Receptor-mediated endocytosis for targeted internalization of c-c chemokine receptor 6

Abstract

Disclosed are compositions that can bind to a CCR6 G Protein-Coupled Receptor (GPCR) and to a transferrin receptor on a cell surface. Once bound, the protein of interest (CCR6) can be internalized and / or degraded inside a cell.

Description

BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO RECEPTOR-MEDIATED ENDOCYTOSIS FOR TARGETED INTERNALIZATION OF C-C CHEMOKINE RECEPTOR 6

[0001] All patents, patent applications and publications cited herein are hereby incorporated by reference in their entirety. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.

[0002] This patent disclosure contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure as it appears in the U. S. Patent and Trademark Office patent file or records, but otherwise reserves any and all copyright rights.RELATED APPLICATIONS

[0003] This application claims priority to U. S. Provisional Application No. 63 / 738,649, filed on December 24, 2024, which is incorporated by reference in its entirety herein.FIELD

[0004] Aspects of the invention are drawn to compositions and methods for targeting C-C chemokine receptor 6 (CCR6) and for treating disease.SEQUENCE LISTING

[0005] The instant application contains a Sequence Listing which has been submitted in.xml format, and is hereby incorporated by reference into the specification in its entirety. The name of the.xml file containing the Sequence Listing is “91016-434626SequenceListing”. The.xml file is 432,828 bytes, was created on December 18, 2025 (2025-12-18), and is being submitted electronically, concurrent with the filing of the specification.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO BACKGROUND

[0006] G protein-coupled receptors (GPCRs) are a large family of membrane proteins. GPCRs can transduce extracellular stimuli into intracellular signals that regulate physiological processes including cell metabolism, cell differentiation, growth, neurotransmission, and sensory perception. GPCRs have also been implicated in a large number of diseases, such as inflammatory and immune disorders, neurological and psychiatric disorders, cardiovascular diseases, metabolic disorders, cancer, infectious diseases, rare and genetic disorders, and sensory disorders.

[0007] C-C chemokine receptor type 6 (CCR6) (also known as CD196) is a G protein-coupled receptor (GPCR) chemokine receptor highly expressed in Th17 cells and also in regulatory T cells, memory T cells, B cells, dendritic cells and other cell types. CCL20, a ligand for CCR6, binds CCR6 on the cell surface and activates CCR6 leading to Th17 cell (e.g., Th17 CD4+ T helper cells) migration to sites of inflammation. See, for example, Shen et al., Front. Immunol., 22 August 2021, Sec. Immunological Tolerance and Regulation Volume 12 - 2021; doi: 10.3389 / fimmu.2021.710750.

[0008] C-C chemokine receptor type 6 (CCR6) is a drug target for autoimmune and inflammatory diseases. Genome-wide association studies have shown a correlation between CCR6 expression and disease seventy in inflammatory bowel disease (IBD), psoriasis, rheumatoid arthritis (RA), and multiple sclerosis (MS). CCR6 knockout mice are resistant to autoimmune diseases, and CCR6 signaling promotes Th17 differentiation. CCR6 expression and activity are implicated in various inflammatory and autoimmune diseases, including, but not limited to, psoriasis, rheumatoid arthritis (RA), multiple sclerosis (MS), intestinal bowel disease (IBD), ankylosing spondylitis, inflammatory bowel disease, ulcerative colitis, psoriatic arthritis, and rheumatoid arthritis.

[0009] Previous efforts to develop CCR6-neutralizing antibodies have seen limited efficacy (see Robert et. al, JCI Insights, 2017), and a small molecule CCR6 antagonist (PF- 07054894) targets multiple receptors (CCR6, CCR7, and CXCR2), posing off-target toxicity risks. There are currently no approved CCR6-blocking agents available for treating autoimmune diseases. Attempts to develop drugs against CCR6 activity have been challenging due to various factors, including shallow binding pockets,BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO competition with endogenous ligands, high local concentrations of chemokines, and allosteric receptor activation (see Wasilko DJ et al., Nature Communications, volume 11, article number: 3031, 2020).

[0010] Further, compositions and methods for binding to and internalizing a protein of interest (POI) are known (see WO 2024 / 064756 A1, published 28 March 2024).Once bound, the POI can be internalized and / or degraded.

[0011] Compositions and methods for binding to and internalizing CCR6, such as for treating inflammatory or autoimmune diseases or conditions, are desirable.SUMMARY

[0012] Disclosed herein are compositions and methods for binding to and internalizing CCR6 GPCR molecules on the surface of cells. In embodiments, compositions disclosed herein are fusion proteins.

[0013] Provided herein are heterodimeric fusion proteins:X-Y (Formula I),wherein:X comprises R1 - R2 (Formula II):wherein,R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6); andR2 is an IgG Fc region; andwherein,Y comprises R3 - R4 (Formula III):wherein,R3 is a transferrin receptor (TR) binding (TRB) means for binding the TR; andR4 is an IgG Fc region; and whereinX and Y form a dimer.Provided herein are heterodimeric fusion proteins as above, where R3 has one TRB means for binding a transferrin receptor (TR). The heterodimer fusion proteins as above, where R3 has two TRB means for binding TRs. The heterodimer fusionBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO proteins as above, wherein the TRB means comprises an antibody or antibody fragment.Provided herein are heterodimeric fusion proteins as above, where R3 has an amino acid sequence of wild-type VHHA (SEQ ID NO: 1 ). The VHHA can have a tyrosine at position 96 of VHHA (VHHA-5), a leucine at position 98 of VHHA (VHHA-7) or a phenylalanine at position 51 of VHHA (VHHA-12). The heterodimer fusion proteins can have an R3 amino acid sequence that has SEQ ID NOs: 2 (VHHA-5), 3 (VHHA-7) or 4 (VHHA-12). The heterodimer fusion proteins as above, wherein the TRB means comprises an H7 scFv.

[0014] Provided herein are heterodimeric fusion proteins as above where R1 and / or R4 are lgG1 regions.

[0015] Provided herein are heterodimeric fusion proteins:X-Y (Formula IV),wherein:X comprises R1 - R2 (Formula V),wherein:R1 is a first protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6); andR2 is an IgG Fc region; andwherein,Y comprises R5 - R4 - R3 (Formula VI),wherein:R5 is a second protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6);R4 is an IgG Fc region; andR3 is a transferrin receptor (TR) binding (TRB) means for binding the TR; and whereinX and Y forms a dimer.

[0016] Provided herein are heterodimeric fusion proteins as above, where R3 has an amino acid sequence of wild-type VHHA (SEQ ID NO: 1 ). The VHHA can have a tyrosine at position 96 of VHHA (VHHA-5), a leucine at position 98 of wild-type VHHABT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO (VHHA-7) or a phenylalanine at position 51 of VHHA (VHHA 12). The heterodimer fusion proteins can have an R3 amino acid sequence that has SEQ ID NOs: 2 (VHHA-5), 3 (VHHA-7) or 4 (VHHA-12).

[0017] Provided herein are heterodimeric fusion proteins as above where R2 and / or R4 are lgG1 regions.

[0018] Provided herein are heterodimeric fusion proteins:X-Y (Formula VII):wherein:X comprises R1 - R2 (Formula VIII):wherein,R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6); andR2 is an IgG Fc region; andwherein,Y comprises R3 - R6- R4 (Formula IX):wherein:R3 is a first transferrin receptor (TR) binding (TRB) means for binding the TR;R6 is a second transferrin receptor (TR) binding (TRB) means for binding the TR, andR4 is an IgG Fc region; and whereinX and Y forms a dimer.

[0019] Provided herein are heterodimeric fusion proteins as above, where R3 and / or R6 have an amino acid sequence of VHHA (SEQ ID NO: 1 ). The VHHA can have a tyrosine at position 96 of VHHA (VHHA-5), a leucine at position 98 of VHHA (VHHA-7) or a phenylalanine at position 51 of VHHA (VHHA-12). The heterodimer fusion proteins can have an R3 and / or R6 amino acid sequence that has SEQ ID NOs: 2 (VHHA-5), 3 (VHHA-7) or 4 (VHHA-12).

[0020] Provided herein are heterodimeric fusion proteins as above where R3 and / or R6 are lgG1 regions.

[0021] Provided herein are homodimeric fusion proteins:BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO X-X’ (X):wherein,X and X’ comprise R1 - R2 - R3 (Formula XI):wherein:R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6);R2 is an IgG Fc region; andR3 is a transferrin receptor (TR) binding (TRB) means for binding the TR; andwhereinX and X’ forms a dimer.

[0022] Provided herein are homodimeric fusion proteins as above, where R3 has an amino acid sequence of VHHA (SEQ ID NO: 1 ). The VHHA can have a tyrosine at position 96 of VHHA (VHHA-5), a leucine at position 98 of VHHA (VHHA-7) or a phenylalanine at position 51 of VHHA (VHHA-12). The homodimeric fusion proteins can have an R3 amino acid sequence that has SEQ ID NOs: 2 (VHHA-5), 3 (VHHA-7) or 4 (VHHA-12).

[0023] Provided herein are homodimeric fusion proteins as above where R2 is an lgG1 region.

[0024] Provided herein are the heterodimeric or homodimeric fusion proteins described above where the POIB means is an antibody. The POIB means can be an antibody fragment. The POIB means can be an scFv.

[0025] Provided herein are the heterodimeric or homodimeric fusion proteins described above where the TRB means is a VHH.

[0026] Provided herein are nucleic acids encoding the heterodimeric or homodimeric fusion proteins as described above.

[0027] Provided herein are pharmaceutical compositions that have any of the heterodimeric or homodimeric fusion proteins described above and a pharmaceutically acceptable carrier, diluent, or excipient.

[0028] Provided herein are methods for administering an effective amount of the heterodimeric or homodimeric fusion proteins described above to a subject in need ofBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO blocking CCR6 activity. The subject can have an autoimmune or inflammation-related disease.

[0029] Provided herein are uses of any of the heterodimeric or homodimeric fusion proteins described above for treating a subject in need of blocking CCR6 activity. The subject can have an autoimmune or inflammation-related disease.BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Certain illustrations, charts, or flow charts are provided to allow for a better understanding for the present invention. It is to be noted, however, that the drawings illustrate only selected embodiments of the inventions and are therefore not to be considered limiting of scope. Additional and equally effective embodiments and applications of the present invention exist.

[0031] Figures 1 A-1 B show SDS-PAGE gel validating embodiments of the CCR6-targeting compositions DJ1, DJ2 and LS9 (Fig. 1A) provided herein and depicted in Fig.1B.

[0032] Figures 2A-2B show dose response curves for binding to CCR6 expressing Jurkat cells (Fig. 2A) for embodiments of CCR6-targeting compositions provided herein (Fig. 2B), DJ1 and DJ2.

[0033] Figure 3 shows embodiments of CCR6-targeting compositions provided herein.

[0034] Figure 4 shows embodiments of CCR6-targeting compositions provided herein.

[0035] Figures 5A-5B show amino acid sequence alignment (Fig. 5A) for Variable Domain of Camelid Heavy Chain-only (VHH) molecule VHH-A, and single mutants VHH-A5, VHH-A7 and VHH-A12. Fig. 5B shows VHH mutations.

[0036] Figure 6 shows CCR6 internalization in CCR6 expressing cells by CCR6-targeting compositions DJ1 and DJ2 (control).

[0037] Figure 7 shows dose-response curve for internalization of FLAG-tagged CCR6 in Jurkat cells treated with the CCR6-targeting composition LS9 provided herein.Fig. 4 also shows IC50 values for binding of LS9 to TfR1, and Dmax.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0038] Figures 8A-8C show dose-response curves for internalization of FLAG-tagged CCR6 (Fig. 8A) and cell surface TfR1 (Fig. 8B) in Jurkat cells treated with the CCR6-targeting compositions DJ1, LS13, LS15, LS16 and LS18 (depicted in Fig. 8C) provided herein.

[0039] Figures 9A-9C show dose-response curves for internalization of FLAG-tagged CCR6 (Fig. 9A) and cell surface TfR1 (Fig. 9B) in Jurkat cells treated with the CCR6-targeting compositions LS19, LS20, and LS21 (depicted in Fig. 9C) provided herein.

[0040] Figures 10A-10D show dose-response curves for internalization of FLAG-tagged CCR6 (Fig. 10A and Fig. 10C) and cell surface TfR1 (Fig. 10B) in Jurkat cells treated with the CCR6-targeting compositions LS26, LS27, LS28, and LS29 (depicted in Fig. 10D) provided herein.

[0041] Figure 11 shows IC50, Dmax and Hook effect for CCR6 targeting compositions described herein.

[0042] Figure 12 shows FLAG tagged-CCR6 internalization by an embodiment of a CCR6 targeting composition including an anti-FLAG antibody (M2) and VHH-A. M1 antibody was used as control.

[0043] Figures 13A-13C show binding of 1 nM (Fig. 13A) and 10 nM (Fig. 13B) concentrations of CCR6 targeting compositions DJ1, LS13, LS15 and LS16 (depicted in Fig. 13C) to CCR6+ (cells expressing CCR6) and CCR6- (cells that do not express CCR6) cells.

[0044] Figure 14 shows dose-response curves for binding of CCR6 targeting compositions DJ1 VHHA), LS13 (VHHA-12), LS15 (VHHA-5), and LS16 (VHHA-7) to CCR6+ (cells expressing CCR6) and CCR6- (cells that do not express CCR6) cells. Developed embodiments of the CCR6-targeting compositions provided herein minimally bind CCR6-negative cells and do not reduce cell-surface TfR1, mitigating potential safety concerns.

[0045] Figures 15A-15C show binding of 1 nM (Fig. 15A) and 10 nM (Fig. 15B) concentrations of the CCR6 targeting compositions LS26, LS27, LS28 and LS29 (depicted in Fig. 15C) to CCR6+ (cells expressing CCR6) and CCR6- (cells that do not express CCR6) cells.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0046] Figures 16A-16B show binding of 1 nM (Fig. 16A) and 10 nM (Fig. 16B) concentrations of the CCR6 targeting compositions LS32, LS33, LS34, LS35 to CCR6+ (cells expressing CCR6) and CCR6- (cells that do not express CCR6) cells. A pictogram of the TransTAC embodiment is shown below the binding quantification.

[0047] Figures 17A-17B show data describing on-cell binding CCR6+ dependency (% binding CCR6- vs. CCR6+) at 1 nM and 10 nM concentrations for embodiments of CCR6 targeting compositions shown in Fig. 17A and depicted in Fig. 17B.

[0048] Figure 18 shows binding affinity (KD) of VHH-A, VHH-A5 and VHH-A7 and VHHA-12 to mouse TfR1.

[0049] Figure 19 shows migration of CCR6+ Jurkat cells treated with 10 nM concentration of embodiments of the CCR6-targeting compositions provided herein DJ1 and DJ2 (control).

[0050] Figure 20 shows dose-response curve for migration of CCR6+ Jurkat cells treated with embodiments of the CCR6-targeting compositions provided herein (DJ1). Performed a full dose-response curve of the migration assay, demonstrating that embodiments of the CCR6-targeting compositions provided herein inhibited migration of CCR6+ Jurkat cells.

[0051] Figure 21 shows inhibition of CCR6+ Jurkat cells migration for various embodiments of CCR6-targeting compositions provided herein, and an anti-CCR6 antibody used as control.

[0052] Figure 22 shows a dose-response curve for migration of CCR6+ Jurkat cells treated with embodiments of the CCR6-targeting compositions provided herein (LS16). Performed a full dose-response curve of the migration assay, demonstrating that embodiments of the CCR6-targeting compositions provided herein inhibited migration of CCR6+ Jurkat cells.

[0053] Figure 23 shows amino acid sequences for the CCR6 targeting compositions described herein.

[0054] Figure 24 shows schematic drawings of different embodiments of the CCR6 targeting compositions disclosed herein. Different embodiments are indicated as A-D.

[0055] Figures 25A-25C show data from biolayer interferometry measurements described in Example 29. Sensorgrams are shown in Figs. 25A-25B. Binding curvesBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO in 25A depict Geometry 4 (homodimer) interaction with recombinant human TfR1 ectodomain; Binding curves in 25B depict Geometry 1 (knob-into-hole heterodimer) interaction with recombinant human TfR1 ectodomain. Kd values obtained using the data that produced the sensorgrams are shown in Fig. 25C.

[0056] Figure 26 shows Western blot analysis and quantification of total CCR6 and TfR1 monomer and dimer protein levels in CCR6+Jurkat cells after 18 h treatment with an embodiment of the disclosure, DJ1 (VHH-A).

[0057] Figure 27 shows Western blot analysis and quantification of total CCR6 and TfR1 protein levels in CCR6+Jurkat cells after 18 h treatment with an embodiment of the disclosure LS13 (VHHA-12).

[0058] Figure 28 shows Western blot analysis and quantification of total CCR6 and TfR1 protein levels in CCR6+Jurkat cells after 18 h treatment with an embodiment of the disclosure LS20 (H7).

[0059] Figure 29 shows [3-arrestin recruitment measured via Tango assay in CCR6-Tango+TfR1+HTLA cells. Cells were pre-treated with 10 nM VHH-A (DJ1) and VHH-A12 (LS13) TransTACs for 1 h, followed by overnight incubation with CCL20.

[0060] Figure 30 shows flow cytometry quantification of total F-actin in CCR6+Jurkat cells with fixation and phalloidin staining. Cells were treated with embodiments of the disclosure DJ2, DJ1 (VHH-A), and LS13 (VHH-A12) TransTAC doses for2 h, followed by 1 min stimulation with 50 nM CCL20.

[0061] Figure 31 shows chemotaxis of CCR6+luciferase-Jurkat cells measured by transwell migration assay after 2 h treatment of one of the TransTAC embodiments of the disclosure (DJ1, DJ2, DJ5, and LS13) and 2 h migration with CCL20 as the chemoattractant.

[0062] Figures 32A-32C show CCR6 is degraded and functionally inhibited by a FLAG-targeting TransTAC. Fig. 32A shows Western blot analysis of total CCR6 levels in FLAG-CCR6-Jurkat cells after 18 h TransTAC treatment (Fig. 32A). Fig. 32B shows flow cytometry analysis of cell surface FLAG-CCR6 expression in CCR6+Jurkat cells after 2 h FLAG Ab / TransTAC treatment. Shown in Fig. 32C, is chemotaxis of FLAG-CCR6+Jurkat cells measured by transwell migration assay after 2 h FLAG Ab / TransTAC treatment and 2 h migration with CCL20 as the chemoattractant.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0063] Figures 33A-33D show four-color live-cell imaging system to track TransTAC trafficking and kinetics. Fig. 33A shows multiplexed four-color live-cell confocal microscopy of HeLa cells expressing Rab 11-mCherry, CCR6-GFP, and TfR1-BFP with 24 h treatment of 10 nM TransTAC conjugated to Alexa Fluor 647 or 50 nM CCL20. Fig.33B shows Pearson colocalization analysis of TfR1-BFP and Rab11-mCherry (recycling endosomes) at different times with treatment with a TransTAC embodiment of the disclosure. Fig. 33C and Fig. 33D show quantification of CCR6-GFP in HeLa cells via confocal microscopy following 1 h, 4 h, or 24 h treatment with a TransTAC embodiment of the disclosure, DJ1 (VHH-A) shown in Fig. 33C and LS13 (VHH-A12) in Fig. 33D.

[0064] Figures 34A-34B show confocal microscopy of HeLa cells expressing CCR6-GFP with 24 h TransTAC treatment in addition to the lysosomal inhibitors bafilomycin and chloroquine or the proteasome inhibitor MG132 visualized via confocal microscopy in Fig. 34A. Peason colocalization analysis of TransTAC embodiments of the disclosure via Lampl, a lysosomal marker following treatment with bafilomycin or chloroquine, shown in Fig. 34B

[0065] Figure 35 shows a transwell chemotaxis assay of CD4+CXCR3' CCR6+primary human Th17 cells following 2 h pretreatment with a TransTAC embodiment of the disclosure and 2 h migration with CCL20 as the chemoattractant..

[0066] Figure 36 shows on-cell binding curves of a TransTAC embodiment of the disclosure (DJ1 (VHH-A) and LS13 (VHH-A12)) in CD3+T cells and Th17 cell populations. As shown in Fig. 36, both TransTAC DJ1 (VHH-A) (left) and LS13 (VHH-A12) (right) as monitored via flow cytometry.

[0067] Figure 37 shows flow cytometry analysis of cell surface CCR6 expression in Th17 cells after 2 h treatment with a TransTAC embodiment of the disclosure.DETAILED DESCRIPTIONOverview

[0068] In some embodiments, the methods and / or compositions described herein can include compositions that bind and / or interact with, and / or internalize, CCR6. In embodiments, the compositions and methods provided herein deplete CCR6 from a cell surface and / or degrade CCR6, which can inhibit or block CCR6 activity. InBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO embodiments, the compositions and methods provided herein can be used to inhibit CCR6 / CCL20-mediated cell migration. In embodiments, the compositions and methods provided herein can be used to degrade CCR6 in lysosomes. In embodiments, the compositions and methods provided herein can be used to block or inhibit CCR6 receptor activity. In some embodiments, the methods and / or compositions described herein can be used for regulating, preventing, and / or treating CCR6-related diseases.

[0069] In embodiments, molecules described herein have a protein of interest binding (POIB) means and a transferrin receptor binding (TRB) means. Herein, a POIB binds to CCR6 on the surface of a target cell. TRB binds to transferrin receptor (TfR or TR) on the surface of a target cell. When compositions disclosed herein bind CCR6 on the surface of a target cell using POIB means, and to TfR or TR on the target cell surface using TRB means, CCR6 can be internalized into the target cell and degraded. Thus, in embodiments, compositions and methods provided herein can induce efficient endocytosis of a protein of interest (POI; e.g., CCR6) / TfR complex and, optionally, subsequent lysosomal-mediated POI (CCR6) degradation. This internalization, and optional degradation, blocks or inhibits CCR6 activity in a target cell.

