Anti-idiotypic antibodies to cluster of differentiation 7-targeted binding domains and related compositions and methods

Abstract

Binding polypeptides (e.g., anti-idiotypic antibodies), or antigen-binding fragments thereof, that specifically bind to an anti-cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof, compositions or articles of manufacture comprising the same, and methods of using such binding polypeptides. In embodiments, an anti-idiotypic antibody, or antigen-binding fragment thereof, specifically binds to the idiotype of an anti-CD7 antibody. In still other embodiments, an anti-idiotypic antibody, or antigen-binding fragment thereof, described herein is useful for identifying, selecting for, depleting, and / or stimulating cells that express an anti-CD7 antigen-binding domain (e.g., an anti-CD7 chimeric antigen receptor (CAR)-T cell) on their surface.

Description

[0001] ANTI-IDIOTYPIC ANTIBODIES TO CLUSTER OF DIFFERENTIATION 7- TARGETED BINDING DOMAINS AND RELATED COMPOSITIONS AND METHODS

[0002] CROSS REFERENCE TO RELATED APPLICATIONS

[0003] The present application claims priority to U.S. Provisional Application No. 63 / 511,135, filed June 29, 2023, the entire contents of which are hereby incorporated by reference in its entirety.

[0004] SEQUENCE LISTING

[0005] This application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. The Sequence Listing XML file, created on June 20, 2024, is named 180802-055502PCT_SL.XML and is 335,505 bytes in size.

[0006] BACKGROUND

[0007] Methods are available for adoptive cell therapy using engineered cells expressing recombinant receptors, such as chimeric antigen receptor (CARs) containing extracellular antigen-binding domains. Various strategies are available to assess the activity of such cells either in vitro or in vivo. Improved methods are needed to specifically assess and / or control the activity of CAR-expressing cells that have been administered to a subject. Accordingly, the present disclosure provides methods and compositions that address this need.

