Receptor-mediated endocytosis for improved targeted internalization and degradation of membrane proteins and cargos

Abstract

Disclosed are improved fusion proteins. Fusion proteins can bind to a protein of interest and to an internalizing receptor on a cell surface. Once bound, the protein of interest can be internalized and / or degraded inside a cell.

Description

RECEPTOR-MEDTATED ENDOCYTOSIS FOR IMPROVED TARGETED INTERNALIZATION AND DEGRADATION OF MEMBRANE PROTEINS AND CARGOS

[0001] This application is an International Application, which claims the benefit of priority from U.S. provisional patent application no. 63 / 566,046, filed on March 15, 2024, U.S. provisional patent application no.63 / 566, 056, filed on March 15, 2024, U.S. provisional patent application no. 63 / 566,069, filed on March 15, 2024, and U.S. provisional patent application no. 63 / 566,076, filed on March 15, 2024, the entire contents of each which are incorporated herein by reference in their entireties.

[0002] 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.

[0003] 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.FIELD

[0004] Aspects of the invention are drawn to improved compositions and methods for modulating molecules on the cell surface of cells, including cell receptors and coreceptors to reversibly control cellular activity to treat related diseases.SEQUENCE LISTING

[0005] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on [ ], is named [ ] and is [ ] bytes in size.BACKGROUND

[0006] Traditional small molecule inhibitor-based therapies have certain disadvantages, such as toxicity and limited efficacy. Examples of inhibitor features that contribute to their disadvantages include a binding affinity that is the determinant of inhibitor potency; a therapeutic response that depends on sustained target binding; a limited functionality on the target protein; and subverted efficacy through target protein overexpression, native ligand competition, and development of target protein mutations that limit binding or facilitate resistance. Thus, a desirable therapeutic modality exhibits low toxicity and high efficacy. For example, a desirable therapeutic modality includes a variety of features that contribute to overall potency; a therapeutic response that does not entirely or mostly depend on sustained target binding; the ability to completely or substantially limit functionality of the target protein; and limited or no ability of a target cell to subvert efficacy, such as through target protein overexpression, native ligand competition, and / or development of target protein mutations that limit binding or facilitate resistance.

[0007] Membrane proteins are central to a myriad of cellular functions and serve as targets for over half of all drugs. Therefore, developing strategies to degrade membrane proteins is of exceptional interest for both basic research and therapeutic intervention purposes.

[0008] Targeted protein degradation (TPD) is a rapidly growing field in drug discovery and pharmacology. Complementing traditional drug modalities, TPD molecules offer a novel therapeutic mechanism to tackle challenging targets or increase the therapeutic potential of currently used drugs.

[0009] Eukaryotic cells use proteosomes to degrade proteins via the ubiquitin-proteosome pathway (UPP), and lysosomes degrade protein aggregates and whole organelles through endocytosis / phagocytosis. They also use lysosomes to degrade proteins and organelles through endocytosis, phagocytosis, and autophagy. An important component of this pathway is the E3 enzyme which recognizes the targeted protein. This interacts with a 26S proteosome which degrades the protein. TPD has a major role in immunology as it protects important mechanisms when pathogens, cancers, and other diseases target the mechanisms that protect and regulate key functions.

[0010] Proof-of-concept strategies for membrane receptor degradation have been described. These strategies use heterobifunctional biologies that recruit a specific “effector” protein such asa membrane E3 ligase (Cotton, A. D., Nguyen, D. P., Gramespacher, J. A., Seiple, I. B. & Wells, J. A. Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1. J Am Chem Soc 143, 593-598 (2021)) or a lysosome shuttling receptor (Ahn, G. et al. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat Chem Biol 17, 937-946 (2021)) to the protein of interest (POI) to induce lysosome-mediated protein degradation. However, the effectiveness of these biological effectors is often limited by their tissue-specific expression patterns. GalNAc-LYTAC, for instance, targets the hepatocyte-specific receptor asialoglycoprotein receptor (ASGPR), making it only suitable for treating liver disease or clearing circulating targets (Ahn, G. et al. Nat Chem Biol 17, 937-946 (2021); Zhou, Y., Teng, P., Montgomery, N. T., Li, X. & Tang, W. Development of Triantennary N-Acetylgalactosamine Conjugates as Degraders for Extracellular Proteins. ACS Cent Sci 7, 499-506 (2021)), while RNF43- or ZNRF3-based methods are more effective for treating Wnt-signaling upregulated disorders where RNF43 and ZNRF3 are expressed at high levels.

[0011] Current technologies are therefore not able to cover the full spectrum of diseases, and developing alternative effectors overexpressed in different diseases and tissues would greatly expand the range of cell surface targets that can be regulated and also increase the targeting specificity.

[0012] Accordingly, there is a need to improve targeted protein degradation, particularly of membrane proteins to treat an array of diseases.SUMMARY

[0013] Disclosed here are new reagents (bispecific modulators, also called fusion proteins) and methods for regulating proteins of interest on the surface of cells.

[0014] In some embodiments, the reagents and methods are used to control the levels of molecules on the surface of cells. In some embodiments, the reagents and methods are bispecific modulators, also called TransTAC molecules (TransTAC is Transferrin receptor-mediated TArgeting Chimera, e g., a type of bispecific modulator), also called fusion proteins, fusion protein homodimers, fusion protein heterodimers).

[0015] Disclosed are fusion proteins of Formula I, R1-R2-R3 (I), wherein R1 is at least one protein of interest (POI) binder (POIB) or POI binding means (also known as a means forbinding POI), R2 is a linker of the formula R4-R5 or R5-R4, wherein R4 is TgG Fc region; and R5 is an optional protease-sensitive linking means (also known as a means for linking), and R3 is a TR binding means (also known as a means for binding TR) wherein the TR binding means (also known as a means for binding TR) is non-competitive with endogenous transferrin for binding to the TR, and optionally, comprising a glycine-rich linker between R2 and R3. The fusion protein can have TR binding means (also known as a means for binding TR) that is an antibody fragment having a heavy chain variable region.

[0016] The TR binding means (also known as a means for binding TR) can be an antibody fragment having a heavy chain variable region. The TR binding means (also known as a means for binding TR) can be VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148). The TR binding means (also known as a means for binding TR) can have: (a) a VH CDR1 having the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 having the amino acid sequence of ITATGNT (SEQ ID NO: 201), and a VH CDR3 having the amino acid sequence of YMLDK (SEQ ID NO: 202) (from VHHA-12); (b) a VH CDR1 having the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 having the amino acid sequence of FTATGNT (SEQ ID NO: 203), and a VH CDR3 having the amino acid sequence of AMLDK (SEQ ID NO: 204) (from VHHA-5); or (c) a VH CDR1 having the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 having the amino acid sequence of FTATGNT (SEQ ID NO: 203), and a VH CDR3 having the amino acid sequence of YMADK (SEQ ID NO: 205) (from VHHA- 7).

[0017] The disclosed fusion proteins can have at least two TR binding means (also known as a means for binding TR) arranged in tandem. The fusion protein can have an optional protease- sensitive linking means (also known as a means for linking) comprises a cathepsin-cleavable peptide. The cathepsin-cleavable peptide linker can be FK, VA, VK, SEQ ID NO: 7, 8, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144 and 145. In the disclosed fusion proteins, the optional glycine- rich linker between R2 and R3 can be SEQ ID NO: 9, 10, 11, 12, 13, 14, 15 or 16.

[0018] The disclosed fusion proteins of Formula I can be homodimers. The TR binding means (also known as a means for binding TR) within a homodimer can have a binding affinity to TR (Ka) of about 1 nM to about 200 nM.

[0019] The disclosed fusion proteins of Formula I can be a heterodimer linked to a fusion protein of Formula II, which is R4’-R3’ (II). In the heterodimer, R4’ can be an IgG Fc region; and R3’ can be a TR binding means (also known as a means for binding TR) wherein the TRB means is non-competitive with endogenous transferrin for binding to the TR, and optionally, having a protease-sensitive linking means (also known as a means for linking) between R3’ and R4’ . The TR binding means (also known as a means for binding TR) within the heterodimer can have a binding affinity to TR (Kd) of about 50 nM to about 0.001 nM.

[0020] The disclosed fusion proteins can have a POIB or POI binding means (also known as a means for binding POI) that is an antibody. The POIB or POI binding means can bind to an extracellular domain of a transmembrane protein. The extracellular regions of the membrane proteins can be a chimeric antigen receptor (CAR), a receptor tyrosine kinase, a checkpoint inhibitor binding molecule, or a cell lineage-specific marker. The POIB or POI binding means (also known as a means for binding POI) can bind to an extracellular domain of an epidermal growth factor receptor (EGFR), a programmed death-ligand 1 (PD-L1), CD 19, or CD20.

[0021] Disclosed are homodimers of a fusion protein of Formula I, R1-R2-R3 (III), wherein R1 is at least one protein of interest (POI) binder (POIB) or POI binding means (also known as a means for binding POI), R2 is a linker of the formula R4-R5 or R5-R4, wherein R4 is IgG Fc region, and R5 is an optional protease-sensitive linking means (also known as a means for linking), and R3 is a TR binding means (also known as a means for binding TR)wherein the TR binding means (also known as a means for binding TR)is non-competitive with endogenous transferrin for binding to the transferrin receptor, and optionally, comprising a glycine-rich linker between R2 and R3.

[0022] Disclosed is a homodimer of a fusion protein of Formula I, R1-R6-R3 (I), wherein R1 is at least one protein of interest (POI) binder (POIB) or POI binding means (also known as a means for binding POI), R6 is a dimerization means (also known as a means for dimerizing), and R3 is a TR binding means (also known as a means for binding TR), wherein the TRB means is non-competitive with endogenous transferrin for binding to the transferrin receptor, and wherein the homodimer optionally has a protease-sensitive linking means (also known as a means for linking) between R1 and R6.

[0023] The homodimers can have a disulfide bond between cysteine amino acids in R4 of separate fusion proteins.

[0024] Disclosed are heterodimers of fusion proteins of Formula IV and V, R1-R2 (IV) andR3-R2’ (V), wherein R1 is a protein of interest (POI) binder (POIB) or POI binding means (also known as a means for binding POI), R2 and R2’ are linkers of the formula R4 or optionally R4- R5, wherein R4 is an IgG Fc region, R5 is an optional protease-sensitive linking means (also known as a means for linking), and R3 is at least one TR binding means (also known as a means for binding TR), wherein the TR binding means (also known as a means for binding TR)is non- competitive with endogenous transferrin for binding to the TR.

[0025] Disclosed are heterodimers of fusion proteins of Formula I and VI, R1-R2-R3 (I) andR2’ (VI), wherein R1 is a protein of interest (POI) binder (POIB) or POI binding means (also known as a means for binding POI), R2 is a linker of the formula R4-R5 or R5-R4, wherein R4 is an IgG Fc region, R5 is an optional protease-sensitive linking means (also known as a means for linking), R3 is at least one TR binding means (also known as a means for binding TR), wherein the TRB means is non-competitive with endogenous transferrin for binding to the TR and R2’ is a linker of the formula R4 or optionally R4-R5.

[0026] The heterodimers can have complementary knob and hole structures in R4 of separate fusion proteins.

[0027] The TR binding means (also known as a means for binding TR) of the fusion proteins that are part of any of the homodimers or heterodimers disclosed herein can be VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148).

[0028] Disclosed are fusion protein of Formula I, R1-R2-R3 (I), wherein R1 is at least one protein of interest (POI) binder (POIB) or POI binding means (also known as a means for binding POI), R2 is a linker of the formula R4-R5 or R5-R4, wherein R4 is IgG Fc region, and R5 is an optional protease-sensitive linking means (also known as a means for linking), and R3 is at least two TR binding means (also known as a means for binding TR) arranged in tandem, and optionally, comprising a glycine-rich linker between R2 and R3. This fusion protein can have a TR binding means (also known as a means for binding TR) that is non-competitive with endogenous transferrin for binding to the transferrin receptor.

[0029] Disclosed are nucleic acid sequences encoding the fusion proteins and homodimers and heterodimers thereof disclosed herein.

[0030] Disclosed are methods for treating a subject by administering the disclosed fusion proteins / homodimers / heterodimers to the subject. The disclosed fusion proteins can be for use in treating a disease in a patient. Disclosed are uses of the disclosed fusion proteins for treating a subject having a subject.

[0031] Disclosed are pharmaceutical compositions of any of the fusion proteins, and homodimers or heterodimers thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0032] 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.

[0033] FIG. 1 illustrates an example schematic of TransTAC (fusion proteins, fusion protein homodimers, fusion protein heterodimers) technology (TransTAC is Transferrin receptor- mediated TArgeting Chimera, e.g., a type of bispecific modulator) (FIG 1A). Extracellular proteins (e.g., target membrane proteins with extracellular domains present in the surface of cells) can be selectively internalized and degraded by tethering (FIG. IB), for example, an antibody to (or a ligand of) the target membrane protein to a transferrin receptor with a bispecific modulator, shown as a membrane protein-specific antibody-transferrin fusion protein.

[0034] FIG. 2 shows TransTACs for various proteins of interest (POIs). FIG. 2A shows a schematic of exemplary membrane proteins targeted by TransTACs. These targets are either synthetic, or native, single- or multi-pass proteins expressed on cells surfaces. FIG. 2B shows PD-L1 degradation by TransTACs in MDA-MB-231 cells analyzed by Western blot and quantified. A scFv format of atezolizumab is used as the PD-L1 binding moiety (Rl; Found in SEQ ID NO: 78 herein). FIG. 2C shows EGFR degradation by TransTAC in A549 cells. An affibody is used as the EGFR binding moiety (Rl; Found in SEQ ID NO: 20 herein). FIG. 2D shows CD20 degradation by TransTAC. A Fab format of rituximab is used as the CD20 binding moiety (Rl; Found in SEQ ID NO: 40 herein). FIG. 2E shows CD19 binding receptor degradation by a TransTAC. An engineered CD19 ectodomain is used as the CAR binding moiety (Rl; Found in SEQ NO: 18 herein). All cells were incubated with TransTACs for 12-18hours. Data are representative of 3 independent experiments. Controls without the TfRl binding domain or the cathepsin cleavable linker showed no or little cleavage. Error bars represent standard deviations. P values were determined by unpaired two-tailed t tests, ns, not significant;* P <0.05; **P <0.01; ***P <0.001. In FIG. 2B-D, R4 is IgG Fc region, R5 is an optional protease-sensitive linking means (R4-R5 and R5-R4 = R2), and R3 is a TR binding means.

[0035] FIG. 3 shows Tf-Tfrl binding interface analysis for TransTACs including second moiety (R3) (R3; transferrin receptor (TR) binder or TR binding means (also known as a means for binding TR)) including H7, VHHA and VHHB binders. FIG. 3A shows example Kd values for H7 (H7 is competitive inhibitor with Tf for TfR binding), VHH-A or VHH-B (non- competitive with Tf for TfR binding) binding to TfRl. FIG. 3B shows example PD-L1 degradation using TransTACs including VHHA (top) or VHHB (bottom) as TfRl binders. FIG. 3C shows example PD-L1 degradation using TransTACs including VHHA (top) or VHHA (bottom) as TfRl binders.

[0036] FIG. 4A shows example IC50 values for PD-L1 degradation by TransTAC variants that include H7 (VI.0 or DP 186), VHHA or VHHB as binders that bind to TfRl. FIG. 4B example shows dose-response curves, IC50 and Dmax for PD-L1 degradation in MDA-MB-231 cells by TransTACs including VHH-A as a TfRl binder. FIG. 4C shows example dose-response curves, IC50 and Dmax for PD-L1 degradation in MDA-MB-231 cells by TransTACs including VHH-B as a TfRl binder.

[0037] FIG. 5 shows amino acid and nucleotide sequences for VHHA (SEQ IDs NO: 146- 147) and VHHB (SEQ IDs NO: 148-149).

[0038] FIG. 6A shows example PD-L1 degradation by binder and linker TransTAC variants. FIG. 6B provides more information on the homodimeric molecules in FIG. 6A, which have different TfR binders.

[0039] FIG. 7 shows amino acid sequences of various TransTACs. FIG. 7A shows amino acid sequences for antiPDLl-linker-Fc(knob) (SEQ ID NO: 150), H7-H7-Fc(hole) (SEQ ID NO: 151) for TransTAC V1.2, and antiPDLl-linker-Fc(knob)-H7 (SEQ ID NO: 152). FIG. 7B shows amino acid sequences for -Fc(hole) H7 (SEQ ID NO: 153) for TransTAC vl.2, pAD2-His8- PDL1 scFV-GFLG-VR-FC-TfR-N5-optimized (SEQ ID NO: 154), and pAD3-His8-PDLl scFV- GFLG-VR-FC-TfR-G9-newer-optimized (SEQ ID NO: 155). FIG. 7C shows amino acid sequences for pAD4-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-A-optimized (SEQ ID NO:156), pAD5-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-B-optimized (SEQ ID NO: 157), and pAD6-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-D-optimized (SEQ ID NO: 158). FIG. 7D shows amino acid sequences for pAD7-His8-PDLl scFV-GFLG-VR-FC-TfR-VHH-A5- optimized (SEQ ID NO: 159) and pAD8-His8-PDLl-scFV-GFLG-VR-FC-TfR-VHH-A7- optimized.dna (SEQ ID NO: 160). The above are laboratory names given to the sequences. In the sequences, yellow is POIB (Rl), blue is R4 (IgG Fc region), green is TRB (R3). Unshaded regions are either leader sequences or GS linkages. The “TS” amino acids at the N-terminus of some of the sequences were added for convenience in constructing plasmids.

[0040] FIG. 8A-B. FIG. 8A shows schematics of CAR-TransTAC variants consisting of one or two copies of anti-POI and anti-TfR binders in different protein geometries. Rl is POIB. R3 is TR binder. FIG. 8B shows cell surface CAR level measurements in CAR-Jurkat cells treated with CAR-TransTAC variants outlined in Data are representative of 3 independent measurements. These molecules target a chimeric antigen receptor (CAR). The TRBs in these molecules are H7.

[0041] FIG. 9 illustrates PDL1 degradation using TransTACs variants with various geometries. FIG. 9A illustrates PDL1 TransTAC variants. FIG. 9B shows results of protein expression of the TransTAC variants. FIG. 9C illustrates results of Western Blot showing PDL1 degradation for each of the TransTAC variants. FIG. 9D shows PD-L1 dose curve degradation for variants vl.4 (top) and vl.2 (bottom).

[0042] FIG. 10A-B shows example TransTAC molecules with different geometries including protease-sensitive linkers at different locations (FIG. 10A) and example data obtained with the different geometries (FIG. 10B).DETAILED DESCRIPTION

[0043] Targeted protein degradation (TPD) is a rapidly growing field in drug discovery and pharmacology. Complementing traditional drug modalities, TPD molecules offer a novel therapeutic mechanism to tackle challenging targets, increase the therapeutic potential of currently used drugs, and the like. While many efforts in this field have focused on small molecules for intracellular targets, inducing targeted degradation of extracellular proteins is a new opportunity. Developing strategies to degrade extracellular proteins is of exceptional interest for both basic research and therapeutic intervention purposes.

[0044] Iron is an essential element for cells, and its transportation is facilitated by transferrin receptor (TfR). TfR undergoes rapid endocytosis as a recycling receptor, with an average internalization rate of 500 molecules per cell per second, making it one of the fastest internalizing receptors known. Furthermore, TfR is upregulated in cells that have a high demand for iron. This includes rapidly dividing rapidly dividing cells and activated T cells. TfR expression in these cells are higher than in non- or slowly- dividing normal tissues. TfR can be expressed on non-cancer cells at sufficient levels where the reagents and methods described herein can be used.

[0045] Herein, these features of TfR were leveraged and employed protein engineering strategies to develop a new technology for degrading membrane proteins. Herein, this technology is called receptor-mediated Targeting Chimeras (TransTACs; also, herein called fusion proteins, homodimers or heterodimers of fusion proteins). In some embodiments, TransTACs are heterobispecific antibodies that bring the protein of interest (POI) and TfR in close proximity at the cell surface and induce endocytosis of the POI / TfR complex and subsequent lysosomal- mediated POI degradation. TransTACs are effective in degrading various types of membrane proteins, including single-pass, multi-pass, native, and synthetic receptors, showing a degradation efficiency of over 80% for all targets in various cellular systems. A notable characteristic of TransTACs is its fast kinetics of targeted internalization, occurring on a timescale of minutes, making it a valuable molecular tool for rapidly knocking down cell-surface expression, offering temporal specificity for cell signaling studies that is not possible with genetic approaches. Moreover, TransTAC molecules are fully recombinant, modular, and disease-specific. These properties make TransTACs a versatile technology for manipulating cell surface targets in disease-specific manners.