[0070] In embodiments, a TRB means disclosed herein has binding affinity to a transferrin receptor (TfR or TR) that can be modulated. Altering binding affinity of a TRB means to TfR affects binding of a composition disclosed herein (e.g., a fusion protein disclosed herein) on a target cell. In embodiments, modulation of TRB binding affinity to TfR can result from certain mutations (e.g., amino acid substitutions) within an amino acid sequence of a TRB (or a TRB means for binding TfR). In embodiments, the affinity of a TRB (or a TRB means for binding TfR) in a composition disclosed herein (e.g., a fusion protein disclosed herein) can be reduced or decreased. In embodiments, a TRB (or a TRB means for binding TfR) with reduced affinity to TfR can be used to reduce the amount of CCR6 on cells and / or block CCR6 activity, while minimizing reduction of TfR on the cells. In embodiments, therefore, blocking of CCR6 activity by the disclosed compositions (e.g., fusion proteins disclosed herein), through intemalization / endocytosis and, optional degradation, can be achieved without reducing levels or minimizing reduction of TfR on targeted cells such that side effects to a subject are reduced or eliminated.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0071] In embodiments, the compositions and methods provided herein are an improved therapeutic approach to target CCR6, and can be used to treat diseases, such as autoimmune diseases and / or inflammation-related diseases. In embodiments, the compositions and methods provided herein can be used to achieve about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 98%, about 99%, or about 100%, or 50%-60%, 60%- 70%, 70%-80%, 80%-90%, 90%-100%, 90%-95%, 95%-100%, or 98%-100% blocking or inhibition of the CCR6 and CCR6 regulatory pathways in target cells.

[0072] In embodiments, the compositions and methods provided herein can be used to achieve about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 98%, about 99%, or about 100%, or 50%-60%, 60%-70%, 70%-80%, 80%-90%, 90%-100%, 90%-95%, 95%- 100%, or 98%-100% inhibition of cell migration (e.g., migration of Th17 CD45+T helper cells) to sites of inflammation.

[0073] In some embodiments, the autoimmune diseases treated by the CCR6 targeting compositions disclosed herein can include any autoimmune disease. In some embodiments, autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, multiple sclerosis, Graves’ disease, celiac disease, ankylosing spondylitis, psoriatic arthritis, cholestatic liver disease, and the like.

[0074] In some embodiments, the diseases treated can include inflammation-related diseases. In some embodiments, the inflammation-related diseases treated by the CCR6 targeting compositions disclosed herein can include inflammatory bowel disease, asthma, psoriasis, gout, chronic obstructive pulmonary disease, endometriosis, asthma, Crohn’s disease, and the like.Terms

[0075] Detailed descriptions of one or more embodiments are provided herein. It is to be understood, however, that the present invention may be embodied in various forms. Therefore, specific details disclosed herein are not to be interpreted as limiting, but rather as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present invention in any appropriate manner.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0076] The singular forms “a”, “an” and “the” include plural reference unless the context clearly dictates otherwise. The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and / or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

[0077] Wherever any of the phrases “for example,” “such as,” “including” and the like are used herein, the phrase “and without limitation” is understood to follow unless explicitly stated otherwise. Similarly, “an example,” “exemplary” and the like are understood to be nonlimiting.

[0078] The term “substantially” allows for deviations from the descriptor that do not negatively impact the intended purpose. Descriptive terms are understood to be modified by the term “substantially” even if the word “substantially” is not explicitly recited.

[0079] The terms “comprising” and “including” and “having” and “involving” (and similarly “comprises”, “includes,” “has,” and “involves”) and the like are used interchangeably and have the same meaning. Specifically, each of the terms is defined consistent with the common United States patent law definition of “comprising” and is therefore interpreted to be an open term meaning “at least the following,” and is also interpreted not to exclude additional features, limitations, aspects, etc. Thus, for example, “a process involving steps a, b, and c” means that the process includes at least steps a, b and c. Wherever the terms “a” or “an” are used, “one or more” is understood, unless such interpretation is nonsensical in context.

[0080] As used herein, the term “about” can refer to approximately, roughly, around, or in the region of. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. The term “about” is used herein to modify a numerical value above and below the stated value by a variance of 20 percent up or down (higher or lower).

[0081] Herein, means plus function claims under 35 U. S. C. § 112(f) that, for example, recite a “a protein of interest binder means” or “a transferrin receptor binding means”BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO are equivalent to and are to be interpreted as “means for binding a protein of interest” or “means for binding transferrin receptor”, respectively.

[0082] The dash notation, between “R”s, as used in the Formulas (e.g., Formulas R1 - R2; R3 - R4; R5 - R4 - R3; R3 - R6 - R4; R1 - R2 - R3) herein, can refer to one or more amino acids or chemical molecules conventionally used to link regions of the composition. In some embodiments, the “dash” indicates a chemical linking means between the “R”s, as described below. A linkage (also known as a “linker” or “linking means” or “means for linking polypeptides”) is a molecule that forms a covalent bond between two polypeptides, generating a single, contiguous polypeptide. A linker can be an amino acid sequence or a chemical molecule. In some embodiments, a linker can occur between the R groups described herein, for example, between R1 and R2, R2 and R3, R3 and R4, R4 and R5, and the like.

[0083] In embodiments, a linker is an amino acid sequence that links two polypeptides into one contiguous polypeptide. In embodiments, a linker is an amino acid sequence linking an IgG Fc domain (e.g., an lgG1 Fc domain) to a protein of interest binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6). In embodiments, a linker is an amino acid sequence linking an IgG Fc domain (e.g., an lgG1 Fc domain) to a transferrin receptor binding (TRB) means (e.g., a TfR binding antibody or antibody fragment, such as a VHH). In embodiments, a linker is an amino acid sequence linking a TRB to a TRB, a TRB to a POIB, a POIB to a POIB, and the like. In embodiments, the linker does not include a protease-cleavable amino acid sequence. A person of ordinary skill in the art understands that peptide linkers are typically about one to 100 amino acids in length (e.g., 1, 2, 3, 4, 5, 10, 12, 1-10, 1-12, or 1-20, or more amino acids) containing various types of amino acids (e.g., US Patent No.11,041,023, incorporated by reference herein in its entirety).

[0084] In embodiments, a linker or linking means includes a protease-cleavable amino acid sequence (also known as a protease-sensitive linking means). In embodiments, the protease-sensitive linking means can be an amino acid sequence that can be cleaved by a protease. In embodiments, the protease can be a protease in an endosome or lysosome. In embodiments, the protease can be a cathepsin (e.g., cathepsin B), and the protease-sensitive linking means can be a cathepsin-cleavableBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO peptide. In embodiments, the linker includes a cathepsin b-cleavable amino acid sequence.

[0085] In embodiments, the linker can be a glycine-rich linker (“GS linker). In embodiments, a “GS” linker can be a combination of glycine and serine amino acids. In embodiments, the GS linker can be GSSGGSGGSGGS (SEQ ID NO: 5). Other sequences are possible. In some embodiments, the GS linker can be SGGGG (SEQ ID NO: 6), SGGGSGGG (SEQ ID NO: 7), GSGS (SEQ ID NO: 8), GSGGS (SEQ ID NO: 9), GSSGSS (SEQ ID NO: 10), GSSSSSS (SEQ ID NO: 11), GGGGS (SEQ ID NO: 12), GGGS (SEQ ID NO: 13), SGGG (SEQ ID NO: 14), and the like. In some embodiments, single or multiple of these or similar sequences are repeated in tandem (e.g., 2, 3, 4 or more times). In embodiments, a GS linker can have at least 4 amino acids that are glycine and / or serine. In embodiments, other amino acids can be part of a GS linker, as long as glycine and serine are in the majority.

[0086] Herein, “binding” (or “binds”) refers to the interaction between a protein or polypeptide (e.g., an antibody or antibody fragment) and a target protein or polypeptide. Binding can be measured in a variety of ways (see, e.g., Antibody Engineering:Methods and Protocols (Damien Nevoltris and Patrick Chames eds., 3d ed. 2018)). In embodiments, binding is measured using methods known in the art. A particular protein or polypeptide (e.g., an antibody or antibody fragment; a ligand or part of a ligand that normally is bound by a receptor), such as a POIB or a TRB, for example in a fusion protein provided herein, binds to a particular target protein or polypeptide, such as a POI or TfR (or TR), respectively, and does not bind in a significant amount to other proteins or polypeptides present in a sample or subject disclosed herein. A particular protein or polypeptide (e.g., an antibody or antibody fragment; a ligand or part of a ligand that normally is bound by a receptor), such as a POIB or a TRB, for example in a fusion protein provided herein, can be a means for binding a particular target protein or polypeptide, such as a POI or TfR (orTR), respectively, when the particular protein or polypeptide binds to the particular target protein or polypeptide and does not bind in a significant amount to other proteins or polypeptides present in a sample or subject disclosed herein. In other words, “a protein or polypeptide means for binding” is a “means for binding a target protein or polypeptide wherein the means is a [particular]BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO protein or polypeptide”. In embodiments, binding occurs between the disclosed protein of interest binder (POIB) and an epitope or target binding site on a target protein or polypeptide (also known as a protein of interest, POI; e.g., CCR6). In embodiments, POIB (e.g., an antibody or antibody fragment, such as an scFv) is a means for binding (also known as a POIB means for binding) to a POI when the POIB binds to the POI and does not bind in a significant amount to other proteins or polypeptides present in a sample or subject disclosed herein. In other words, “POIB means for binding a POI” is a “means for binding the POI wherein the means is a POIB”. In embodiments, binding occurs between the disclosed transferrin receptor binder (TRB) and an epitope or target binding site on transferrin receptor (TfR). In embodiments, a TRB (e.g., an antibody or antibody fragment, such as a VHH; transferrin or certain fragments of transferrin) is a means for binding (also known as a TRB means for binding) to TfR (also referred to herein as TR) when the TRB binds to the TfR or TR and does not bind in a significant amount to other proteins or polypeptides present in a sample or subject disclosed herein. In other words, “TRB means for binding TfR” is a “means for binding TfR wherein the means is a TRB”.

[0087] Herein, “non-competitive” or “non-competitive binding” refers to a protein or polypeptide that binds at a first target protein site that is separate from a second protein or polypeptide binding site on the same target protein. In embodiments, a transferrin receptor binder (TRB) binds transferrin receptor non-competitively relative to the cognate transferrin. In other embodiments, a TRB binds transferrin receptor competitively relative to transferrin. In the competitive binding situation, the TRB may bind to transferrin receptor at a site that is the same, or overlapping with, a site on the transferrin receptor to which transferrin binds.

[0088] Herein, “epitope” refers to discrete sites of a molecule (e.g., protein) recognized by the disclosed antibodies and fragments thereof (e.g., POIBs and / or TRBs). Epitopes may be linear or three-dimensional. An antibody binds to a target protein when the interaction has a KD of less than 10’6molar, such as less than 10’7molar, less than 10-8molar, less than 10-9molar, or less than 10-10molar.

[0089] Herein, an “Fc region” (fragment crystallizable region) refers to the constant region fragment of an antibody, which is separated from two fragment antigen-bindingBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO regions when an antibody is digested by the enzyme papain. The constant region defines the isotype of an antibody. In embodiments, Fc regions of the present disclosure include lgG1 Fc regions. In some embodiments the Fc regions can be from lgG2, lgG3 or lgG4 subclasses of IgG. Other Fc regions are possible. In embodiments, the antibodies of the present disclosure have one or more modifications in the Fc region, as described herein. Such modifications can reduce effector function of the antibodies and / or affect half-life of the antibodies, for example.Compositions

[0090] In some embodiments, methods provided herein for depleting CCR6 from a cell surface and / or degrading CCR6 comprise using a composition disclosed here. In some embodiments, a composition provided herein can have at least two moieties. The moieties can be, for example, a protein of interest binding (POIB) means that binds to an extracellular region of C-C chemokine receptor 6 (CCR6), or a transferrin receptor (TfR or TR) binding means that binds to TR, or an IgG Fc region. In embodiments, the compositions are heterodimeric or homodimeric fusion proteins. The compositions can have 2, 3, 4, 5, 6 or more moieties, as described above.

[0091] A POIB means or means for binding a POI can be a ligand that the cellsurface molecule(s) can bind or an antibody or antibody fragment (e.g., an scFv) that can bind to the cell-surface molecule(s) (e.g., CCR6). In some embodiments herein, POIBs for CCR6 can be referred to as R1 or R5. In some embodiments, the POIBs for CCR6 are antibodies or antibody fragments. In some embodiments, these antibodies or antibody fragments can have CDRs that include GFSFSDYY (SEQ ID NO: 15), ITTGGRT (SEQ ID NO: 16), TSPLRGAWFAY (SEQ ID NO: 17), or sequences at least 90 to 99% identical thereto. In some embodiments, these CDRs can be from a heavy chain.

[0092] In some embodiments, these antibodies or antibody fragments can have CDRs that include QSIVHSNANTY (SEQ ID NO: 18), KVS (SEQ ID NO: 19), FQGTYLPLT (SEQ ID NO: 20), or sequences at least 90 to 99% identical thereto. In some embodiments, these CDRs can be from a light chain.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0093] CDRs can be grafted to other antibody scaffold sequences to generate POIBs for CCR6.

[0094] A transferrin receptor binder (TRB) means or means for binding TfR (also called TR herein) can bind to TfR on a cell. In embodiments, the TRB means can be an antibody or antibody fragment that binds to transferrin receptor on a cell. In embodiments, the TRB means can be a nanobody (also called camelid antibodies or single-domain antibodies) that binds to an internalizing receptor or membrane protein on a cell. In some embodiments, the nanobody can be called a VHH. In some embodiments, the VHH includes VHHA (SEQ ID NO: 1 ). In some embodiments, the VHH includes VHHB (SEQ ID NO: 21 ). In some embodiments, the TRB means can be transferrin or a fragment of transferrin that binds to TfR. In some embodiments, the antibodies or antibody fragments disclosed herein can be humanized.

[0095] In some embodiments, CDRs of the antibodies or antibody fragments of the TRB means can be GTDFSINF (SEQ ID NO: 22), FTATGNT (SEQ ID NO: 23), YMLDK (SEQ ID NO: 24), or sequences at least 90 to 99% identical thereto. In some embodiments, CDRs of the antibodies or antibody fragments of the TRB means can be GTDFSINF (SEQ ID NO: 22), ITATGNT (SEQ ID NO: 25), YMLDK (SEQ ID NO: 24), or sequences at least 90 to 99% identical thereto. In some embodiments, CDRs of the antibodies or antibody fragments of the TRB means can be GTDFSINF (SEQ ID NO: 22), FTATGNT (SEQ ID NO: 23), AMLDK (SEQ ID NO: 26), or sequences at least 90 to 99% identical thereto. In some embodiments, CDRs of the antibodies or antibody fragments of the TRB means can be GTDFSINF (SEQ ID NO: 22), FTATGNT (SEQ ID NO: 23), YMADK (SEQ ID NO: 27), or sequences at least 90 to 99% identical thereto. In some embodiments, these CDRs can be from a heavy chain. CDRs can be grafted to other antibody scaffold sequences to generate TRBs.

[0096] The compositions provided herein can have different arrangements of components. In some embodiments, different arrangements can be referred to as different “geometries” of the compositions provided herein. The different geometries can include different numbers of various components including, for example, POIB means that bind to CCR6, and TRB means that bind to TfR (e.g., see Fig. 24). InBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO various embodiments, the compositions provided herein can be dimers. In embodiments, the dimers can be heterodimers or homodimers (e.g., Fig. 24).

[0097] In embodiments, compositions provided herein having a POIB means and a TRB means can bind both to a POI (e.g., CCR6) and a TfR internalizing receptor on a cell. After such binding, the TfR can cause the POI, bound by the POIB means, to be internalized into the cell (e.g., endocytosis). In embodiments, an internalized POI can be degraded. In embodiments, internalization and / or degradation decreases the amount of the POI on the surface of a cell. In embodiments, an internalized POI is not functional (e.g., it does not function as when it is present on a cell surface). In embodiments, binding and / or internalization results in blocking or inhibiting CCR6 activity.

[0098] In some embodiments, administering a composition provided herein to a subject can be used for internalization of POIBs, including CCR6. In some embodiments, administering a composition provided herein to a subject can be used for degradation of POIBs, including CCR6.

[0099] In some embodiments, adding a composition provided herein to cells or administering to a patient can cause internalization and / or degradation of CCR6, for example, on the surface of a cell or outside of a cell. In some embodiments, CCR6 can be internalized by compositions provided herein, but not degraded, or can be both internalized and degraded. In some embodiments, degradation is facilitated by the presence of a protease-sensitive linker as component of a composition provided herein. In some embodiments, degradation occurs without the presence of a protease-sensitive linker as component of a composition provided herein. In some embodiments, placement of a protease-sensitive linker within a composition provided herein can provide release of a targeted cellular protein of interest from the composition inside of a cell.

[0100] In some embodiments, internalization and / or degradation of CCR6, for example, can kill the cell. In some embodiments, internalization and / or degradation of CCR6 does not kill the cell. In some embodiments, targeting molecules as described herein for CCR6 can inhibit Th17 cell migration to sites of inflammation. In someBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO embodiments, targeting molecules for CCR6 can treat various autoimmune diseases and / or inflammation-related disease.

[0101] In some embodiments, the molecule can have multiple distinct polypeptides that form a dimer. In embodiments, a dimer can be a heterodimer or homodimer. In some embodiments, knob-into-hole technology can be used to facilitate association of two distinct polypeptides that form a dimers. Knob-into-hole technologies are well known in the art (Xu et al., MAbs. 2015 Jan-Feb; 7(1): 231-242).

[0102] In some embodiments, the compositions provided herein can include dimers. The dimers can be heterodimers or homodimers of polypeptides that can be fusion proteins. In some embodiments, the fusion proteins can contain both a POIB means and a TRB means of a composition provided herein. In some embodiments the fusion proteins can contain a POIB. In some embodiments, the fusion proteins can contain a TRB. In some embodiments, the fusion proteins can include an IgG Fc region.

[0103] In some embodiments, a POIB means can be an antibody or antibody fragment (e.g., nanobody, peptide, such as an scFv) that binds, for example, to CCR6.

[0104] In some embodiments, the POIB means that is an antibody or antibody fragment can be an scFv, Fab, single-domain antibody, nanobody, monobody, DARPin or affibody. Antibody fragments and other molecules can be used.

[0105] As discussed, the TRB means, in some embodiments can be a part of a naturally occurring ligand. For example, the ligand can be part of transferrin that can be bound by transferrin receptor. In some embodiments, the TRB means that is a ligand can be transferrin or a fragment of transferrin.

[0106] In some embodiments, the TRB means can be an antibody, antibody fragment or other molecule that can bind TfR (also referred to herein as TR). In some embodiments, the TRB means can be a scFv, Fab, single-domain antibody, nanobody, monobody, DARPin or affibody.

[0107] In some embodiments, a TRB means that is an antibody or antibody fragment, which can bind transferrin receptor, can be an anti-TfR1 antagonistic scFv antibody identified through phage display. One such antibody can be called “H7” (Goenaga, Anne-Laure, et al. " Identification and characterization of tumor antigens by using antibody phage display and intrabody strategies." Molecular immunology 44.15, 2007:BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO 3777-3788; Tillotson, Benjamin J., et al. " Engineering an anti-transferrin receptor ScFv for pH-sensitive binding leads to increased intracellular accumulation." PLoS One 10.12, 2015: e0145820).

[0108] In some embodiments, an amino acid sequence of H7 or M16 molecules can include the molecules below, or can include molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the amino acid sequences below:TRB Sequences

[0109] H7 scFV-LC (SEQ ID NO: 28):

[0110] SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG*

[0111] H7 scFV-HC (SEQ ID NO: 29):

[0112] QVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVA VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYP DYWGQGTLVTVSS

[0113] H7 -scFv (SEQ ID NO: 30)

[0114] SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVL GGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVR QAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CARDLSGYGDYPDYWGQGTLVTVSS

[0115] M16 (SEQ ID NO: 31):

[0116] SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVL GGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRYPFHHHDHHWVR QAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYY CARDLSGYGDYPDYWGQGTLVTVSS

[0117] Compositions provided herein can employ TRB means that compete with natural transferrin (Tf) for binding to TfR1 (Tf-competitive binder). TRB means recognizing a non-competitive epitope on TfR1 (Tf non-competitive binder) can be effective at degrading a POI while reducing potential toxicity due to effects on iron import. Nanobodies VHHA and VHHB can bind to TfR1 using an epitope that is noncompetitive with Tf. VHHA or VHHB can drive POI internalization and, optionally, degradation.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0118] In some embodiments, a TRB means that is an antibody or antibody fragment can be a nanobody. This nanobody can be called “VHHA.” In some embodiments, VHHA can bind to an epitope in TfR1 that does not compete for binding with natural / endogenous Tf. In some embodiments binding of the binding composition including VHHA to TfR1 is non-competitive with natural Tf. In some embodiments, noncompetitive TRB means can limit toxicity that can occur if transferrin binding to TfR is affected by using a TRB that competes with transferrin for binding to TfR.

[0119] In some embodiments, a TRB means that is an antibody or antibody fragment can be a nanobody. This nanobody can be called “VHHB.” In some embodiments, VHHB can bind to an epitope in TfR1 that does not compete for binding with natural / endogenous Tf. In some embodiments binding of the binding composition including VHHB to TfR1 is non-competitive with natural Tf.

[0120] In some embodiments, the TRB means can include modified VHHA nanobodies that have amino acid substitutions as compared to the VHHA sequence. In some embodiments, such VHHA antibodies can include the amino acid sequences shown in Fig. 5A-B. Some examples of these molecules include VHHA 12 (substitution of F at position 51 with I), VHHA 5 (substitution of Y at position 96 with A), and VHHA 7 (substitution of L at position 98 with A).

