e.g., having confirmed expression of the chTCR, STAR, mutSTAR, TCR, scTCR, or HIT receptor and / or having a confirmed introduced splicing site or stop codon).

65. A polypeptide dimer comprising:(i) a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, the VH of the SLAMF7- specific antibody HuLuc63; and a second polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, the VL of the SLAMF7-specific antibody HuLuc63;(ii) a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, the VH of the SLAMF7- specific antibody HuLuc63; and a second polypeptide comprising a human TCR alpha chain constantdomain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, the VL from the SLAMF7-specific antibody HuLuc63;(iii) a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker- VH orientation); and a second polypeptide comprising, consisting essentially of, or consisting of, a human TCR alpha chain constant domain (or an engineered variant thereof);(iv) a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker- VH orientation); and a second polypeptide comprising, consisting essentially of, or consisting of, a human TCR alpha beta constant domain (or an engineered variant thereof);(v) a first polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker- VH orientation); and a second polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to a N-terminus thereof, a BCMA-specific scFv comprising the VH and VL of the BCMA-specific antibody Cl 1D5.3 (in VH-linker-VL or VL-linker-VH orientation);(vi) a first polypeptide comprising a human TCR alpha chain constant domain (or an engineered variant thereof) and, linked or fused to an N-terminus thereof, a SLAMF7-specific scFv comprising the VH and VL of the SLAMF7-specific antibody HuLuc63 (in VH-linker-VL or VL-linker- VH orientation); and a second polypeptide comprising a human TCR beta chain constant domain (or an engineered variant thereof) and, linked or fused to a N-terminus thereof, a BCMA-specific scFv comprising the VH and VL of the BCMA-specific antibody Cl 1D5.3 (in VH-linker-VL or VL-linker-VH orientation); or(viii) a “full” chTCR format as shown for Figure 31 A.

66. A polypeptide dimer, or a polynucleotide encoding the polypeptide dimer, wherein the polypeptide dimer comprises: a first polypeptide comprising, in N-terminal to C-terminal direction: a SLAMF7-specific scFv comprising the VH of HuLuc63, a linker (e.g., (GL^Scrf). and the VL of HuLuc63; and a human TCR beta chain constant domain (or an engineered variant thereof); and second polypeptide comprising, in N-terminal to C-terminal direction, a BCMA-specific scFv comprising: theVH of Cl 1D5.3, a linker (e.g., (Gk^Scrjs). and the VL of Cl 1D5.3; and a human TCR alpha chain constant domain (or an engineered variant thereof).

67. A polynucleotide or expression construct comprising, in 5’ to 3’ direction: an optional expression control sequence, e.g. a promoter, such as an EFla promoter; a sequence encoding a first polypeptide comprising, in N-terminal to C-terminal direction: a SLAMF7-specific scFv comprising the VH of HuLuc63, a linker (e.g., (GL^Scrf). and the VL of HuLuc63; and a human TCR beta chain constant domain (or an engineered variant thereof); a sequence encoding a furin cleavage site and a 2A peptide (e.g., a P2A peptide), in either order; and a sequence encoding a second polypeptide comprising, in N-terminal to C-terminal direction, a BCMA-specific scFv comprising: the VH of Cl 1D5.3, a linker (e.g., (Gly4Ser)s), and the VL of Cl 1D5.3; and a human TCR alpha chain constant domain (or an engineered variant thereof).

68. A composition comprising:(i) the host cell of any one of claims 54-60;(ii) the polypeptide dimer of claim 65 or 66; or(iii) the polynucleotide of claim 67, optionally comprised in a lipid formulation, and a pharmaceutically acceptable carrier, excipient, or diluent.

69. A method of treating a disease or condition in a subject, the method comprising administering to the subject an effective amount of:(i) the host cell of any one of claims 54-60;(ii) the polypeptide dimer of claim 65 or 66;(iii) the polynucleotide of claim 67; and / or(iv) the composition of claim 68.

70. The host cell of any one of claims 54-60, the polypeptide dimer of claim 65 or 66, the the polynucleotide of claim 67, and / or (iv) the composition of claim 68, for use in a method of treating a disease or condition in a subject, or for use in the preparation of a medicament for treating a disease or condition in a subject.