[0046] TransTAC can have broad applicability in both basic research and translational applications. Herein is demonstrated non-limiting applications of TransTACs in reversible control of cells. TransTACs represent a new molecular archetype to control cell surface proteins.

[0047] TransTAC is the first bispecific antibody technology that repurposes a recycling ligand / receptor interaction for targeted protein internalization and degradation, which can significantly expand the scope of effectors at the cell surface amenable for such purposes.

[0048] Herein are disclosed new, modular, and reversible strategies for modulating cells activities. Generally, the methods do not require additional genetic engineering of T cells. Insome embodiments, these strategies are based on reversible internalization of cell surface molecules present in cells.

[0049] In some embodiments, a bispecific modulator (fusion protein), including for example a transferrin receptor-mediated targeting chimera or TransTAC molecule, can colocalize a receptor to an internalizing cell surface protein. In some embodiments, fusion proteins can downregulate cell surface levels of said receptor. In some embodiments, the fusion proteins can inhibit T cell activation and / or function.

[0050] In embodiments, the fusion proteins can have a first portion or moiety (Rl) that is an antibody, antibody fragment or an that specifically binds to a target molecule on a cell (protein of interest), and a second portion or moiety (R3) (e.g., transferrin or an antibody or antibody fragment) that can bind to an internalizing molecule on the cell surface (e.g., transferrin receptor or TR). In embodiments, the fusion proteins can have a first portion that is an antigen or ligand for a target protein on a cell (e.g., CD19 antigen or its variants for a CD19-specific CAR). In embodiments, the fusion proteins can have a first portion that is an antibody or antibody fragment that can specifically bind a target molecule (e.g., protein of interest or POI) on a cell. The fusion proteins can have a second portion that binds to an internalizing protein on the cell surface (e.g., transferrin receptor or TR). Binding of a fusion protein to the target molecule and to the internalizing protein results in internalization of the target molecule.

[0051] In some embodiments, the fusion proteins do not require engineering of the CAR-T receptor or CAR-T cells and can be applied to CAR-T therapies that are already approved or in clinical development.

[0052] In other embodiments, the fusion proteins can be reversible. Reversibility can provide for fine tuning of cell, including CAR-T cell, activities, for example for toxicity management and / or to rejuvenate the cells for continued treatment. In some embodiments, fusion proteins can be tailored to CAR-T cells that target different tumor antigens, for example, by replacing the components used in the designs (i.e., the traps and / or modulators can be modular).

[0053] Disclosed are approaches for enhancing cells efficacy for controlling and / or treating diseases. In some embodiments, by alternating cells status between an “active” and a “resting” state, the disclosed reversible modulators can control / treat diseases.

[0054] Also disclosed are approaches for enhancing CAR-T efficacy. Temporal “rest” of CAR-T cells can reverse CAR-T exhaustion. In some embodiments, by alternating CAR-T cellsbetween an “active” and a “resting” state, the disclosed reversible CAR modulators can increase efficacy of CAR-T cells.

[0055] Disclosed are development of TransTAC degraders to target POIs. Herein is shown that (1) TransTAC can effectively degrade target proteins and (2) that the geometry of TransTAC molecules can influence TransTAC target degrading activities.

[0056] 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.

[0057] 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.”

[0058] 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.

[0059] 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.

[0060] 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.

[0061] 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).Fusion Proteins

[0062] In some embodiments, strategies disclosed herein for regulating a protein of interest on a cell surface (e.g., proteins of interest) and / or regulatory activity of such proteins can use a fusion protein approach. In some embodiments, a fusion protein molecule can have at least two moieties. A first moiety (Rl) can be a ligand that the cell-surface molecule(s) can bind or an antibody or antibody fragment that can bind to the cell-surface molecule(s) (e.g., proteins of interest). Rl can be a protein of interest (POI) binder (POIB) or POI binding means (also known as a means for binding POI). A second moiety (R3) can be a molecule that can bind to an internalizing receptor on a cell (e.g., transferrin receptor or TR). In some embodiments, a second moiety can be an antibody or antibody fragment that binds to an internalizing receptor or membrane protein on a cell. In some embodiments, R3 can bind transferrin receptor (TR) and can be called a transferrin receptor binder (TRB or TR binder). R3 can be a TR binding means (also known as a means for binding TR). In some embodiments, the fusion protein (or homodimer or heterodimer thereof) can be a bispecific antibody.

[0063] In some embodiments, the fusion protein approach can regulate molecules other than those on a cell surface. In some embodiments, the fusion protein can bind and internalize (and, optionally, degrade) proteins present in the extracellular / extemal environment.

[0064] In embodiments, a fusion protein having these two moieties can bind, or be bound by, proteins of interest, and can bind to an internalizing receptor or membrane protein (e.g. TR). After such bindings, the internalizing receptor or membrane protein can cause the cell-surface or other molecule to be internalized into the cell (e.g., endocytosis). In embodiments, the internalized cell-surface or other molecule can be degraded. In embodiments, this decreases the amount of the cell-surface molecule on the surface of a cell. In embodiments, the internalized cell-surface molecules are not functional. In some embodiments, the cell-surface molecule that is targeted by the first moiety of a fusion protein is different than the molecule targeted by the second moiety.

[0065] In some embodiments, administering the fusion proteins to a subject can be used for targeted internalization of membrane or other proteins. In some embodiments, administering the fusion proteins to a subject can be used for targeted degradation of membrane or other proteins.

[0066] In some embodiments, adding the fusion proteins to cells or administering to a patient can cause targeted internalization and / or degradation of proteins on the surface of a cell or outside of a cell. In some embodiments, this intemalization / degradation is reversible. For example, when a cell is no longer exposed to the disclosed fusion proteins, the membrane proteins to which the fusion proteins are specific are no longer intemalized / degraded. Generally, the membrane proteins are still synthesized and trafficked to the cell membrane. Therefore, when the fusion proteins are removed or are no longer administered to a subject, there is not a stimulus to internalize / degrade the proteins. In some embodiments, a cellular membrane protein that can be internalized by a fusion protein, but not degraded, can be both internalized and degraded using a fusion protein that also contains an optional protease-sensitive linker or protease-sensitive linking means (also known as a means for linking). As discussed elsewhere, placement of an optional protease-sensitive linker or protease-sensitive linking means (also known as a means for linking) within a disclosed fusion protein can provide release of a targeted cellular protein of interest from the fusion protein inside of a cell.

[0067] In some embodiments, internalization and degradation of a protein of interest can kill the cell (e.g., in embodiments where the cell surface molecule is required for cell viability or cell division; EGFR in some embodiments). In some embodiments, internalization and degradation of the protein of interest does not kill the cell (e.g., in embodiments where the cell surface or other molecule is not required for cell viability or cell division: CD 19 binding receptor in some embodiments).

[0068] In some embodiments, internalization of fusion proteins or parts thereof can involve receptor-mediated endocytosis, also called clathrin-mediated endocytosis. In some embodiments, internalization of fusion proteins can involve clathrin-independent endocytosis. In some embodiments, internalization of fusion proteins can involve phagocytosis.

[0069] In embodiments, the protein of interest that is targeted by the first moiety (Rl) can be a CAR molecule (a protein). In some embodiments, the CAR molecule can be on a CAR-T cell. In some embodiments, a strategy for regulating CAR-T activities includes internalizing CAR receptors with a fusion protein. In some embodiments, the protein of interest targeted by the firstmoiety (Rl) can be a cell regulator, like proteins that are part of immune checkpoint pathways (e.g., PD-L1) or other signal-transducing protein (e.g., EGFR). In some embodiments the protein of interest can be a marker of a certain cell type (e.g., CD20 for B-cells).

[0070] In some embodiments, the protein of interest targeted by the first moiety (Rl) can be a protein. In some embodiments, the protein of interest can be a membrane protein. The membrane protein can be an integral membrane protein. The membrane protein can be a transmembrane protein that has one or more transmembrane domains. In some embodiments, the protein of interest can be a protein external to a cell, for example, an autoantibody, cytokine, enzyme, and the like.

[0071] In some embodiments, the protein of interest can bind a hormone, cytokine, growth factor, neurotransmitter, lipophilic signaling molecule (e g., prostaglandin) or cell recognition protein (e.g., integrin, selectin). The protein of interest can be a receptor. The receptor can be a G-protein coupled receptor (GPCR), receptor tyrosine kinase (RTK) or transmembrane receptor (TMR).

[0072] In some embodiments, the protein of interest can be a ligand-gated ion channel -linked receptor or an enzyme-linked receptor. Non-limiting embodiments of a ligand-gated ion channel-linked receptor can Na+, K+, Ca2+, or CT channels. Non-limiting embodiments of an enzyme-linked receptor can be a receptor tyrosine kinase, tyrosine-kinase-associated receptor (e g., enzymes that associate with cytokines), receptor-like tyrosine phosphatase (e.g., that remove phosphate groups from tyrosines of intracellular proteins), receptor serine / threonine kinase, receptor guanylyl cyclase, or histidine-kinase-associated receptor. In some embodiments, the protein of interest can be a tumor-specific antigen (TSA) or tumor-associated antigen (TAA).

[0073] In some embodiments, the protein of interest can be a transporter. In some embodiments, the protein of interest can be an ion transporter.

[0074] In some embodiments, the molecule that is targeted by the first moiety of a fusion protein (i.e., protein of interest) can be a different molecule than the molecule targeted by the second moiety (e.g., transferrin receptor) of a fusion protein.

[0075] In some embodiments, the fusion protein is a single molecule. In some embodiments, the fusion protein can be a single polypeptide. In some embodiments, a single polypeptide can contain both the first moiety (Rl) and the second moiety (R3) of a fusion protein.

[0076] In some embodiments, the first moiety (Rl) can be an antigen or epitope to which the protein of interest can bind. In some embodiments, the antigen or epitope can bind to a receptor on a cell. In some embodiments, the antigen or epitope can be a ligand for the receptor. In embodiments, the receptor can be a chimeric antigen receptor (CAR).

[0077] In some embodiments, the antibody that is the first moiety (Rl) can be an scFv, Fab, single-domain antibody, nanobody, monobody, DARP in or affibody. Antibody fragments and other molecules that can be used are described in the section titled, “Antibodies” in this application.

[0078] In embodiments, the second moiety (R3) binds to a transferrin receptor or TR. In some embodiments, the receptor or membrane protein bound by the second moiety (R3) is an internalizing receptor or membrane protein. In some embodiments, the internalizing receptor or membrane protein can mediate endocytosis. In some embodiments, the endocytosis can involve clathrin-coated pits. In some embodiments, the endocytosis may be clathrin independent. In some embodiments, the second moiety (R3) can bind a receptor that mediates phagocytosis. In embodiments, the second moiety (R3) can also be an antibody, antibody fragment, or other molecule.

[0079] In some embodiments, the first and / or second moi eties can be polypeptides, ligands, aptamers, and the like.

[0080] In embodiments, a non-limiting list of POIs that can be targeted by fusion proteins includes receptor tyrosine kinases (RTK) and transmembrane receptors (TMR) (Xu, Yanjie, et al. "Endocytosis and membrane receptor internalization: implication of F-BAR protein Carom." Frontiers in bioscience (Landmark edition) 22 (2017): 1439). In embodiments, RTKs can include colony stimulating factor receptors, epidermal growth factor receptors, tyrosine kinase receptors, fibroblast growth factor receptors, insulin-like growth factor receptors, platelet-derived growth factor receptors, transforming growth factor receptors and the like. In some embodiments, TMRs can include folate receptors, interleukin receptors (e.g., IL-2 receptors), low density lipoprotein receptors, transferrin receptors and the like.

[0081] In some embodiments, the second moiety (R3) can bind to a transferrin receptor (TfR) and is a non-competitive transferrin receptor binder that does not compete or competes insignificantly with endogenous (wild-type, full-length transferrin) transferrin for binding to transferrin receptor. In some embodiments, the TR binder or TR binding means (also known as ameans for binding TR) that does not compete or competes insignificantly with endogenous Tf for binding to TfR can be more efficient in binding, internalizing and / or degrading cell surface molecular targets (e.g., protein of interest or POI) than TransTAC molecules having a TR binder or TR binding means (also known as a means for binding TR) that is competitive with endogenous Tf for binding to TfR.

[0082] In some embodiments, a competitive inhibitor of Tf binding to TfR can prevent or reduce Tf binding to TfR. In some embodiments, a competitive inhibitor of Tf binding to TfR does not bind to a TfR simultaneously with the non-competitive inhibitor (they both cannot bind to the same receptor). In some embodiments, a non-competitive inhibitor of Tf binding to TfR can bind to a TfR simultaneously with Tf binding to TfR (both molecules can simultaneously bind to a TfR). In some embodiments, a non-competitive inhibitor can insignificantly compete with Tf for binding to TfR. In some embodiments, insignificantly compete means that that less than 50, 40, 30, 20, 10, 5 or 1% of non-competitive inhibitor molecules that bind to TfR inhibit a Tf from binding to TfR. In some embodiments, the non-competitive transferrin receptor binder binds to a different region of the transferrin receptor than does Tf. In some embodiments, the transferrin receptor binders used in the molecules disclosed herein are VHHA, VHHA-12, VHHA-5, VHHA-7 or VHHB. Other non-competitive transferrin receptor binders can be used.

[0083] In some embodiments, when a non-competitive inhibitor is added to TfR in the presence of Tf, binding of Tf to TfR is not affected. In some embodiments, when increasing amounts of a non-competitive inhibitor are added to TfR in the presence of Tf, binding of Tf to TfR is affected less than if increasing amounts of a competitive inhibitor, instead of the non- competitive inhibitor, were used.

[0084] In some embodiments, the second moiety binds to a transferrin receptor (R3 or TR binder or TR binding means (also known as a means for binding TR)) on a cell. In some embodiments, the receptor or membrane protein bound by the second moiety is an internalizing receptor or membrane protein. In some embodiments, the TR binder or TR binding means (also known as a means for binding TR) can mediate endocytosis. In embodiments, the second moiety can also be an antibody or antibody fragment that binds the transferrin receptor.

[0085] In some embodiments, the second moiety (R3) can be an antibody or antibody fragment that can bind transferrin receptor. In some embodiments, the R3 does not compete or competes insignificantly with endogenous Tf for binding to TfR. In some embodiments, theantibody or antibody fragment thereof (e.g., nanobody) that does not compete or competes insignificantly with endogenous Tf for binding to TfR can be VHHA or VHHB. VHHA or VHHB that have certain amino acid substitutions (i.e., VHHA-12, VHHA-5, and VHHA-7) can also be non-competitive with endogenous transferrin for binding to transferrin receptor. In some embodiments, VHHA can be more efficient in binding, internalizing and / or degrading POI targets than TransTAC molecules having a TR binder or TR binding means (also known as a means for binding TR) that is competitive with endogenous Tf for binding to TfR. In some embodiments, VHHB can be more efficient in binding, internalizing and / or degrading POI targets than TransTAC molecules having a TR binder or TR binding means (also known as a means for binding TR) that is competitive with endogenous Tf for binding to TfR.

[0086] In some embodiments, the internalizing receptor or membrane protein can be a transferrin receptor (TfR). The transferrin receptor can be transferrin receptor 1 or transferrin receptor 2.

[0087] In some embodiments, transferrin receptor can have a high endocytosis rate of around 500 molecules per cell per second, making it good for inducing protein endocytosis. In some embodiments, transferrin receptor expression can be expressed in a variety of cells and tissues. In some embodiments, transferrin receptor expression can be expressed in healthy tissues. In some embodiments, transferrin receptor expression can be expressed in non-healthy (e.g., disease) tissues. In some embodiments, transferrin receptor expression can efficiently endocytose and degrade target proteins (POI) when the transferrin receptor is expressed. Transferrin receptor can be expressed in tissues from organs including, but not limited to brain, liver, breast, lung, colon, pancreas, skin, spleen, lymph nodes, bone marrow, thymus, kidneys, heart, and the like.

[0088] In some embodiments, the second moiety (R3) can be an antibody, antibody fragment, or other molecule (e.g., nanobody) that can bind the internalizing receptor or membrane protein. In some embodiments, the second moiety (R3) can be a scFv, Fab, single-domain antibody, nanobody, monobody, DARP in or affibody.

[0089] In some embodiments, H7 is competitive with transferrin for binding to TfR. M16 is competitive with transferrin for binding to TfR.

[0090] Variable Domain of Camelid Heavy Chain-only (VHH) antibodies that bind to transferrin receptor are disclosed in U.S. Patent Publication Number 2023 / 0414780 Al,published on December 28, 2023, and fded on June 22, 2023, and which is incorporated herein by reference.

[0091] In one embodiment, an amino acid sequence of a competitive TRB, H7, 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:

[0092] H7 scF V-LC (SEQ ID NO : 1 ) :

[0093] SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNE RPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLG*

[0094] H7 scFV-HC (SEQ ID NO:2):

[0095] QVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVI SYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPD YWGQGTLVTVSS

[0096] H7 -scFv (SEQ ID NO: 3)

[0097] SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNE RPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGG GGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKG LEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSG YGDYPD YWGQGTLVTVSS

[0098] M16 (SEQ ID NO: 4):

[0099] SELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNE RPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGG GGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRYPFHHHDHHWVRQAPGKG LEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSG YGDYPD YWGQGTLVTVSS

[0100] VHHA (SEQ ID NO: 146):

[0101] EVQLVESGGGVVQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTA TGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVS S

[0102] VHHB (SEQ ID NO: 148)

[0103] EVQLVESGGGVVQPGGSLRLSCAASGEIFSINFMRWYRQAPGKQREWVAGFTRDGSTNYPDSAKGRFTISRDNAKNTVYLQIDSLKPEDTAVYYCYMLDTWGQGTQV TVSS

[0104] TfRl includes epitopes that are recognized and bound by the natural TFR1 ligand Transferrin (Tf) (Tf-competitive epitopes) and epitopes that are not recognized / bound by Tf (Tf non-competitive epitopes). TransTAC designs including second moi eties (R3) with binders that compete with natural transferrin (Tf) for binding to Tf competitive epitopes (called Tf competitive TransTACs, e.g., vl.O including H7 as a binder) can affect iron import and cause toxicities to certain cells and tissues. TransTAC designs including second moieties (R3) that do not compete with endogenous transferrin for binding to non-competitive epitopes (non- competitive TransTACs) can be effective at degrading a POI while reducing toxicity. These binders can be non-competitive with transferrin in binding to transferrin receptor. In some embodiments, non-competitive TR binder or TR binding means (also known as a means for binding TR) can limit toxicity that can occur when transferrin binding to transferrin receptor is affected (as when R3 is competitive with transferrin for binding to TfR).

[0105] In some embodiments, an antibody or antibody fragment that can bind a transferrin receptor (TR) can be a nanobody. This nanobody can be called “VHHA.” In some embodiments, VHHA can bind to a non-competitive TfRl epitope. Nanobodies VHHA and VHHB can bind to non-competitive TfRl epitopes. TransTACs including VHHA and / or VHHB are non-competitive TransTACs that can drive POI degradation independently of the presence of Tf. VHHA and VHHB TransTACs can induce POI degradation potently and effectively.

[0106] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including a molecule (e.g., a peptide, a nanobody, VHHA, VHHB) that can bind to a non-competitive epitope in an internalizing molecule (e.g., a non-competitive epitope in TfRl) can drive the internalization and degradation of the POI.

[0107] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including VHHA can bind to TfR and drive POI internalization / degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including VHHA can bind to a non-competitive epitope in TfR and drive POI degradation. In some embodiments, a TransTACincluding a first moiety (R1 ; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including a TRB that is non-competitive with transferrin in binding a transferrin receptor can bind to a epitope in TfR and drive POI degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including VHHA can bind to TfR and drive POI degradation more efficiently and potently than a TransTAC including the same POI and a second moiety (R3) including a moiety that can bind a competitive TfRl epitope (e.g., H7).