[0121] In some embodiments, such modified VHHA molecules can have TfR binding characteristics that are different than binding characteristics of VHHA. In some embodiments, these binding characteristics can include I Cso, Dmax, Kd, presence of a hook effect, and others (e.g. see Fig. 3, Fig. 4, Fig. 11, Fig. 17A, Fig.18 and Fig.25C). In some embodiments, various factors can affect the values obtained when measuring the binding characteristics. In some embodiments, one of these factors can be the geometry of a composition provided herein (Fig. 25C).

[0122] In some embodiments, an amino acid sequence of a TRB means that is a VHHA molecule can include the molecules below, or can include molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the amino acid sequences below:BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0123] EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGF TATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVT VSS*** (111 amino acids; SEQ ID NO: 1 ).

[0124] In some embodiments, an amino acid substitution can occur at amino acid positions 51, 96, or 98 of SEQ ID NO: 1, or a combination thereof.

[0125] In some embodiments, a nucleotide sequence of a TRB means that is a VHHA molecule can include the molecules below, or can include molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the nucleotide sequences below:

[0126] GAGGTGcAGCTGGTGGAGTCTGGGGGAGGCGTGGTGCAGCCTGGGGGG TCTCTAAAACTCTCCTGCGTAGCCTCGGGAACGGACTTCAGTATCAATTTTATACG CTGGTACCGCCAGGCTCCAGGGAAGCAGCGCGAGTTCGTCGCAGGATTTACTGC GACTGGTAACACAAACTATGCAGACTCCATGAAGGGGCGATTCACCATCTCCAGA GACAACACCAAGAACGCGGTGTATCTGCAAATAGACAGCCTGAAACCTGAGGACA CGGCCGTGTATTACTGCTATATGTTGGACAAGTGGGGCCAGGGGACCCAGGTCAC AGTATCCTCC*** (SEQ ID NO: 32).

[0127] In some embodiments, an amino acid sequence of a TRB means that is VHHA-5 (SEQ ID NO: 2) can include the sequence below, or a sequence at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical thereto:

[0128] EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGF TATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCAMLDKWGQGTQVT VSS (111 amino acids; SEQ ID NO: 2). For example, an alanine is substituted for a tyrosine at amino acid position 96 of SEQ ID NO: 1, as shown as a shaded amino acid in SEQ ID NO: 2.

[0129] In some embodiments, an amino acid sequence of a TRB means that is VHHA-7 (SEQ ID NO: 3) can include the sequence below, or a sequence at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical thereto:

[0130] EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGF TATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMADKWGQGTQVTBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VSS (111 amino acids; SEQ ID NO: 3). For example, a leucine is substituted for an alanine at amino acid position 98 of SEQ ID NO: 1, as shown as a shaded amino acid in SEQ ID NO: 3.

[0131] In some embodiments, an amino acid sequence of a TRB means that is VHHA-12 (SEQ ID NO: 4) can include the sequence below, or a sequence at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical thereto:

[0132] EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAG ATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTV SS (111 amino acids; SEQ ID NO: 4). For example, a phenylalanine is substituted for an isoleucine at amino acid position 51 of SEQ ID NO: 1, as shown as a shaded amino acid in SEQ ID NO: 4.

[0133] In one embodiment, an amino acid sequence of a TRB means that is a VHHB molecule can include the molecules below, or can include molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the amino acid sequences below:

[0134] EVQLVESGGGWQPGGSLRLSCAASGEIFSINFMRWYRQAPGKQREWVAG FTRDGSTNYPDSAKGRFTISRDNAKNTVYLQIDSLKPEDTAVYYCYMLDTWGQGTQVT VSS*** (SEQ ID NO: 33).

[0135] In some embodiments, a nucleotide sequence of a TRB means that is a VHHB molecule can include the molecules below, or can include molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the nucleotide sequences below:

[0136] GAgGTGCAGCTGGTGGAGTCTGGGGGagGCGTGGTGCAGCCTGGGGGG TCTCTGAGACTCTCCTGTGCAGCCTCTGGAGAGATCTTCAGTATCAATTTTATGCG CTGGTACCGCCAGGCTCCAGGGAAGCAGCGCGAGTGGGTCGCAGGTTTTACTAG GGATGGAAGCACAAACTATCCAGACTCCGCGAAGGGCCGATTCACCATCTCTAGA GACAACGCCAAGAACACGGTGTATCTGCAAATAGACAGCCTGAAACCTGAGGACA CGGCCGTCTATTATTGTTATATGTTGGACACCTGGGGCCAGGGGACCCAGGTCAC AGTATCCTCC*** (SEQ ID NO: 34).BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0137] In some embodiments, the TRB means can be a polypeptide. In some embodiments, the TRB means can be a ligand or part of a ligand to which the transferrin receptor can bind (e.g., transferrin). In some embodiments, a part of transferrin that can be used as a TRB means is below (SEQ ID NO: 35):

[0138] VPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAI AANEADAVTLDAGLVYDAYLAPNNLKPWAEFYGSKEDPQTFYYAVAWKKDSGFQM NQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDF PQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHSTIFENLANKADRDQYE LLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKE FQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDEC KPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFV YIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAV GRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNK EGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYELLCLDGT RKPVEEYANCHLARAPNHAWTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRS ETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP(SEQ ID NO: 35).

[0139] In some embodiments, an Fc region that can be used as a component or module of a targeting composition molecule can be from IgG. In some embodiments, an Fc region can be (SEQ ID NO: 36):

[0140] DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPE VKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK (SEQ ID NO: 36).

[0141] In some embodiments, the Fc regions can dimerize, forming homodimers or heterodimer structures. In some embodiments, the Fc regions can have, or can be modified to have, cysteine amino acids that are capable of forming disulfide bonds. In some embodiments, dimers of polypeptides can form through disulfide bonds (1 or more, such as 2 disulfide bonds) between cysteine residues in Fc regions of separate fusion protein molecules.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0142] In some embodiments, the Fc region can be a variant comprising one or more amino acid substitutions that alter antigen-independent effector functions, like the circulating half-life of a molecule to which it is linked. Molecules linked to these Fc regions can exhibit either increased or decreased binding to FcRn compared to Fc regions lacking these substitutions and can have an increased or decreased half-life in serum, respectively. Fc variants with improved affinity for FcRn are anticipated to have longer serum half-lives, and such molecules have useful applications in methods in which long half-life of the linked molecule is desired. In contrast, Fc variants with decreased FcRn binding affinity are expected to have shorter half-lives, and such molecules are also useful, for example, where a shortened circulation time can be advantageous. In some embodiments, Fc variants with decreased FcRn binding affinity are also less likely to cross the placenta. In addition, other applications in which reduced FcRn binding affinity can be desired include those applications in which localization to the brain, kidney, and / or liver is desired. In some embodiments, the Fc variant-linked molecules can exhibit reduced transport across the epithelium of kidney glomeruli from the vasculature.

[0143] In some embodiments, the Fc region can be a variant comprising one or more amino acid substitutions that alter Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement activation activities, like the altered binding to FcyRs or C1qs. In some embodiments, the Fc region can be a variant comprising one or more amino acid substitutions that improve thermal stability, reduce aggregation, or enhance expression yields. In some embodiments, the Fc region can be a variant comprising one or more amino acid substitutions that facilitate heterodimerization or multivalency to generate bispecific or multispecific antibodies.

[0144] In another embodiment, the Fc variant-linked molecules can exhibit reduced transport across the blood brain barrier (BBB), from the brain into the vascular space. In some embodiments, an Fc region with altered FcRn binding comprises an Fc domain having one or more amino acid substitutions within the " FcRn binding loop" of an Fc domain. The FcRn binding loop is comprised of amino acid residues 280-299 (according to EU numbering). Exemplary amino acid substitutions with altered FcRn binding activityBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO are disclosed in PCT Publication No. WO05 / 047327 which is incorporated by reference herein. In certain exemplary embodiments, the targeting compositions disclosed herein comprise an Fc domain having one or more of the following substitutions: V284E, H285E, N286D, K290E and S304D (EU numbering).

[0145] In some embodiments, a composition provided herein can have an Fc variant comprising an amino acid substitution which alters glycosylation. For example, the Fc variant can have reduced glycosylation (e.g., N- or O-linked glycosylation). In some embodiments, the Fc variant comprises reduced glycosylation of the N-linked glycan normally found at amino acid position 297 (EU numbering). In another embodiment, the molecules can have an amino acid substitution near or within a glycosylation motif, for example, an N-linked glycosylation motif that contains the amino acid sequence NXT or NXS. In a particular embodiment, the Fc variant can have amino acid substitution at amino acid position 228 or 299 (EU numbering). Exemplary amino acid substitutions which confer reduced or altered glycosylation are described in PCT Publication No., WO 2005 / 018572, which is incorporated by reference herein in its entirety.

[0146] In some embodiments, a composition provided herein can be modified to eliminate glycosylation and can be referred to as "agly" molecules. Exemplary agly molecules, can have an aglycosylated Fc region of an lgG4 antibody which is devoid of Fc-effector function thereby eliminating the potential for Fc mediated toxicity to the normal vital tissues and cells. In yet other embodiments, the molecules disclosed herein can have an altered glycan. For example, there can be a reduced number of fucose residues on an N-glycan at Asn297 of the Fc region, i.e., is afucosylated. In some embodiments, there can be an altered number of sialic acid residues on the N-glycan at Asn297 of the Fc region.

[0147] In some embodiments, the CH2 or CH3 region of an Fc antibody domain can be truncated or modified to adjust the half-life of the molecule. In some embodiments, an Fc truncation includes CH3 or CH2 (e.g., Gehlsen, Kurt R., et al. " Pharmacokinetics of engineered human monomeric and dimeric CH2 domains." MAbs. Vol. 4. No. 4.Taylor & Francis, 2012; Ying, Tianlei, et al. " Engineered soluble monomeric lgG1 CH3 domain: generation, mechanisms of function, and implications for design of biological therapeutics." Journal of Biological Chemistry 288.35 (2013): 25154-25164).BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0148] In some embodiments, a dimerization domain can be a component or module of a composition provided herein. The dimerization domain can be any region that can associate with another dimerization domain, through covalent or non-covalent bonds, to form a dimer (e.g., a composition provided herein that is a homodimer or heterodimer).

[0149] There are many protein dimerization domains known in the art (e.g., see Dang, Dung Thanh. " Molecular Approaches to Protein Dimerization: Opportunities for Supramolecular Chemistry." Frontiers in Chemistry 10 (2022): 829312). An example dimerization domain can include zipper motifs, like a leucine zipper.

[0150] In some embodiments, the dimerization can form between Fc regions of a composition provided herein. In some embodiments, dimerization can form between regions of a composition provided herein that are not Fc regions.

[0151] In some embodiments, a composition provided herein comprises a proteasesensitive linking means or linker. In some embodiments, a composition provided herein comprises a linking means or linker that is not protease-sensitive. In some embodiments, the protease-sensitive linking means or linker is an amino acid sequence that can be cleaved by a protease. In some embodiments, the protease can be a protease in an endosome or lysosome. In some embodiments, the protease can be a cathepsin (e.g., cathepsin B) and the protease-sensitive linking means or linker can be a cathepsin-cleavable peptide. The protease-sensitive linking means or linker can be an amino acid sequence that can be cleaved by a protease. In some embodiments, the protease-sensitive linking means or linker has an amino acid sequence that can be recognized by a cathepsin protease. In some embodiments, cleavage of the proteasesensitive linking means or linker within the context of a composition provided herein can result in an internalized GPCR (e.g., CCR6) being degraded. In some embodiments, recycling of an internalized TfR can also be improved.

[0152] Some example protease-sensitive linking means or linkers are shown below. In some embodiments, the protease-sensitive linking means or linker can be GGFLGGVRGVDG (SEQ ID NO: 37) or GSGSGGEVRGVDG (SEQ ID NO: 38).Sequences of other protease-sensitive linking means or linkers are disclosed herein. Functional alternative amino acid sequences that can be cleaved by a protease (e.g.,BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO cathepsin) are known in the art. Use of other protease-sensitive linking means or linkers are contemplated.

[0153] In some embodiments, a linking means or linkage (e.g., linker) can be located between various components or modules of a composition provided herein. In some embodiments, the linking means or linkage can be a glycine-rich linker (“GS linker). In some embodiments, a “GS” linking means or linker can be a combination of glycine and serine amino acids. In some embodiments, the GS linking means or linker can be GSSGGSGGSGGS (SEQ ID NO: 39). Other sequences are possible. In some embodiments, the GS linking means or linker can be SGGGG (SEQ ID NO: 40), SGGGSGGG (SEQ ID NO: 41), GSSGGSGGSGGS (SEQ ID NO: 42), GSGS (SEQ ID NO: 43), GSGGS (SEQ ID NO: 44), GSSGSS (SEQ ID NO: 45), GSSSSSS (SEQ ID NO: 46) and the like. In some embodiments, a GS linking means or linker can have at least 4 amino acids that are glycine and / or serine. In some embodiments, other amino acids can be part of a GS linking means or linker, as long as glycine and serine are in the majority.

[0154] In some embodiments, compositions provided herein can include the following nucleotide and amino acid sequences, and molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the nucleotide and amino acid sequences below. Specifically, amino acid sequences that can be included in a composition provided herein can be labeled as follows, below:

[0155] Times New Roman font underlined is signal peptide;

[0156] Times New Roman font bolded is anti-protein of interest Fab-heavy chain, scFv, or affibody;

[0157] Times New Roman italicized font is linker encoded by restriction enzyme site creation;

[0158] Times New Roman underlined and bolded font is GS linker;

[0159] Times New Roman underlined, italicized, and bolded font is cleavable linker;

[0160] Courier New font is H7-scFv;

[0161] Courier New underlined font is Fc domain;

[0162] Courier New bolded font is TEV site;

[0163] Courier New italicized font is fragment from Transferrin;

[0164] Courier New underlined and bolded font is His-Tag;

[0165] Courier New bolded and italicized is light chain, and

[0166] Courier New underlined, italicized, and bolded font is Avi-Tag.SequencesBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0167] pDP14-CD19 ETD Hole Fc (SEQ ID NO: 47)

[0168] atgcgAatgcagctgctgctgctgattgcgctgagcctggcgctggtgaccaacagcactagtcccgaggaacctc tagtggtgaaggtggaagagggagataacgctgtgctgcagtgcctcaaggggacctcagatggccccactcagcagctgacctggtctc gggagtccccgcttaaacccttcttaaaactcagcctggggctgccaggcctgggaatccacatgaggcccctggccatctggcttttcatct tcaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgt ggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggcccca gctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcc caccgagggacagcctgaaccagagcctcagccaggacctcaccatggcccctggctccacactctggctgtcctgtggggtaccccctg actctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgccc ggccagagatatgtgggtaatggagacgggtctgttgttgccccgggccacagctcaagacgctggaaagtattattgtcaccgtggcaac ctgaccatgtcattccacctggagatcactgctcggccagtactatggcactggctgctgaggactggtggctggaagactagtTCTGG TGGTGGTGGTGAGAATCTGTACTTTCAGAGCTCGGGCGGAGGATCgggtggaggcgagccca aatcttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCTGGGCGGACCCAGCGT GTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAGCCGAACCCCTGAGGT GACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGT ATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTA CAACAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCACCAGGACTGGCTGA ACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAG AAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCC CCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGAGCTGTGCCGTGAAAG GCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAACGGGCAGCCCGAGAAC AACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAGCTTCTTCCTGGTGAGC AAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGTGTTCAGCTGCTCTGT GATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTCTCAGTCTGAGCCCGG GAAAGGGTGGAGGCGGATCCGGCCTGAACGACATCTTCGAGGCTCAGAAAATCGAA TGGCACGAAGGCtaa

[0169] (SEQ ID NO: 48)

[0170] MRMOLLLLIALSLALVTNSZSPEEPLVVKVEEGDNAVLQCLKGTSDGPTQ QLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQ PGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEI WEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSL LSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWH WLLRTGGWK 7,'S'SGGGGE NL Y FQ S SGGGSGGGEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGKGGGGSGLNDIFEAQKIEWHEG*

[0171] pDP16-EGFR-Affibody-FC-Tf (SEQ ID NO:49)

[0172] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTGG GAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGC GAGCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAGC TAAATGATGCTCAGGCGCCGAAAGTAGACGGCAGCGGCAGCGACAAAACTCACACA TGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO CCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGT GGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCG TGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTA CCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCC AAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGA TGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAG CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTG GACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGC TCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggg gaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttc cgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccat tgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtgg ccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccag ctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccga gccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtg tcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcga cgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaaca ccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaaga ggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagtccagctgtcagcagcccccacg gcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacg tgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagcca ccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtat cgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgct ggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagc gacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgct gtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagct gtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggaga agggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacg agaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcac gccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgact gcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccgga acacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgc acctttcgcagacctT AA

[0173] (SEQ ID NO: 50)

[0174] MYRMQLLSCIALSLALVTNSLQVDNKFNKEMWAAWEEIRNLPNLNG WQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDG5G5DKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSE 7WfFG4ESE HEA TKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADA VTLDAGL VYDA YLAPNN LKPVVAEFYGSKEDPQTFYYA VA VTKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCD LPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGABT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO GDVAFVKHSTJFENJ. ANKADRDQYELLCLDNTRKPVDEYKDCHLAQVPSHTVlrARSMGGKE DLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVT AIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAK1MNG EADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAWKKSASDLTWDNLKG KKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEP NNKEGYYGYTGAFRCL VEKGD VAFVKHQTVPQNTGGKNPDPWAKNLNEKDYELLCLDGTR KPVEEYANCHLARAPNHAWTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLL FRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0175] pDP18-EGFR-affibody (SEQ ID NO: 51)

[0176] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTGG GAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGC GAGCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAGC TAAATGATGCTCAGGCGCCGAAAGTAGACGGTGAGAATCTGTACTTTCAGAGCTCG GGCGGAGGATCGGGTGGAGGCCACCACCATCATCACCACCATCACGGATCCGGCCT GAACGACATCTTCGAGGCTCAGAAAATCGAATGGCACGAAGGCggatcctctgggggaagtgg aggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagctccgggacc acatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgcca atgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttct acggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcgggg caagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccgga agcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtg ccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggcctt cgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaag cccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgat ctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggat ctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgcc atccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagc ggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagat catgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgaga actacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacc tgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaa gatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgg gcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaaggggga cgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggac tacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggt cacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcgg caacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacaccta cgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcg cagacctTAA

[0177] (SEQ ID NO: 52)

[0178] MYRMQLLSC1ALSLALVTNSLOVDNKFNKEMWAAWEEIRNLPNLNG WQMTAFIASLVDDPSOSANLLAEAKKLNDAQAPKVDGENLYFOSSGGGSGGGHHH HHHHHGSGLNDIFEAQKIEWHEGGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCOSBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO FRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKP VVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYC DLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLK DGAGDVAFVKHSTIFENLANKADRDQYELLCLDNTRKPVDEYKDCHLAQVPSHTVVAR SMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAK MYLGYEYVTA1RNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGK1ECVS AETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAI AVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPG SKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGG KNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKIL RQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAV GNLRKCSTSSLLEACTFRRP*

[0179] pDP20-EGFR-Affibody-FC (SEQ ID NO: 53)

[0180] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTGG GAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGC GAGCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAGC TAAATGATGCTCAGGCGCCGAAAGTAGACGGCAGCGGCAGCGACAAAACTCACACA TGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCC CCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGT GGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCG TGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTA CCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCC AAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGA TGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAG CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTG GACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGC TCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATAA

[0181] (SEQ ID NO: 54)

[0182] MYRMQLLSCIALSLALVTNSLQVDNKFNKEMWAAWEEIRNLPNLNG WQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDGAGADKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR DELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVF SC S VMHE ALHNHYTQK SLSL SPGK *

[0183] pDP22-EGFR-affibody (SEQ ID NO: 55)

[0184] ATGCGAATGCAGCTGCTGCTGCTGATTGCGCTGAGCCTGGCGCTGGTG ACCAACAGCACTAGTCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGC GTGGGAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTA TTGCGAGCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAA AAGCTAAATGATGCTCAGGCGCCGAAAGTAGACGGCAGCGGCAGCACTAGTTCTGGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO TGGTGGTGGTGAGAATCTGTACTTTCAGAGCTCGGGCGGAGGATCGGGTGGAGGCC ACCACCATCATCACCACCATCACGGATCCGGCCTGAACGACATCTTCGAGGCTCAGA AAATCGAATGGCACGAAGGCTAA

[0185] (SEQ IDNO: 56)

[0186] MRMOLLLL1ALSLALVTNST LO VDNKFNKEMWAAWEE1RNLPNLNGW OMTAFIASLVDDPSOSANLLAEAKKLNDAQAPKVDG5G5TS5GGGGENLYFOSSGGGSG GG E GSGLNDIFEAQKIEWHEG*

[0187] pDP24-CD19-FC-Tf (SEQ ID NO: 57)

[0188] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGcccgaggaacctctagtggtgaaggtggaagagggagataacgctgtgctgcagtgcctcaaggggacctca gatggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttcttaaaactcagcctggggctgccaggcctgggaatcc acatgaggcccctggccatctggcttttcatcttcaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgaga aggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtg gcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccct gagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccagagcctcagccaggacctcaccatggcccctggct ccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtc attgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatggagacgggtctgttgttgccccgggccacagctca agacgctggaaagtattattgtcaccgtggcaacctgaccatgtcattccacctggagatcactgctcggccagtactatggcactggctgct gaggactggtggctggaagGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGTG CCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAA GGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGA GCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCAT AATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCA GCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGG GCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCA AGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCG TGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggt tctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtg atccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgc cgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaaga ggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtc acaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaa ggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggc tgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggcctcgtgaagcacag caccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgag tacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctg aaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaagga cagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctga gagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcg acgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO aggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaag agcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatct gaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccact gcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctg aacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtg aaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctg tgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaagg acaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctg ttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacct gggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0189] (SEQ IDNO: 58)