71. The method of claim 69 or the use of claim 70, wherein the disease or condition comprises or is a hyperproliferative disease, a proliferative disease, an autoimmune disease, a neurodegenerative disease, or an infection, wherein, optionally, the disease or condition is a cancer, such as a hematological cancer or a solid cancer, wherein, further optionally:(1) the cancer comprises a myeloma (e.g. multiple myeloma), a carcinoma, a sarcoma, a glioma, a lymphoma, a leukemia, a or any combination thereof; and / or(2) the cancer comprises a cancer of the head or neck, melanoma, pancreatic cancer, cholangiocarcinoma, hepatocellular cancer, breast cancer including triple -negative breast cancer (TNBC), gastric cancer, non-small-cell lung cancer, prostate cancer, esophageal cancer, mesothelioma, small-cell lung cancer, colorectal cancer, glioblastoma, or any combination thereof; and / or(3) the cancer comprises Askin's tumor, sarcoma botryoides, chondrosarcoma, Ewing's sarcoma, PNET, malignant hemangioendothelioma, malignant schwannoma, osteosarcoma, alveolar soft part sarcoma, angiosarcoma, cystosarcoma phyllodes, dermatofibrosarcoma protuberans (DFSP), desmoid tumor, desmoplastic small round cell tumor, epithelioid sarcoma, extraskeletal chondrosarcoma, extraskeletal osteosarcoma, fibrosarcoma, gastrointestinal stromal tumor (GIST), hemangiopericytoma, hemangiosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, lymphosarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor (MPNST), neurofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, linitis plastic, vipoma, cholangiocarcinoma, hepatocellular carcinoma, adenoid cystic carcinoma, renal cell carcinoma, Grawitz tumor, ependymoma, astrocytoma, oligodendroglioma, brainstem glioma, optice nerve glioma, a mixed glioma, Hodgkin’s lymphoma, a B-cell lymphoma, non-Hodgkin’s lymphoma (NHL), Burkitt's lymphoma, small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B -lymphoblastic lymphoma, and mantle cell lymphoma, Waldenstrom's macroglobulinemia, CD37+dendritic cell lymphoma, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, adult T-cell lymphoma, extranodal NK / T-cell lymphoma, nasal type, enteropathy-associated T-cell lymphoma, hepatosplenic T- cell lymphoma, blastic NK cell lymphoma, Sezary syndrome, angioimmunoblastic T cell lymphoma, anaplastic large cell lymphoma, or any combination thereof, wherein, still further optionally. the solid tumor is a sarcoma or a carcinoma, wherein, further optionally, the solid tumor is selected from: chondrosarcoma; fibrosarcoma (fibroblastic sarcoma); Dermatofibrosarcoma protuberans(DFSP); osteosarcoma; rhabdomyosarcoma; Ewing’s sarcoma; a gastrointestinal stromal tumor; Leiomyosarcoma; angiosarcoma (vascular sarcoma); Kaposi’s sarcoma; liposarcoma; pleomorphic sarcoma; or synovial sarcoma, wherein, even further optionally, the solid tumor is selected from a lung carcinoma (e.g., Adenocarcinoma, Squamous Cell Carcinoma (Epidermoid Carcinoma); Squamous cell carcinoma; Adenocarcinoma; Adenosquamous carcinoma; anaplastic carcinoma; Large cell carcinoma; Small cell carcinoma; a breast carcinoma (e.g., Ductal Carcinoma in situ (non-invasive), Lobular carcinoma in situ (non-invasive), Invasive Ductal Carcinoma, Invasive lobular carcinoma, Non-invasive Carcinoma); a liver carcinoma (e.g., Hepatocellular Carcinoma, Cholangiocarcinomas or Bile Duct Cancer); Large-cell undifferentiated carcinoma, Bronchioalveolar carcinoma); an ovarian carcinoma (e.g., Surface epithelial-stromal tumor (Adenocarcinoma) or ovarian epithelial carcinoma (which includes serous tumor, endometrioid tumor and mucinous cystadenocarcinoma), Epidermoid (Squamous cell carcinoma), Embryonal carcinoma and choriocarcinoma (germ cell tumors)); a kidney carcinoma (e.g., Renal adenocarcinoma, hypernephroma, Transitional cell carcinoma (renal pelvis), Squamous cell carcinoma, Bellini duct carcinoma, Clear cell adenocarcinoma, Transitional cell carcinoma, Carcinoid tumor of the renal pelvis); an adrenal carcinoma (e.g., Adrenocortical carcinoma), a carcinoma of the testis (e.g., Germ cell carcinoma (Seminoma, Choriocarcinoma, Embryonal carciroma, Teratocarcinoma), Serous carcinoma); Gastric carcinoma (e.g., Adenocarcinoma); an intestinal carcinoma (e.g., Adenocarcinoma of the duodenum); a colorectal carcinoma; or a skin carcinoma (e.g., Basal cell carcinoma, Squamous cell carcinoma), and / or wherein the solid tumor is an ovarian carcinoma, an ovarian epithelial carcinoma, a cervical adenocarcinoma or small cell carcinoma, a pancreatic carcinoma, a colorectal carcinoma (e.g., an adenocarcinoma or squamous cell carcinoma), a lung carcinoma, a breast ductal carcinoma, or an adenocarcinoma of the prostate, wherein, still further optionally, the disease or condition is multiple myeloma.

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