[0108] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including VHHB can bind to TfR and drive POI internalization / degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including VHHB can bind to a non-competitive epitope in TfR and drive POI degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including H7 can bind to a competitive epitope in TfR and drive POI degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind any of the POI described herein, and a second moiety (R3) including VHHB can bind to TfR and drive POI degradation more efficiently and potently than a TransTAC including the same POI and a second moiety (R3) including a moiety that can bind a competitive TfRl epitope (e.g., H7).

[0109] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CD20, and a second moiety (R3) including VHHA can bind to a non-competitive epitope in TfR and drive CD20 degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CD20, and a second moiety (R3) including VHHA can bind to TfR and drive POI degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means(also known as a means for binding POT)) including a molecule that can bind CD20, and a second moiety (R3) including VHHA can bind to TfR and drive CD20 degradation more efficiently and potently than a TransTAC including CD20 and a second moiety (R3) that can bind a competitive TfRl epitope (e.g., H7). In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means (also known as a means for binding TRB) that binds a transferrin competitive epitope.

[0110] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind EGFR, and a second moiety (R3) including VHHA can bind to a non-competitive epitope in TfR and drive EGFR degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind EGFR, and a second moiety (R3) including VHHA can bind to TfR and drive EGFR degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind EGFR, and a second moiety (R3) including VHHA can bind to TfR and drive EGFR degradation more efficiently and potently than a TransTAC including EGFR and a second moiety (R3) that can bind a competitive TfRl epitope (e.g., H7). In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope. In some embodiments, non-competitive TR binders or TR binding means (also known as a means for binding TR) can limit toxicity thatcan occur when transferrin binding to TfR is affected by using an R3 that competes with transferrin for binding to TfR.[001111 In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind a CAR, and a second moiety (R3) including VHHA can bind to a non-competitive epitope in TfR and drive CAR degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CAR, and a second moiety (R3) including VHHA can bind to TfR and drive CAR degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CAR, and a second moiety (R3) including VHHA can bind to TfR and drive CAR degradation more efficiently and potently than a TransTAC including CAR and a second moiety (R3) that can bind a competitive TfRl epitope (e.g., H7). In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope.

[0112] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CD20, and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to a non-competitive epitope in TfR and drive CD20 degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CD20, and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to TfR and drive POI degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CD20, and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to TfR anddrive CD20 degradation more efficiently and potently than a TransTAC including CD20 and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) that can bind a competitive TfRl epitope (e g., H7). In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TRB that binds a transferrin competitive epitope.

[0113] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind EGFR, and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to a non-competitive epitope in TfR and drive EGFR degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind EGFR, and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to TfR and drive EGFR degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind EGFR, and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to TfR and drive EGFR degradation more efficiently and potently than a TransTAC including EGFR and a second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) that can bind a competitive TfRl epitope (e.g., H7). In some embodiments, a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means (also known as a means for binding TR) that binds a transferrin competitive epitope. In some embodiments, a TR binder or means for binding TR that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TRB that binds a transferrin competitive epitope.

[0114] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind a CAR, anda second moiety (R3; TR binder or TR binding means (also known as a means for binding TR)) including VHHB can bind to a non-competitive epitope in TfR and drive CAR degradation. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CAR, and a second moiety (R3) including VHHB can bind to TfR and drive CAR degradation. In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind CAR, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to TfR and drive CAR degradation more efficiently and potently than a TransTAC including CAR and a second moiety (R3) that can bind a competitive TfRl epitope (e.g., H7). In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TRB that binds a transferrin competitive epitope.

[0115] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to TfRl with a Kd at least about 2, 4, 5, 10, 30, 50, 100, 300, 400, 600, 1000, 1500, 2000 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3;TR binder or TR binding means) including a binder that can bind to H7. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to TfRl with a Kd between about 10 and about 100 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to H7. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to an internalizingmolecule (e.g., TfRl) with a Kd at least about 100 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder (e.g., H7) that can bind to a competitive epitope in an internalizing molecule (e g TfRl).

[0116] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to an internalizing molecule (e.g., TfRl) with a Kd at least about 100 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to a competitive epitope in an internalizing molecule (e.g. TfRl). In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to TfRl with a Kd of about 1.7 nM (nanomolar) and the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to a competitive epitope (H7) in an internalizing molecule (e.g. TfRl) can be about 160 pM (picomolar). In some embodiments, a TR binder that binds a transferrin non- competitive epitope (e.g., VHHA) may not bind to transferrin receptor better or substantially better than a TRB that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means that binds a transferrin competitive epitope.

[0117] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to TfRl with a Kd at least about 2, 4, 5, 10, 30, 50, 100, 300, 400, 600, 1000, 1500, 2000 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder orTR binding means) including a binder that can bind to H7. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to TfRl with a Kd between about 10 and about 100 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to H7. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to an internalizing molecule (e.g., TfRl) with a Kd at least about 100 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder (e.g., H7) that can bind to a competitive epitope in an internalizing molecule (e.g. TfRl).

[0118] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to an internalizing molecule (e.g., TfRl) with a Kd at least about 100 times the Kd of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to a competitive epitope in an internalizing molecule (e.g. TfRl). In some embodiments, the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to TfRl with a Kd of about 2.7 nM (nanomolar) and the TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to a competitive epitope (H7) in an internalizing molecule (e.g. TfRl) can be about 160 pM (picomolar). In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope (e.g., VHHB) may not bind to transferrin receptor better orsubstantially better than a TRB that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means that binds a transferrin competitive epitope.

[0119] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to TfRl with an affinity at least about 1, 5, 10, 50, 100, 2000, 500, 1000 higher that a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to H7.In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TRB that binds a transferrin competitive epitope. In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means that binds a transferrin competitive epitope.

[0120] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to TfRl with an affinity at least about 1, 5, 10, 50, 100, 2000, 500, 1000 higher that a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder that can bind to H7. In some embodiments, a TR binder or TR binding means that binds a transferrin non-competitive epitope may not bind to transferrin receptor better or substantially better than a TR binder or TR binding means that binds a transferrin competitive epitope. In some embodiments, a TR binder that binds a transferrin non- competitive epitope may drive internalization and / or degradation of a POI better than a TR binder or TR binding means that binds a transferrin competitive epitope.

[0121] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD- L1 and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to TfRand drive PD-L1 degradation independently of the presence of natural transferrin (Tf). In some embodiments binding of the TransTAC including VHHA to TfRl is non-competitive with natural Tf.

[0122] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1 and a second moiety (R3; TR binder or TR binding means) including VHHB can bind to TfR and drive PD-L1 degradation independently of the presence of natural transferrin (Tf). In some embodiments binding of the TransTAC including VHHB to TfRl is non-competitive with natural Tf.

[0123] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can internalize and / or degrade the PD-L1 (e.g., TfRl) with an IC50 at least about 1, 2, 4, 5, 10, 30 times smaller than the IC50 of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder (e.g., H7) that binds to a competitive epitope in an internalizing molecule (e.g. TfRl). In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can internalize and / or degrade the PD-L1 with an IC50 between about 0.05 to about 0.5 nM. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including H7 can internalize and / or degrade the PD-L1 with an IC50 of about 1.1 mM. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including H7 can internalize and / or degrade PD-L1 with an IC50 of about 1.2 mM. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including H7 can internalize and / or degrade PD-L1 with an IC50 of about 1.7 mM.

[0124] In some embodiments, a TransTAC including a first moiety (R1 ; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can internalize and / or degrade PD-L1 with an IC50 at least about 1, 2, 4, 5, 10, 30 times smaller than the IC50 of a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder (e.g., H7) that binds to a competitive epitope in an internalizing molecule (e.g. TfRl). In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHB can internalize and / or degrade PD-L1 with an IC50 between about 0.05 to about 0.5 nM. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including H7 can internalize and / or degrade PD-L1 with an IC50 of about 0.26 mM. In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including H7 can internalize and / or degrade PD-L1 with an IC50 of about 0.1 mM.

[0125] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including VHHA can bind to, internalize and / or degrade the POI using an internalizing molecule (e.g. TfRl) with at least about 1, 5, 10, 50, 100, 200, 500, or 1000 times higher than a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder (e.g., H7) that can bind to a competitive epitope in an internalizing molecule (e.g. TfRl).

[0126] In some embodiments, a TransTAC including a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3) including VHHB can bind to an internalizing molecule (e.g. TfRl) can bind to, internalize and / or degrade the POI with an affinity at least about 1, 5, 10, 50, 100, 200, 500, or 1000 times higher than the affinity of a TransTAC including a first moiety (Rl; POIB orPOI binding means (also known as a means for binding POI)) including a molecule that can bind PD-L1, and a second moiety (R3; TR binder or TR binding means) including a binder (e.g., H7) that can bind to a competitive epitope in an internalizing molecule (e.g. TfRl).

[0127] In some embodiments, a TransTAC including VHHA can bind to, internalize and / or degrade a POI with a potency of about between 0.01 and 0.03 nM IC50, about between 0.02 and 0.05 nM IC50, about between 0.04 and 0.1 nM IC50, about between 0.08 and 0.2 nM IC50, about between 0.15 and 0.3 nM IC50, about between 0.25 and 0.5 nM IC50, about between 0.4 and 1 nM IC50. In some embodiments, a TransTAC including VHHA (SEQ. ID NO: 146-147) can bind to, internalize and / or degrade a POI with a potency of about 0.2 nM IC50. In some embodiments, a TransTAC including VHHA (SEQ. ID NO: 146-147) and a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) that can bind, internalize and / or degrade PD-L1 with a potency of about 0.17 nM IC50. In some embodiments, a TransTAC including VHHA (SEQ. ID NO: 146-147) and a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) that can bind PD-LI can bind to, internalize and / or degrade PD-LI with a potency of about 0.15 nM IC50.

[0128] In some embodiments, a TransTAC including VHHA can degrade a POI with an efficiency of between about 50% and about 60%, between about 55% and about 65%, between about 65% to about 75%, between about 70% and about 80%, between about 80% to 90%, or between about 85% and about 95%, or between about 90% and about 100%. In some embodiments, a TransTAC including a VHHA can degrade a POI with an efficiency of about 80%.

[0129] In some embodiments, a TransTAC including VHHB can degrade a POI with a potency of about between 0.01 and 0.03 nM IC50, about between 0.02 and 0.05 nM IC50, about between 0.04 and 0.1 nM IC50, about between 0.08 and 0.2 nM IC50, about between 0.15 and 0.3 nM IC50, about between 0.25 and 0.5 nM IC50, about between 0.4 and 1 nM IC50. In some embodiments, a TransTAC including VHHB (SEQ. ID NO: 148-149) can degrade a POI with a potency of 0.1 nM IC50. In some embodiments, a TransTAC including VHHB (SEQ. ID NO: 148-149) and a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) that can bind PD-LI and can degrade PD-LI with a potency of about 0.1 nM IC50. In some embodiments, a TransTAC including VHHB (SEQ. ID NO: 148-149) and a first moiety(R1 ; POIB or POI binding means (also known as a means for binding POI)) that can bind PD-LI and can degrade PD-LI with a potency of about 0.26 nM IC50.

[0130] In some embodiments, a TransTAC including VHHB can degrade a POI with an efficiency of between about 50% and about 60%, between about 55% and about 65%, between about 65% to about 75%, between about 70% and about 80%, between about 80% to 90%, or between about 85% and about 95%, or between about 90% and about 100%. In some embodiments, a TransTAC including VHHB can degrade a POI with an efficiency of about 100%. In some embodiments, a TransTAC including VHHB can degrade a POI with an efficiency of about 99%. In some embodiments, a TransTAC including VHHB can degrade a POI with an efficiency of about 98%. In some embodiments, a TransTAC including VHHB can degrade a POI with an efficiency of about 97%. In some embodiments, a TransTAC including VHHB can degrade a POI with an efficiency of about 96%.

[0131] In some embodiments, a TransTAC includes a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) that binds to any of the first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) targets described herein, and a second moiety (R3; TR binder or TR binding means) that binds to VHHB. In some embodiments, a TransTAC includes a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) that binds to any of the first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) targets described herein, and a second moiety (R3) that binds to TfR and / or internalizes and / or degrades the target with an IC50 of about 0.26 (FIG. 4A). In some embodiments, a TransTAC includes a first moiety (Rl; POIB or POI binding means (also known as a means for binding POI)) that binds to PD-LI, and a second moiety (R3; TR binder or TR binding means) that binds to TfR and / or internalizes and / or degrades PD-LI with an IC50 of about 0.26 (FIG. 4A).

[0132] In some embodiments, a TransTAC including VHHA can bind to TfRl with a KD of about 2.7 nM. In some embodiments, a TransTAC including VHHB can bind to TfRl with a KD of about 1.7 nM. In some embodiments, a TransTAC including H7 can bind to TfRl with a KD of 160 pM.

[0133] In some embodiments, a TransTAC including VHHA and a first motif that binds to PD-LI can bind to TfRl more efficiently than a TransTAC including H7 and a first motif that binds to PD-LI (FIG. 4A). In some embodiments, a TransTAC including VHHB and a firstmotif that binds to PD-L1 can bind to TfRl more efficiently than a TransTAC including H7 and a first motif that binds to PD-L1. In some embodiments, VHHA and VHHB can bind TfR similarly to H7.

[0134] In some embodiments, a TransTAC including VHHA and a first motif that binds to PD-L1 can degrade a POI more potently than a TransTAC including H7 and a first motif that binds to PD-L1. In some embodiments, a TransTAC including VHHB and a first motif that binds to PD-L1 can degrade a POI more potently than a TransTAC including H7 and a first motif that binds to PD-L1. In some embodiments, a TransTAC including VHHA and a first motif that binds to PD-L1 can degrade a POI more efficiently than a TransTAC including H7 and a first motif that binds to PD-L1. In some embodiments, a TransTAC including VHHB and a first motif that binds to PD-L1 can degrade a POI more efficiently than a TransTAC including H7 and a first motif that binds to PD-L1.

[0135] In some embodiments, a TransTAC including VHHA can degrade a POI more potently than a TransTAC including H7. In some embodiments, a TransTAC including VHHB can degrade a POI more potently than a TransTAC including H7. In some embodiments, a TransTAC including VHHA can degrade a POI more efficiently than a TransTAC including H7. In some embodiments, a TransTAC including VHHB can degrade a POI more efficiently than a TransTAC including H7.

[0136] In one embodiment, an amino acid sequence of VHHA molecules can include the polypeptides 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:

[0137] EVQLVESGGGVVQPGGSLKLSCVASGTDFSINFIRWYRQAPGKQREFVAGFTA TGNTNYADSMKGRFTISRDNTKNAVYLQIDSLKPEDTAVYYCYMLDKWGQGTQVTVS S***(SEQ ID NO: 146)

[0138] In one embodiment, a nucleotide sequence encoding a VHHA nucleotide 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:

[0139] GAGGTGcAGCTGGTGGAGTCTGGGGGAGGCGTGGTGCAGCCTGGGGGGTC TCTAAAACTCTCCTGCGTAGCCTCGGGAACGGACTTCAGTATCAATTTTATACGCTGGTACCGCCAGGCTCCAGGGAAGCAGCGCGAGTTCGTCGCAGGATTTACTGCGACTG GTAACACAAACTATGCAGACTCCATGAAGGGGCGATTCACCATCTCCAGAGACAAC ACCAAGAACGCGGTGTATCTGCAAATAGACAGCCTGAAACCTGAGGACACGGCCGT GTATTACTGCTATATGTTGGACAAGTGGGGCCAGGGGACCCAGGTCACAGTATCCTC C***(SEQ ID NO: 147)

[0140] In embodiments, the VHHA TR binder or TR binding means can be modified as follows:EVOLVESGGGVVQPGGSLKLSCVASGTDFNFVFlRWYROAPGKOREFVAGiZ4TGN7N Y AD SMKGRFTISRDNTKNA VYLQID SLKPEDT AVYYCMMWGOGTO VT VS S * * * (111 amino acids; SEQ ID NO: 146). The italicized, bolded and underlined amino acid sections correspond to CDR1, CDR2, and CDR3, respectively. In embodiments, the shaded amino acids in CDR2 and CDR3 can be substituted for a neutral amino acid(s). In embodiments, the modifications can be amino acid substitutions in CDR2. In embodiments, the modifications can be amino acid substitutions in CDR3.

[0141] Table 1. Amino Acid Sequences of VHHA Molecules Disclosed Herein.

[0142] Table 2 Amino Acid Sequences of Complementarity Determining Regions (CDRs) of VHHA Molecules Disclosed Herein.

[0143] In one embodiment, an amino acid sequence of VHHB 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:

[0144] EVQLVESGGGVVQPGGSLRLSCAASGEIFSINFMRWYRQAPGKQREWVAGFT RDGSTNYPDSAKGRFTISRDNAKNTVYLQIDSLKPEDTAVYYCYMLDTWGQGTQVTVS S***(SEQ ID NO: 148)

[0145] In one embodiment, a nucleotide sequence encoding a VHHB nucleotide 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:

[0146] GAgGTGCAGCTGGTGGAGTCTGGGGGagGCGTGGTGCAGCCTGGGGGGTCT CTGAGACTCTCCTGTGCAGCCTCTGGAGAGATCTTCAGTATCAATTTTATGCGCTGGT ACCGCCAGGCTCCAGGGAAGCAGCGCGAGTGGGTCGCAGGTTTTACTAGGGATGGAAGCACAAACTATCCAGACTCCGCGAAGGGCCGATTCACCATCTCTAGAGACAACGC CAAGAACACGGTGTATCTGCAAATAGACAGCCTGAAACCTGAGGACACGGCCGTCT ATTATTGTTATATGTTGGACACCTGGGGCCAGGGGACCCAGGTCACAGTATCCTCC** *(SEQ ID NO: 149)

[0147] Herein, we disclose new mechanisms for modulating proteins at the cell membrane. In some embodiments, the TransTACs and mechanisms described herein can induce about 100%degradation of a POI or target. Endocytosis is a common machinery of regulating membrane protein recycling and degradation. Among the various transmembrane proteins regulated by endocytosis, transferrin receptor (TfR) is a well-characterized recycling receptor with a rapid internalization rate (500 molecules / cell / s). TfR imports iron by binding to a plasma protein transferrin (Tf) in complex with iron. TfR is expressed in various cell types and tissues including, but not limited to, CD4+ T cells and CD8+ T cells, HEK193T cells, and Raji cells

[0148] The method is a new and generic archetype to degrade proteins with fully recombinant biological molecules. A universal approach for degrading membrane / extracellular proteins can open up unlimited possibilities to manipulate cell behaviors, thus serving as important research tools as well as expanding the PROTAC field’s attempts to target challenging extracellular targets. The fully recombinant nature of TransTAC allows for simple generalization to broad range of targets and optimization of binding properties.

[0149] In some embodiments, the fusion proteins disclosed herein have an antigen to which a receptor can bind and a ligand for an internalizing receptor or membrane protein (e.g., transferrin receptor). In some embodiments, the fusion proteins disclosed herein have an antibody (Rl) that can bind to a POI on the cell surface, and a ligand for an internalizing receptor (TfR) (e.g., a nanobody including VHHA and VHHB).

[0150] In some embodiments, the fusion proteins can be fusion proteins of the formula Rl- R2-R3. In some embodiments, the fusion proteins can be fusion proteins of the formula R3-R2- R1. For example, Rl or R3 can be located at the C-terminus or N-terminus of fusion proteins disclosed herein. In some embodiments, the fusion proteins can be dimers of R1-R2-R3 or R3- R2-R1 (homodimers).

[0151] In some embodiments, Rl can be a protein of interest binder (POIB) or a or POI binding means (also known as a means for binding POI). In some embodiments, the POIB or POI binding means (also known as a means for binding POI) can be an antibody. The POIB or POI binding means (also known as a means for binding POI) can bind to a protein of interest, on a cell surface. In some embodiments, the POIB or POI binding means (also known as a means for binding POI) can bind to an extracellular domain of a transmembrane protein. In some embodiments, the POIB or POI binding means (also known as a means for binding POI) can bind to an extracellular domain of a receptor or co-receptor, like a CAR, a receptor tyrosine kinase, a checkpoint inhibitor binding molecule, a cell lineage-specific marker, and the like. Insome embodiments, the POIB or POI binding means (also known as a means for binding POI) can bind to an extracellular domain of an epidermal growth factor receptor (EGFR), a programmed death-ligand (PD-L1) or CD20.