[0190] MYRMOLLSCIALSLALVTNSPEEPLVVKVEEGDNAVLOCLKGTSDGPTQ QLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQ PGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEI WEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSL LSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWH WLLRTGGWKEDG5G DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGG SVPDKTVRWCAVSEHEATKCQSFRDHMKSVLPSDGPSVACVKKASYLDCLRAFAANEADAVTLDA GLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGW NIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAF KCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YKDCHLAQVPSHTVVARSM GGKEDLFWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYV TALRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKFECVSAETTEDCLAKLMNG EADAMSLDGGFVYLAGKCGL VPVLAENYNKSDNCED TPEAGYFALAVVKKSASDL TWDNLKGKK SCHTAVGRTAGWNLPMGLLYNKLNHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKE GYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YAN CHLARAPNHAVVTRKDKEACVHKFLRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAK LHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0191] pDP25-pFUSE-Tf-knob-Fc (SEQ ID NO: 59)

[0192] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccggga ccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgc caatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagt tctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcgg ggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccg gaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctg tgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggc cttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaa agcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctg atctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaagg atctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO ccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacga gcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaa gatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccg agaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctg acctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaa caagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcat gggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggg gacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaagg actacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtg gtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcg gcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacct acgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttc gcagacctCCATGGgagcccaaatcttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGC TGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCA GCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG GTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCC CAGGGAGGAGCAGTACGGAAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGC ACCAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTG CCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCA GGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGT GGTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAAC GGGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAG CTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACG TGTTCAGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTC TCAGTCTGAGCCCGGGAAAGggtggctctcatcatcaccatcaccactga

[0193] (SEQ ID NO: 60)

[0194] MYRMQLLSCIALSLALVTNSVPDKTVRWCAVSEHEATKCOSFRDHMKSV IPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSK EDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPL EKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAF VKHSTIFENLANKADRDQYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDL IWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYV TAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIA KIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSAS DLTWDNLKGKK SCHT A VGRT AGWNIPMGLLYNKINHCRFDEFF SEGC APGSKKD S SLC KLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWA KNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLF GSNVTDC SGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKC S T S SLLEACTFRRPPWEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEOYGSTYRVVSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGOPREPOVYTLPPSRDELTKNQVSLWCLVKGFYPSDI AVEWESNGOPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWOQGNVFSCSVMHEALHN HYTQKSLSLSPGKGGSHHHHHH*

[0195] pDP32-CD19-FC-CD19 (SEQ ID NO: 61)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0196] atgcgAatgcagctgctgctgctgattgcgctgagcctggcgctggtgaccaacagcactagtcccgaggaacctc tagtggtgaaggtggaagagggagataacgctgtgctgcagtgcctcaaggggacctcagatggccccactcagcagctgacctggtctc gggagtccccgcttaaacccttcttaaaactcagcctggggctgccaggcctgggaatccacatgaggcccctggccatctggcttttcatct tcaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgt ggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggcccca gctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcc caccgagggacagcctgaaccagagcctcagccaggacctcaccatggcccctggctccacactctggctgtcctgtggggtaccccctg actctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgccc ggccagagatatgtgggtaatggagacgggtctgttgttgccccgggccacagctcaagacgctggaaagtattattgtcaccgtggcaac ctgaccatgtcattccacctggagatcactgctcggccagtactatggcactggctgctgaggactggtggctggaagactagtTCTGG TGGTGGTGGTGAGAATCTGTACTTTCAGAGCTCGGGCGGAGGATCgggtggaggcgagccca aatcttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCTGGGCGGACCCAGCGT GTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAGCCGAACCCCTGAGGT GACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGT ATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTA CAACAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCACCAGGACTGGCTGA ACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAG AAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCC CCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGACCTGTCTGGTGAAAG GCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAACGGGCAGCCCGAGAAC AACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAGCTTCTTCCTGTATAGC AAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGTGTTCAGCTGCTCTGT GATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTCTCAGTCTGAGCCCGG GAAAGGGTGGAGGCGGATCCggaggtagcggtggttctGGAcccgaggaacctctagtggtgaaggtggaagagg gagataacgctgtgctgcagtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgcttaaaccctt cttaaaactcagcctggggctgccaggcctgggaatccacatgaggcccctggccatctggcttttcatcttcaacgtctctcaacagatggg gggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgt tccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcat gagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaacc agagcctcagccaggacctcaccatggcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccct ctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaat ggagacgggtctgttgttgccccgggccacagctcaagacgctggaaagtattattgtcaccgtggcaacctgaccatgtcattccacctgg agatcactgctcggccagtactatggcactggctgctgaggactggtggctggaagGGCCTGAACGACATCTTCGAG GCTCAGAAAATCGAATGGCACGAAGGCtaa

[0197] (SEQ IDNO: 62)

[0198] MRMQLLLL1ALSLALVTNS / : S'PEEPLVVI< VEEGDNAVLOCLI< GTSDGPTO QLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQ PGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPET WEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSL LSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWH WLLRTGGWKTSSGGGGENLYFQSSGGGSGGGEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGKGGGGSGGSGGSGPEEPLVVKVEEGDNAVLQCLKGTSDGPTOQLTWSRESBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO PLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNV EGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCL PPRD SLNQ SL SQDLTMAPGSTLWLSCGVPPD S VSRGPL S WTHVHPKGPK SLLSLELKDD RPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLLRTGG WKGLNDIFEAQKIEWHEG*

[0199] pDP44-CD19 NT.l-FC-Tf (SEQ ID NO: 63)

[0200] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGcccgaggaacctctagtggtgaaggtggaagagggagataccgctgctctgtggtgcctcaaggggacctca gatggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtcc acgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctga gaaggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggct gtggcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgc cctgagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccagagcctcagcagggacctcaccgtagcccctg gctccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaa gtcattgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatgggtacgtcactgatgttgccccgggccacagct caagacgctggaaagtggtattgtcaccgtggcaacgtaaccacctcattccacctggaggtaatcgctcggccagtaaaggctcactcag acctgaggactggtggctggaagGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACC GTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACC CAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGT GAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGC ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTC AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA GGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAG GGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCC GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAG GTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtg gttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccg tgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgac gccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaa gaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctg tcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaa aggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtgg ctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcaca gcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacga gtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgct gaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaagg acagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctg agagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgc gacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggc gaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaa gagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatc tgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccacBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO tgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcct gaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggcctccggtgtctggtggagaagggggacgtggctttgt gaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgct gtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaag gacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcct gttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacc tgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0201] (SEQ ZD NO 64)

[0202] MYRMQLLSCIALSLALVTNSPEEPLVVK VEEGDTAALWCLKGT SDGPTQ QLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAW QPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPE IWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSL LSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSFHLEVIARPVKAH SDLRTGGWKJ / DG5,G DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSH EDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS VPDKTVRWCAVSEHEATKCQSFRDHMKSVLPSDGPSVACVKKASYLDCLRALAANEADAVTLDA GLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGW NIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAF KCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YKDCHLAQVPSHTWARSM GGKEDLLWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYV TALRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKLECVSAETTEDCLAKLMNG EADAMSLDGGFVYIAGKCGL VPVLAENYNKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKK SCHTAVGRTAGWNLPMGLLYNKLNHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKE GYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YAN CHLARAPNHAVVTRKDKEACVHKLLRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAK LHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0203] pDP49-CD19 NT.l-FC-GFLG-Tf (SEQ ID NO: 65)

[0204] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGcccgaggaacctctagtggtgaaggtggaagagggagataccgctgctctgtggtgcctcaaggggacctca gatggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtcc acgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctga gaaggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggct gtggcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgc cctgagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccagagcctcagcagggacctcaccgtagcccctg gctccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaa gtcattgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatgggtacgtcactgatgttgccccgggccacagct caagacgctggaaagtggtattgtcaccgtggcaacgtaaccacctcattccacctggaggtaatcgctcggccagtaaaggctcactcag acctgaggactggtggctggaagGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACC GTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACC CAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGT GAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGC ATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAA GGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAG GGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCC GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGT GCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAG GTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCA CTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctggggggTTCCTGggaagc ggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaa gtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgagg ccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggca gcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaa gtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctct ggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccgg ctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaa gcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtg gacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctggga gctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgt tcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccgg aacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctg aagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatga acggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactac aacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctggga caatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatca accactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagc ggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtgg cttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacga actgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcaccc ggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaactt ctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgaga agtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagac ctaccggtCACCACCATCATCACCACCATCACTAA

[0205] (SEQ ID NO: 66)

[0206] MYRMQLLSCIALSLALVTNSPEEPLVVK VEEGDTAALWCLKGT SDGPTQ QLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAW QPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPE IWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSL LSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSFHLEVIARPVKAH SDLRTGGWKF£> G G DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSH EDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSWIHEALHNHYTQKSLSLSPGKGSSGGFLGSGGS V PDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAG LVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWN IPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO CLKDGAGDVAFVKHSTIFENLANKADRDQYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMG GKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVT AIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGE ADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKS CHTAVGRTAGWNIPMGLL YNKINHCRFDEFFSEGCAPGSKKDSSL CKL CMGSGLNL CEPNNKEG YYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANC HLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKL HDRNTYEKYLGEE YVKAVGNLRKCS TSSLLEACTFRRPTGWRHWHR*

[0207] pDP50-His8-CD19 NT.l-GFLG-FC-Tf (SEQ ID NO: 67)

[0208] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGgga ggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTG GGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCC CGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGT CAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGC GGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCAC CAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCC AGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGG TGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCT GCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTT CTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCT TCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCT CCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgc gccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctg tgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacg atgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtgg ccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctg gaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctg cgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctac agcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggc cgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgcca tctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaagga caagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccc cagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccacc gatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO atcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggct tcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggcc ggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgt gggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctg cgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagaggg ctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccgg cggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtgga ggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgc ggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttcc gggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaa tctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0209] (SEQ ID NO: 68)

[0210] MYRMQLLSCIALSLALVTNSGHHHHHHHH / PEEP L VVKVEEGDT AALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFAGGEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPCKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCOSFRDHMKSVIPSDGPSVACVKKASYLD CIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQ LRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCP GCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YK DCHLAQVPSHTVVARSMGGKEDLLWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFL KVPPRMDAKMYLGYEYVTALRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKLE CVSAETTEDCLAKLMNGEADAMSLDGGFVYLAGKCGLVPVLAENYNKSDNCEDTPEAGYFALAV VKKSASDL TWDNLKGKKS CHTAVGR TAGWNLPMGLL YNKLNHCRFDEFFSEGCAPGSKKDSSL C KL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD Y ELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFR SETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0211] pDP85-cd20-scfv-GFLG-FC-Tf (SEQ ID NO: 69)

[0212] ATGTACAGGATGCAACTCCTGTCTTGC ATTGCACTAAGTCTTGCACTTG TCACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAG GCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGT TCCAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTG GCGAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTG ACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGAC GAGTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTG GTTCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCT GGTGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGG GTACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCT TGGAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO TTCAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAG TTGTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATT ATGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCG CGGGTGGCAGCGGCAGCggtgggTTCCTGggaGGCGTAGACGGCGACAAAACTCACACA TGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCC CCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGT GGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCG TGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTA CCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGT ACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCC AAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGA TGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAG CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTG GACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGC TCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggg gaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttc cgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccat tgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtgg ccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccag ctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccga gccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtg tcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcga cgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaaca ccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaaga ggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacg gcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacg tgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagcca ccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtat cgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgct ggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagc gacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgct gtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagct gtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggaga agggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacg agaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcac gccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgact gcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccgga acacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgc acctttcgcagacctT AA

[0213] (SEQ ID NO: 70)

[0214] MYRMQLLSCIALSLALVTNSQIVL SQSPAIL S ASPGEK VTMTCRAS S S VS YI HWFQQKPGSSPKPW1YATSNLASGVPVRFSGSGSGTSYSLT1SRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGAGSGGFLGGEOGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCS HEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVFDKTV CA VSEHEATKCQSFRDH MKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKE DPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANF FSGSCAPCADGTDFPQL CQL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANK ADRDQYELLCLDNTRKPVDE YKDCHLAQVPSHTVVARSMGGKEDL IWELLNQAQEHFGKDKSKE FQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWC ALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLA ENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINH CRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQT VPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKIL RQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKC STSSLLEACTFRRP*

[0215] pDP95-Herceptin_HC_Fc-N297G, S427C (SEQ ID NO: 71)

[0216] ATGTACAGGATGCAACTCCTGTCTTGC ATTGCACTAAGTCTTGCACTTG TCACGAATTCGgaggtcagctggtggagtctggcggtggcctggtgcagccagggggctcactccgtttgtcctgtgcagcttc tggcttcaacATCAAGGACACCTATATCcactgggtgcgtcaggccccgggtaagggcctggaatgggttgcaCGCA TC T AC C C GACGA AT GGC T AC AC GC GC T atgccgat AGC tcaagggccgtttcactataagcGC AG AC A CATCCAAAAACACAGCCtacctacaaatgaacagcttaagagctgaggacactgccgtctattattgtTCACGCTGG GGGGGAGATGGGTTTTATGCAATGgactactggggtcaaggaaccctggtcaccgtctcctcggcctccaccaagg gtccatcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccga accggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctc agcagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggtcga caaAAAGGTCgagcccaaatcttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCTG GGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAGC CGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGT GAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCCA GGGAGGAGCAGTACGGCAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCAC CAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCC GGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAG GTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGAC CTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAACG GGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAGC TTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGT GTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTCT CAGTCTGAGCCCGGGAAAGtaa

[0217] (SEQ ID NO: 72)

[0218] MYRMQLLSCIALSLALVTNSEVOLVESGGGLVOPGGSLRLSCAASGFNIK DTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRA EDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG CL VKD YFPEP VT VS WNSGALT SGVHTFP A VLQ S SGL YSL S SWT VP S S SLGTQTYICN VNBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO HKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDV SHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFCCSVMHEALHNHYTQKSLSLSPGK*

[0219] pDP69-His8-CD19 NT.l-2XGFLG-FC-Tf (SEQ ID NO: 73)

[0220] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgtccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtggaTTtCTGggcg gcgggTTCCTGggaggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCAC CTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCC TCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAA GACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCA CCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAAC AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG AGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGG TCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGG AGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCA GGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCA GAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgata agacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgac ggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactgga tgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccaga ccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctg ggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggcca acttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctg aaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgag aacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgc cacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggccca ggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacg gctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacct gtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcg tgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccat gagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcg aggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaa agctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO ttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcc caacaacaaagagggctactacggctacacaggggcctccggtgtctggtggagaagggggacgtggctttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0221] (SEQ ZD NO 74)

[0222] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWT VNVEG SGELFRWNVSDLGGLGC GLKNRS SEGP S SP SGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFAGGGFZGGFDGDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGRGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVPPSDGPSVACVK KASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDS GFQMNQLRGKKS CHTGL GRSAGWNIPIGLL YCDL PEPRKPLEKAVANFFSGS CAPCADGTDFPQ L CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRK PVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKD SAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVN SVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAG YFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSK KDSSLCKL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKN LNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKYLRQQQHLFGSNVTDCSG NFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0223] pDP70-His8-CD19 NT.l-3XGFLG-FC-Tf (SEQ ID NO: 75)

[0224] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaaccctcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtggaTTCCTGggc ggcgggTTtCTGggaggcggaTTtCTGggaggcGTAGACGGCGACAAAACTCACACATGCCCAC CGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAAC CCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTG CAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTG ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGA GCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA ACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggta gcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatg aagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatga ggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacg gcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaa gaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagc ctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccc cggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgt gaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagccc gtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctg ggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctg ctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatc cggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcgg ctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatca tgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaac tacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctg ggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaaga tcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggca gcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgt ggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactac gaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcac ccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaa cttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacga gaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcag acctTAA

[0225] (SEQ ID NO: 76)

[0226] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFAGGGFZGGGFLGGEDGDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL WR TQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPS VACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VKKDSGFQMNQLRGKKSCHTGLGRSAGWNLPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADG TDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CL DNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKD LLFKDSAHGFLKVPPRMDAKMYLGYEYVTALRNLREGTCPEAPTDECKPVKWCALSHHERLKCD EWSVNSVGKLECVSAETTEDCLAKLMNGEADAMSLDGGFVYLAGKCGLVPVLAENYNKSDNCED TPEAGYFALAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNLPMGLLYNKLNHCRFDEFFSEGC APGSKKDSSLCKL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPD PWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKLLRQQQHLFGSNV TDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTF RRP*

[0227] pDP71-His8-CD19 NT.l-GFLG-FK-FC-Tf (SEQ ID NO: 77)

[0228] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGgga ggcTTCAAAggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG AACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCA TGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGAC CCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC AAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA ACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCA GCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA CGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGA AGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataaga cagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacgg ccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatg ccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagacc ttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctggg cagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaact tcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaa ccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaa cctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgcca cctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccagg aacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggc tttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO cccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtg aacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatga gcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgag gatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaag ctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagtt cttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagccc aacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0229] (SEQ IDNO: 78)

[0230] MYRMOLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGG AGGFAGFDGDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK S SLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVACVKKA SYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGF QMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLC QL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPV DEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSA HGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSV GKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYF AIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKD SSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLN EKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNF CLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0231] pDP72-His8-CD19 NT.l-GFLG-VA-FC-Tf (SEQ ID NO: 79)

[0232] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaaccctcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGgga ggcGTAgctggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGA ACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCAT GATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACA AAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGT CCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG CCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAA CCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGA GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGAC GGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGG GAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAA GAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagaca gtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggcc ctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgcc ggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagacctt ctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggca gaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttct tcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaacc agtacttcggctacagcggcgcctcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacc tggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacct cgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaa cacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggcttt ctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcc cgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaa cagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagc ctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgagga tacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagct gccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttctt cagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaa caacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgc cccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcaccc ggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgt ccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaa aggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtg aaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0233] (SEQ ID NO: 80)

[0234] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGF£GGE4GFDGDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS L S L S PGKGS SGGSGGSGGS VPDKTVRWCAVSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQ MNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQ LCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHSTIFENLANKADRDQYELLCLDNTRKPVD EYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAH GFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVG KIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFA IAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMGLL YNKINHCRFDEFFSEGCAPGSKKDS SL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNE KD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFC LFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0235] pDP73-His8-CD19 NT.l-GFLG-VK-FC-Tf (SEQ ID NO: 81)

[0236] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgtccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGgga ggcGTAAAAggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG AACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCA TGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGAC CCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC AAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA ACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCA GCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA CGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGA AGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataaga cagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacgg ccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatg ccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagacc ttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctggg cagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaact tcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaa ccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaaBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO cctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgcca cctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccagg aacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggc tttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgt cccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtg aacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatga gcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgag gatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaag ctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagtt cttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagccc aacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0237] (SEQ ID NO: 82)

[0238] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFAGGFKGFDGDKTHTCPPCPAPELLGGPSVFLEPPKP KDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVACVKKA SYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGF QMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLC QL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPV DEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSA HGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSV GKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYF AIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKD SSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLN EKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNF CLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0239] pDP74-His8-CD19 NT.l-GFLG-VR-FC-Tf (SEQ ID NO: 83)

[0240] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGgga ggcGTACGGggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTG AACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCA TGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGAC CCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGAC AAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCG TCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAA GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGA ACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCA GCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGA CGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGG GGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGA AGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataaga cagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacgg ccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccatgccgccaatgaggccgacgccgtgacactggatg ccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagacc ttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctggg cagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaact tcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaa ccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaa cctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgcca cctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccagg aacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggc tttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgt cccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtg aacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatga gcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgag gatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaag ctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagtt cttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagccc aacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0241] (SEQ ID NO: 84)

[0242] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFAGGFRGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS L S L S PGKGS SGGSGGSGGS VPDKTVRWCAVSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQ MNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQ LCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHSTIFENLANKADRDQYELLCLDNTRKPVD EYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAH GFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVG KIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFA IAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMGLL YNKINHCRFDEFFSEGCAPGSKKDS SL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNE KD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFC LFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0243] pDP75-His8-CD19 NT.l-GFLG-GGFG-FC-Tf (SEQ ID NO: 85)

[0244] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgtgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGgga ggcggtgggTTCgggGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCT GAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGA CCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGA CAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG AACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGA GAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCG ACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG AAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataag acagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacg gccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO gccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagac ctctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgg gcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaa cttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctga accagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgaga acctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgcc acctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccag gaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacgg ctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctg tcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgt gaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatg agcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcga ggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaa gctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagt tcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcc caacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0245] (SEQ ID NO:86)

[0246] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFZGGGG GPDGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KS L 5 L S PGKGSSGGSGGSGGS VPDKTVRWCAVSEHEA TKCQSFRDHMKSVIPSDGPSVACVKK ASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSG FQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKP VDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDS AHGFLKVPPRMDAKMYL G YE YVTAFRNLREGTCPEAPTDECKPVKWCAL SHHERLKCDEWSVNS VGKLECVSAETTEDCLAKFMNGEADAMSLDGGFVYFAGKCGL VPVLAENYNKSDNCED TPEAGY FALAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNLPMGLLYNKLNHCRFDEFFSEGCAPGSKK DSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNL NEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKLLRQQQHLFGSNVTDCSGN FCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0247] pDP76-His8-CD19 NT.l-FK-FC-Tf (SEQ ID NO: 87)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0248] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaaccctcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcTTCAAAggcG TAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGG GGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAA GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGG AGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAG GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGC CCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT ACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGC CTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCA GCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTT CCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC TGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgt gtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtga agaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcc tacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtg gtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaac atccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcc ccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcg gcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgac cgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctca cacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaag agcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccaga atggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatg agtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcg agtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgt gtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggct actttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtggga aggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagtcttcagcgagggctgcgctc ccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctacta cggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggca agaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaata cgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcag cagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO gacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcg gaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0249] (SEQ ID NO: 88)