[0152] In some embodiments, the POIB or POI binding means (also known as a means for binding POI) can bind to an extracellular domain of a B cell receptor (BCR), human leukocyte antigen (HLA), fibroblast growth factor receptor (FGFR), Notch proteins, or claudin-18.2. Binding of a POIB or POI binding means (also known as a means for binding POI) to other transmembrane proteins is contemplated. The POIB or POI binding means (also known as a means for binding POI) (Rl), as part of a fusion protein (R1-R2-R3), can bind to a POI on the surface of a cell and can result in the POI being internalized and, optionally degraded, as described below.

[0153] In some embodiments, R3 can be a transferrin receptor binder (TR binder) or TR binding means (also known as a means for binding TR). In some embodiments, the TR binder or TR binding means is non-competitive with endogenous transferrin for binding to TfR. The TR binder or TR binding means binds to a transferrin receptor on the surface of cells. In some embodiments, the TR binder or TR binding means can be an antibody that binds to the transferrin receptor. In some embodiments, the TR binder or TR binding means can be a nanobody that binds to the transferrin receptor. In some embodiments, the TR binder or TR binding means can be a nanobody that binds to the transferrin receptor without competing with endogenous Tf for binding to the TfRl. In some embodiments, the TR binder or TR binding means can be VHHA (SEQ IDs NO: 146-147). In some embodiments, the TRB can be VHHB (SEQ IDs NO: 148-149).

[0154] In some embodiments, a TR binder or TR binding means (also known as a means for binding TR can have CDRs. In some embodiments, the CDRs can be a VH CDR1 comprising the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 comprising the amino acid sequence of ITATGNT (SEQ ID NO: 201), and a VH CDR3 comprising the amino acid sequence of YMLDK (SEQ ID NO: 202), a VH CDR1 comprising the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 comprising the amino acid sequence of FTATGNT (SEQ ID NO: 203), and a VH CDR3 comprising the amino acid sequence of AMLDK (SEQ ID NO: 204), or a VH CDR1 comprising the amino acid sequence of GTDFSINF (SEQ ID NO:200), a VH CDR2 comprising the amino acid sequence of FTATGNT (SEQ ID NO: 203), and a VH CDR3 comprising the amino acid sequence of YMADK (SEQ ID NO: 205).[001551 In some embodiments, the TR binder or TR binding means can be a molecule that binds to a transferrin receptor (TfR). In some embodiments, the TR binder or TR binding means can be transferrin or a part of transferrin that can bind to a TfR. In some embodiments, the TR binder or TR binding means can be an antibody that binds to the transferrin receptor. In some embodiments, a TR binder or TR binding means can be non-competitive for binding to a TfR (e.g., VHHA or VHHB). The TR binder or TR binding means (R3), as part of a fusion protein molecule (e.g., R1-R2-R3), can bind to transferrin (Tf) on the surface of a cell and be internalized into the cell. When the POIB or POI binding means (also known as a means for binding POI) (Rl) in the fusion protein binds a protein of interest (POI) on a cell surface, internalization of the TR binder or TR binding means can also cause internalization of the POI. Internalized POIs can be degraded once internalized by a cell.

[0156] In some embodiments, R2 can be a linker of the formula R4-R5 or R5-R4. In some embodiments, R4 can be an Fc region from an antibody. In some embodiments, R4 can be an Fc region from IgG, IgM, IgA, IgE or IgD. In some embodiments, R5 is an optional protein- sensitive linking means. In some embodiments, an Fc region can be (SEQ ID NO: 6):

[0157] DKTHTCPPCP APELLGGP S VFLFPPKPKDTLMISRTPEVTC VVVD VSHEDPEVK FNWYVDGVEVHNAKTI<PREEQYNSTYRVVSVLTVLHQDWLNGKEYI<CI<VSNI<ALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 6)

[0158] 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 the R1-R2-R3 fusion proteins can form through disulfide bonds (1 or more, such as 2 disulfide bonds) between cysteine residues in R2 regions of separate fusion protein molecules. In some embodiments, the disulfide bonds form between R4 in separate fusion molecules (e.g., Fc with disulfides can be a type of dimerization domain). In some embodiments, disulfide bonds form between fusion proteins of a homodimer.

[0159] In some embodiments (e.g., heterodimers), one monomer of the heterodimer can have a “knob”, and the second monomer of the heterodimer can have a “hole” structure. In some embodiments, the knob and hole structures of two monomers can be in the Fc regions (R4) of the monomers. Knob-into-hole technologies are well known in the art (Xu et al., MAbs. 2015 Jan- Feb; 7(1): 231-242).

[0160] Disulfide bonds and knob-into-hole technologies can be example dimerization means (also known as means for dimerizing).

[0161] In certain embodiments, the Fc region can be a variant comprising an amino acid substitution which alters 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 (neonatal Fc receptor) 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 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. 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 one embodiment, the Fc variant-linked molecules can exhibit reduced transport across the epithelium of kidney glomeruli from the vasculature. See Ko, S., Jo, M. & Jung, S.T. Recent Achievements and Challenges in Prolonging the Serum Half-Lives of Therapeutic IgG Antibodies Through Fc Engineering. BioDrugs 35, 147-157 (2021).

[0162] 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 one embodiment, 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 activity are disclosed in PCT Publication No. WO05 / 047327 which is incorporated by reference herein. In certain exemplary embodiments, thefusion proteins disclosed herein comprise an Fc domain having one or more of the following substitutions: V284E, H285E, N286D, K290E and S304D (EU numbering).

[0163] In some embodiments, a molecule disclosed herein can be linked to 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, W005 / 018572, which is incorporated by reference herein in its entirety.

[0164] In some embodiments, the molecules disclosed 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 IgG4 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.

[0165] In some embodiments, the CH2 or CH3 region of the 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 IgGl CH3 domain: generation, mechanisms of function, and implications for design of biological therapeutics." Journal of Biological Chemistry 288.35 (2013): 25154-25164).

[0166] In some embodiments, R4 can be a dimerization domain. 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 fusion protein that is a homodimer or heterodimer).

[0167] 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.

[0168] In some embodiments, the dimerization can form between regions of the fusion proteins that are not R4 regions.

[0169] In some embodiments, R5 can be an optional protease-sensitive linker or protease- sensitive linking means (also known as a means for linking). In some embodiments, R5 is an optional feature. In some embodiments, the optional protease-sensitive linker or protease- sensitive linking means (also known as a means for linking) can be 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 can be a cathepsin-cleavable peptide. In some embodiments, the optional protease-sensitive linker or protease-sensitive linking means (also known as a means for linking) can be GGFLGGVRGVDG (SEQ ID NO: 7) or GSGSGGEVRGVDG (SEQ ID NO: 8). Sequences of other optional protease-sensitive linker or protease-sensitive linking means (also known as a means for linking) are disclosed herein (e.g., FK, VA, VK, SEQ ID NO: 7, 8, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, orl45). In some embodiments, sequences that are at least 80, 84, 88, 92 or 96 percent identical to these sequences can be used. Functional alternative amino acid sequences that can be cleaved by a protease (e.g., cathepsin) are known in the art. Use of other optional protease-sensitive linker or protease- sensitive linking means (also known as a means for linking) are contemplated.

[0170] In some embodiments, the optional protease-sensitive linker or protease-sensitive linking means (also known as a means for linking) can modulate efficiency of the fusion protein at internalizing and / or degrading a POI. In some embodiments, the location of the optional protease-sensitive linker or protease-sensitive linking means (also known as a means for linking) in the fusion protein can modulate efficiency of the fusion protein at internalizing and / or degrading a POI. In some embodiments, a fusion protein can include the optional protease- sensitive linker or linking means, cathepsin B-sensitive linker between the Fc domain (R4) and the R3. In some embodiments, a fusion protein includes a cathepsin B-sensitive linker betweenR1 and the Fc domain (R4). Tn some embodiments, a fusion protein including a cathepsin In- sensitive linker between R1 and the Fc domain is more efficient at internalizing and / or degrading a POT than a fusion protein including a cathepsin B-sensitive linker between the Fc domain and the R3.

[0171] In some embodiments, a linkage noted(not R2) is located between various sections of the R1-R2-R3 fusion protein. In some embodiments, a linkage can be located between R2 and R3. In some embodiments, this linkage can be located between R1 and R2. In some embodiments, the linkage can be an optional glycine-rich linker (“GS linker). In some embodiments, a “GS” linker can be a combination of glycine and serine amino acids. In some embodiments, the GS linker can be GSSGGSGGSGGS (SEQ ID NO: 9). Other sequences are possible. In some embodiments, the GS linker can be SGGGG (SEQ ID NO: 10), SGGGSGGG (SEQ ID NO: 11), GSSGGSGGSGGS (SEQ ID NO: 12), GSGS (SEQ ID NO: 13), GSGGS (SEQ ID NO: 14), GSSGSS (SEQ ID NO: 15), GSSSSSS (SEQ ID NO: 16) and the like. In some embodiments, a GS 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 linker, as long as glycine and serine are in the majority. In some embodiments, optionally, a linker (e.g., glycine-rich) can be comprised between R2 and R3. In some embodiments, optionally, a linker can be comprised between R1 and R2.

[0172] In some embodiments, the GS linkers are one to 50 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 on March 14, 2024). In some embodiments, the GS linker is 12 amino acids in length. In some embodiments, the GS linker can be 20, 25, 30, 35, 40, 45 or 50 amino acids in length. In embodiments, the amino acids include a combination of one or more glycine(s) and / or serine(s). In embodiments, the peptide linker comprises the amino acid sequence comprising GGGGS (SEQ ID NO: 311). In embodiments, the peptide linker comprises or consists of 2, 3, 4, 5, 6, or 7 consecutive repeats of the amino acid sequence GGGGS (SEQ ID NO: 312). Particularly in embodiments, the peptide linker comprises or consists of the amino acid sequence GGGGS GGGGS GGGGS (SEQ ID NO: 313).

[0173] In some embodiments, fusion proteins that can bind to a dimeric TfR can be more efficient at internalizing and / or degrading a POI than a fusion protein that can bind a monomericTfR (e.g., that can bind to one TfR). In some embodiments, fusion proteins can include one copy of R3. In some embodiments, fusion proteins can include two copies of R3. In some embodiments, fusion proteins can include three or more copies of R3. In some embodiments, different R3s can be combined in a fusion protein.

[0174] In some embodiments, a fusion protein with two R3 can be more efficient at internalizing and / or degrading a POI than a fusion protein including two R1 (e.g., v0.6 vs. v0.7). In some embodiments, a fusion protein with two R3 can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI than a fusion protein including two R1.

[0175] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively, and another monomer including an Fc (hole), a linker (not R2), and one copy of R3, wherein both monomers are bound by knob / hole interactions (e.g., v0.6 FIG. 8A) can be more efficient at internalizing and / or degrading a POI (e.g., CD20, EGFR, PD-L1, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.7 in FIG. 8A).

[0176] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively; and another monomer including an Fc (hole), a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.6) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI (e.g., CD20, EGFR, PD-L1, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.7).

[0177] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively; and another monomer including an Fc (hole) a linker (not R2) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.6) can be more efficient at internalizing and / or degrading a POI than heterodimeric fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of CD19NT. 1, a linker (not R2), an Fc (knob), a linker (not R2) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.7).

[0178] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively, and another monomer including an Fc (hole) a linker (not R2) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.6) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI (e.g., CD 19 binding receptor) than heterodimeric fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), an Fc (knob), a linker (not R2) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions^. g., v0.7).

[0179] In some embodiments, a fusion protein with two R3 can be more efficient at internalizing and / or degrading a POI than a fusion protein including one R3 (FIG. 8A). In some embodiments, a fusion protein with two R3 can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI than a fusion protein including one R3.

[0180] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, and another monomer including one copy of Rl, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by the Fc (e.g., v0.5 FIG. 8A) can be more efficient at internalizing and / or degrading a POI (e.g., CD20, EGFR, PD-L1, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.7 in FIG. 8A).

[0181] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, and another monomer including one copy of Rl, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by the Fc (e.g., v0.5 in FIG. 8A) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI (e.g., CD20, EGFR, PD-L1, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), and an Fc, and a second monomer including from N terminus to Cterminus one copy of Rl, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.7 in FIG.8A)

[0182] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of a CD19NT.1 binder, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, and another monomer including one copy of a CD19NT.1 binder, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by the Fc (e.g., v0.5 FIG. 8A) can be more efficient at internalizing and / or degrading a POI (e.g., CD20, EGFR, PD-L1, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of a CD19NT.1 binder, a linker (not R2), and an Fc, and a second monomer including from N terminus to C terminus one copy of a CD19NT.1 binder, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e g., v0.7 in FIG.8A)

[0183] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of a CD19NT.1 binder, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, and another monomer including one copy of a CD19NT.1 binder, a linker (not R2), an Fc, a linker (not R2), and one copy of R3 respectively, wherein both monomers are bound by the Fc (e.g., v0.5 in FIG. 8A) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient more efficient at internalizing and / or degrading a POI (e.g., CD20, EGFR, PD-L1, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of a CD19NT.1 binder, a linker (not R2), and an Fc, respectively, and a second monomer including from N terminus to C terminus one copy of a CD19NT.1 binder, a linker (not R2), an Fc, a linker (not R2), and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.7 in FIG. 8A).

[0184] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), and an Fc (hole), respectively, and asecond monomer including from N terminus to C terminus one copy of R3, a linker (not R2) and an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.8; FIG. 8A), can be more efficient at internalizing and / or degrading a POI than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (hole), a linker (not R2), and one copy of R3, respectively, and another monomer including an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.9; FIG. 8A).

[0185] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of R3, a linker (not R2), and an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.8), can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI (e.g., CD20, PD-L1, EGFR, and the like) than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (hole), a linker (not R2), and one copy of R3, respectively, and another monomer including an Fc (knob), wherein both monomers are bound by knob / hole interactions (e.g., v0.9).

[0186] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), and an Fc (hole), and a second monomer including from N terminus to C terminus one copy of R3, a linker (not R2) and an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.8), can be more efficient at internalizing and / or degrading a POI than heterodimeric fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), an Fc (hole), a linker (not R2), and one copy of R3, respectively, and another monomer including an Fc (knob), wherein both monomers are bound by knob / hole interactions (e.g., v0.9).

[0187] In some embodiments, heterodimeric fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), and an Fc(hole), respectively, and a second monomer including from N terminus to C terminus one copy of R3, a linker (not R2), and an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., v0.8), can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI than fusion proteins including one monomer including from N terminus to C terminus one copy of CD19NT.1, a linker (not R2), an Fc (hole), a linker (not R2), and one copy of R3, respectively, and another monomer including an Fc (knob), wherein both monomers are bound by knob / hole interactions (e.g., v0.9).

[0188] In some embodiments, a fusion protein can include two or more copies of an R3 located in tandem (e.g., two or more R3 contiguous to each other; one behind the other; e.g., vl.2 in FIG. 9A). In some embodiments, more than two R3 can be in tandem.

[0189] In some embodiments, a fusion protein with two or more R3s located in tandem (e.g., two or more R3 contiguous to each other; e.g., vl.2 in FIG 9A and SEQ ID NO: 150-151, FIG. 7A) can be more efficient at internalizing and / or degrading a POI than a fusion protein including two R3 that are not in tandem (e.g., vl .4 in FIG 9A; SEQ IDs NO: 152-153; FIG. 7B; and vl.O in FIG. 1A)

[0190] In some embodiments, a fusion protein with two R3s located in tandem (e.g., two R3 contiguous to each other; e.g., vl.2 in FIG 9A and SEQ ID NO: 150-151, FIG. 7A) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI than a fusion protein including two R3 that are not in tandem (e.g., vl .4 in FIG. 9A; SEQ IDs NO: 152-153 in FIG. 7B; and vl.O in FIG. 9A).

[0191] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), respectively, and another monomer including from N terminus to C terminus two in tandem copies of R3, and an Fc(knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl .2; FIG. 9A) can be more efficient at internalizing and / or degrading a POI than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), and one copy of R3, respectively, and a second monomer including from N terminus to C terminus an Fc (hole) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.4; FIG. 7 and FIG. 9).

[0192] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), respectively, and another monomer including from N terminus to C terminus two in tandem copies of R3, and an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.2), can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI than fusion proteins including one monomer including from N terminus to C terminus one copy of Rl, a linker (not R2), an Fc (knob), and one copy of R3, respectively, and a second monomer including from N terminus to C terminus an Fc (hole) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.4; FIG. 7 and FIG. 9).

[0193] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of a or POI binding means (also known as a means for binding POI), a linker (not R2), an Fc (knob), respectively, and another monomer including from N terminus to C terminus two in tandem copies of R3, and an Fc (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.2), can be more efficient at internalizing and / or degrading a POI than heterodimeric fusion proteins including one monomer including from N terminus to C terminus one copy of an PD-L1 binder, a linker (not R2), an Fc (knob), and one copy of R3, respectively, and a second monomer including from N terminus to C terminus an Fc (hole) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.4; FIG. 7 and FIG. 9).

[0194] In some embodiments, fusion proteins including one monomer including from N terminus to C terminus one copy of a or POI binding means (also known as a means for binding POI), a linker (not R2), an Fc (knob), respectively, and another monomer including from N terminus to C terminus two in tandem copies of R3, and an FC (knob), respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.2), can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI than heterodimeric fusion proteins including one monomer including from N terminus to C terminus one copy of a POIB or POI binding means (also known as a means for binding POI), a linker (not R2), an Fc (knob), and one copy of R3, respectively, and a second monomer including from N terminus to C terminus an Fc (hole) and one copy of R3, respectively, wherein both monomers are bound by knob / hole interactions (e.g., vl.4; FIG. 7 and FIG. 9).

[0195] In some embodiments, the location of an optional protease-sensitive linker or protease- sensitive linking means (also known as a means for linking) (e.g., cathepsin sensitive linker) within a fusion protein can modulate the efficiency of the fusion protein at internalizing and / or degrading a POI. In some embodiment, a fusion protein can include a cathepsin B-sensitive linker between the Fc domain and the R3 (e.g., v0.3, FIG. 10). In some embodiments, a fusion protein can include a cathepsin B-sensitive linker between R1 and the Fc domain (e.g., v0.4, FIG. 10A). In some embodiments, a fusion protein including a cathepsin B-sensitive linker between R1 and the Fc domain (e.g., v0.4) can be more efficient at internalizing and / or degrading a POI than a fusion protein including a cathepsin B-sensitive linker between the Fc domain and the R3 (e.g., v0.3; FIG. 10B).

[0196] In some embodiments, a fusion protein including a cathepsin B-sensitive linker between R1 and the Fc domain (e.g., v0.4) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 toabout 100% more efficient at internalizing and / or degrading a POI than a fusion protein including a cathepsin B-sensitive linker between the Fc domain and the R3 (e.g., v0.3; FIG. 10B).

[0197] In some embodiments, a fusion protein including two monomers bound by Fc interactions, each monomer including from N terminus to C terminus and Rl, a cathepsin linker, and Fc, and an R3 (e.g., v0.4) can be more efficient at internalizing and / or degrading a POI than a fusion protein including two monomers bound by Fc interactions, each monomer including from N terminus to C terminus and Rl, and Fc, a cathepsin linker, and an R3 (e.g., v0.3; FIG. 10).

[0198] In some embodiments, a fusion protein including two monomers bound by Fc interactions, each monomer including from N terminus to C terminus and Rl, a cathepsin linker, and Fc, and an R3 (e.g., v0.4) can be at least between about 10 to about 20%, about 15 to about 25%, about 20% to about 30%, about 25 to about 35%, about 30 and about 40%, about 35 and about 45%, about 40% and about 50%, about 45 and about 55%, about 50 to about 60%, about 55 to about 65%, about 60 to about 70%, about 65 to about 75%, about 70% to about 80%, about 75% to about 85%, about 80 to about 90%, about 85% to about 95%, about 90 to about 100% more efficient at internalizing and / or degrading a POI (e.g., CD20, PD-L1, EGFR, CD19 binding chimeric receptor, and the like) than a fusion protein including two monomers bound by Fc interactions, each monomer including from N terminus to C terminus and Rl, and Fc, a cathepsin linker, and an R3 (e.g., v0.3; FIG. 10B).

[0199] In some embodiments, the fusion proteins disclosed 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, the amino acid sequences of the fusion proteins can be labeled as follows:

[0200] Times New Roman font underlined is signal peptide;

[0201] Times New Roman font bolded is anti-protein of interest Fab-heavy chain, scFv, or affibody;

[0202] Times New Roman italicized font is linker encoded by restriction enzyme site creation,

[0203] Times New Roman underlined and bolded font is GS linker;

[0204] Times New Roman underlined, italicized, and bolded font is cleavable linker.

[0205] Couri er New font i s H7 - s cFv;

[0206] Couri er New underl ined font i s Fc domain ;

[0207] Courier New bolded font i s TEV si te;

[0208] Couri er New i tali ci zed font i s fragment from Transferrin,'

[0209] Courier New underlined and bolded font i s Hi s -Tag;

[0210] Courier New bolded, and italicized is light chain, and

[0211] Courier New underlined, italicized, and bolded font is Avi-Tag.

[0212] pDP14-CD19 ETD Hole Fc Nucleic Acid Sequence (SEQ ID NO: 17)

[0213] atgcgAatgcagctgctgctgctgattgcgctgagcctggcgctggtgaccaacagcactagtcccgaggaacctctagtg gtgaaggtggaagagggagataacgctgtgctgcagtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcggga gtccccgcttaaacccttcttaaaactcagcctggggctgccaggcctgggaatccacatgaggcccctggccatctggcttttcatcttcaa cgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtgga gggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagct ccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccac cgagggacagcctgaaccagagcctcagccaggacctcaccatggcccctggctccacactctggctgtcctgtggggtaccccctgact ctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccgg ccagagatatgtgggtaatggagacgggtctgttgttgccccgggccacagctcaagacgctggaaagtattattgtcaccgtggcaacctg accatgtcattccacctggagatcactgctcggccagtactatggcactggctgctgaggactggtggctggaagactagtTCTGGTG GTGGTGGTGAGAATCTGTACTTTCAGAGCTCGGGCGGAGGATCgggtggaggcgagcccaaatc ttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCTGGGCGGACCCAGCGTGT TCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAGCCGAACCCCTGAGGTGA CCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGTAT GTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTACA ACAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCACCAGGACTGGCTGAAC GGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAGAA GACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCCCC CCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGAGCTGTGCCGTGAAAGGC TTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAACGGGCAGCCCGAGAACAA CTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAGCTTCTTCCTGGTGAGCAA GCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGTGTTCAGCTGCTCTGTGA TGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTCTCAGTCTGAGCCCGGGA AAGGGTGGAGGCGGATCCGGCCTGAACGACATCTTCGAGGCTCAGAAAATCGAATG GCACGAAGGCtaa

[0214] pDP14-CD19 ETD Hole Fc Amino Acid Sequence (SEQ ID NO: 18)

[0215] MRMQLLLLIALSLALVTNSZ5PEEPLVVKVEEGDNAVLOCLKGTSDGPTOQ LTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEK AWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMS FHLEITARPVLWHWLLRTGGWKASSGGGGENLYFQSSGGGSGGGEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRD ELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGLNDJFEAQKJE¥HEG*

[0216] pDP16-EGFR-Affibody-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 19)

[0217] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTGGGAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGCGA GCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAGCTA AATGATGCTCAGGCGCCGAAAGTAGACGGCAGCGGCAGCGACAAAACTCACACATG CCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCC AAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGG TGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACC GTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAA AGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATG AGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGC GACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGG ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctggggg aagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttcc gggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccatt gccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggc cgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagc tgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgag ccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtc agctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgac gtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacac cagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagag gatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacgg caaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgt gaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccac cacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatc gccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctg gccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcg acctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctg tacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctg tgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaa gggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacga gaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacg ccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaa cacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgca cctttcgcagacctT AA

[0218] pDP16-EGFR-Affibody-FC-Tf Amino Acid Sequence (SEQ ID NO: 20)[00219J MYRMQLLSC1ALSLALVTNSLOVDNKFNKEMWAAWEE1RNLPNLNGWOMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDG'AG'ADKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT!QKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVAC VKKAS YLDCIRAIAANEADAVTLDAGLVYDA YLAPNNLKPVVAEFYGSKEDPQ TFYYAVAVVKK DSGFQMNQLRGKKS CHTGL GRSAGWNIPIGLL YCDL PEPRKPLEKAVANFFSGS CAPCADGTDF PQL CQL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNT RKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLF KDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREG TCPEAPTDECKPVKWCAL SHHERLKCDEWS VNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPE AGYFAIAWKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMGLL YNKINHCRFDEFFSEGCAPG SKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNPDPWA KNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDC SGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0220] pDP18-EGFR-affibody Nucleic Acid Sequence (SEQ ID NO: 21)

[0221] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTGGGAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGCGA GCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAGCTA AATGATGCTCAGGCGCCGAAAGTAGACGGTGAGAATCTGTACTTTCAGAGCTCGGG CGGAGGATCGGGTGGAGGCCACCACCATCATCACCACCATCACGGATCCGGCCTGAACGACATCTTCGAGGCTCAGAAAATCGAATGGCACGAAGGCggatcctctgggggaagtggaggt agcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacat gaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatg aggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctac ggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggca agaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaag cctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgcc ccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcg tgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcc cgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatct gggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatct gctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccat ccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcg gctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatc atgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaa ctacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacct gggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgg gcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaaggggga cgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggac tacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggt cacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcgg caacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacaccta cgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcg cagacctTAA

[0222] pDP18-EGFR-affibody Amino Acid Sequence (SEQ ID NO: 22)

[0223] MYRMQLLSCIALSLALVTNSLOVDNKFNKEMWAAWEEIRNLPNLNGWQM TAFIASLVDDPSOSANLLAEAKKLNDAOAPKVDGENLYFQSSGGGSGGGHHHHHHHHG SGLNDIFEAQKIEWHEGGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVFPSDG PSVACVKKAS YLDCIRAIAANEADAVTLDAGLVYDA YLAPNNLKPVVAEFYGSKEDPQ TFYYAV AVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCA DGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLFWELLNQAQEHFGKDKSKEFQLFSSPHG KDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLK CDEWSVNSVGKFECVSAETTEDCFAKFMNGEADAMSLDGGFVYFAGKCGLVPVLAENYNKSDNC ED TPEAGYFAIAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNLPMGLL YNKLNHCRFDEFFSE GCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKN PDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKFLRQQQHLFGS NVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEAC TFRRP*

[0224] pDP20-EGFR-Affibody-FC Nucleic Acid Sequence (SEQ ID NO: 23)

[0225] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTGGGA AGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGCGA GCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAGCTA AATGATGCTCAGGCGCCGAAAGTAGACGGCAGCGGCAGCGACAAAACTCACACATG CCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCC AAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGG TGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACC GTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAA AGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGC GACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCA CGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGG ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATAA

[0226] pDP20-EGFR-Affibody-FC Amino Acid Sequence (SEQ ID NO: 24)

[0227] MYRMOLLSCIALSLALVTNSLQVDNKFNKEMWAAWEETRNLPNLNGWOMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDG'AG'ADKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKG FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPGK*

[0228] pDP22-EGFR-affibody Nucleic Acid Sequence (SEQ ID NO: 25)

[0229] ATGCGAATGCAGCTGCTGCTGCTGATTGCGCTGAGCCTGGCGCTGGTGACC AACAGCACTAGTCTGCAGGTAGATAACAAATTCAACAAAGAAATGTGGGCGGCGTG GGAAGAAATTCGCAACCTGCCGAACCTGAACGGCTGGCAGATGACCGCGTTTATTGCGAGCCTGGTGGATGACCCAAGCCAAAGCGCTAACTTGCTAGCAGAAGCTAAAAAG CTAAATGATGCTCAGGCGCCGAAAGTAGACGGCAGCGGCAGCACTAGTTCTGGTGG TGGTGGTGAGAATCTGTACTTTCAGAGCTCGGGCGGAGGATCGGGTGGAGGCCACC ACCATCATCACCACCATCACGGATCCGGCCTGAACGACATCTTCGAGGCTCAGAAA ATCGAATGGCACGAAGGCTAA

[0230] pDP22-EGFR-affibody Amino Acid Sequence (SEQ ID NO: 26)

[0231] MRMQLLLLIALSLALVTNSrALOVDNKFNKEMWAAWEEIRNLPNLNGWO MTAFIASLVDDPSOSANLLAEAKKLNDAOAPKVDGAGATAAGGGGENLYFOSSGGGSGGGHHHHHHHHGSGANDZFEAQKZETfHEG*

[0232] pDP24-CD19-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 27)

[0233] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGcccgaggaacctctagtggtgaaggtggaagagggagataacgctgtgctgcagtgcctcaaggggacctcagat ggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttcttaaaactcagcctggggctgccaggcctgggaatccaca tgaggcccctggccatctggcttttcatcttcaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaag gcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggc ctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctga gatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccagagcctcagccaggacctcaccatggcccctggctcca cactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattg ctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatggagacgggtctgttgttgccccgggccacagctcaaga cgctggaaagtattattgtcaccgtggcaacctgaccatgtcattccacctggagatcactgctcggccagtactatggcactggctgctgag gactggtggctggaagGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGTGCC CAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGG ACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCC ACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGT CCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAG CCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAA CCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGA GTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGG ACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGC AGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACA CGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatcccc agcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccatgccgccaatgaggccgacgccgtga cactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggac ccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacac cggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggcc gtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgca gcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcacc atcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtaca aggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaac caggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacag cgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagag agggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacg agtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgagg ccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagc gacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaa gggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgca gattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaac ctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaa caccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgt ctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggaca aagaggcctgcgtccacaagatcctgcggcagcagcagcacctgtcggcagcaacgtgaccgactgcagcggcaactctgcctgttca gaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctggg cgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0234] pDP24-CD19-FC-Tf Amino Acid Sequence (SEQ ID NO: 28)

[0235] MYRMQLLSCIALSLALVTNSPEEPLVVKVEEGDNAVLOCLKGTSDGPTOO LTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWT HVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLLRTGGWKFDGSGS'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL s PGKGSSGGSGGSGGS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLD CIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQ LRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCP GCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YK DCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFL KVPPRMDAKMYLGYEYVTAFRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKLE CVSAETTEDCLAKFMNGEADAMSLDGGFVYFAGKCGLVPVLAENYNKSDNCEDTPEAGYFALAV VKKSASDL TWDNLKGKKS CHTAVGR TAGWNFPMGLL YNKLNHCRFDEFFSEGCAPGSKKDSSL C KL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD Y ELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKLLRQQQHLFGSNVTDCSGNFCLFR SETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0236] pDP25-pFUSE-Tf-knob-Fc Nucleic Acid Sequence (SEQ ID NO: 29)

[0237] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggacca catgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaa tgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttcta cggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggc aagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaa gcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgc cccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttc gtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagc ccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatc tgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatct gctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccat ccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcg gctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatc atgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaa ctacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacct gggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaa gatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgg gcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaaggggga cgtggctttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggac tacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggt cacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcgg caacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacaccta cgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcg cagacctCCATGGgagcccaaatcttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCT GGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAG CCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGG TGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCC AGGGAGGAGCAGTACGGAAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCA CCAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCA GGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGT GGTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAAC GGGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAG CTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACG TGTTCAGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTC T C AGT C T GAGC C C GGGAAAGggtggctctcatcatcaccatcaccactga

[0238] pDP25-pFUSE-Tf-knob-Fc Amino Acid Sequence (SEQ ID NO: 30)

[0239] MYRMQLLSCIALSLALVTNS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPS VACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAV VKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADG TDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CL DNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKD LLFKDSAHGFLKVPPRMDAKMYLGYEYVTALRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCED TPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEGC APGSKKDSSLCKL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPD PWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNV TDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTF RRPEIEEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK FNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK AKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG SFFLYSKLTVDKSRWQQGNVFSCSWIHEALHNHYTQKSLSLSPGKGGSHHHHHH*

[0240] pDP32-CD19-FC-CD19 Nucleic Acid Sequence (SEQ ID NO: 31)

[0241] atgcgAatgcagctgctgctgctgattgcgctgagcctggcgctggtgaccaacagcactagtcccgaggaacctctagtg gtgaaggtggaagagggagataacgctgtgctgcagtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcggga gtccccgcttaaacccttcttaaaactcagcctggggctgccaggcctgggaatccacatgaggcccctggccatctggcttttcatcttcaa cgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtgga gggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagct ccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccac cgagggacagcctgaaccagagcctcagccaggacctcaccatggcccctggctccacactctggctgtcctgtggggtaccccctgact ctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccgg ccagagatatgtgggtaatggagacgggtctgttgttgccccgggccacagctcaagacgctggaaagtattattgtcaccgtggcaacctg accatgtcattccacctggagatcactgctcggccagtactatggcactggctgctgaggactggtggctggaagactagtTCT GGT G GTGGTGGTGAGAATCTGTACTTTCAGAGCTCGGGCGGAGGATCgggtggaggcgagcccaaatc ttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCTGGGCGGACCCAGCGTGT TCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAGCCGAACCCCTGAGGTGA CCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGTAT GTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTACA ACAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCACCAGGACTGGCTGAAC GGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAGAA GACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCCCC CCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGACCTGTCTGGTGAAAGGC TTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAACGGGCAGCCCGAGAACAA CTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAGCTTCTTCCTGTATAGCAA GCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGTGTTCAGCTGCTCTGTGA TGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTCTCAGTCTGAGCCCGGGA AAGGGTGGAGGCGGATCCggaggtagcggtggttctGGAcccgaggaacctctagtggtgaaggtggaagagggag ataacgctgtgctgcagtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttctta aaactcagcctggggctgccaggcctgggaatccacatgaggcccctggccatctggcttttcatcttcaacgtctctcaacagatgggggg cttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttcc ggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatga gccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccag agcctcagccaggacctcaccatggcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctc ctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatgga gacgggtctgttgttgccccgggccacagctcaagacgctggaaagtattattgtcaccgtggcaacctgaccatgtcattccacctggaga tcactgctcggccagtactatggcactggctgctgaggactggtggctggaagGGCCTGAACGACATCTTCGAGGCT CAGAAAATCGAATGGCACGAAGGCtaa

[0242] pDP32-CD19-FC-CD19 Amino Acid Sequence (SEQ ID NO: 32)

[0243] MRMQLLLLIALSLALVTNS7NPEEPLVVKVEEGDNAVLOCLKGTSDGPTOQ LTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEK AWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWT HVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYYCHRGNLTMS FHLEITARPVLWHWLLRTGGWKrASGGGGENLYFQSSGGGSGGGEPKSCDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPR EEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRD ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGSGGSGPEEPLVVKVEEGDNAVLQCL KGTSDGPTQQLTWSRESPLKPFLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSQDLTMAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMETGLLLPRATAQDAGKYY CHRGNLTMSFHLEITARPVLWHWLLRTGGWKGI.NDZFEAQKZEKHEG*

[0244] pDP44-CD19 NT.1-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 33)

[0245] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGcccgaggaacctctagtggtgaaggtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagat ggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccac gtcaggcccgatgccatctctgtcgtcatcaggaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgaga aggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtg gcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccct gagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggct ccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtc attgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctca agacgctggaaagtggtattgtcaccgtggcaacgtaaccacctcattccacctggaggtaatcgctcggccagtaaaggctcactcagac ctgaggactggtggctggaagGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGT GCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCA AGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTG AGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA TAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCA GCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGG GCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCA AGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCG TGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggt tctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtg atccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgc cgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaaga ggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtc acaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggc tgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacag caccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgag tacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctg aaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaagga cagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctga gagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcg acgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcg aggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaag agcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatct gaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccact gcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctg aacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtg aaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctg tgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaagg acaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctg ttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacct gggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0246] pDP44-CD19 NT. l-FC-Tf Amino Acid Sequence (SEQ ID NO: 34)

[0247] MYRMQLLSCIALSLALVTNSPEEPLVVKVEEGDTAALWCLKGTSDGPTOO LTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTT SFHLEVIARPVKAHSDLRTGGWKFDG'YG'ADKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGKGSSGGSGGSGGS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLD CIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQ LRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCP GCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YK DCHLAQVPSHTVVARSMGGKEDLFWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFL KVPPRMDAKMYLGYEYVTALRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKLE CVSAETTEDCLAKFMNGEADAMSLDGGFVYFAGKCGLVPVLAENYNKSDNCEDTPEAGYFALAV VKKSASDL TWDNLKGKKS CHTAVGR TAGWNFPMGLL YNKLNHCRFDEFFSEGCAPGSKKDSSL C KL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD Y ELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFR SETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0248] pDP49-CD19 NT.1-FC-GFLG-Tf Nucleic Acid Sequence (SEQ ID NO: 35)

[0249] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGcccgaggaacctctagtggtgaaggtggaagagggagataccgctgctctgtggtgcctcaaggggacctcagat ggccccactcagcagctgacctggtctcgggagtccccgcttaaacccttcttaaaatacagcctgggggtgccaggcctgggagtccac gtcaggcccgatgccatctctgtcgtcatcaggaacgtctctcaacagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagcggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtg gcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccct gagatctgggagggagagcctccgtgtctcccaccgagggacagcctgaaccagagcctcagcagggacctcaccgtagcccctggct ccacactctggctgtcctgtggggtaccccctgactctgtgtccaggggccccctctcctggacccatgtgcaccccaaggggcctaagtc attgctgagcctagagctgaaggacgatcgcccggccagagatatgtgggtaatgggtacgtcactgatgttgccccgggccacagctca agacgctggaaagtggtattgtcaccgtggcaacgtaaccacctcattccacctggaggtaatcgctcggccagtaaaggctcactcagac ctgaggactggtggctggaagGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGT GCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCA AGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTG AGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCA TAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCA GCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGG GCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCA AGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCG TGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctggggggTTCCTGggaagcgg tggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtc cgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccg acgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagca aagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtc ctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctgg aaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctg tggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagca cagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggac gagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagct gctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttca aggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaac ctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagt gcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacg gcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaac aagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaa tctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaacc actgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggc ctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggctttt gtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactg ctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaa ggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcc tgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtac ctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctacc ggtCACCACCATCATCACCACCATCACTAA

[0250] pDP49-CD19 NT.1-FC-GFLG-Tf Amino Acid Sequence (SEQ ID NO: 36)

[0251] MYRMQLLSCIALSLALVTNSPEEPLVVKVEEGDTAALWCLKGTSDGPTOQ LTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEK AWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVW AKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSWT HVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTT SFHLEVIARPVKAHSDLRTGGWKPDGffGS'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL s PGKGSSGGFLGSGGS VPDKTVRWCA VSEHEA TKCQSFRDHMKSVIPSDGPSVACVKKAS YLD CLRALAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQ LRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCADGTDFPQLCQLCP GCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELL CLDNTRKPVDE YK DCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFL KVPPRMDAKMYLGYEYVTAFRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKFE CVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAV VKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMGLL YNKINHCRFDEFFSEGCAPGSKKDSSL C KL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD Y ELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFR SETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRFT:GHHHHHH HH*

[0252] pDP50-His8-CD19 NT.1-GFLG-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 37)

[0253] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGggaggc GTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGG GGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCG GACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCA AGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGG GAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCA GGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAG CCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTG TACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTG CCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGC AGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCT TCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTC TCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgcc gtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgt gaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatg cctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggcc gtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctgg aacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgc gccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctaca gcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggcc gaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccat ctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaagga caagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccc cagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccacc gatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaag atcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggct tcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggcc ggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgt gggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctg cgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagaggg ctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccgg cggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtgga ggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgc ggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttcc gggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaa tctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0254] pDP50-His8-CD19 NT.1-GFLG-FC-Tf Amino Acid Sequence (SEQ ID NO: 38)

[0255] MYRMOLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWCLKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGN VTTSFHLE VIARPVKAHSDLRTGGWKGGFLGGFflGDKT H TCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM REALRRRYHQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPS DGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYY AVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAP CADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YE LLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSP HGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHER LKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSD NCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFF SEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGG KNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGS NVTDCSGNFCLFRSE TKDLLFRDD TVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSSLLE ACTFRRP*

[0256] pDP85-cd20-scfv-GFLG-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 39)