[0250] MYRM0LLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGF 'GFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDCI RAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLR GKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGC GCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPVDE YKDC HLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKV PPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECV SAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVK KSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKL CMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYEL LCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSE TKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0251] pDP77-His8-CD19 NT.l-VA-FC-Tf (SEQ ID NO: 89)

[0252] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcGTAgctggcGT AGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGG GACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGA CCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAG TTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGA GGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGG ACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTA CACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCT GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCC TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG TCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtc tgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaaga aggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctac ctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggt caagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacat ccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcccc ttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggc gccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccg ggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcaca cagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagag caaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaat ggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgag tgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagt gcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgta cattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctact ttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaag gaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctccc ggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacg gctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaag aaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacg ccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagca gcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacga caccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcgga agtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0253] (SEQ ID NO: 90)

[0254] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGE4GEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDCI RAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLR GKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGC GCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPVDE YKDC HLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKV PPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECV SAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVK KSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO CMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYEL LCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSE TKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0255] pDP78-His8-CD19 NT.l-VK-FC-Tf (SEQ ID NO: 91)

[0256] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaaccctcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcGTAAAAggcG TAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGG GGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAA GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGG AGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAG GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGC CCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT ACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGC CTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCA GCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTT CCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC TGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgt gtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtga agaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcc tacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtg gtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaac atccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcc ccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcg gcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgac cgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctca cacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaag agcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccaga atggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatg agtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcg agtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgt gtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggct actttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtggga aggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctc ccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactaBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO cggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggca agaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaata cgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcag cagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggac gacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcg gaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0257] (SEQ ID NO: 92)

[0258] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGFXGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGS VPDK TVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDCI RAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLR GKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGC GCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPVDE YKDC HLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKV PPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECV SAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVK KSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKL CMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYEL LCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSE TKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0259] pDP79-His8-CD19 NT.l-VR-FC-Tf (SEQ ID NO: 93)

[0260] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgtgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcGTACGGggcG TAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGG GGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAA GTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGG AGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO GACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGC CCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGT ACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGC CTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCA GCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTT CCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCT CATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCC TGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgt gtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtga agaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcc tacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtg gtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaac atccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcc ccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcg gcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgac cgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctca cacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaag agcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccaga atggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatg agtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcg agtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggctcgt gtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggct actttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtggga aggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctc ccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctacta cggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggca agaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaata cgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcag cagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggac gacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcg gaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0261] (SEQ IDNO: 94)

[0262] MYRM0LLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGFRGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDCI RAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLR GKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGC GCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPVDE YKDCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO HLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKV PPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECV SAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVK KSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKL CMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYEL LCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSE TKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0263] pDP80-His8-CD19 NT.l-GGFG-FC-Tf (SEQ ID NO: 95)

[0264] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaag gtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtcccc gcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtct ctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggc agcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctcccct tccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgag ggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtg tccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccag agatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaacc acctcattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCggaggc GTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCG GACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCA AGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGG GAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCA GGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAG CCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTG TACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTG CCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT TCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTC TCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC CTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgcc gtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgt gaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatg cctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggcc gtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctgg aacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgc gccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctaca gcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggcc gaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccat ctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaagga caagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccc cagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccacc gatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaag atcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggctBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO tcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggcc ggctacttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgt gggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctg cgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagaggg ctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccgg cggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtgga ggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgc ggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttcc gggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaa tctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0265] (SEQ IDNO: 96)

[0266] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFGGFD DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGSSGGSGGSGGS VPDK TVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLDC IRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQL RGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPG CGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHSTIFENLANKADRDQYELLCLDNTRKPVDEYKD CHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLK VPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIEC VSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVV KKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCK LCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYE LLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRS ETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0267] pDP86-PDLl-scfv-GFLG-fc-Tf (SEQ ID NO: 97)

[0268] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGATATACAGATGACCCAATCCCCATCCAGCTTGTCCGCTAGCGTAG GCGATAGAGTAACTATTACATGCCGCGCTAGTCAAGACGTGTCAACTGCAGTCGCGT GGTACCAACAAAAGCCTGGCAAAGCTCCGAAACTGCTGATTTACAGCGCGTCTTTCC TTTACTCTGGGGTACCTAGCCGATTTTCTGGGTCTGGTAGCGGAACCGATTTCACGCT TACAATTTCTAGCCTCCAACCCGAAGATTTCGCGACGTACTACTGCCAACAATACCT TTACCATCCAGCCACATTTGGACAGGGCACGAAGGTTGAAATAAAAGGCGGAGGTG GATCTGGCGGAGGAGGAAGTGGGGGTGGAGGTTCAGAAGTTCAGCTGGTTGAATCA GGCGGCGGACTTGTTCAGCCGGGCGGAAGCCTTCGGCTTAGCTGTGCTGCCAGTGGC TTCACATTCAGTGATAGCTGGATTCATTGGGTTCGCCAGGCACCAGGCAAAGGTTTG GAGTGGGTCGCCTGGATTAGTCCGTATGGGGGCTCCACCTACTACGCTGACTCAGTG AAAGGGCGGTTTACCATTAGTGCTGATACGTCCAAAAATACAGCTTACCTTCAGATGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO AACTCTCTGAGGGCCGAAGATACTGCTGTGTACTACTGCGCTCGGAGACATTGGCCA GGAGGGTTCGATTACTGGGGGCAAGGCACTTTGGTGACAGTCAGTTCAGGTGGTTCC GGCAGCGCAGGAggtgggTTCCTGggaGGCGTAGACGGCGACAAAACTCACACATGCCC ACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAA ACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGG ACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGT GGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGT GCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCT GACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACA TCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAG AGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCAC AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggagg tagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacat gaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatg aggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctac ggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggca agaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaag cctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgcc ccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcg tgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcc cgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatct gggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatct gctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccat ccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcg gctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatc atgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaa ctacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacct gggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaa gatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgg gcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaaggggga cgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggac tacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggt cacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcgg caacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacaccta cgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcg cagacctTAA

[0269] (SEQ ID NO: 98)

[0270] MYRMQLLSCIALSLALVTNSDIOMTQSPSSLSASVGDRVTITCRASODVST AVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQY LYHPATFGQGTKVE1KGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGF TF SD S WIHWVRQ APGKGLEWVAWISP YGG ST YYAD S VKGRFTIS ADT SKNTAYLQMNS LRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFZGGEDGDKTHTCPPCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSViAREALWWYTQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDH MKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKE DPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANF FSGSCAPCADGTDFPQL CQL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANK ADRDQYELLCLDNTRKPVDE YKDCHLAQVPSHTVVARSMGGKEDL IWELLNQAQEHFGKDKSKE FQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWC ALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLA ENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINH CRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQT VPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKIL RQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKC STSSLLEACTFRRP*

[0271] pDP96-CD20_HC_Fc-N297G, S427C-Tf (SEQ ID NO: 99)

[0272] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAG GCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGT TCCAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTG GCGAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTG ACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGAC GAGTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTG GTTCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCT GGTGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGG GTACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCT TGGAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAG TTCAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAG TTGTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATT ATGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCG CGGGTGTAGACGGCAGCGGCAGCgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAAT TGCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGA TCAGCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCC GAGGTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAA GCCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGC TGCACCAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCT CTGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACC GCAGGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCC TGACCTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTA ACGGGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGC AGCTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAA CGTGTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAG TCTCAGTCTGAGCCCGGGAAAGggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgc ggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagc gtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcct ggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactaBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO cgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagc gccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagc ggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtact tcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggcc aacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgccc aggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttc ggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaa ggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgag gcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagc gtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctgg acggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacc cccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgcca caccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagc gagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaac aaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgcccca gaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaa gccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccac aagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaagga cctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaagg ccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0273] (SEQ ID NO: 100)

[0274] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGEDGAGSDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFCCSVMH EALHNHYTQKSLSLSPGKGSSGGSGGSGGSVPFK RPIZCA VSEHEATKCQSFRDHMKSVLPSD GPSVACVKKAS YLDCIRAIAANEADAVTLDAGLVYDA YLAPNNLKPVVAEFYGSKEDPQ TFYYA VAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPC ADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQYEL L CLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQAQEHFGKDKSKEFQLFSSPH GKDLLFKDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERL KCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDN CEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFS EGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGK NPDPWAKNLNEKD YELL CLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKLLRQQQHLFG SNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEA CTFRRP*

[0275] pDP97-cd20-scfv-GFLG-FC-N297G, S427C-Tf (SEQ ID NO: 101)

[0276] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO GCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGT TCCAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTG GCGAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTG ACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGAC GAGTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTG GTTCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCT GGTGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGG GTACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCT TGGAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAG TTCAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAG TTGTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATT ATGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCG CGGGTGGCAGCGGCAGCggtgggTTCCTGggaGGCGTAGACGGCgacaaaactcacacatgcCCCC CCTGCCCAGCGCCAGAATTGCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAAC CTAAAGACACCCTGATGATCAGCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGAC GTGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGT CCACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTA GTGAGCGTCTTGACCGTGCTGCACCAGGACTGGCTGAACGGCAAGGAATACAAATG CAAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAA AGGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCCCCCCAGCCGGGACGAGCTG ACCAAGAACCAGGTGTCCCTGACCTGTCTGGTGAAAGGCTTCTACCCCAGCGACATC GCTGTGGAGTGGGAGAGTAACGGGCAGCCCGAGAACAACTACAAGACCACGCCTCC TGTGCTGGACAGCGACGGCAGCTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAG CAGGTGGCAACAGGGCAACGTGTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACA ACCATTACACCCAGAAGAGTCTCAGTCTGAGCCCGGGAAAGggatcctctgggggaagtggaggt agcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacat gaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatg aggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctac ggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggca agaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaag cctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgcc ccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcg tgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcc cgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatct gggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatct gctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccat ccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcg gctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatc atgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaa ctacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacct gggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaa gatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgg gcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaaggggga cgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggac tacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggt cacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO caacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacaccta cgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcg cagacctTAA

[0277] (SEQ IDNO: 102)

[0278] MYRMOLLSC1ALSLALVTNSQ1VLSOSPA1LSASPGEKVTMTCRASSSVSY1 HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGSGSGGFZGGFDGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFCCSVMREALRNR TQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDH MKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKE DPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANF FSGSCAPCADGTDFPQL CQL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANK ADRDQYELLCLDNTRKPVDE YKDCHLAQVPSHTVVARSMGGKEDL IWELLNQAQEHFGKDKSKE FQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWC ALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLA ENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINH CRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQT VPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKIL RQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKC STSSLLEACTFRRP*

[0279] pDP98-CD20_HC_Fc-N297G, S427C (SEQ ID NO: 103)

[0280] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAG GCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGT TCCAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTG GCGAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTG ACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGAC GAGTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTG GTTCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCT GGTGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGG GTACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCT TGGAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAG TTCAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAG TTGTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATT ATGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCG CGGGTGTAGACGGCAGCGGCAGCgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAAT TGCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGA TCAGCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCC GAGGTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAA GCCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO TGCACCAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCT CTGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACC GCAGGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCC TGACCTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTA ACGGGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGC AGCTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAA CGTGTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAG TCTCAGTCTGAGCCCGGGAAAGTAA

[0281] (SEQ IDNO: 104)

[0282] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGEDGAGSDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFCCSVMH EALHNHYTQKSLSLSPGK*

[0283] cd20-scFV-FC-Tf (SEQ ID NO: 105)

[0284] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAG GCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGT TCCAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTG GCGAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTG ACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGAC GAGTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTG GTTCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCT GGTGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGG GTACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCT TGGAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAG TTCAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAG TTGTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATT ATGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCG CGGGTGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGA AGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCA AGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAA CAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCC GAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAG GTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTC CGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO AGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGC AGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggtctgtgcccga taagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcg acggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactg gatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggaccccca gaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcct gggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggcc aacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccct gaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcga gaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactg ccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggccc aggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccac ggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcac ctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagc gtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgcca tgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgc gaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaa aagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacga gttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagc ccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagacc gtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggca cccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcct gcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgag acaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaata tgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0285] (SEQ ID NO: 106)

[0286] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGED 5 DKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALWR TQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVLPSD GPSVACVKKAS YLDCIRAIAANEADAVTLDAGLVYDA YLAPNNLKPVVAEFYGSKEDPQ TFYYA VAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPC ADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQYEL L CLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQAQEHFGKDKSKEFQLFSSPH GKDLLFKDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERL KCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDN CEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFS EGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGK NPDPWAKNLNEKD YELL CLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKLLRQQQHLFGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO SNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEA CTFRRP*

[0287] PD-Ll-scFV-FC-Tf (SEQ ID NO: 107)

[0288] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTG TCACGAATTCGGATATACAGATGACCCAATCCCCATCCAGCTTGTCCGCTAGCGTAG GCGATAGAGTAACTATTACATGCCGCGCTAGTCAAGACGTGTCAACTGCAGTCGCGT GGTACCAACAAAAGCCTGGCAAAGCTCCGAAACTGCTGATTTACAGCGCGTCTTTCC TTTACTCTGGGGTACCTAGCCGATTTTCTGGGTCTGGTAGCGGAACCGATTTCACGCT TACAATTTCTAGCCTCCAACCCGAAGATTTCGCGACGTACTACTGCCAACAATACCT TTACCATCCAGCCACATTTGGACAGGGCACGAAGGTTGAAATAAAAGGCGGAGGTG GATCTGGCGGAGGAGGAAGTGGGGGTGGAGGTTCAGAAGTTCAGCTGGTTGAATCA GGCGGCGGACTTGTTCAGCCGGGCGGAAGCCTTCGGCTTAGCTGTGCTGCCAGTGGC TTCACATTCAGTGATAGCTGGATTCATTGGGTTCGCCAGGCACCAGGCAAAGGTTTG GAGTGGGTCGCCTGGATTAGTCCGTATGGGGGCTCCACCTACTACGCTGACTCAGTG AAAGGGCGGTTTACCATTAGTGCTGATACGTCCAAAAATACAGCTTACCTTCAGATG AACTCTCTGAGGGCCGAAGATACTGCTGTGTACTACTGCGCTCGGAGACATTGGCCA GGAGGGTTCGATTACTGGGGGCAAGGCACTTTGGTGACAGTCAGTTCAGGTGGTTCC GGCAGCGCAGGAGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGT GCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCA AGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTG AGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA TAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCA GCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGG GCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCA AGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCG TGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggt tctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtg atccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgc cgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaaga ggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtc acaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaa ggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggc tgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacag caccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgag tacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctg aaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaagga cagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctga gagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcg acgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcg aggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaag agcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO gaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccact gcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctg aacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtg aaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctg tgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaagg acaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctg ttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacct gggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0289] (SEQ ID NO: 108)

[0290] MYRMOLLSCIALSLALVTNSDIOMTQSPSSLSASVGDRVTITCRASODVST AVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQY LYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGF TFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNS LRAEDTAVYYCARRHWPGGFDYWGQGTLVTV SGGSGSAGJVKAS' A'DKTHTCPPCP P ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS VFAK RiYCAVSE’HEATKCQSFRDHMKS VIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQ TFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSG S CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADR DQ YELLCLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQAQEHFGKDKSKEFQL FSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALS HHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENY NKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMGLL YNKINHCRF DEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQ NTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQ QHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTS SLLEACTFRRP*

[0291] pDP124-cd20-scfv-FC-TfR-H7 (SEQ ID NO: 109)

[0292] MYRMQLLSCIALSLALVTNSQIVLSOSPAIL S ASPGEKVTMTCRAS S S VS YI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGEDG5G5DKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASW YQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPV FGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVR QAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSG YGDYPDYWGQGTLVTVS S *- 1 -BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0293] pDP125-cd20-scfv-FC-TfR-M16 (SEQ ID NO: 110)

[0294] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDG G5DKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASW YQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPV FGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRYPFHHHDHHWVR QAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSG YGDYPDYWGQGTLVTVS S *

[0295] pDP126-cd20-scfv-GFLG-FC-TfR-H7 (SEQ ID NO: 111)

[0296] MYRMOLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGG5G5GGFLGGEDGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS VAL GQ T YR I T C QGD S LRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGW DDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFS SYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARDLSGYGDYPDYWGQGTLVTVSS*

[0297] pDP127-cd20-scfv-GFLG-FC-TfR-M16 (SEQ ID NO: 112)

[0298] MYRMQLLSCIALSLALVTNSQIVL SQSPAIL S ASPGEKVTMTCRAS S S VS YI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGG5G5GGFAGGFDGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS VAL GQ T VR I T C QGD S LRSYYASWYQQKPGQAPVLYMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGW DDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRYPFH HHDHHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARDLSGYGDYPDYWGQGTLVTVSS*

[0299] pDP155-His8-CD19 NT.l-2XGFLG-FC-TfR-H7 (SEQ ID NO: 113)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0300] MYRM0LLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFFGGGFAGGFFGDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGKGSSGGSGGSGGSSELTQDP VSVALGQTVRITCQGDSLRSYYASWYQQKPGQA PVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLT VLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLE WVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYW GQGTLVTVSS*

[0301] pDP156-His8-CD19 NT l-3XGFLG-FC-TfR-H7 (SEQ ID NO: 114)

[0302] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFFGGGFFGGGFLGGFDGDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQ KPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGG GTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAP GKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGD YPDYWGQGTLVTVSS*

[0303] pDP157-His8-CD19 NT.1-GFLG-FK-FC-TIR-H7 (SEQ ID NO: 115)

[0304] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFLGGFXGFDGDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPV LVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVL GGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWV AVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQ GTLVTVSS*BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0305] pDP158-His8-CD19 NT.1-GFLG-VA-FC-TIR-H7 (SEQ ID NO: 116)

[0306] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDA1SVV1RNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFZGGE4GPDGDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW5VLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGKGSSGGSGGSGGSSELTQDPAVSV LGQTVRITCQGDSLRSYYASWYQQKPGQAPVL VMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG GGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVA VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQG TLVTVSS*

[0307] pDP159-His8-CD19 NT.l-GFLG-VK-FC-TfR-H7 (SEQ ID NO: 117)

[0308] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGG ZGG GFDGDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK SLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPV LVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVL GGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWV AVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQ GTLVTVSS*

[0309] pDP160-His8-CD19 NT.1-GFLG-VR-FC-TIR-H7 (SEQ ID NO: 118)

[0310] MYRMQLLSCIALSLALVTNSGHHHHHHHH 7 GPEEP L VVKVEEGDT AALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFZGGPRGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVL VMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG GGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVABT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQG TLVTVSS*

[0311] pDP161-His8-CD19 NT.1-GFLG-GGFG-FC-TIR-H7 (SEQ ID NO: 119)

[0312] MYRMQLLSCIALSLALVTNSGHHHHHHHH TGPEEPL VVKVEEGDT AALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFTGGGGFGFDGDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ KSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAP VLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTV LGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEW VAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWG QGTLVTVSS*

[0313] pDP162-His8-CD19 NT.l-FK-FC-TfR-H7 (SEQ ID NO: 120)

[0314] MYRMQLLSCIALSLALVTNSGHHHHHHHH TGPEEPL VVKVEEGDT AALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGF GEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGSSELTQDPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVLVMYGR NERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGS GGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYD GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTV

[0315] pDP163-His8-CD19 NT.l-VA-FC-TfR-H7 (SEQ ID NO: 121)

[0316] MYRMQLLSCIALSLALVTNSGHHHHHHHH TGPEEPL VVKVEEGDT AALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGE4GIF> GDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGSSELTODPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVLVMYGRBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO NERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGS GGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYD GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTV SS*

[0317] pDP164-His8-CD19 NT.l-VK-FC-TfR-H7 (SEQ ID NO: 122)

[0318] MYRMQLLSCIALSLALVTNSGHHHHHHHH 7 GPEEP L VVKVEEGDT AALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGFXGIZ£> GDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGSSELTODPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVLVMYGR NERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGS GGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYD GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTV

[0319] pDP165-His8-CD19 NT.l-VR-FC-TfR-H7 (SEQ ID NO: 123)

[0320] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGERGF GDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGK EYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP GKGSSGGSGGSGGSSELTQDPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVLVMYGR NERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGS GGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYD GSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTV SS*

[0321] pDP166-His8-CD19 NT.l-GGFG-FC-TfR-H7 (SEQ ID NO: 124)

[0322] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFGGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNG KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMY RNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGG SGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISY DGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVT VSS*

[0323] pDP167-CD20_HC_Fc-N297G, S427C-TfR-H7 (SEQ ID NO: 125)

[0324] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDG5GSDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFCCSVMH EALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQ DSLRSYYASW YQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPV FGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVR QAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSG YGDYPDYWGQGTLVTVS S *

[0325] pDP168-CD20-scfv-GFLG-FC-N297G, S427C-TfR-H7 (SEQ ID NO: 126)

[0326] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGG G GGFAGGFDGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFCCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS VAL GQ T VR I T C QGD S LRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGW DDSLTGPVEGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRETES SYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARDLSGYGDYPDYWGQGTLVTVSS*

[0327] pDP169-cd20-scfv-GFLG-FK-FC-(N297G, S427C)-TfR-H7 (SEQ ID NO: 127)

[0328] MYRMQLLSCIALSLALVTNSOIVLSOSPAIL S ASPGEKVTMTCRAS S S VS YI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGG G GGFAGGFAGIDGDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO QGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRITCQ GDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYC AGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRF TFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0329] pDP170-cd20-scfv-GFLG-VR-FC-(N297G, S427C)-TIR-H7 (SEQ ID NO: 128)

[0330] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGSGSGGFZGGERGPDGDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS RDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRITCQ GDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYC AGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRF TFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0331] pDP171-His8-EGFR affi-FC-TfR-H7 (SEQ ID NO: 129)