[0257] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAGGCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGTTC CAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTGGC GAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTGAC AATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGACGA GTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTGGT TCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCTGG TGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGGGT ACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCTTG GAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAGTT CAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAGTT GTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATTA TGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCGC GGGTGGCAGCGGCAGCggtgggTTCCTGggaGGCGTAGACGGCGACAAAACTCACACAT GCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCC CAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTG GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTA CAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCA AAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAT GAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAG CGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACC ACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTG GACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGC TCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggg gaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttc cgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccat tgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtgg ccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccag ctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccga gccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtg tcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcga cgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaaca ccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaaga ggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacg gcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacg tgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagcca ccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtat cgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggctcgtgtacattgccggcaagtgcggcctggtgcctgtgct ggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgct gtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagct gtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggaga agggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacg agaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcac gccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgact gcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccgga acacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgc acctttcgcagacctT AA

[0258] pDP85-cd20-scfv-GFLG-FC-Tf Amino Acid Sequence (SEQ ID NO: 40)

[0259] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGYGAGGFLGGEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVPDRWRPIZCAVSE HEATKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNL KPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPE PRKPLEKAVANFFSGSCAPCADGTDFPQL CQL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFV KHS TIFENLANKADRDQ YELLCLDNTRKPVDE YKDCHLAQVPSHTVVARSMGGKEDL IWELLNQ AQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPE APTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVY IAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWN IPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLV EKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVT RKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSSLLEACTFRRP*

[0260] pDP95-Herceptin_HC_Fc-N297G,S427C Nucleic Acid Sequence (SEQ ID NO: 41)

[0261] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGgaggttcagctggtggagtctggcggtggcctggtgcagccagggggctcactccgtttgtcctgtgcagcttctgg cttcaacATC AAGGAC ACCTAT ATCcactgggtgcgtcaggccccgggtaagggcctggaatgggttgcaC GC AT C TACCCGACGAATGGCTACACGCGCTatgccgatAGCgtcaagggccgtttcactataagcGCAGACACA TCCAAAAACACAGCCtacctacaaatgaacagcttaagagctgaggacactgccgtctattattgtTCACGCTGGGG GGGAGATGGGTTTTATGCAATGgactactggggtcaaggaaccctggtcaccgtctcctcggcctccaccaagggtc catcggtcttccccctggcaccctcctccaagagcacctctgggggcacagcggccctgggctgcctggtcaaggactacttccccgaac cggtgacggtgtcgtggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcctacagtcctcaggactctactccctcag cagcgtggtgaccgtgccctccagcagcttgggcacccagacctacatctgcaacgtgaatcacaagcccagcaacaccaaggtcgaca aAAAGGTCgagcccaaatcttgtgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATTGCTGG GCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGATCAGCC GAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGTG AAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCTGCACC AGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTCTGCCG GCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAGGT GTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGACCT GTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTAACGGG CAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGCAGCTT CTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGTGT TCTGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAGTCTCA GTCTGAGCCCGGGAAAGtaa

[0262] pDP95-Herceptin_HC_Fc-N297G,S427C Amino Acid Sequence (SEQ ID NO: 42)

[0263] MYRMQLLSCIALSLALVTNSEVOLVESGGGLVQPGGSLRLSCAASGFNIKD TYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSL RAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGG TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRT PEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFCCSVMHEALHNHYTQKSLSLSPGK*

[0264] pDP69-His8-CD19 NT. l-2XGFLG-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 43)

[0265] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtggaTTtCTGggcggcg ggTTCCTGggaggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCT GAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGA CCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGA CAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAA AGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAG AACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTC AGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGA GAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCG ACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAG GGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAG AAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataag acagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggat gccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagac cttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgg gcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaa cttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctga accagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgaga acctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgcc acctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccag gaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacgg ctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctg tcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgt gaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatg agcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcga ggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaa gctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagt tcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcc caacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0266] pDP69-His8-CD19 NT. l-2XGFLG-FC-Tf Amino Acid Sequence (SEQ ID NO: 44)

[0267] MYRMOLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCLKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGN VTTSFHLE VIARP VKAHSDLRTGGWKGGFFGGGFLGG EDGDKT H T C P P C PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS C S VMHE ALHNH Y T QKS L S L S P GKGSSGGSGGSGGS VPDKTVRWCAVSEHEA TKCQSFRDHMK SVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDP QTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFS GS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKAD RDQ YELLCLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQAQEHFGKDKSKEFQ LFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAEN YNKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMGLL YNKINHCR FDEFFSEGCAPGSKKDSSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCL VEKGDVAFVKHQ TVP QNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAWTRKDKEACVHKILRQ QQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCST SSLLEACTFRRP*

[0268] pDP70-His8-CDl 9 NT. l-3XGFLG-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 45)

[0269] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtggaTTCCTGggcggc gggTTtCTGggaggcggaTTtCTGggaggcGTAGACGGCGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCC AAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGT 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 tgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccac tgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcct gaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgt gaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgct gtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaag gacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacc tgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA[002701 pDP70-His8-CD19 NT. l-3XGFLG-FC-Tf Amino Acid Sequence (SEQ ID NO: 46)

[0271] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLWKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFFGGGFFGGGFLGGFDGPKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVFFKTWPIZCAVSEFFATKCQS FRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFY GSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKA VANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFEN LANKADRDQ YELLCLDNTRKPVDE YKDCHLAQVPSHTVVARSMGGKEDL IWELLNQAQEHFGKD KSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKP VKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLV PVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYN KINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFV KHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACV HKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP*

[0272] pDP71-His8-CD19 NT.1-GFLG-FK-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 47)

[0273] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGggaggc TTCAAAggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAA CTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAA AGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGC CCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAAC CACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACG GCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGG AACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAG AGCC T C TCC C T GTCTC C GGGT A A Aggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagt gcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggcccta gcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggc ctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctac tacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaa gcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttca gcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagt acttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctgg ccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgc ccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacact tcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctga aggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccga ggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacag cgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctg gacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatac ccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgcc acaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttctcag cgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaa caaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgcccc agaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccgga agccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtcca caagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaagg acctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaag gccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0274] pDP71-His8-CD19 NT.1-GFLG-FK-FC-Tf Amino Acid Sequence (SEQ ID NO: 48)

[0275] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLWKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGFFGKDGDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SWHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVFDXTVWCAVSEHEATKCQSFROHMKSV IPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQT FYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRD QYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLF SSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSH HERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFD EFFSEGCAPGSKKDSSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQ TVPQN TGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQ HLFGSNVTDCSGNFCLFRSE TKDLLFRDD TVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSS LLEACTFRRP*

[0276] pDP72-His8-CD19 NT.1-GFLG-VA-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 49)

[0277] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGggaggc GTAgctggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAC TCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGA TCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAA GCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCC TGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACC ACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCC TGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGC AATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGG CTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGA ACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGA GCC T C TCC C T GT C TC C GGGT AAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtg cggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctag cgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcc tggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctact acgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaag cgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcag cggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagta cttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggc caacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcc caggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacactt cggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctga aggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccga ggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacag cgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctg gacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatac ccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcag cgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaa caaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgcccc agaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccgga agccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtcca caagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaagg acctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaag gccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0278] pDP72-His8-CD19 NT.1-GFLG-VA-FC-Tf Amino Acid Sequence (SEQ ID NO: 50)

[0279] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCLKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGN VTTSFHLE VIARPVKAHSDLRTGGWKGGFLGGE4 GEDGDKT H T C P P C PAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SWHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVPDKWWCAVSEHFATKCQFFROHMKSV IPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQT FYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRD QYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLF SSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYN KSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFD EFFSEGCAPGSKKDSSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQ TVPQN TGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQ HLFGSNVTDCSGNFCLFRSE TKDLLFRDD TVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSS LLEACTFRRP*

[0280] pDP73-His8-CD19 NT.1-GFLG-VK-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 51)

[0281] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGggaggc GTAAAAggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAA CTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAA AGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGC CCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAAC CACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACG GCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGG AACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAG AGCC T C TC CCTGTCTC CGGGT A A Aggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagt gcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggcccta gcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggc ctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctac tacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaa gcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttca gcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagt acttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctgg ccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgc ccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacact tcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctga aggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccga ggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacag cgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctg gacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatac ccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgcc acaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcag cgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaa caaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgcccc agaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccgga agccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtcca caagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaagg acctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaag gccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0282] pDP73-His8-CD19 NT.1-GFLG-VK-FC-Tf Amino Acid Sequence (SEQ ID NO: 52)

[0283] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGEFGEDGDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SWHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVPDKTVWCAVSEHFATKCQFFROHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQT FYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRD QYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLF SSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSH HERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYN KSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFD EFFSEGCAPGSKKDSSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQ TVPQN TGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQ HLFGSNVTDCSGNFCLFRSE TKDLLFRDD TVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSS LLEACTFRRP*

[0284] pDP74-His8-CD19 NT.1-GFLG-VR-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 53)

[0285] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGggaggc GTACGGggcGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAA CTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAA AGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTC CTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGC CCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAAC CACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGC CTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAG CAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACG GCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGG AACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAG AGCC T C TC CC T GTCTC C GGGT A A Aggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagt gcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggcccta gcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggc ctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctac tacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaa gcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttca gcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagt acttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctgg ccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgc ccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctga aggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccga ggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacag cgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctg gacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatac ccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgcc acaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcag cgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaa caaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgcccc agaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccgga agccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtcca caagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaagg acctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaag gccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0286] pDP74-His8-CD19 NT.1-GFLG-VR-FC-Tf Amino Acid Sequence (SEQ ID NO: 54)

[0287] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLWKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGKRGKDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVFDXTVRWCAVSEHEATKCQSFRFHMKSV IPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQT FYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRD QYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLF SSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSH HERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYN KSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFD EFFSEGCAPGSKKDSSL CKL CMGSGLNL CEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQ TVPQN TGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQ HLFGSNVTDCSGNFCLFRSE TKDLLFRDD TVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSSLLEACTFRRP*

[0288] pDP75-His8-CD19 NT.1-GFLG-GGFG-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 55)

[0289] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttccgggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCCTGggaggc ggtgggTTCgggGTAGACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGA ACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCAT GATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACC CTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACA AAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGT CCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAG CCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAA CCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGA GCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGAC GGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGG GAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAA GAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagaca gtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggcc ctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgcc ggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagacctt ctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggca gaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttct tcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaacc agtactcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacc tggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacct cgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaa cacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggcttt ctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcc cgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaa cagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagc ctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgagga tacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagct gccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttctt cagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaa caacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgc cccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcaccc ggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgt ccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaa aggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtg aaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0290] pDP75-His8-CD19 NT.1-GFLG-GGFG-FC-Tf Amino Acid Sequence (SEQ ID NO: 56)

[0291] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLWKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFFGGGGFGVDGDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS CSVMREALWRYYQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKS 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*

[0292] pDP76-His8-CD19 NT.1-FK-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 57)

[0293] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcTTCAAAggcGTAG ACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGA CCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTT CAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGG AGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACT GGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCC ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACAC CCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGT CAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG AGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCT ACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCT CCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgag cacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctgg cccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagacctctactacgccgtggccgtggtcaag aaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatcccca tcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgc tgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttc aagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggacc agtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtg gtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaag agttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacg ccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaa gcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgt gagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattg ccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgcc atcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccg ccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcag caagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctac acaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaacc ccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaa ctgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcag cacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacacc gtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtg cagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0294] pDP76-His8-CD19 NT.1-FK-FC-Tf Amino Acid Sequence (SEQ ID NO: 58)

[0295] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGFFGVPGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LWRYYQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGP SVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVA VVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCAD G TDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLC LDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGK DLLFKDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERLKC DEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCE DTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEG CAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNP DPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSN VTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACT FRRP*

[0296] pDP77-His8-CDl 9 NT.1-VA-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 59)

[0297] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcGTAgctggcGTAGA CGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGAC CGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCC CTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGG AGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACT GGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCC ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACAC CCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGT CAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGG AGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCT ACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCT CCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgag cacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaagg ccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctgg cccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaag aaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacatcccca tcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgc tgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttc aagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggacc agtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtg gtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaag agttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacg ccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaa gcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgt gagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattg ccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctactttgcc atcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccg ccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcag caagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctac acaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaacc ccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaa ctgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcag cacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtg cagcacctctagcctgctggaagcctgcaccttcgcagacctTAA[002981 pDP77-His8-CD19 NT.1-VA-FC-Tf Amino Acid Sequence (SEQ ID NO: 60)

[0299] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGE4GW)GDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALWRYTQKSLSLSPGRGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGP SVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVA VVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCAD G TDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLC LDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGK DLLFKDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERLKC DEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCE DTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEG CAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNP DPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSN VTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACT FRRP*

[0300] pDP78-His8-CD19 NT.1-VK-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 61)

[0301] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTCACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcGTAAAAggcGTA GACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGG ACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGT TCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAG GAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCC CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCC TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG TCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtc tgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaaga aggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctac ctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggt caagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacat ccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcccc ttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggc gccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccg ggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcaca cagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagag caaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaat ggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgag tgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagt gcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgta cattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctact ttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaag gaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttctcagcgagggctgcgctccc ggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacg gctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaag aaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacg ccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagca gcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacga caccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcgga agtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0302] pDP78-His8-CD19 NT.1-VK-FC-Tf Amino Acid Sequence (SEQ ID NO: 62)

[0303] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLWKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKG'EK'GTDG'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LWRYTQKSLSLSPGRGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGP SVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVA VVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCAD G TDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLC LDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGK DLLFKDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERLKC DEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEG CAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNP DPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSN VTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACT FRRP*

[0304] pDP79-His8-CD19 NT.1-VR-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 63)

[0305] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggcGTACGGggcGTA GACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGG ACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGAC CCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGT TCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAG GAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCC CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCT GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCC TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG TCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtc tgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaaga aggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctac ctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggt caagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacat ccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcccc ttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggc gccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccg ggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcaca cagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagag caaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaaggtgccccccagaat ggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgag tgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagt gcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgta cattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctact ttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctccc ggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacg gctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaag aaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacg ccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagca gcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacga caccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcgga agtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0306] pDP79-His8-CD19 NT.1-VR-FC-Tf Amino Acid Sequence (SEQ ID NO: 64)

[0307] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGERGEPGDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LWRYYQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGP SVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVA VVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPCAD G TDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLC LDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSPHGK DLLFKDSAHGFLKVPPRMDAKMYL G YE YVTAIRNLREGTCPEAPTDECKPVKWCAL SHHERLKC DEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSDNCE DTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWNIPMGLLYNKINHCRFDEFFSEG CAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGGKNP DPWAKNLNEKDYELLCLDGTRKPVEEYANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSN VTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACT FRRP*

[0308] pDP80-His8-CD19 NT.1-GGFG-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 65)

[0309] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGGCCACCACCATCATCACCACCATCACaccggtcccgaggaacctctagtggtgaaggtg gaagagggagataccgctgctctgtggtgcctcaaggggacctcagatggccccactcagcagctgacctggtctcgggagtccccgctt aaacccttcttaaaatacagcctgggggtgccaggcctgggagtccacgtcaggcccgatgccatctctgtcgtcatcaggaacgtctctca acagatggggggcttctacctgtgccagccggggcccccctctgagaaggcctggcagcctggctggacagtcaatgtggagggcagc ggggagctgttccggtggaatgtttcggacctaggtggcctgggctgtggcctgaagaacaggtcctcagagggccccagctccccttcc gggaagctcatgagccccaagctgtatgtgtgggccaaagaccgccctgagatctgggagggagagcctccgtgtctcccaccgaggga cagcctgaaccagagcctcagcagggacctcaccgtagcccctggctccacactctggctgtcctgtggggtaccccctgactctgtgtcc aggggccccctctcctggacccatgtgcaccccaaggggcctaagtcattgctgagcctagagctgaaggacgatcgcccggccagaga tatgtgggtaatgggtacgtcactgatgttgccccgggccacagctcaagacgctggaaagtggtattgtcaccgtggcaacgtaaccacct cattccacctggaggtaatcgctcggccagtaaaggctcactcagacctgaggactggtggctggaagggtgggTTCggaggcGTA GACGGCGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGG ACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGT TCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAG GAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGA CTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCC CCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCT GGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGC CGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCC TCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTG TCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtc tgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaaga aggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcctggtgtacgatgcctac ctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctactacgccgtggccgtggt caagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagcgccggctggaacat ccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagcggcagctgcgcccc ttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtacttcggctacagcggc gccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccg ggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgcccaggtgccatctcaca cagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttcggcaaggacaagag caaagagttccagctgttcagcagcccccacggcaaggatctgctgtcaaggacagcgcccacggctttctgaaggtgccccccagaat ggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgaggcccccaccgatgag tgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagt gcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctggacggcggcttcgtgta cattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacccccgaggccggctact ttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgccacaccgccgtgggaag gaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagcgagggctgcgctccc ggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacg gctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaag aaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacg ccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagca gcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacga caccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcgga agtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0310] pDP80-His8-CD19 NT.1-GGFG-FC-Tf Amino Acid Sequence (SEQ ID NO: 66)

[0311] MYRMQLLSCIALSLALVTNSGHHHHHHHHZGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFGGEPGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALWHEEQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPS VAC VKKAS 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*

[0312] pDP86-PDLl-scfv-GFLG-fc-Tf Nucleic Acid Sequence (SEQ ID NO: 67)

[0313] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGATATACAGATGACCCAATCCCCATCCAGCTTGTCCGCTAGCGTAGGC GATAGAGTAACTATTACATGCCGCGCTAGTCAAGACGTGTCAACTGCAGTCGCGTGG TACCAACAAAAGCCTGGCAAAGCTCCGAAACTGCTGATTTACAGCGCGTCTTTCCTT TACTCTGGGGTACCTAGCCGATTTTCTGGGTCTGGTAGCGGAACCGATTTCACGCTT ACAATTTCTAGCCTCCAACCCGAAGATTTCGCGACGTACTACTGCCAACAATACCTT TACCATCCAGCCACATTTGGACAGGGCACGAAGGTTGAAATAAAAGGCGGAGGTGG ATCTGGCGGAGGAGGAAGTGGGGGTGGAGGTTCAGAAGTTCAGCTGGTTGAATCAG GCGGCGGACTTGTTCAGCCGGGCGGAAGCCTTCGGCTTAGCTGTGCTGCCAGTGGCT TCACATTCAGTGATAGCTGGATTCATTGGGTTCGCCAGGCACCAGGCAAAGGTTTGG AGTGGGTCGCCTGGATTAGTCCGTATGGGGGCTCCACCTACTACGCTGACTCAGTGA AAGGGCGGTTTACCATTAGTGCTGATACGTCCAAAAATACAGCTTACCTTCAGATGA ACTCTCTGAGGGCCGAAGATACTGCTGTGTACTACTGCGCTCGGAGACATTGGCCAG GAGGGTTCGATTACTGGGGGCAAGGCACTTTGGTGACAGTCAGTTCAGGTGGTTCCG GCAGCGCAGGAggtgggTTCCTGggaGGCGTAGACGGCGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAA CCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGT GCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTG CAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCA AAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTG ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTC CCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGA GCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACA ACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggta gcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatg aagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatga ggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacg gcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaa gaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagc ctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccc cggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagccc gtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctg ggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctg ctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatc cggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcgg ctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatca tgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaac tacaacaagagcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctg ggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaaga tcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggca gcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgt ggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactac gaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcac ccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaa cttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacga gaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcag acctTAA

[0314] pDP86-PDLl-scfv-GFLG-fc-Tf Amino Acid Sequence (SEQ ID NO: 68)

[0315] MYRMQLLSCIALSLALVTNSDIOMTQSPSSLSASVGDRVTITCRASODVSTA VAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSC AASGFTFSDSWIHW VRQAPGKGLEWVA WISPY GGSTYYADSVKGRFTISADTSKNT AYLQMNSLRAEDTAVYYCARRHWPGGFDYWGOGTLVTVSSGGSGSAGGGFLGGFPGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVESCSWHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVFOKTVWCAVSE’.H EATKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLK PVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEP RKPLEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVK HS TIFENLANKADRDQYELLCLDNTRKPVDE YKDCHLAQVPSHTVVARSMGGKEDL IWELLNQA QEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEA PTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYI AGKCGL VPVLAENYNKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNI PMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVE KGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTR KDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSSLLEACTFRRP*