[0332] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GLQVDNKFNKEMWAAW EEIRNLPNLNGWQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDG5G5EDGDK THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGS GGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSG VPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSG GGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWV AVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDY PDYWGQGTLVTVSS*

[0333] pDP172-His8-EGFR affi-GFLG-FC-TfR-H7 (SEQ ID NO: 130)

[0334] MYRMQLLSCIALSLALVTNSGHHHHHHHHrGLQVDNKFNKEMWAAW EEIRNLPNLNGWQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDGGFZGGEDG DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSG GSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERP SGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGG SGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLE WVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGY GDYPDYWGQGTLVTVSS*BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0335] pDP173-His8-EGFR affi-GFLG-FK-FC-TIR-H7 (SEQ ID NO: 131)

[0336] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGLQVDNKFNKEMWAAW EEIRNLPNLNGWQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDGGFLGGFFG EDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP1EK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGG SGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGG GGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGK GLEWVA VIS YDGSNKYYAD S VKGRFTISRDNSKNTL YLQMNSLRAEDT AVYYC ARDL S GYGDYPDYWGQGTLVTVSS*

[0337] pDP174-His8-EGFR affi-GFLG-VR-FC-T£R-H7 (SEQ ID NO: 132)

[0338] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGLQVDNKFNKEMWAAW EEIRNLPNLNGWQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDGGFLGGFFG KDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGG SGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGG GGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGK GLEWVA VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLS GYGDYPDYWGQGTLVTVSS*

[0339] pDP210-CD20-HC-(EVR)-FC (GRLR) -N297G-TIR-H7 (SEQ ID NO: 133)

[0340] MYRMOLLSCIALSLALVTNSOVQLOQPGAELVKPGASVKMSCKASGYTF TSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLT SED S AVYYC ARSTYYGGDWYFNVWGAGTT VT VS A ASTKGP S VFPL AP S SK ST SGGT AA LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKAEPKSCGG^GSGGFEFGF’DGDKTHTCPPCPAPELLRGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQD WLNGKEYKCKVSNKARPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGKGSSGGSGGSGGSSELTODPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVL VMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG GGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSY MHWVRQAPGKGLEWV VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQG TLVTVSS*

[0341] pDP213-CD20-HC-(EVR)-FC (GRLR) -N297G (SEQ ID NO: 134)

[0342] MYRMOLLSCIALSLALVTNSOVQLOQPGAELVKPGASVKMSCKASGYTF TSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLT SED S AVYYC ARSTYYGGDWYFNVWGAGTT VT VS A ASTKGP S VFPL AP S SK ST SGGT AABT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKAEPKSCGGAS’GSGGFIFGFDGDKTHTCPPCPAPELLRGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQD WLNGKEYKCKVSNKARPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGK*

[0343] pDP219-FC-TfR-H7 (SEQ ID NO: 135)

[0344] MYRMQLLSCIALSLALVTNSGHHHHHHHHrGGGGGFW? GEDG5G5GF£ G5GSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSG GSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGR NERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG GGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPG KGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDL SGYGD YPD YWGQGTL VTVS S *

[0345] pDP223-pFUSE-H7 scFV-knob-Fc-His (SEQ ID NO: 136)

[0346] MYRMQLLSCIALSLALVTNSSELTODPAVSVALGOTVRITCOGDSLRSYY ASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAG WDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSC AASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLY LQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSFIFEPKSCDKTHTCPPCP APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGOPREPO VYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGOPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQOGNVFSCSVMHEALHNHYTQKSLSLSPGKGGSHHHHHH*

[0347] pDP224-pFUSE-CD 19 NT.l-knob-Fc-H7 scFV-His (SEQ ID NO: 137)

[0348] MYRMQLLSCIALSLALVTNSPEEPLVVK VEEGDTAALWCLKGT SDGPTQ QLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAW QPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPE IWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSL LSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSFHLEVIARPVKAH SDLRTGGWKPIFEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAP IEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTP PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGG SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSK SGTSASL ISGLQPEDE NYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQ ESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGGSHHHHHH*

[0349] pDP225-2-Hole Fc_H7 scFV (SEQ ID NO: 138)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0350] MRMQLLLLIALSLALVTNS ZSGEPKSCDKTHTCPPCPAPELLGGPS VFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRIT CQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLA1SGLQPE DEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVV QPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0351] pDP226-Hole Fc_-avitag (SEQ ID NO: 139)

[0352] MRMQLLLLIALSLALVTNSZSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGI< GGGGSG'£A7) / E£ / 1(> A7£IP / / £ *

[0353] pDP227-Knob Fc_H7 scFV-His (SEQ ID NO: 140) MRMOLLLLIALSLALVTNSZSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT PEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG SSGGSGGSGGSSELTODPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVLVMYGRNER PSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGG GSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSN KYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSG GSHHHHHH*

[0354] PD-L1 TransTAC (pDP186) (SEQ ID NO: 141)

[0355] MYRMQLLSCIALSLALVTNSDIOMTOSPSSLSASVGDRVTITCRASODVST AVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQY LYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGF TFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNS LRAEDTAVYYCARRHWPGGFDYWGOGTLVTVSSGGSGSAGGGFZGGEEGEDGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSV LGQTVRITC QGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYY CAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASR FTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED TAVYYCARDLSGYGDYPDYWGQGTLVTVSS

[0356] CD20 TransTAC:

[0357] Heavy Chain (pDP210) (SEQ ID NO: 142)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0358] MYRMQLLSCIALSLALVTNSOVOLOQPGAELVKPGASVKMSCKASGYTF TSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLT SED S A VYYC ARSTYYGGDWYFNVWGAGTT VT VS A ASTKGP S VFPL AP S SK ST SGGT AA LGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKAEPKSCGGSGSGGEI? GEZ)GDKTHTCPPCPAPELLRGPSVFLFPPKPK DTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQD WLNGKEYKCKVSNKARPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGKGSSGGSGGSGGSSELTQDPAVSV LGQTVRITCQGDSLRSYYASWYQQKPGQ PVL VMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG GGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSC SRFTFSSY MHWVRQ PGKGLEWVA VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQG TLVTVSS

[0359] Light Chain (pDPl 18) (SEQ ID NO: 143)

[0360] MYRMQLLSCIALSLALVTNSQIVLSOSPAILSASPGEKVTMTCRASSSVSYI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWCVDN ALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR GEC

[0361] CD20 TransTAC -Ml 6 version (pDP127):

[0362] Heavy chain (SEQ ID NO: 144) (the light chain is as immediately above)

[0363] MYRMQLLSCIALSLALVTNSOIVLSOSPAIL S ASPGEKVTMTCRAS S S VS YI HWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWT SNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYT FTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSL TSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGSGSGGFZGGFDGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPRE EQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS VAL GQ T VR I T C QGD S LRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGW DDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRYPFH HHDHHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVY YCARDLSGYGDYPDYWGQGTLVTVSS*

[0364] EGFR TransTAC (pDP211) (SEQ ID NO: 145)

[0365] MYRMQLLSCIALSLALVTNSLQVDNKFNKEMWAAWEEIRNLPNLNG WQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDGGGGFF7? GEDGDKTHTCPPC PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLT VDKSRWQQGN VF SC S VMHEALHNH YTQK SL SL SPGKGSSGGSGGSGGSSELTQD PAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSK SGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO SQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSN KYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGT LVTVSS

[0366] CD 19 binding receptor TransTAC (pDP 160) (SEQ ID NO: 146)

[0367] MYRMQLLSC1ALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGALGGFFGFFGDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS LSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVL VMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG GGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVA VISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQG T LVTVSS

[0368] CD19 binding receptor TransTAC earlier version (pDP50) (SEQ ID NO: 147)

[0369] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWC LKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLC QPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPK LYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSW THVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSF HLEVIARPVKAHSDLRTGGWKGGFAGGEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL SPGRGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVLPSDGPSVACVKKASYLD CIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQ LRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCP GCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YK DCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFL KVPPRMDAKMYLGYEYVTALRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKLE CVSAETTEDCLAKLMNGEADAMSLDGGFVYLAGKCGLVPVLAENYNKSDNCEDTPEAGYFALAV VKKSASDL TWDNLKGKKS CHTAVGR TAGWNLPMGLL YNKLNHCRFDEFFSEGCAPGSKKDSSL C KL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD Y ELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKLLRQQQHLFGSNVTDCSGNFCLFR SETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP

[0370] Additional targeting compositions disclosed herein can include the following amino acid sequences, and molecules at least 60, 65, 70, 75, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99 percent identical to the amino acid sequences below.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0371] pAD2-His8-PDLl scFV-GFLG-VR-FC-TfR-N5-optimized (SEQ ID NO: 148)

[0372] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSW1HWVRQAPGKGLEWVAW1SPYGGSTYYADSVKGRFT1SADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFD YWGQGTL VTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPP VLD SDGSFFL YSKLT VDKSRWQQGNVF SC S VMHE ALHNHYTQK SL SLSPGK GSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVM YGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLT VLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFNNYAMHWVRQ APGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCA RDL SGYGD YPD YWGQGTL VTVS S

[0373] pAD3-His8-PDLl scFV-GFLG-VR-FC-TIR-G9-newer-optimized (SEQ ID NO: 149)

[0374] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFD YWGQGTL VTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPP VLD SDGSFFL YSKLT VDKSRWQQGNVF SC S VMHE ALHNHYTQK SL SLSPGK GSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIY GKNNRPSGIPDRFSGSGSGNTASLTITGAQAEDEADYYCAAWDDSLSGPVFGGGTKVTV LGGGGGSGGGGSGGGGSQVQLVESGGGLVEPGGSLRLSCAASGFTFSNYAINWVRQAP GKGLEWVANIHHDGNGKYYVDSVEGRFTISRDNAKNSLYLQMDSLRAEDTAIYYCARD GYGGYLDLWGQGTLVT VS S

[0375] pAD4-His8-PDLl scFV-GFLG-VR-FC-TIR-VHH-A-optimized (SEQ ID NO: 150)

[0376] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP AP1EKT1SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD1AVEWESNGQPEN NYKTTPP VLD SDGSFFL YSKLTVDKSRWQQGNVF SC S VMHE ALHNHYTQK SL SLSPGK GSSGGSGGSGGSEVQLVESGGGVVQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQG TQVTVSS

[0377] pAD5-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-B-optimized (SEQ ID NO: 151)

[0378] MYRMQLLSC1ALSLALVTNSGHHHHHHHHTGD1QMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK GSSGGSGGSGGSEVQLVESGGGVVQPGGSLRLSCAASGEIFSINFMRWYRQAPGKQRE WVAGFTRDGSTNYPDSAKGRFTISRDNAKNTVYLQIDSLKPEDTAVYYCYMLDTWGQ GTQVTVSS

[0379] pAD6-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-D-optimized (SEQ ID NO: 152)

[0380] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVE VEIN AKTKPREEQYNSTYRVVSVETVEHQDWLNGKEYKCKVSNK ALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK GSSGGSGGSGGSEVQLVESGGGEVQPGGSLKLSCVASGTDFSINFVRWYRQRPGKQRE WVAGFTANGDTNYPDSMKGRFTISRDNAKNTVYLQINSLKSEDTAVYYCYMLDNWGQ GTQVTVSS

[0381] pAD7-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-A5 -optimized (SEQ ID NO: 153)

[0382] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN N YKTTPP VLD SDGSFFL Y SKLT VDKSRWQQGN VF SC S VMHE ALHNH YTQK SL SLSPGK GSSGGSGGSGGSEVQLVESGGGVVQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCAMLDKWGQG TQVTVSS

[0383] pAD8-His8-PDLl-scFV-GFLG-VR-FC-TfR-VHH-A7-optimized.dna (SEQ ID NO: 154)

[0384] MYRMQLLSC1ALSLALVTNSGHHHHHHHHTGD1QMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLG GVRGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALP APIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK GSSGGSGGSGGSEVQLVESGGGVVQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREF VAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMADKWGQG TQVTVSS

[0385] pKR50-His8-PDLl scFV-GRLVGFG-FC-TfR-H7 (new linker) (SEQ ID NO: 155)

[0386] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGRLV GFGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSG GSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGG GGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGK GLEWVA VIS YDGSNKYYAD S VKGRFTISRDNSKNTL YLQMNSLRAEDT AVYYC ARDL S GYGDYPDYWGQGTLVTVSS

[0387] pKR51-His8-PDL1 scFV-RRLYAFL-FC-TfR-H7 (new linker) (SEQ ID NO: 156)

[0388] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDR VTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQ PEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPG GSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADT SKNT A YLQMNSLRAEDT AVYYC ARRHWPGGFDYWGQGTLVT VS SGGSGSAGGRRLY AFLGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAP1E KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYK TTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO GSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRN ERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGG GGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGK GLEWVA VIS YDGSNKYYAD S VKGRFTISRDNSKNTL YLQMNSLRAEDT AVYYC ARDL S GYGDYPDYWGQGTLVTVSS

[0389] vl.2 antiPDLl-linker-Fc(knob) (SEQ ID NO: 157)

[0390] TSDIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLI YSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKG GGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKG LEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHW PGGFDYWGQGTLVTVSSGGSGSAGGGFLGGVRGGSGEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY GSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR DELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVF SC S VMHEALHNHYTQKSL SLSPGKGS SHHHHHH

[0391] H7-H7-Fc(hole) (SEQ ID NO: 158)

[0392] TSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMY GRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTV LGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQA PGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR DLSGYGDYPDYWGQGTLVTVSSGGGGSSGGSGGGGSSELTQDPAVSVALGQTVRITCQ GDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDE ANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQP GRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISR DNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGGGGSGGG GSGGGGSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS HEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKV SNKALP APIEKTISK AKGQPREPQ VYTLPP SRDELTKNQ VSL SC A VKGF YP SDIAVEWES NGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGKGGGGSGLNDIFEAQKIEWHEG

[0393] vl.4 antiPDLl-linker-Fc(knob)-H7 (SEQ ID NO: 159)

[0394] TSDIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLI YSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKG GGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKG LEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHW PGGFDYWGQGTLVTVSSGGSGSAGGGFLGGVRGGSGEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY GSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR DELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVAL GQTVR1TCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASL AISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQ ESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS GGSHHHHHH

[0395] Fc(hole)-H7 (SEQ ID NO: 160)

[0396] TSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV DVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYT QKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQK PGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGP VFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSS YAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRA EDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS

[0397] In some embodiments, compositions provided herein can be one polypeptide chain. In some embodiments, compositions provided herein can be two polypeptide chains. In some embodiments of a two-polypeptide configuration, two binders are encoded in two polypeptide chains. In some embodiments, the two polypeptide chains can be linked or connected by a dimerizing domain. In some embodiments, the two polypeptide chains can be linked or connected by a knob-in-hole Fc.

[0398] Further provided herein are heterodimeric fusion proteins.

[0399] Some of the heterodimeric fusion proteins disclosed herein have the formula X-Y (Formula I)

[0400] X in X-Y includes R1-R2 (Formula II), wherein, R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor6 (CCR6), and R2 is an IgG Fc region.

[0401] R2 can have a means for dimerizing with R4. In some embodiments, the means for dimerizing in R2 can be a “knob” or “hole” of the knob-in hole technology.

[0402] Y in X-Y includes R3-R4 (Formula III), wherein R3 is a transferrin receptor binding (TRB) means for binding a transferrin receptor (TfR or TR), and R4 is an IgG Fc region.

[0403] R4 can have a means for dimerizing with R2. In some embodiments, the means for dimerizing can be a “knob” or “hole” of the knob-in hole technology. If R2 has a knob, then R4 has a hole. If R2 has a hole, then R4 has a knob.

[0404] In some embodiments, this provides for X and Y to form heterodimers.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0405] In embodiments, a linkage between R1 and R2 of Formula II is a glycine-rich linker, or a linkage between R3 and R4 of Formula III is a glycine-rich linker.

[0406] An example of this molecule is shown in Fig. 24A.

[0407] Some of the heterodimeric fusion proteins disclosed herein have the formula X-Y (Formula IV).

[0408] X in X-Y includes R1-R2 (Formula V), wherein, R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor6 (CCR6), and R2 is an IgG Fc region.

[0409] R2 can have a means for dimerizing with R4. In some embodiments, the means for dimerizing in R2 can be a “knob” or “hole” of the knob-in hole technology.

[0410] Y in X-Y includes R5-R4-R3 (Formula VI), wherein R5 is a second protein of interest (POI) binder means, R4 is an IgG Fc region, and R3 is a transferrin receptor binding (TRB) means.

[0411] R4 can have a means for dimerizing with R2. In some embodiments, the means for dimerizing can be a “knob” or “hole” of the knob-in hole technology. If R2 has a knob, then R4 has a hole. If R2 has a hole, then R4 has a knob.

[0412] This provides for X and Y to form heterodimers.

[0413] In embodiments, a linkage between R1 and R2 of Formula V is a glycine-rich linker, a linkage between R5 and R4 of Formula VI is a glycine-rich linker, and / or a linkage between R4 and R3 of Formula VI is a glycine-rich linker.

[0414] An example of this molecule is shown in Fig. 24C.

[0415] Some of the heterodimeric fusion proteins disclosed herein have the formula X-Y (Formula VII)

[0416] X in X-Y includes R1-R2 (Formula VIII), wherein, R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor6 (CCR6), and R2 is an IgG Fc region.

[0417] R2 can have a means for dimerizing with R4. In some embodiments, the means for dimerizing in R2 can be a “knob” or “hole” of the knob-in hole technology.

[0418] Y in X-Y includes R3-R6-R4 (Formula IX), wherein R3 is a first transferrin receptor binding (TRB) means, R6 is a second transferrin receptor binding (TRB) means, and R4 is an IgG Fc region.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0419] R4 can have a means for dimerizing with R2. In some embodiments, the means for dimerizing can be a “knob” or “hole” of the knob-in hole technology. If R2 has a knob, then R4 has a hole. If R4 has a hole, then R2 has a knob.

[0420] This provides for X and Y to form heterodimers.

[0421] In embodiments, a linkage between R1 and R2 of Formula VIII is a glycine-rich linker, a linkage between R3 and R4 of Formula IX is a glycine-rich linker, and / or a linkage between R6 and R4 of Formula IX is a glycine-rich linker.

[0422] An example of this molecule is shown in Fig. 24D.

[0423] In some embodiments, compositions provided herein are homodimer fusion proteins.

[0424] Some of the homodimeric fusion proteins disclosed herein have the formula X-X’ (Formula X)

[0425] X and X’ include R1-R2-R3 (Formula XI), wherein, R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor6 (CCR6), R2 is an IgG Fc region, and R3 is a is a transferrin receptor binding (TRB) means for binding transferrin receptor (TfR or TR).

[0426] X and X’ form homodimers.

[0427] In embodiments, a linkage between R1 and R2 of Formula XI is a glycine-rich linker, or a linkage between R2 and R3 of Formula XI is a glycine-rich linker.

[0428] An example of this molecule is shown in Fig. 24B.

[0429] In some embodiments of the above, the CCR6 POIB means has the amino acid sequence as shown in Table 1 below, or a combination thereof. In some embodiments, the heterodimeric fusion protein has a POIB means comprising the amino acid sequences shown in Table 1 below.

[0430] In some embodiments, the TRB means has a variable heavy chain (VH) amino acid sequence, VHHA, shown in Table 1. In some embodiments the TRB means has a variable heavy chain (VH) amino acid sequence, VHHA 12, VHHA 5, VHHA 7, as shown in Table 1, or combinations thereof. In some embodiments, the TRB means is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the sequences shown in Table 1. In some embodiments, the antibody fragment is a single chain variable fragment (scFv) comprising an amino acid sequence shown in Table 1.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0431] In some embodiments, the heterodimeric fusion protein includes a TRB means that is one or more transferrin ligands, including the amino acid sequence set forth in Table 1.

[0432] In some embodiments of the heterodimeric fusion protein, the transferrin receptor binding (TRB) means is non-competitive with endogenous transferrin or binds to a different epitope on transferrin receptor than does endogenous transferrin.

[0433] In some embodiments of the heterodimeric fusion protein, the TRB means comprises an antibody, an antibody fragment, or a nanobody.

[0434] In some embodiments of the heterodimeric fusion protein, the TRB means comprises a variable heavy chain (VH) or a single chain variable fragment (scFv).

[0435] In some embodiments, compositions disclosed herein can be homodimeric.

[0436] Any of the compositions described herein can have peptide linkers.

[0437] In some embodiments, the heterodimeric fusion protein (DJ1) includes from N terminus to C terminus, one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including one copy of VHHA, a linker, and an Fc (hole), respectively; wherein both components are bound by knob / hole interactions.

[0438] In some embodiments, the heterodimeric fusion protein (DJ2) includes from N terminus to C terminus, one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including one copy of an Fc, respectively; wherein both monomers are bound by knob / hole interactions.

[0439] In some embodiments, the heterodimeric fusion protein (LS13) includes from N terminus to C terminus one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including one copy of VHHA-12, a linker, and an Fc (hole), respectively; wherein both monomers are bound by knob / hole interactions.

[0440] In some embodiments, the heterodimeric fusion protein (LS15) includes from N terminus to C terminus one component including one polypeptide including a lightBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including one copy of VHHA-5, a linker, and an Fc (hole), respectively, wherein both components are bound by knob / hole interactions.

[0441] In some embodiments, the heterodimeric fusion protein (LS16) includes from N terminus to C terminus one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including one copy of VHHA-7, a linker, and an Fc (hole), respectively, wherein both components are bound by knob / hole interactions.

[0442] In some embodiments, the heterodimeric fusion protein (LS18) includes from N terminus to C terminus one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including one copy of transferrin ligand, a linker, and an Fc (hole), respectively, wherein both components are bound by knob / hole interactions.

[0443] In some embodiments, the heterodimeric fusion protein (LS19) includes from N terminus to C terminus one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including a copy of G9, a linker, and an Fc (hole), respectively, wherein both components are bound by knob / hole interactions.