[0316] pDP96-CD20_HC_Fc-N297G,S427C-Tf Nucleic Acid Sequence (SEQ ID NO: 69)

[0317] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAGGC GAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGTTC CAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTGGC GAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTGACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGACGA GTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTGGT TCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCTGG TGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGGGT ACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCTTG GAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAGTT CAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAGTT GTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATTA TGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCGC GGGTGTAGACGGCAGCGGCAGCgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATT GCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGAT CAGCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCG AGGTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAG CCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCT GCACCAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTC TGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCG CAGGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCT GACCTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTA ACGGGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGC AGCTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAA CGTGTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAG TCTCAGTCTGAGCCCGGGAAAGggatcctctgggggaagtggaggtagcggtggttctgtgcccgataagacagtgc ggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgacggccctagc gtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactggatgccggcct ggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccagaccttctacta cgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctgggcagaagc gccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggccaacttcttcagc ggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctgaaccagtact tcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgagaacctggcc aacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgccacctcgccc aggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggcccaggaacacttc ggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacggctttctgaa ggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacctgtcccgag gcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcgtgaacagc gtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccatgagcctgg acggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcgaggatacc cccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaaagctgcca caccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgagttcttcagc gagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaac aaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgtgcccca gaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcacccggaa gccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctgcgtccac aagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgagacaaagga cctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatatgtgaagg ccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0318] pDP96-CD20_HC_Fc-N297G,S427C-Tf Amino Acid Sequence (SEQ ID NO: 70)

[0319] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDGAGffDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFCCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVP£).KWR^CAVSE.HEATKCQS FRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFY GSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKA VANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFEN LANKADRDQ YELLCLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQAQEHFGKD KSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKP VKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLV PVLAENYNKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKKSCHTAVGR TAGWNIPMGLL YN KINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFV KHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACV HKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGN LRKCSTSSLLEACTFRRP*

[0320] pDP97-cd20-scfv-GFLG-FC-N297G, S427C-Tf Nucleic Acid Sequence (SEQ ID NO: 71)

[0321] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAGGC GAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGTTC CAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTGGC GAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTGAC AATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGACGA GTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTGGT TCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCTGG TGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGGGT ACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCTTG GAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAGTTCAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAGTT GTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATTA TGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCGC GGGTGGCAGCGGCAGCggtgggTTCCTGggaGGCGTAGACGGCgacaaaactcacacatgcCCCCC CTGCCCAGCGCCAGAATTGCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACC TAAAGACACCCTGATGATCAGCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACG TGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTC CACAATGCCAAAACGAAGCCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTAG TGAGCGTCTTGACCGTGCTGCACCAGGACTGGCTGAACGGCAAGGAATACAAATGC AAGGTCAGCAATAAGGCTCTGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAA GGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCTGACCTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCG CTGTGGAGTGGGAGAGTAACGGGCAGCCCGAGAACAACTACAAGACCACGCCTCCT GTGCTGGACAGCGACGGCAGCTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAG CAGGTGGCAACAGGGCAACGTGTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACA ACCATTACACCCAGAAGAGTCTCAGTCTGAGCCCGGGAAAGggatcctctgggggaagtggaggt agcggtggttctgtgcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacat gaagtccgtgatccccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatg aggccgacgccgtgacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctac ggcagcaaagaggacccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggca agaagtcctgtcacaccggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaag cctctggaaaaggccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgcc ccggctgtggctgcagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcg tgaagcacagcaccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcc cgtggacgagtacaaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatct gggagctgctgaaccaggcccaggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatct gctgttcaaggacagcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccat ccggaacctgagagagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcg gctgaagtgcgacgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatc atgaacggcgaggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaa ctacaacaagagcgacaactgcgaggatacccccgaggccggctacttgccatcgcagtcgtgaagaagtccgccagcgacctgacct gggacaatctgaagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatatcctatggggctgctgtacaacaa gatcaaccactgcagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgg gcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaaggggga cgtggcttttgtgaaacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggac tacgaactgctgtgtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggt cacccggaaggacaaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcgg caacttctgcctgttcagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacaccta cgagaagtacctgggcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcg cagacctTAA

[0322] pDP97-cd20-scfv-GFLG-FC-N297G, S427C-Tf Amino Acid Sequence (SEQ ID NO: 72)

[0323] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGAGAGGFLGGFDG'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFCCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS VPmWRiVCAVSE HEATKCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNL KPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPE PRKPLEKAVANFFSGSCAPCADGTDFPQL CQL CPGCGCS TLNQ YFGYSGAFKCLKDGAGDVAFV KHS TIFENLANKADRDQ YELLCLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQ AQEHFGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVY IAGKCGLVPVLAENYNKSDNCEDTPEAGYFAIAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWN IPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLV EKGDVAFVKHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGE E YVKAVGNLRKCS TSSLLEACTFRRP*

[0324] pDP98-CD20_HC_Fc-N297G,S427C Nucleic Acid Sequence (SEQ ID NO: 73)

[0325] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTCACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAGGC GAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGTTC CAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTGGC GAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTGACAATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGACGA GTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTGGT TCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCTGG TGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGGGTACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCTTG GAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAGTT CAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAGTT GTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATTATGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCGC GGGTGTAGACGGCAGCGGCAGCgacaaaactcacacatgcCCCCCCTGCCCAGCGCCAGAATT GCTGGGCGGACCCAGCGTGTTCCTGTTCCCCCCCAAACCTAAAGACACCCTGATGAT CAGCCGAACCCCTGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAGGTGAAGTTCAACTGGTATGTGGACGGCGTGGAGGTCCACAATGCCAAAACGAAG CCCAGGGAGGAGCAGTACGGCAGCACCTACAGGGTAGTGAGCGTCTTGACCGTGCT GCACCAGGACTGGCTGAACGGCAAGGAATACAAATGCAAGGTCAGCAATAAGGCTC TGCCGGCTCCTATCGAGAAGACAATCAGCAAGGCAAAGGGCCAGCCACGCGAACCGCAGGTGTATACTCTGCCCCCCAGCCGGGACGAGCTGACCAAGAACCAGGTGTCCCT GACCTGTCTGGTGAAAGGCTTCTACCCCAGCGACATCGCTGTGGAGTGGGAGAGTA ACGGGCAGCCCGAGAACAACTACAAGACCACGCCTCCTGTGCTGGACAGCGACGGC AGCTTCTTCCTGTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAACAGGGCAACGTGTTCTGCTGCTCTGTGATGCACGAGGCCCTGCACAACCATTACACCCAGAAGAG TCTCAGTCTGAGCCCGGGAAAGTAA

[0326] pDP98-CD20_HC_Fc-N297G,S427C Amino Acid Sequence (SEQ ID NO: 74)

[0327] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDGYGADKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFCCSVMHEALHNHYTQKSLSLSPGK*

[0328] cd20-scFV-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 75)

[0329] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGCAGATTGTTCTGAGCCAGTCCCCGGCAATCCTCTCTGCCAGCCCAGGCGAAAAGGTGACAATGACTTGCCGAGCGAGTTCCAGTGTCTCTTATATCCACTGGTTC CAGCAAAAGCCGGGAAGCAGCCCTAAACCATGGATATATGCAACGTCTAACCTGGC GAGCGGGGTCCCAGTGAGATTTTCCGGAAGCGGCAGCGGAACTAGTTACTCTTTGAC AATAAGCAGAGTGGAGGCTGAGGACGCTGCTACTTACTATTGCCAGCAATGGACGA GTAACCCGCCGACGTTTGGAGGTGGAACGAAGCTGGAGATTAAAGGTGGAGGTGGT TCTGGCGGAGGTGGTTCCGGTGGTGGTGGAAGTCAGGTGCAGCTCCAACAGCCTGG TGCCGAACTTGTCAAACCTGGGGCTAGTGTGAAGATGAGTTGCAAAGCTTCAGGGT ACACGTTTACGTCATACAACATGCATTGGGTAAAGCAAACACCAGGACGCGGCTTG GAATGGATCGGCGCGATATATCCAGGAAACGGTGACACTTCTTATAACCAGAAGTT CAAGGGGAAAGCTACTCTCACAGCGGACAAATCTTCTTCAACAGCGTATATGCAGTT GTCAAGCCTTACTAGCGAGGACAGTGCTGTTTATTACTGCGCCCGGTCCACCTATTA TGGGGGTGATTGGTACTTTAATGTTTGGGGCGCGGGTACTACCGTTACTGTGTCCGC GGGTGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGTGCCCAGCAC CTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCC TCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAA GACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCA CCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAAC AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCG AGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGG AGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCA GGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCA GAAGAGC CTCTCCCT GT C TC C GGGT A A Aggatcctctgggggaagtggaggtagcggtggttctgtgcccgata agacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatccccagcgac ggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgtgacactgga tgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagaggacccccaga ccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcacaccggcctg ggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaaggccgtggcca acttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctgcagcaccctg aaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagcaccatcttcgag aacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagtacaaggactgc cacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctgaaccaggccca ggaacacttcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggacagcgcccacg gcttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgagagagggcacct gtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcgacgagtggagcg tgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcgaggccgatgccat gagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaagagcgacaactgcg aggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctgaagggcaagaaa agctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactgcagattcgacgag ttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctgaacctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtgaaacaccagaccgt gccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgtgtctcgacggcac ccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaaggacaaagaggcctg cgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgttcagaagcgaga caaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgggcgaggaatat gtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0330] cd20-scFV-FC-Tf Amino Acid Sequence (SEQ ID NO: 76)

[0331] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFPGAGADKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGWFSCSWHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVPFKWWCAVS.E.HEATKCQS FRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFY GSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGS CAPCADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFEN LANKADRDQ YELLCLDNTRKPVDE YKDCHLAQVPSHTWARSMGGKEDL IWELLNQAQEHFGKD KSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKP VKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLV PVLAENYNKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKKSCHTAVGR TAGWNIPMGLL YN KINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFV KHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACV HKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGN LRKCSTSSLLEACTFRRP*

[0332] PD-Ll-scFV-FC-Tf Nucleic Acid Sequence (SEQ ID NO: 77)

[0333] ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTC ACGAATTCGGATATACAGATGACCCAATCCCCATCCAGCTTGTCCGCTAGCGTAGGC GATAGAGTAACTATTACATGCCGCGCTAGTCAAGACGTGTCAACTGCAGTCGCGTGG TACCAACAAAAGCCTGGCAAAGCTCCGAAACTGCTGATTTACAGCGCGTCTTTCCTT TACTCTGGGGTACCTAGCCGATTTTCTGGGTCTGGTAGCGGAACCGATTTCACGCTT ACAATTTCTAGCCTCCAACCCGAAGATTTCGCGACGTACTACTGCCAACAATACCTT TACCATCCAGCCACATTTGGACAGGGCACGAAGGTTGAAATAAAAGGCGGAGGTGG ATCTGGCGGAGGAGGAAGTGGGGGTGGAGGTTCAGAAGTTCAGCTGGTTGAATCAG GCGGCGGACTTGTTCAGCCGGGCGGAAGCCTTCGGCTTAGCTGTGCTGCCAGTGGCT TCACATTCAGTGATAGCTGGATTCATTGGGTTCGCCAGGCACCAGGCAAAGGTTTGG AGTGGGTCGCCTGGATTAGTCCGTATGGGGGCTCCACCTACTACGCTGACTCAGTGA AAGGGCGGTTTACCATTAGTGCTGATACGTCCAAAAATACAGCTTACCTTCAGATGA ACTCTCTGAGGGCCGAAGATACTGCTGTGTACTACTGCGCTCGGAGACATTGGCCAG GAGGGTTCGATTACTGGGGGCAAGGCACTTTGGTGACAGTCAGTTCAGGTGGTTCCG GCAGCGCAGGAGTAGACGGCAGCGGCAGCGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGC CACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAA TGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCA GCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGA ACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGG AGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGG CAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAggatcctctgggggaagtggaggtagcggtggttctgt gcccgataagacagtgcggtggtgcgccgtgtctgagcacgaggccaccaagtgccagagcttccgggaccacatgaagtccgtgatcc ccagcgacggccctagcgtggcctgtgtgaagaaggccagctacctggactgcatccgggccattgccgccaatgaggccgacgccgt gacactggatgccggcctggtgtacgatgcctacctggcccccaacaacctgaagcccgtggtggccgagttctacggcagcaaagagg acccccagaccttctactacgccgtggccgtggtcaagaaggacagcggcttccagatgaaccagctgcggggcaagaagtcctgtcac accggcctgggcagaagcgccggctggaacatccccatcggcctgctgtactgcgatctgcccgagccccggaagcctctggaaaagg ccgtggccaacttcttcagcggcagctgcgccccttgtgctgacggaaccgacttcccccagctgtgtcagctgtgccccggctgtggctg cagcaccctgaaccagtacttcggctacagcggcgccttcaagtgcctgaaggacggcgctggcgacgtggccttcgtgaagcacagca ccatcttcgagaacctggccaacaaggccgaccgggaccagtacgagctgctgtgcctggacaacaccagaaagcccgtggacgagta caaggactgccacctcgcccaggtgccatctcacacagtggtggcccggtccatgggcggcaaagaggatctgatctgggagctgctga accaggcccaggaacactcggcaaggacaagagcaaagagttccagctgttcagcagcccccacggcaaggatctgctgttcaaggac agcgcccacggctttctgaaggtgccccccagaatggacgccaagatgtacctgggctacgagtacgtgaccgccatccggaacctgag agagggcacctgtcccgaggcccccaccgatgagtgcaagcccgtgaagtggtgcgccctgagccaccacgagcggctgaagtgcga cgagtggagcgtgaacagcgtgggcaagatcgagtgcgtgagcgccgagacaaccgaggactgtatcgccaagatcatgaacggcga ggccgatgccatgagcctggacggcggcttcgtgtacattgccggcaagtgcggcctggtgcctgtgctggccgagaactacaacaaga gcgacaactgcgaggatacccccgaggccggctactttgccatcgcagtcgtgaagaagtccgccagcgacctgacctgggacaatctg aagggcaagaaaagctgccacaccgccgtgggaaggaccgccgggtggaatattcctatggggctgctgtacaacaagatcaaccactg cagattcgacgagttcttcagcgagggctgcgctcccggcagcaagaaagacagcagcctgtgcaagctgtgcatgggcagcggcctga acctgtgcgagcccaacaacaaagagggctactacggctacacaggggccttccggtgtctggtggagaagggggacgtggcttttgtga aacaccagaccgtgccccagaacaccggcggcaagaaccccgacccctgggccaagaacctgaacgagaaggactacgaactgctgt gtctcgacggcacccggaagccagtggaggaatacgccaactgtcacctggccagagcccccaatcacgccgtggtcacccggaagga caaagaggcctgcgtccacaagatcctgcggcagcagcagcacctgttcggcagcaacgtgaccgactgcagcggcaacttctgcctgtt cagaagcgagacaaaggacctcctgttccgggacgacaccgtgtgtctggccaagctgcacgaccggaacacctacgagaagtacctgg gcgaggaatatgtgaaggccgtgggcaatctgcggaagtgcagcacctctagcctgctggaagcctgcacctttcgcagacctTAA

[0334] PD-Ll-scFV-FC-Tf Amino Acid Sequence (SEQ ID NO: 78)

[0335] MYRMQLLSCIALSLALVTNSDIOMTOSPSSLSASVGDRVTITCRASODVSTA VAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSC AASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNT AYLOMNSLRAEDTAVYYCARRHWPGGFDYWGOGTLVTVSSGGSGSAGFDGSGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSVPAKTVRIVCAVSEEEAT KCQSFRDHMKSVIPSDGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNLPLGLLYCDLPEPRKP LEKAVANFFSGSCAPCADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHST IFENLANKADRDQ YELL CLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDL LWELLNQAQEH FGKDKSKEFQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTD ECKPVKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCFAKIMNGEADAMSLDGGFVYIAGK CGL VPVLAENYNKSDNCED TPEAGYFAIAVVKKSASDL TWDNLKGKKS CHTAVGR TAGWNIPMG LLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGD VAFVKHQ TVPQNTGGKNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDK EACVHKFLRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKLHDRNTYEKYLGEEYVKAVGNLRKCS TSSLLEACTFRRP*

[0336] pDP124-cd20-scfv-FC-TfR-H7 Amino Acid Sequence (SEQ ID NO: 79)

[0337] MYRMOLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMOLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDGAGADKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRITC QGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYY CAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASR FTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED TAVYYCARDLS GYGDYPDYWGQGTLVTVS S *

[0338] pDP125-cd20-scfv-FC-TfR-M16 Amino Acid Sequence (SEQ ID NO: 80)

[0339] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMOLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDGAGADKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRITC QGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYY CAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASR YPFHHHDHHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED TAVYYCARDLS GYGDYPDYWGQGTLVTVS S *

[0340] pDP126-cd20-scfv-GFLG-FC-TfR-H7 Amino Acid Sequence (SEQ ID NO: 81)

[0341] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGXGAGGFLGGPDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVAL GQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQ PEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSL RLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQ MNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0342] pDP127-cd20-scfv-GFLG-FC-TfR-M16 Amino Acid Sequence (SEQ ID NO: 82)

[0343] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMOLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGXG5GGFLGGPDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVAL GQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQ PEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSL RLSCAASRYPFHHHDHHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQ MNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0344] pDP155-His8-CD19 NT.1-2XGFLG-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO:83)

[0345] MYRMQLLSCIALSLALVTNSGHHHHHHHHFGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGGFLGGFDGDKTHTCPPCPA PELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDD SLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSY AMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYC ARDLSGYGDYPDYWGQGTLVTVSS*

[0346] pDP156-His8-CD19 NT.1-3XGFLG-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO:84)

[0347] MYRMQLLSCIALSLALVTNSGHHHHHHHHFGPEEPLWKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFFGGGFFGGGFLGGEDGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRITC QGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYY CAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASR FTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED TAVYYCARDLS GYGDYPDYWGQGTLVTVS S *[003481 pDP157-His8-CD19 NT. 1-GFLG-FK-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 85)

[0349] MYRMOLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGN VTTSFHLE VIARP VKAHSDLRTGGWKGGFFGGFFG EDGDKT H T C P P C PAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSY YASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSL TGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAM HWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*[00350J pDP158-His8-CD19 NT. 1-GFLG-VA-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 86)

[0351] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGN VTTSFHLE VIARP VKAHSDLRTGGWKGGFL GGE4 GFDGDKT H T C P P C PAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SW[HEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSY YASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSL TGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAM HWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0352] pDP159-His8-CD19 NT 1-GFLG-VK-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 87)

[0353] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGVFGFDGDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSY YASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSL TGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAM HWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCAR DLSGYGDYPDYWGQGTLVTVSS*

[0354] pDP160-His8-CD19 NT. l-GFLG-VR-FC-TfR-H7 Amino Acid Sequence (SEQ IDNO: 88)

[0355] MYRMQLLSCIALSLALVTNSGHHHHHHHHrGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGERGKDGDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSY YASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSL TGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAM HWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCAR DLSGYGDYPDYWGQGTLVTVSS*

[0356] pDP161-His8-CD19 NT. l-GFLG-GGFG-FC-TfR-H7 Amino Acid Sequence (SEQ ID NO: 89)

[0357] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFEGGGGFGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY NSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRS YYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAI SGLQPEDEANYYCAGWDDS LTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYA MHWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCA RDLSGYGDYPDYWGQGTLVTVSS*

[0358] pDP162-His8-CD19 NT. l-FK-FC-TfR-H7 Amino Acid Sequence (SEQ ID NO: 90)

[0359] MYRMQLLSCIALSLALVTNSGHHHHHHHH7UPEEPLVVKVEEGDTAALWCLKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGFTrGWJGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWYQ QKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFG GGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYG DYPDYWGQGTLVTVSS*

[0360] pDP163-His8-CD19 NT.1-VA-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 91)

[0361] MYRMQLLSCIALSLALVTNSGHHHHHHHHrGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGE4GFPGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS FFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWYQ QKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFG GGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYG DYPDYWGQGTLVTVSS*

[0362] pDP164-His8-CD19 NT.1-VK-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 92)

[0363] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWCLKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGEK'GFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWYQ QKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFG GGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQA PGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0364] pDP165-His8-CD19 NT.1-VR-FC-T1R-H7 Amino Acid Sequence (SEQ ID NO: 93)