[0444] In some embodiments, the heterodimeric fusion protein (LS20) includes from N terminus to C terminus one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-CCR6 Fab, a linker, and an Fc-knob; and another component including a copy of H7, a linker, and an Fc (hole), respectively, wherein both components are bound by knob / hole interactions.

[0445] In some embodiments, the heterodimeric fusion protein (LS21 ) includes from N terminus to C terminus one component including one polypeptide including a light chain of an anti-CCR6 Fab linked to a polypeptide including a heavy chain of an anti-BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO CCR6 Fab, a linker, and an Fc-knob; and another component including a copy of N5, a linker, and an Fc (hole), respectively, wherein both components are bound by knob / hole interactions.

[0446] In some embodiments, a fusion protein provided herein is LS26, LS27, LS28, LS29, LS32, LS33, LS34, LS35 or LS9.

[0447] In some embodiments, the heterodimeric fusion proteins described herein incorporate knob-into-hole technology to provide efficient association of separate polypeptide chains. This technology is well known in the field of antibody engineering and can be used promote formation of heterodimeric antibodies, rather than homodimeric antibodies.

[0448] In some embodiments, the compositions provided herein include a transferrin receptor binding means or a transferrin receptor binder. The TRB means or transferrin receptor binder binds to transferrin receptor on a cell. In some embodiments, the TRB means or transferrin receptor binder can include any other molecule that can bind to the transferrin receptor. In some embodiments, the TRB means or transferrin receptor binder can be a part of transferrin. In some embodiments, the TRB means or transferrin receptor binder is Tf or a fragment thereof.

[0449] In some embodiments, a TRB means or transferrin receptor binder can be competitive with transferrin for binding to a TfR (e.g., H7, N5 or G9). In some embodiments, a TRB means or transferrin receptor binder can be non-competitive for binding to a TfR (e.g., VHHA or variants thereof). The TRB means or transferrin receptor binder, as part of any of the compositions provided herein, can bind to transferrin (Tf) on the surface of a cell and be internalized into the cell.

[0450] In embodiments, the TRB means or transferrin receptor binder is an antibody or fragment thereof (e.g., an antibody, antibody fragment or other molecule that can bind a transferrin receptor). In some embodiments, the TRB means or transferrin receptor binder can be a scFv, Fab, single-domain antibody, nanobody, monobody, DARPin or affibody.

[0451] In some embodiments, the TRB means or transferrin receptor binder is an scFV that can bind to the transferrin receptor. In some embodiments, the scFV includesBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO any of the amino acid sequences set forth in Table 1. In some embodiments, the scFV is G9. In some embodiments, the scFV is H7. In some embodiments, the scFV is N5.

[0452] In some embodiments, an antibody or antibody fragment that binds a transferrin receptor can be an anti-TfR1 antagonistic scFv antibody identified through phage display. This antibody can be called “H7” (Goenaga, Anne-Laure, et al." Identification and characterization of tumor antigens by using antibody phage display and intrabody strategies." Molecular immunology 44.15, 2007: 3777-3788; Tillotson, Benjamin J., et al. " Engineering an anti-transferrin receptor ScFv for pH-sensitive binding leads to increased intracellular accumulation." PLoS One 10.12, 2015: e0145820).

[0453] In some embodiments, the TRB means or transferrin receptor binder can be a VHH that binds to a transferrin receptor. In some embodiments, the TRB means or transferrin receptor binder includes one or more VHHs that bind to a transferrin receptor. In some embodiments, the TRB means or transferrin receptor binder includes one VHH that binds to a transferrin receptor. In some embodiments, the TRB means or transferrin receptor binder includes two VHH that bind to the transferrin receptor. In some embodiments, the two VHH can be positioned “in tandem” (Fig. 24D). In some embodiments, a heterodimer or homodimer molecule as disclosed herein can have multiple TRBs. In some embodiments, for example, a heterodimer can have two TRBs in tandem (e.g., Fig. 24D). In some embodiments, for example, a homodimer can have a TRB in both of the fusion proteins that comprise the homodimer (e.g., Fig. 24B)

[0454] In some embodiments, the VHH includes one or more VHHs including any of the amino acid sequences set forth in herein, or any combination thereof.

[0455] In some embodiments, the TRB means or transferrin receptor binder can be a ligand that a transferrin receptor can bind. In some embodiments, the ligand can be transferrin or a fragment of transferrin. In some embodiments, the internalizing receptor can be a transferrin receptor (TfR). In some embodiments, the transferrin receptor can be transferrin receptor 1 or transferrin receptor 2.Table 1pLS15 Anti-CCR6 B368-G29A HC-Knob Fc-His (SEQ ID NO: 161)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGSGGSGTDKTHTCPPCPAPEL / _GGPS\ / FLFPP / < P / < DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVS VL TVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKN QVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSHHHHHH [SEQ ID NO: 161] [CCR6 Binder: SEQ ID NO: 216; Fc Region: SEQ ID NO: 217]pLS16-Anti-CCR6_B3G8-G29A_LC (SEQ ID NO: 162) MYRMQLLSCIALSLALVTNSDWMTQSPLSLPVTLGQPASISCRSSQSIVHSNANTY LEWYQQRPGQSPRLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYY CFQGTYLPLTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC [SEQ ID NO: 162][CCR6 Binder: SEQ ID NO: 218]plKA5-VHHA-Hole (SEQ ID NO: 163)M RM Q LLLL I ALS LALVTNSTS EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRW YRQAPGKQREFVAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAV YYCYMLDKWGQGTQVTVSSGTGGDKTHTCPPCPAPEU_GGPS\ / F / _FPP / < P / < D7L / W / SRTPEVTC VVVD VSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYR VVS VLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLS CA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFL VSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 163][TfR1 Binder: SEQ ID NO: 219; Fc Region: SEQ ID NO: 220]pLS21-Tf-Hole (SEQ ID NO: 164) MRMQLLLLIALSLALVTNSTSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPS VACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPWAEFYGSKEDPQT FYYAVAWKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKA VANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAF VKHSTIFENLANKADRDQYELLCLDNTRKPVDEYKDCHLAQVPSHTWARSMGGKE DLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLG YEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAE TTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAWKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCABT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO PGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQ NTGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAWTRKDKEA CVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLG EEYVKAVGNLRKCSTSSLLEACTFRRPGTGGDKTHTCPPCPAPE / _LGGPSI / F / -FPP KPKD TLMISRTPEVTC VVVD VSHEDPEVKFNWYVDG VE VHNAKTKPREEQ YNS TYR VVS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKNQ VSLSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFL VSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 164][TfR1 Binder: SEQ ID NO: 221; Fc Region: SEQ ID NO: 222]pLS23-VHHA12-Hole (SEQ ID NO: 165)M RM QLLLLIALSLALVTNSTSEVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRW YRQAPGKQREFVAGITATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVY YCYMLDKWGQGTQVTVSSGTGGDKTHTCPPCPAPELLGGPSV'FLFPPKPKDTL / W / S R TPE VTC VVVD VSHEDPE VKFNWYVDG VEVHNAKTKPREEQ YNSTYR VVS VLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQ VSLSC A VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFL VSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 165][TfR1 Binder: SEQ ID NO: 223; Fc Region: SEQ ID NO: 224]pLS25-VHHA5-Hole (SEQ ID NO: 166)M RM QLLLLIALSLALVTNSTSEVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRW YRQAPGKQREFVAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAV YYCAMLDKWGQGTQVTVSSGTGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL / W / SRTPEVTC VVVD VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVS VLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLS CA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFL VSKLTVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 166][TfR1 Binder: SEQ ID NO: 225; Fc Region: SEQ ID NO: 226]pLS26-VHHA7-Hole (SEQ ID NO: 167)M RM QLLLLIALSLALVTNSTSEVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRW YRQAPGKQREFVAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAV YYCYMADKXNGQGTQNTVSSGTGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQ VSL SCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFL VSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 167]BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO [TfR1 Binder: SEQ ID NO: 227; Fc Region: SEQ ID NO: 228]plKA5.1-G9-Hole (SEQ ID NO: 168) MRMQLLLLIALSLALVTNSTSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQ KPGQAPVLVIYGKNNRPSGIPDRFSGSGSGNTASLTITGAQAEDEADYYCAAWDDS LSGPVFGGGTKVTVLGGGGGSGGGGSGGGGSQVQLVESGGGLVEPGGSLRLSCA ASGFTFSNYAINWVRQAPGKGLEWVANIHHDGNGKYYVDSVEGRFTISRDNAKNSL YLQMDSLRAEDTAIYYCARDGYGGYLDLWGQGTLVTVSSGTGGDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSD GSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 168][TfR1 Binder: SEQ ID NO: 229; Fc Region: SEQ ID NO: 230]plKA5.2-H7-Hole (SEQ ID NO: 169) MRMQLLLLIALSLALVTNSTSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQ KPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDD SLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLS CAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSK NTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGTGGDKTHTCP PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLSCA VKGFYPSDIA VEWESNGQPENNYKTTPP VLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK[SEQ ID NO: 169][TfR1 Binder: SEQ ID NO: 231; Fc Region: SEQ ID NO: 232]plKA5.3-N5-Hole (SEQ ID NO: 170) MRMQLLLLIALSLALVTNSTSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQ KPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDD SLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLS CAASRFTFNNYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSK NTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGTGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLSCA VKGFYPSDIA VEWESNGQPENNYKTTPP VLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK [SEQ ID NO: 170][TfR1 Binder: SEQ ID NO: 233; Fc Region: SEQ ID NO: 234]pLS30-CCR6_HC-Fc-TfR1 VHHA12 (SEQ ID NO: 171) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAFELLGGFSyFLFFFKFKDTL MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR VVS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKNQ VS LTCLVKGLYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSENQLVESGGGVVQPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGITATGNTNYADSMKGRFTISRD NTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSS [SEQ ID NO: 171] [CCR6 Binder: SEQ ID NO: 235; Fc Region: SEQ ID NO: 236; TfR1 Binder: SEQ ID NO: 237] pLS31-CCR6_HC-Fc-TfR1 VHHA5 (SEQ ID NO: 172) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCFAFELLGGFSyFLFFFKFKDTL MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR VVS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKNQ VS LTCLVKGLYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSE\ / QL\ / ESGGG\ / \ / QPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISR DNTKNAVYLQIDSLKPEDTAVYYCAMLDKWGQGTQVTVSS [SEQ ID NO: 172] [CCR6 Binder: SEQ ID NO: 238; Fc Region: SEQ ID NO: 239; TfR1 Binder: SEQ ID NO: 240] pLS32-CCR6_HC-Fc-TfR1 VHHA (SEQ ID NO: 173) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKD7L MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR V VS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCL VKGL YPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFL YSKL TVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSEVQLVESGGGWQPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISR DNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSS [SEQ ID NO: 173] [CCR6 Binder: SEQ ID NO: 241; Fc Region: SEQ ID NO: 242; TfR1 Binder: SEQ ID NO: 243]pLS33-CCR6_HC-Hole Fc-VHHA12 (SEQ ID NO: 174) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKD7L MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR V VS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSEVQLX / ESGGGWQPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGITATGNTNYADSMKGRFTISRD NTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSS [SEQ ID NO: 174] [CCR6 Binder: SEQ ID NO: 244; Fc Region: SEQ ID NO: 245; TfR1 Binder: SEQ ID NO: 246]pLS34-CCR6_HC- Hole Fc-VHHA5 (SEQ ID NO: 175) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKD7L MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR V VS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSE\ / QL\ / ESGGGWQPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISR DNTKNAVYLQIDSLKPEDTAVYYCAMLDKWGQGTQVTVSS[SEQ ID NO: 175] [CCR6 Binder: SEQ ID NO: 247; Fc Region: SEQ ID NO: 248; TfR1 Binder: SEQ ID NO: 249]pLS35-CCR6_HC-Hole Fc-VHHA (SEQ ID NO: 176) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR V VS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKNQ VS LSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSENQLVESGGGVVQPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISR DNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSfSEQ ID NO: 176] [CCR6 Binder: SEQ ID NO: 250; Fc Region: SEQ ID NO: 251; TfR1 Binder: SEQ ID NO: 252]pLS36-CCR6_HC-Hole FC-VHHA7 (SEQ ID NO: 177) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKD7L MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR VVS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKNQ VS LSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSE\ / QL\ / ESGGG\ / \ / QPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISR DNTKNAVYLQIDSLKPEDTAVYYCYMADKWGQGTQVTVSS [SEQ ID NO: 177] [CCR6 Binder: SEQ ID NO: 253; Fc Region: SEQ ID NO: 254; TfR1 Binder: SEQ ID NO: 255]pLS37-CCR6_HC-Fc-TfR1 VHHA7 (SEQ ID NO: 178) MRMQLLLLIALSLALVTNSTSEVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMY WVRQAPGKGLEWVSYITTGGRTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDT AVYYCTSPLRGAWFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCGGVDGDKTHTCPPCPAPELLGGPSVFLFPPKPKD7L MISRTPE VTC VVVD VSHEDPE VKFNWYVDG VE VHNAKTKPREEQ YNS TYR VVS VL T VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGLYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSE\ / QL\ / ESGGGWQPG GSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISR DNTKNAVYLQIDSLKPEDTAVYYCYMADKWGQGTQVTVSS [SEQ ID NO: 178] [CCR6 Binder: SEQ ID NO: 256; Fc Region: SEQ ID NO: 257; TfR1 Binder: SEQ ID NO: 258]BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO pJD47-VHHA-VHHA-Hole Fc (SEQ ID NO: 179)M RM QLLLLIALSLALVTNSTSEVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRW YRQAPGKQREFVAGFTATGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAV YYCYMLDKWGQGTQVTVSSGGGGSSGGSGGGGSEVQLVESGGGVVQPGGSLKL SCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGNTNYADSMKGRFTISRDNTKN AVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSSGTGGDKTHTCPPCPAPELLG GPS VFLFPPKPKDTLM / SRTPEVTC VVVD VSHEDPEVKFNWYVDG VEVHNAKTKPR EEQ YNS TYRVVS VL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VY TLPPSRDELTKNQ VSLSCA VKGFYPSDIA VEWESNGQPENNYKTTPPVLDSDGSFF LVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK[SEQ ID NO: 179] [TfR1 Binder: SEQ ID NO: 259; Fc Region: SEQ ID NO: 260]Anti-CCR6_B368-G29A_HC (SEQ ID NO: 180) EVQLVESGGGLVQPGGSLRLSCAASGFSFSDYYMYWVRQAPGKGLEWVSYITTGG RTYYPDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTSPLRGAWFAYWGQG TLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCAnti-CCR6_B3G8-G29A_LC (SEQ ID NO: 181) DWMTQSPLSLPVTLGQPASISCRSSQSIVHSNANTYLEWYQQRPGQSPRLLIYKVS NRFSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGTYLPLTFGQGTKLEIKRT VAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC VHHA (SEQ ID NO: 1) EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGN TNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSSTf (SEQ ID NO: 261) VPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEA DAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAWKKDSGFQMNQLR GKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQ LCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHSTIFENLANKADRDQYEL LCLDNTRKPVDEYKDCHLAQVPSHTWARSMGGKEDLIWELLNQAQEHFGKDKSKE FQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTD ECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDG GFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAWKKSASDLTWDNLKGKKSC HTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLC EPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYEL LCLDGTRKPVEEYANCHLARAPNHAWTRKDKEACVHKILRQQQHLFGSNVTDCSG NFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRPBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WOVHHA12 (SEQ ID NO:4) EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGITATGN TNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVSSVHHA5 (SEQ ID NO: 2) EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGN TNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCAMLDKWGQGTQVTVSSVHHA7 (SEQ ID NO: 3) EVQLVESGGGWQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTATGN TNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMADKWGQGTQVTVSSG9 (SEQ ID NO: 262) SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVIYGKNNRPSGI PDRFSGSGSGNTASLTITGAQAEDEADYYCAAWDDSLSGPVFGGGTKVTVLGGGG GSGGGGSGGGGSQVQLVESGGGLVEPGGSLRLSCAASGFTFSNYAINWVRQAPG KGLEWVANIHHDGNGKYYVDSVEGRFTISRDNAKNSLYLQMDSLRAEDTAIYYCAR DGYGGYLDLWGQGTLVTVSSH7 (SEQ ID NO: 263) SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSG VPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGG GGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQA PGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDLSGYGDYPDYWGQGTLVTVSSN5 (SEQ ID NO: 264) SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSG VPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGG GGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFNNYAMHWVRQA PGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDLSGYGDYPDYWGQGTLVTVSSLinker (SEQ ID NO: 265)GGSGGSGTDKTHTCLinker (SEQ ID NO: 266)GTGGDKTHTCPPCpJD27-Hole Fc-avitag (SEQ ID NO: 267)BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO MRMQLLLLIALSLALVTNSTSGDKTHTCPPCPAPELLGGPSV^LFPPKP / CDTL / W / SRT PEVTCVVVD VSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYR VVS VLTVLHQ DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCA VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGKGGGGSGLND\FEAQK\E\N^EGpJD33-Knob Fc-His (SEQ ID NO: 268) MRMQLLLLIALSLALVTNSTSDKTHTCPPCPAPELLGGPSV'FLFPPKP / (D7L / W / SR7P EVTC VVVD VSHEDPE VKFNWYVDG VEVHNAKTKPREEQ YGS TYR VVS VL TVLHQD WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDEL TKNQ VSLWCL V KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVMHEALHNHYTQKSLSLSPGKGSSHHHHHHCCR6 binder is in Bold. Fc Region is italicized. TfR1 binder is underlined.

[0456] In some embodiments, binding affinities of a TRB means or transferrin receptor binder for TfR, can be altered or adjusted to obtain a composition as provided herein that can bind and internalize most or all of the CCR6 on a cell surface, while, at the same time, minimizing the loss of TfR on the cell surface. In some embodiments, a panel of TRB means or transferrin receptor binders having different affinities for binding TfR may be assembled. Combinations of the POIB binding means or protein of interest binders with different TRB binding means or transferrin receptor binders will result in a library of compositions. Library clones can be tested for both internalization of TfR and amounts of TfR on a cell surface. In this way, compositions provided herein can be obtained that both efficiently reduce the amount of CCR6 or a cell surface, while minimizing loss of TfR on the cell surface. In some embodiments, particular embodiments of compositions as provided herein may be subjected to mutation and / or selection using various means (e.g., phage display methods) to identify and isolate variant compositions having these characteristics. There can be other methods used to obtain embodiments of compositions as provided here having the desired functional properties.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO Anti-CCR6 and anti-TfR antibodies

[0457] Provided herein are composition molecules that, in some embodiments, are fusion proteins (e.g., antibodies or fragments thereof, such as scFvs or nanobodies) that can recognize and bind simultaneously CCR6 and transferrin receptor on target cells.

[0458] Herein, POIB means or POIB that bind CCR6 are used in the compositions provided herein. In some embodiments, the POIB means or POIB that bind CCR6 are antibodies that bind to CCR6. In some embodiments, the POIB means or POIB that bind CCR6 can be part of a ligand that binds to CCR6. In some embodiments, a ligand can be a part of the CCL20 ligand that binds to CCR6.

[0459] Antibodies that bind to CCR6 are known in the art. Such antibodies are described in published PCT patent applications WO2013184218A1, WO2013005649A1 and WO2016059253A1. Anti-CCR6 antibodies include 53103 (R& D Systems, Minneapolis, MN, USA), 11A9 (BD Biosciences, Franklin Lakes, NJ, USA), 4C6 (ATGen, Montevideo, Uruguay), R6H1 (eBioscience, San Diego, CA, USA), G034E3 (BioLegend, San Diego, CA, USA) and MM0066-3L1 (abeam, Cambridge, UK).

[0460] Anti-CCR6 recombinant monoclonal antibodies, or fragments thereof, are also disclosed herein. In some embodiments, the anti-CCR6 recombinant monoclonal antibodies, or fragments thereof, can be part of the CCR6 targeting compositions disclosed herein. In embodiments, the anti-CCR6 recombinant monoclonal antibodies, or fragments thereof, is a protein of interest (POI) binder (POIB) means or POIB for binding an extracellular region of C-C chemokine receptors (CCR6), or R1, included in any of the compositions provided herein. In some embodiments, the POIB means or POIB that bind CCR6 can be a Fab’ fragment that binds to an extracellular region of C-C chemokine receptor 6 (CCR6).

[0461] Described herein are also antibodies or fragments thereof that can recognize and bind to a transferrin receptor (TRB means or TRB). In some embodiments, the antibodies or fragments thereof that recognize and bind to a transferrin receptor can be part of the compositions provided herein. In some embodiments, the anti-CCR6 recombinant monoclonal antibodies, or fragments thereof, have a transferrin receptor binding means or TRB included in any of the compositions provided herein.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO

[0462] In some embodiments, the heavy chain of an anti-CCR6 antibody can be (SEQ ID NO: 182):EVQLVESGGGL QPGGSLRLSCAASGESFSDYYMY VRQAPG GLE VSYITTGGRTYYPD SVEGRFTI3RGKSKNTLYLQMNSLRAEDTAVYYCTSPLRGAWFAYWGQGTLVTVS3ASTKG PSV. EPLAPSSKS SGG A GCLVKDYFPEPV SWMSG TS V|HTE. PAVLQSS LYSLS SVVTVPSSSLGTQTEICNVNHRPSETKVDKKVEPKSC

[0463] In some embodiments, the light chain of an anti-CCR6 antibody can be (SEQ ID NO: 183):DFVMTGSPLSLPVTLGQPABISCRSSQSTVESRAETYLE Y QRRGQSPRLLIYKESNRES GVPDRFSGSGSGTDFTLKISRVEAEDVGVY¥CFQGT¥LPLTFGQGTKLEIKRTVAAPSVFI FPPSDEQLKSGTASWCLLNNE¥PREAKVQ KREEALQSGESQESV¥EODSKD3T¥SLS3T LTL3KARYEKHK¥YACEVTH GLSSPV'TK3EA. RGEE

[0464] In some embodiments, the epitope that an anti-CCR6 antibody binds to in CCR6 is FSDVFDSSE (SEQ ID NO: 184).