[0365] MYRMQLLSCIALSLALVTNSGHHHHHHHHTIJPEEPLVVKVEEGDTAALWCLKGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGERGFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWYQ QKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFG GGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYG DYPDYWGQGTLVTVSS*

[0366] pDP166-His8-CD19 NT.1-GGFG-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO:94)

[0367] MYRMQLLSCIALSLALVTNSGHHHHHHHHrGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFGGEDGPKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH EALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAVS VAL GQ T VR I T C QGD S LRS Y YAS W YQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPV FGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT ISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSG YGDYPDYWGQGTLVTVS S *

[0368] pDP167-CD20_HC_Fc-N297G,S427C-TfR-H7 Amino Acid Sequence (SEQ ID NO:95)

[0369] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGFDGAGADKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW QQGNVFCCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRITC QGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYY CAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASR FTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAED TAVYYCARDLS GYGDYPDYWGQGTLVTVS S *

[0370] pDP168-CD20-scfv-GFLG-FC-N297G, S427C-TfR-H7 Amino Acid Sequence (SEQ ID NO: 96)

[0371] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGAGAGGFLGGEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFCCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVAL GQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQ PEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSL RLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQ MNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0372] pDP 169-cd20-scfv-GFLG-FK-FC-(N297G, S427C)-TfR-H7 Amino Acid Sequence (SEQ ID NO: 97)

[0373] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSC KASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGAGAGGFLGGF / TG'FDG'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS VALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAIS GLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPG RSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTL YLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0374] pDP 170-cd20-scfv-GFLG-VR-FC-(N297G, S427C)-TfR-H7 Amino Acid Sequence (SEQ ID NO: 98)

[0375] MYRMQLLSCIALSLALVTNSOIVLSOSPATLSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGAGAGGFLGG F / ?G'PDG'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS VALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAIS GLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPG RSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTL YLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0376] pDP171-His8-EGFR affi-FC-TfR-H7 Amino Acid Sequence (SEQ ID NO: 99)

[0377] MYRMQLLSCIALSLALVTNSGHHHHHHHH7ULOVDNKFNKEMWAAWEEIRN LPNLNGWQMTAFIASLVDDPSQSANLLAEAKKLNDAQAPKVDGAGAFDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPR EEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSEL T QDPAVS VALGQT VR I T CQGD SLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAG WDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFS S YAMHWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAV YYCARDLSGYGDYPDYWGQGTLVTVSS*

[0378] pDP172-His8-EGFR affi-GFLG-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO:100)

[0379] MYRMQLL SCIAL SLALVTNSGHHHHHHHH EGLQ VDNKFNKEMWAA WEEIRN LPNLNGWQMTAFIASLVDDPSOSANLLAEAKKLNDAQAPKVDGGFLGGEDGDKTHT CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVALGQTVRI TC QGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYY CAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASR FTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLS GYGDYPDYWGQGTLVTVS S *

[0380] pDP173-His8-EGFR affi-GFLG-FK-FC-TfR-H7 Amino Acid Sequence (SEQ ID NO:101)

[0381] MYRMQLLSCIALSLALVTNSGHHHHHHHH7GLQVDNKFNKEMWAAWEEIRN LPNLNGWOMTAFIASLVDDPSOSANLLAEAKKLNDAQAPKVDGGFLGGF / rGEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QDPAVS VALGQT V RITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDE ANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSC AASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL RAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0382] pDP174-His8-EGFR affi-GFLG-VR-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 102)

[0383] MYRMQLL SCIAL SLALVTNSGHHHHHHHH 7GLQ VDNKFNKEMWAA WEEIRN LPNLNGWOMTAFIASLVDDPSOSANLLAEAKKLNDAOAPKVDGGFZGGERGEOGD KTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QDPAVS VALGQT V RITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDE ANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSC AASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL RAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0384] pDP210-CD20-HC-(EVR)-FC (GRLR) -N297G-TfR-H7 Amino Acid Sequence (SEQ ID NO: 103)

[0385] MYRMOLLSCIALSLALVTNSOVOLOOPGAELVKPGASVKMSCKASGYTFT SYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSS LTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSG GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TQTYICNVNHKPSNTKVDKKAEPKSCGGAGAGGEERGEDGDKTHTCPPCPAPELLRGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRV VSVLTVLHQDWLNGKEYKCKVSNKARPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWY QQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQ APGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGY GDYPDYWGQGTLVTVSS*

[0386] pDP213-CD20-HC-(EVR)-FC (GRLR) -N297G Amino Acid Sequence (SEQ ID NO: 104)

[0387] MYRMQLLSCIALSLALVTNSOVOLOOPGAELVKPGASVKMSCKASGYTFT SYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSS LTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSG GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLG TQTYICNVNHKPSNTKVDKKAEPKSCGGAGAGGEFRGEDGDKTHTCPPCPAPELLRGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRV VSVLTVLHQDWLNGKEYKCKVSNKARPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK*

[0388] pDP219-FC-TIR-H7 Amino Acid Sequence (SEQ ID NO: 105)

[0389] MYRMOLLSCIALSLALVTNSGHHHHHHHH / GGY / GGEEFGEDGAG.S'GFEG.S'G.S’DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QDPAVS VALGQT V RITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDE ANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSL RAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0390] pDP223-pFUSE-H7 scFV-knob-Fc-His Amino Acid Sequence (SEQ ID NO: 106)

[0391] MYRMQLLSCIALSLALVTNSSELTODPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAP GKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGD Y P D YWGQG T L VT VS SP IFEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCV WDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYKCKVSNK ALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGSHHHHHH*

[0392] pDP224-pFUSE-CD 19 NT.l-knob-Fc-H7 scFV-His Amino Acid Sequence (SEQ ID NO: 107)

[0393] MYRMQLLSCIALSLALVTNSPEEPLVVKVEEGDTAALWCLKGTSDGPTOQ LTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEK AWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDSVSRGPLSWT HVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKWYCHRGNVTT SFHLEVIARPVKAHSDLRTGGWKFIPEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWL NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWYQQKPGQAPVLVM YGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGG GGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVI SYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVT VS SGGSHHHHHH*

[0394] pDP225-2-Hole Fc_H7 scFV Amino Acid Sequence (SEQ ID NO: 108)

[0395] MRMQLLLLIALSLALVTNSTNGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGKGSSGGSGGSGGSSELTODPAVSVALGOTVRITCOGDSLRSYYASWYOOKPGOAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGG GGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAV ISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGT LVTVSS*

[0396] pDP226-Hole Fc_-avitag Amino Acid Sequence (SEQ ID NO: 109)

[0397] MRMQLLLLIALSLALVTNSZS'GEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGLNDIFEAQKIEWHEG*

[0398] pDP227-Knob Fc_H7 scFV-His Amino Acid Sequence (SEQ ID NO: 110)MRMOLLLLIALSLALVTNSASGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRT PEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRWSVLTVLHQDWLNGKEYK CKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG SSGGSGGSGGSSELTODPAVSVALGOTVRI TCOGDSLRSYYASWYOOKPGOAPVLVMYGRNER PSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGG GSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSN KYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGGSHHHHHH*

[0399] PD-L1 TransTAC (pDP186) Amino Acid Sequence (SEQ ID NO: 111)

[0400] MYRMQLLSCIALSLALVTNSDIOMTOSPSSLSASVGDRVTITCRASODVSTA VAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSC AASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNT AYLOMNSLRAEDTAVYYCARRHWPGGFDYWGOGTLVTVSSGGSGSAGGGFLGGFFGFDG'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNS T YRWS VLTVLHQDWLNGKE YKCKVSNKALPAP I EKT I SKAKGQP REPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSS E L T QD PAYS V ALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISG LQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGR SLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLY LQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS

[0401] CD20 TransTAC:

[0402] Heavy Chain (pDP210) Amino Acid Sequence (SEQ ID NO: 112)

[0403] MYRMQLLSCIALSLALVTNSOVOLOOPGAELVKPGASVKMSCKASGYTFT SYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSS LTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAASTKGPSVFPLAPSSKSTSG GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKAEPKSCGGAGAGGFERGEDGDKTHTCPPCPAPELLRGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKARPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSYYASWY QQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVF GGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMHWVRQ APGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGY GDYPDYWGQGTLVTVSS

[0404] Light Chain (pDPl 18) Amino Acid Sequence (SEQ ID NO: 113)

[0405] MYRMOLLSCIALSLALVTNSQIVLSOSPAJI,SASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTF GGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWCVDNALQSGNSQES VTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

[0406] CD20 TransTAC -M 16 version (pDP 127) :

[0407] Heavy chain Amino Acid Sequence (SEQ ID NO: 114) (the light chain is as immediately above)

[0408] MYRMQLLSCIALSLALVTNSOIVLSOSPAILSASPGEKVTMTCRASSSVSYIH WFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQ WTSNPPTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSS TAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSAGGAGAGGFLGGEDG'DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDG VEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGS SELTQDPAVSVAL GQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQ PEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSL RLSCAASRYPFHHHDHHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQ MNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS*

[0409] EGFR TransTAC (pDP211) Amino Acid Sequence (SEQ ID NO: 115)

[0410] MYRMQLLSCIALSLALVTNSLQVDNKFNKEMWAAWEEIRNLPNLNGWOMTAFIASLVDDPSOSANLLAEAKKLNDAQAPKVDGGGGEFFGEDGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS VMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYY ASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLT GPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAMH WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARD LSGYGDYPDYWGQGTLVTVSS

[0411] CD19 CAR TransTAC (pDP160) Amino Acid Sequence (SEQ ID NO: 116)

[0412] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAAL WCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGNVTTSFHLEVIARPVKAHSDLRTGGWKGGFLGGERGEDGDKTHTCPPCPAPE LLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRI TCQGDSLRSY YASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSL TGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGWQPGRSLRLSCAASRFTFSSYAM HWVRQAPGKGLEWVAVI S YDGSNKYYADSVKGRFT I SRDNSKNTLYLQMNSLRAEDTAVYYCAR DLSGYGDYPDYWGQGTLVTVSS

[0413] CD19 CAR TransTAC earlier version (pDP50) Amino Acid Sequence (SEQ ID NO: 117)

[0414] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGPEEPLVVKVEEGDTAALWCL KGTSDGPTQQLTWSRESPLKPFLKYSLGVPGLGVHVRPDAISVVIRNVSQQMGGFY LCQPGPPSEKAWQPGWTVNVEGSGELFRWNVSDLGGLGCGLKNRSSEGPSSPSGK LMSPKLYVWAKDRPEIWEGEPPCLPPRDSLNQSLSRDLTVAPGSTLWLSCGVPPDS VSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMWVMGTSLMLPRATAQDAGKW YCHRGN VTTSFHLE VIARPVKAHSDLRTGGWKGGFFGGEOGDKT H TCPPCPAPELLG GPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM REALWRYYQKSLSLSPGKGSSGGSGGSGGSVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPS DGPSVACVKKASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYY AVAVVKKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAP CADGTDFPQL CQL CPGCGCS TLNQ YFG YSGAFKCLKDGAGDVAFVKHS TIFENLANKADRDQ YELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKEFQLFSSP HGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKPVKWCALSHHER LKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGKCGLVPVLAENYNKSD NCED TPEAGYFAIAVVKKSASDL TWDNLKGKKSCHTAVGR TAGWNIPMGLL YNKINHCRFDEFF SEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAFRCLVEKGDVAFVKHQTVPQNTGG KNPDPWAKNLNEKD YELLCLDGTRKPVEE YANCHLARAPNHAVVTRKDKEACVHKILRQQQHLF GSNVTDCSGNFCLFRSE TKDLLFRDD TVCLAKLHDRNTYEKYLGEE YVKAVGNLRKCS TSSLLE ACTFRRP

[0415] Additional fusion proteins 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.

[0416] vl.2 antiPDLl-linker-Fc(knob) Amino Acid Sequence

[0417] TSDIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSA SFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKGGGG SGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEW VAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLGGVRGGSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSHHHHHH (SEQ ID NO: 300)

[0418] H7-H7-Fc(hole) Amino Acid Sequence

[0419] TSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGGGGSSGGSGGGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGGGGSGGGGSGGGGSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGLNDIFEAQKIEWHEG (SEQ ID NO: 301)

[0420] vl.4 antiPDLl-linker-Fc(knob)-H7 Amino Acid Sequence

[0421] TSDIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVSSGGSGSAGGGFLGGVRGGSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYGSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLWCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSSGGSHHHHHH (SEQ ID NO: 302)

[0422] Fc(hole)-H7 Amino Acid Sequence

[0423] TSGEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLSCAVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLVSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSSGGSGGSGGSSELTQDPAVSVALGQTVRITCQGDSLRSYYASWYQQKPGQAPVLVMYGRNERPSGVPDRFSGSKSGTSASLAISGLQPEDEANYYCAGWDDSLTGPVFGGGTKLTVLGGGGGSGGGGSGGGGSQVQLQESGGGVVQPGRSLRLSCAASRFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDLSGYGDYPDYWGQGTLVTVSS (SEQ ID NO: 303)[004241 pAD2-His8-PDLl scFV-GFLG-VR-FC-TIR-N5-optimized Amino Acid Sequence

[0425] MYRMQLLSCIALSLALVTNSGHHHHHHHHTGDIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTLT1SSLQPEDFATYYC...

Claims

CLAIMSWhat is claimed:

1. A fusion protein of Formula I:R1-R2-R3 (I): wherein:R1 is at least one protein of interest (POI) binder (POIB) or POI binding means;R2 is a linker of the formula R4-R5 or R5-R4, wherein:R4 is IgG Fc region; andR5 is an optional protease-sensitive linking means; andR3 is a TR binding means wherein the TR binding means is non-competitive with endogenous transferrin for binding to the TR and optionally, comprising a glycine-rich linker between R2 and R3.

2. The fusion protein of claim 1, wherein the TR binding means is an antibody fragment having a heavy chain variable region.

3. The fusion protein of claim 1, wherein the TR binding means is VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148).

4. The fusion protein of claim 1, wherein the TR binding means comprises: a. a VH CDR1 comprising the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 comprising the amino acid sequence of ITATGNT (SEQ ID NO: 201), and a VH CDR3 comprising the amino acid sequence of YMLDK (SEQ ID NO: 202). b. a VH CDR1 comprising the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 comprising the amino acid sequence of FTATGNT (SEQ ID NO: 203), and a VH CDR3 comprising the amino acid sequence of AMLDK (SEQ ID NO: 204); orc. a VH CDR1 comprising the amino acid sequence of GTDFSINF (SEQ ID NO: 200), a VH CDR2 comprising the amino acid sequence of FTATGNT (SEQ ID NO: 203), and a VH CDR3 comprising the amino acid sequence of YMADK (SEQ ID NO: 205).

5. The fusion protein of claim 1, wherein R3 is at least two TR binding means arranged in tandem.

6. The fusion protein of claim 1, wherein the optional protease-sensitive linking means comprises a cathepsin-cleavable peptide.

7. The fusion protein of claim 6, wherein the cathepsin-cleavable peptide is selected from the group consisting of FK, VA, VK, SEQ ID NO: 7, 8, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144 and 145.8 The fusion protein of claims 1, wherein the fusion protein of Formula I is a homodimer.

9. The fusion protein of claim 8, wherein the TR binding means within the homodimer has a binding affinity to TR (Kd) of about 0.001 nM to about 50 nM.

10. The fusion protein of claims 1, wherein the fusion protein of Formula I is a heterodimer linked to a fusion protein of Formula II:R4’-R3’ (II): wherein:R4’ is IgG Fc region; andR3’ is a TR binding means wherein the TRB means is non-competitive with endogenous transferrin for binding to the TR; and optionally, comprising a protease-sensitive linking means between R3’ and R4’.11 . The fusion protein of claim 10, wherein the TR binding means within the heterodimer has a binding affinity to TR (Kd) of about 0.1 nM to about 200 nM.

12. The fusion protein of claim 1, wherein the POIB or POI binding means comprises an antibody.

13. The fusion protein of claim 1, wherein the POIB or POI binding means binds to an extracellular domain of a transmembrane protein.

14. The fusion protein of claim 13, wherein the extracellular region of the membrane protein comprises a chimeric antigen receptor (CAR), a receptor tyrosine kinase, a checkpoint inhibitor binding molecule, or a cell lineage-specific marker.

15. The fusion protein of any one of claim 1, wherein the POIB or POI binding means binds to an extracellular domain of an epidermal growth factor receptor (EGFR), a programmed death- ligand 1 (PD-L1), CD19, or CD20.

16. The fusion protein of any one of claims 1-14, wherein the optional glycine-rich linker between R2 and R3 is selected from the group consisting of SEQ ID NO: 9, 10, 11, 12, 13, 14, 15 and 16.

17. A nucleic acid sequence encoding the fusion protein of any one of claim 1.

18. A method for treating a subject that has a disease, comprising administering the fusion protein of claim 1 to the subject.

19. The fusion protein of claim 1 for use in treating a disease in a patient.

20. Use of the fusion protein of claim 1 for treating a subject.

21. A homodimer of a fusion protein of Formula I:R1-R2-R3 (III): wherein:R1 is at least one protein of interest (POI) binder (POIB) or POI binding means;R2 is a linker of the formula R4-R5 or R5-R4, wherein:R4 is IgG Fc region; andR5 is an optional protease-sensitive linking means; andR3 is a TR binding means wherein the TR binding means is non-competitive with endogenous transferrin for binding to the transferrin receptor, and optionally, comprising a glycine-rich linker between R2 and R3.

22. The homodimer of a fusion protein of claim 21, wherein the TR binding means is VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148).

23. The homodimer of claim 21, additionally comprising a disulfide bond between cysteine amino acids in R4 of separate fusion proteins.

24. A homodimer of a fusion protein of Formula I:R1-R6-R3 (I): wherein:R1 is at least one protein of interest (POI) binder (POIB) or POI binding means;R6 is a dimerization means; andR3 is a TR binding means, wherein the TRB means is non-competitive with endogenous transferrin for binding to the transferrin receptor; and wherein the homodimer optionally has a protease-sensitive linking means between R1 and R6.

25. The homodimer of a fusion protein of claim 24, wherein the TR binding means is VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148).

26. A pharmaceutical composition, comprising the fusion protein or homodimer of a fusion protein of any one of claims 1, 8, 10, 21 or 24.

27. A heterodimer of fusion proteins of Formula IV and V:R1-R2 (IV);R3-R2’ (V): wherein:R1 is a protein of interest (POI) binder (POIB) or POI binding means;R2 and R2’ are linkers of the formula R4 or optionally R4-R5, wherein:R4 is an IgG Fc region;R5 is an optional protease-sensitive linking means; andR3 is at least one TR binding means, wherein the TR binding means is non-competitive with endogenous transferrin for binding to the TR.

28. The heterodimer of fusion proteins of claim 27, wherein the TR binding means is VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148).

30. The heterodimer of fusion proteins of claim 27, wherein the R4 of separate fusion proteins have complementary knob and hole structures.

31. A heterodimer of fusion proteins of Formula I and VI:R1-R2-R3 (I);R2’ (VI): wherein:R1 is a protein of interest (POI) binder (POIB) or POI binding means;R2 is a linker of the formula R4-R5 or R5-R4, wherein:R4 is an IgG Fc region;R5 is an optional protease-sensitive linking means;R3 is at least one TR binding means, wherein the TRB means is non-competitive with endogenous transferrin for binding to the TR; andR2’ is a linker of the formula R4 or optionally R4-R5.

32. The heterodimer of fusion proteins of claim 31, wherein the TR binding means is VHHA-12 (SEQ ID NO: 154), VHHA (SEQ ID NO: 146), VHHA-5 (SEQ ID NO: 155), VHHA-7 (SEQ ID NO: 156) or VHHB (SEQ ID NO: 148).

33. The heterodimer of fusion proteins of claim 31, wherein the R4 of separate fusion proteins have complementary knob and hole structures.

34. A fusion protein of Formula I:R1-R2-R3 (I): wherein:R1 is at least one protein of interest (POI) binder (POIB) or POI binding means;R2 is a linker of the formula R4-R5 or R5-R4, wherein:R4 is IgG Fc region; andR5 is an optional protease-sensitive linking means; andR3 is at least two TR binding means arranged in tandem, and optionally, comprising a glycine-rich linker between R2 and R3.

35. The fusion protein of claim 34, wherein the TR binding means are non-competitive with endogenous transferrin for binding to the transferrin receptor.

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