[0465] “Recombinant” as it pertains to polypeptides (such as antibodies) or polynucleotides refers to a form of the polypeptide or polynucleotide that does not exist naturally, a non-limiting example of which can be created by combining polynucleotides or polypeptides that would not normally occur together. “Polypeptide” as used herein can encompass a singular “polypeptide” as well as plural “polypeptides,” and refers to a molecule composed of components (amino acids) linearly linked by amide bonds (also known as peptide bonds). The term “polypeptide” refers to any chain or chains of two or more amino acids and does not refer to a specific length of the product. Thus, peptides, dipeptides, tripeptides, oligopeptides, “protein,” “amino acid chain,” or any other term used to refer to a chain or chains of two or more amino acids, can refer to “polypeptide” herein, and the term “polypeptide” can be used instead of, or interchangeably with any of these terms. “Polypeptide” can also refer to the products of post-expression modifications of the polypeptide, including without limitation glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting / blocking groups, proteolytic cleavage, or modification by non-naturally occurring amino acids. A polypeptide can be derived from a natural biological source or produced by recombinant technology but is not necessarily translated from a designated nucleic acid sequence. It may be generated in any manner, including by chemical synthesis. As to amino acid sequences, one of skill in the art will readily recognize that individual substitutions,BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds, deletes, or substitutes a single amino acid or a small percentage of amino acids in the encoded sequence is collectively referred to herein as a "conservatively modified variant". In some embodiments the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants of the antibodies disclosed herein can exhibit increased crossreactivity in comparison to an unmodified antibody.

[0466] For example, a “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), betabranched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a nonessential amino acid residue in an immunoglobulin polypeptide is replaced with another amino acid residue from the same side chain family. In another embodiment, a string of amino acids can be replaced with a structurally similar string that differs in order and / or composition of side chain family members.

[0467] Some embodiments also feature antibodies that have a specified percentage identity or similarity to the amino acid or nucleotide sequences of the antibodies described herein. For example, “homology” or “identity” or “similarity” refers to sequence similarity between two peptides or between two nucleic acid molecules.Homology can be determined by comparing a position in each sequence, which may be aligned for purposes of comparison. When a position in the compared sequence is occupied by the same base or amino acid, then the molecules are homologous at that position. A degree of homology between sequences is a function of the number of matching or homologous positions shared by the sequences. For example, the antibodies can have 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%,BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO 96%, 97%, 98%, 99%, or higher amino acid sequence identity when compared to a specified region or the full length of any one of the antibodies described herein. For example, the antibodies can have 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher nucleic acid identity when compared to a specified region or the full length of any one of the antibodies described herein.Sequence identity or similarity to the nucleic acids and proteins of the present invention can be determined by sequence comparison and / or alignment by methods known in the art, for example, using software programs known in the art, such as those described in Ausubel et al. eds. (2007) Current Protocols in Molecular Biology. For example, sequence comparison algorithms (i.e., BLAST or BLAST 2.0), manual alignment or visual inspection can be utilized to determine percent sequence identity or similarity for the nucleic acids and proteins of the present invention.

[0468] The term “isolated” as used herein with respect to cells, nucleic acids, such as DNA or RNA, refers to molecules separated from other DNAs or RNAs, respectively, that are present in the natural source of the macromolecule. The term “isolated” can also refer to a nucleic acid or peptide that is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. For example, an “isolated nucleic acid” can include nucleic acid fragments which are not naturally occurring as fragments and would not be found in the natural state. “Isolated” can also refer to cells or polypeptides which are isolated from other cellular proteins or tissues. Isolated polypeptides can include both purified and recombinant polypeptides.

[0469] As used herein, an “antibody” or “antigen-binding polypeptide” can refer to a polypeptide or a polypeptide complex that specifically recognizes and binds to an antigen. An antibody can be a whole antibody and any antigen binding fragment or a single chain thereof. For example, “antibody” can include any protein or peptide containing molecule that comprises at least a portion of an immunoglobulin molecule having biological activity of binding to the antigen. Non-limiting examples a complementarity determining region (CDR) of a heavy or light chain or a ligand binding portion thereof, a heavy chain or light chain variable region, a heavy chain or light chain constant region, a framework (FR) region, or any portion thereof, or at least one portionBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO of a binding protein. As used herein, the term "antibody" can refer to an immunoglobulin molecule and immunologically active portions of an immunoglobulin (Ig) molecule, i.e., a molecule that contains an antigen binding site that specifically binds (immunoreacts with) an antigen. " Specifically binds" or "immunoreacts with" can refer to the antibody reacting with one or more antigenic determinants of the desired antigen and does not react with other polypeptides.

[0470] The terms “antibody fragment” or “antigen-binding fragment”, as used herein, is a portion of an antibody such as F(ab')2, F(ab)2, Fab', Fab, Fv, scFv and the like.Regardless of structure, an antibody fragment binds with the same antigen that is recognized by the intact antibody. The term “antibody fragment” can include aptamers (such as spiegelmers), minibodies, and diabodies. The term “antibody fragment” can also include any synthetic or genetically engineered protein that acts like an antibody by binding to a specific antigen to form a complex. Antibodies, antigen-binding polypeptides, variants, or derivatives described herein include, but are not limited to, polyclonal, monoclonal, multispecific, human, humanized or chimeric antibodies, single chain antibodies, epitope-binding fragments, e.g., Fab, Fab' and F(ab')2, Fd, Fvs, singlechain Fvs (scFv), single-chain antibodies, dAb (domain antibody), minibodies, disulfide-linked Fvs (sdFv), fragments comprising either a VL or VH domain, fragments produced by a Fab expression library, and anti-idiotypic (anti-ld) antibodies.

[0471] A “single-chain variable fragment” or “scFv” refers to a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins. A single chain Fv ("scFv") polypeptide molecule is a covalently linked VH: VL heterodimer, which can be expressed from a gene fusion including VH- and VL-encoding genes linked by a peptide-encoding linker. (See Huston et al. (1988) Proc Nat Acad Sci USA 85(16):5879-5883). In some aspects, the regions are connected with a short linker peptide of ten to about 25 amino acids. The linker can be rich in glycine for flexibility, as well as serine or threonine for solubility, and can either connect the N-terminus of the Vnwith the C-terminus of the VL, or vice versa. This protein retains the specificity of the original immunoglobulin, despite removal of the constant regions and the introduction of the linker. A number of methods have been described to discern chemical structures for converting the naturally aggregated, but chemically separated, light and heavyBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO polypeptide chains from an antibody V region into an scFv molecule, which will fold into a three-dimensional structure substantially similar to the structure of an antigen-binding site. See, e.g., U. S. Patent No. 5,091,5 13; No. 5,892,019; No. 5,132,405; and No. 4,946,778, each of which are incorporated by reference in their entireties.

[0472] Light chains are classified as either kappa or lambda (K, A). Each heavy chain class can be bound with either a kappa or lambda light chain. For example, the light and heavy chains are covalently bonded to each other, and the “tail” portions of the two heavy chains are bonded to each other by covalent disulfide linkages or non-covalent linkages when the immunoglobulins are generated either by hybridomas, B cells, or genetically engineered host cells. In the heavy chain, the amino acid sequences run from an N-terminus at the forked ends of the Y configuration to the C-terminus at the bottom of each chain.

[0473] Both the light and heavy chains are divided into regions of structural and functional homology. The terms “constant” and “variable” are used functionally. The variable domains of both the light (VL) and heavy (VH) chain portions determine antigen recognition and specificity. Conversely, the constant domains of the light chain (CL) and the heavy chain (CH1, CH2 or CH3) confer important biological properties such as secretion, transplacental mobility, Fc receptor binding, complement binding, and the like. The term "antigen-binding site," or "binding portion" can refer to the part of the immunoglobulin molecule that participates in antigen binding. The antigen binding site is formed by amino acid residues of the N-terminal variable (" V") regions of the heavy (" H") and light (" L") chains. Three highly divergent stretches within the V regions of the heavy and light chains, referred to as "hypervariable regions," are interposed between more conserved flanking stretches known as "framework regions," or " FRs". Thus, the term " FR" can refer to amino acid sequences which are naturally found between, and adjacent to, hypervariable regions in immunoglobulins. In an antibody molecule, the three hypervariable regions of a light chain and the three hypervariable regions of a heavy chain are disposed relative to each other in three-dimensional space to form an antigen-binding surface. The antigen-binding surface is complementary to the three-dimensional surface of a bound antigen, and the three hypervariable regions of each of- Ill -BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO the heavy and light chains are referred to as "complementarity-determining regions," or " CDRs."

[0474] The six CDRs present in each antigen-binding domain are short, noncontiguous sequences of amino acids that are specifically positioned to form the antigen-binding domain as the antibody assumes its three-dimensional configuration in an aqueous environment. The remainder of the amino acids in the antigen-binding domains, the FR regions, show less inter-molecular variability. The framework regions largely adopt a [3-sheet conformation and the CDRs form loops which connect, and in some cases form part of, the p-sheet structure. The framework regions act to form a scaffold that provides for positioning the CDRs in correct orientation by inter-chain, non-covalent interactions. The antigen-binding domain formed by the positioned CDRs provides a surface complementary to the epitope on the immunoreactive antigen, which promotes the non-covalent binding of the antibody to its cognate epitope. The amino acids comprising the CDRs and the framework regions, respectively, can be readily identified for a heavy or light chain variable region by one of ordinary skill in the art, since they have been previously defined (See, “Sequences of Proteins of Immunological Interest,” Kabat, E., et al., U. S. Department of Health and Human Services, (1983); and Chothia and Lesk, J. Mol. Biol., 196:901-917 (1987)).

[0475] Where there are two or more definitions of a term which is used and / or accepted within the art, the definition of the term as used herein is intended to include all such meanings unless explicitly stated to the contrary. A specific example is the use of the term “complementarity determining region” (“CDR”) to describe the noncontiguous antigen combining sites found within the variable region of both heavy and light chain polypeptides. This region has been described by Kabat et al., U. S. Dept, of Health and Human Services, “Sequences of Proteins of Immunological Interest” (1983) and by Chothia et al., J. Mol. Biol. 196:901-917 (1987), which are incorporated herein by reference in their entireties. The CDR definitions according to Kabat and Chothia include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or variants thereof is intended to be within the scope of the term as defined and used herein. The appropriate amino acid residues which encompass the CDRs as defined byBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO each of the above cited references are set forth in the table below as a comparison. The exact residue numbers which encompass a particular CDR will vary depending on the sequence and size of the CDR. Those skilled in the art can routinely determine which residues comprise a particular CDR given the variable region amino acid sequence of the antibody.CDR Kabat ChothiaNumbering NumberingVH CDR1 31-35 26-32VH CDR2 50-65 52-58VH CDR3 95-102 95-102VL CDR1 24-34 26-32VL CDR2 50-56 50-52VL CDR3 89-97 91-96

[0476] Kabat et al. defined a numbering system for variable domain sequences that is applicable to any antibody. The skilled artisan can unambiguously assign this system of “Kabat numbering” to any variable domain sequence, without reliance on any experimental data beyond the sequence itself. As used herein, “Kabat numbering” refers to the numbering system set forth by Kabat et al., U. S. Dept, of Health and Human Services, “Sequence of Proteins of Immunological Interest” (1983).

[0477] In addition to table above, the Kabat number system describes the CDR regions as follows: CDR-H1 begins at approximately amino acid 31 (i.e., approximately 9 residues after the first cysteine residue), includes approximately 5-7 amino acids, and ends at the next tryptophan residue. CDR-H2 begins at the fifteenth residue after the end of CDR-H1, includes approximately 16-19 amino acids, and ends at the next arginine or lysine residue. CDR-H3 begins at approximately the thirty third amino acid residue after the end of CDR-H2; includes 3-25 amino acids; and ends at the sequence W-G-X-G, where X is any amino acid. CDR-L1 begins at approximately residue 24 (i.e., following a cysteine residue); includes approximately 10-17 residues; and ends at the next tryptophan residue. CDR-L2 begins at approximately the sixteenth residue after theBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO end of CDR-L1 and includes approximately 7 residues. CDR-L3 begins at approximately the thirty third residue after the end of CDR-L2 (i.e., following a cysteine residue); includes approximately 7-11 residues and ends at the sequence F or W-G-X-G, where X is any amino acid.

[0478] As used herein, the term "epitope" can include any protein determinant that can specifically bind to an immunoglobulin, a scFv, or a T-cell receptor. The variable region allows the antibody to selectively recognize and specifically bind epitopes on antigens. For example, the VL domain and VH domain, or subset of the complementarity determining regions (CDRs), of an antibody combine to form the variable region that defines a three-dimensional antigen-binding site. More specifically, the antigen-binding site is defined by three CDRs on each of the VH and VL chains (i.e., CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3).

[0479] As used herein, the terms "immunological binding," and "immunological binding properties" can refer to the non-covalent interactions of the type which occur between an immunoglobulin molecule and an antigen for which the immunoglobulin is specific. The strength, or affinity of immunological binding interactions can be expressed in terms of the dissociation constant (Kd) of the interaction, wherein a smaller Kd represents a greater affinity. Immunological binding properties of selected polypeptides can be quantified using methods well known in the art. One such method entails measuring the rates of antigen- binding site / antigen complex formation and dissociation, wherein those rates depend on the concentrations of the complex partners, the affinity of the interaction, and geometric parameters that equally influence the rate in both directions. Thus, both the "on rate constant" (Kon) and the "off rate constant" (Koff) can be determined by calculation of the concentrations and the actual rates of association and dissociation. (See Nature 361: 186-87 (1993)). The ratio of Koff / Kon allows the cancellation of all parameters not related to affinity, and is equal to the equilibrium binding constant, KD. (See, generally, Davies et al. (1990) Annual Rev Biochem 59:439-473). An antibody of the invention can specifically bind to an epitope when the equilibrium binding constant (KD) is <1 mM, <10 pM, < 10 nM, < 10 pM, or < 100 pM to about 1 pM, as measured by kinetic assays such as radioligand binding assays or similar assays known to those skilled in the art, such as BIAcore or Octet (BLI). ForBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO example, in some embodiments, the KD is between about 1 E-12 M and a KD about 1 E-11 M. In some embodiments, the KD is between about 1 E-11 M and a KD about 1 E-10 M. In some embodiments, the KD is between about 1 E-10 M and a KD about 1 E-9 M. In some embodiments, the KD is between about 1 E-9 M and a KD about 1 E-8 M. In some embodiments, the KD is between about 1 E-8 M and a KD about 1 E-7 M. In some embodiments, the KD is between about 1 E-7 M and a KD about 1 E-6 M. For example, in some embodiments, the KD is about 1 E-12 M while in other embodiments the KD is about 1 E-11 M. In some embodiments, the KD is about 1 E-10 M while in other embodiments the KD is about 1 E-9 M. In some embodiments, the KD is about 1 E-8 M while in other embodiments the KD is about 1 E-7 M. In some embodiments, the KD is about 1 E-6 M while in other embodiments the KD is about 1 E-5 M. In some embodiments, for example, the KD is about 3 E-11 M, while in other embodiments the KD is about 3E-12 M. In some embodiments, the KD is about 6E-11 M. “Specifically binds” or “has specificity to,” can refer to an antibody that binds to an epitope via its antigen-binding domain, and that the binding entails some complementarity between the antigen-binding domain and the epitope. For example, an antibody is said to “specifically bind” to an ep...

Claims

1. BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO CLAIMSWhat is claimed:

1. A heterodimeric fusion protein:X-Y (l),wherein:X comprises R1 - R2 (II):wherein,R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6); andR2 is an IgG Fc region; andwherein,Y comprises R3 - R4 (III):wherein,R3 is a transferrin receptor (TR) binding (TRB) means for binding the TR; andR4 is an IgG Fc region; and whereinX and Y form a dimer.

2. The heterodimeric fusion protein of claim 1, wherein R3 comprises one TRB means.

3. The heterodimeric fusion protein of claim 1, wherein R3 comprises two TRB means.

4. The heterodimeric fusion protein of claim 1, wherein the TRB means comprises an antibody or antibody fragment.

5. The heterodimeric fusion protein of claim 1, wherein R3 comprises SEQ ID NO: 1 (VHHA).

6. The heterodimeric fusion protein of claim 5, wherein tyrosine at position 96 of SEQ ID NO: 1 is substituted for alanine (VHHA-5).BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO6. The heterodimeric fusion protein of claim 4, wherein leucine at position 98 of SEQ ID NO: 1 is substituted for alanine (VHHA-7).

7. The heterodimeric fusion protein of claim 4, wherein phenylalanine at position 51 of SEQ ID NO: 1 is substituted for isoleucine (VHHA-12).

8. The heterodimeric fusion protein of claim 1, wherein R3 comprises SEQ ID NOs: 2, 3, or 4 (VHHA-5, -7, or -12).

9. The heterodimeric fusion protein of claim 1, wherein the TRB means comprises an H7 scFv.

10. The heterodimeric fusion protein of claim 1, wherein R2 and / or R4 are lgG1 regions.

11. A heterodimeric fusion protein:X-Y (IV),wherein:X comprises R1 - R2 (V),wherein:R1 is a first protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6); andR2 is an IgG Fc region; andwherein,Y comprises R5 - R4 - R3 (VI),wherein:R5 is a second protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6);R4 is an IgG Fc region; andR3 is a transferrin receptor (TR) binding (TRB) means for binding the TR; and whereinBT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO X and Y forms a dimer.

12. The heterodimeric fusion protein of claim 11, wherein R3 comprises SEQ ID NO: 1 (VHHA).

13. The heterodimeric fusion protein of claim 12, wherein tyrosine at position 96 of SEQ ID NO: 1 is substituted for alanine (VHHA-5).

14. The heterodimeric fusion protein of claim 12, wherein leucine at position 98 of SEQ ID NO: 1 is substituted for alanine (VHHA-7).

15. The heterodimeric fusion protein of claim 12, wherein phenylalanine at position 51 of SEQ ID NO: 1 is substituted for isoleucine (VHHA-12).

16. The heterodimeric fusion protein of claim 11, wherein R3 comprises SEQ ID NOs: 2, 3, or 4 (VHHA-5, -7, or -12).

17. The heterodimeric fusion protein of claim 11, wherein R2 and / or R4 are IgG 1 regions.

18. A heterodimeric fusion protein:X-Y (VII):wherein:X comprises R1 - R2 (VIII):wherein,R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6); andR2 is an IgG Fc region; andwherein,Y comprises R3 - R6 - R4 (IX):wherein:BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO R3 is a first transferrin receptor (TR) binding (TRB) means for binding the TR;R6 is a second transferrin receptor (TR) binding (TRB) means for binding the TR, andR4 is an IgG Fc region; and whereinX and Y forms a dimer.

19. The heterodimeric fusion protein of claim 18, wherein R3 and / or R6 comprises SEQ ID NO: 1 (VHHA).

20. The heterodimeric fusion protein of claim 19, wherein tyrosine at position 96 of SEQ ID NO: 1 is substituted for alanine (VHHA-5).

21. The heterodimeric fusion protein of claim 19, wherein leucine at position 98 of SEQ ID NO: 1 is substituted for alanine (VHHA-7).

22. The heterodimeric fusion protein of claim 19, wherein phenylalanine at position 51 of SEQ ID NO: 1 is substituted for isoleucine (VHHA-12).

23. The heterodimeric fusion protein of claim 18, wherein R3 and / or R6 comprises SEQ ID NOs: 2, 3, or 4 (VHHA-5, -7, or -12).

24. The heterodimeric fusion protein of claim 18, wherein R3 and / or R6 are lgG1 regions.

25. A homodimeric fusion protein:X-X’ (X):wherein,X and X’ comprise R1 - R2 - R3 (XI):wherein:BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO R1 is a protein of interest (POI) binder (POIB) means for binding an extracellular region of C-C chemokine receptor 6 (CCR6);R2 is an IgG Fc region; andR3 is a transferrin receptor (TR) binding (TRB) means for binding the TR; andwhereinX and X’ forms a dimer.

26. The homodimeric fusion protein of claim 25, wherein R3 comprises SEQ ID NO: 1 (VHHA).

27. The homodimeric fusion protein of claim 26, wherein tyrosine at position 96 of SEQ ID NO: 1 is substituted for alanine (VHHA-5).

28. The homodimeric fusion protein of claim 26, wherein leucine at position 98 of SEQ ID NO: 1 is substituted for alanine (VHHA-7).

29. The homodimeric fusion protein of claim 26, wherein phenylalanine at position 51 of SEQ ID NO: 1 is substituted for isoleucine (VHHA-12).

30. The homodimeric fusion protein of claim 25, wherein R3 comprises SEQ ID NOS: 2, 3, or 4 (VHHA-5, -7, and -12).

31. The homodimeric fusion protein of claim 25, wherein R2 is an lgG1 region.

32. The fusion protein of any one of claims 1, 11, 18 or 25, wherein the POIB means comprises an antibody.

33. The fusion proteins of any one of claims 1, 11, 18 or 25, wherein the POIB means is an antibody fragment.BT Docket No.: 91016-434626DFCI Ref. No.: 3562. W01WO 34. The fusion proteins of any one of claims 1, 11, 18 or 25, wherein the TRB means is a VHH.

35. A nucleic acid encoding the fusion protein of any one of claims 1, 11, 18 or 25.

36. A pharmaceutical composition comprising the fusion protein of any one of claims 1-34 and a pharmaceutically acceptable carrier, diluent, or excipient.

37. A method, comprising administering an effective amount of the fusion protein of any one of claims 1-34 to a subject in need of blocking C-C chemokine receptor type 6 (CCR6) activity.

38. The method of claim 37, wherein the subject has an autoimmune or inflammation-related disease.

39. Use of the fusion protein of any one of claims 1-34 for treating a subject in need of blocking CCR6 activity.

40. Use of the fusion protein for any one of claim 1-34 for treating a subject having an autoimmune or inflammation-related disease.

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