[0008] SUMMARY

[0009] Featured herein are binding polypeptides (e.g., anti-idiotypic antibodies), or antigen- binding fragments thereof, that specifically bind to an anti-cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof, compositions or articles of manufacture comprising the same, and methods of using such binding polypeptides. In embodiments, an anti-idiotypic antibody, or antigen-binding fragment thereof, specifically binds to the idiotype of an anti-CD7 antibody. In still other embodiments, an anti-idiotypic antibody, or antigen- binding fragment thereof, described herein is useful for identifying, selecting for, depleting, and / or stimulating cells that express an anti-CD7 antigen-binding domain (e.g., an anti-CD7 chimeric antigen receptor (CAR)-T cell) on their surface. In one aspect, the disclosure features an antibody or an antigen-binding fragment thereof that specifically binds to an anti-cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof. The binding polypeptide contains one or more complementarity determining regions (CDRs) selected from one or more of heavy chain variable region (VH) CDR1, VH CDR2, VH CDR3, light chain variable region (VL) CDR1, VL CDR2, and VL CDR3. The VH CDR1 contains the following amino acid sequence: GX2X3X4X5X6X7X8X9, where X2 is F, I, or S, X3 is D, I, S, or T, X4 is F, I, or L, X5 is I or S, X6 is G, N, null, P, S, or T, X7 is A, D, G, S, V, or Y, X8 is H, N, or Y, and X9 is A, C, D, F, G, R, S, W, or Y. The VH CDR2 contains the following amino acid sequence: X10X11X12X13X14X15X16X17X18, where X10 is A, G, I, null, R, T, or V, X11 is A, D, F, G, H, N, null, S, V, W, or Y, X12 is A, C, D, G, I, N, null, P, T, or V, X13 is A, D, G, I, L, null, R, S, T, or V, X14 is D, G, I, N, null, R, S, T, or V, X15 is D, H, N, S, T, or V, X16 is D, G, null, S, or V, X17 is D, I, K, N, null, P, R, S, T, V, or Y, and X18 is A, I, N, null, or T. The VH CDR3 contains the following amino acid sequence: X19X20X21X22X23X24X25X26X27X28X29X30X31X32X33X34X35X36X37X38X39X40X41X42, where X19is A or V, X20is K, R, or S, X21is A, D, E, G, I, R, S, or V, X22is D, E, G, L, P, or T, X23is A, D, G, I, N, null, S, T, V, or Y, X24is A, D, F, G, H, L, null, S, V, W, or Y, X25is D, G, N, null, S, T, or V, X26is A, D, E, F, G, null, S, V, or Y, X27is A, D, E, G, N, null, S, T, V, W, or Y, X28is A, D, G, null, V, W, or Y, X29is D, null, or Y, X30is A, D, E, F, G, L, M, null, S, T, V, W, or Y, X31is A, D, G, L, N, null, P, or T, X32is A, D, G, L, N, null, or V, X33is A, F, null, R, or Y, X34 is F or null, X35 is A, G, L, or null, X36 is G, Y, or null, X37 is G, I, N, null, T, or Y, X38 is A, D, null, T, or Y, X39 is A, G, null, P, or T, X40 is F, I, L, M, V, W, or Y, X41 is A, D, or N, and X42 is F, I, L, or P. The VL CDR1 contains the following amino acid sequence: X43X44X45X46X47X48X49X50 , where X43 is E or Q, X44 is D, H, N, R, or S, X45 is I or V, X46 is A, D, G, N, S, or Y, X47 is G, N, R, S, T, or V, X48 is A, D, G, H, K, L, N, R, S, W, or Y, X49 is N or null, and X50 is C, F, or null. The VL CDR2 contains the following amino acid sequence: X51X52S, where X51 is A, D, G, K, Q, S, T, W, or Y, and X52 is A, S, or T. The VL CDR3 contains the following amino acid sequence: X54X55X56X57X58X59X60X61X62X63X64X65X66X67X68X69X70X71, where X54 is A, L, or Q, X55 is C, G, Q, S, or Y, X56is A, D, E, F, G, P, T, V, or Y, X57is A, C, D, F, G, R, S, T, V, W, or Y, X58is A, D, G, H, L, N, S, T, V, or Y, X59is G or null, X60is G or null, X61is A, C, D, G, I, S, or Y, X62is D, G, I, L, N, R, S, T, or Y, X63is F, G, I, N, R, S, or V, X64is A, D, F, G, I, P, S, T, V, or Y, X65is A, D, E, G, H, I, N, R, S, or V, X66is A, C, F, G, H, I, N, null, P, R, S, T, V, W, or Y, X67is A, F, G, I, N, null, R, S, T, V, W, or Y, X68is A, F, N, null, P, V, or Y, X69is A, F, null, or V, X70is F or null, and X71is A or null. In another aspect, the invention features an antibody or an antigen-binding fragment thereof that specifically binds to an anti-cluster of differentiation 7 antibody, or an antigen-binding fragment thereof. The antibody contains a) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to an amino acid sequence selected from one or more of: QSVEESGGRLVTPGTPLTLTCTVSGFSLSDYYMSWVRQAPGKGLEWIGIIYGSGTTYYATWA KGRFTISKTSSTTVDLKMTSLTASDTATYFCARALYADSNYWPLYFNFWGQGTLVTVSS (1H2; SEQ ID NO: 22), QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA SWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARSDYTGGNYFNLWGQGTLVTVSS (2H3; SEQ ID NO: 23), QSLEESGGDLVKPGASLTLTCTASGFSFSSSYWMCWVRQAPGKGLEWIACIHAGSSGSIYYA NWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDYHYGGTGYAYNLWGQGTLVTVSS (43H1; SEQ ID NO: 24), QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDIYGYAGYAYATAFNLWGQGTLVTV SS (15H3; SEQ ID NO: 25), QEQLEESGGDLVKPEGSLTLTCTASGFSFSSSYRICWVRQAPGKGLEWIACIYAGNSSYTHY ATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFCARDDTVSFGYPYGYFNLWGQGTLVTVS S (29H3; SEQ ID NO: 26), QSLEESGGDLVQPEGSLTLTCTASGSDISGYSLCWVRQAPGKGLEWIACIGNGDGNTYYASW AKGRFTISKTSSTTVTLQMTSLTAADTATYFCASDTHDYVGFNLWGQGTLVTVSS (30H3; SEQ ID NO: 27); QEQLVESGGGLVQPEGSLTLTCTASGFSFSSSYYMCWVRQAPGKGLEWIGCIAIGSGSAYYA NWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFCARDDYAGGGYFNLWGQGTLVTVSS (SEQ ID NO: 323; 5H1); QSLEESGGDLVKPGASLTLTCTASGFDFSSSYYMCWVRQAPGKGPEWIACIWGGSSGTTYYA NWAKGRFTISRTSSTTVTLQMTSLTAADTATYFCARDDYAGGGYINLRGQGTLVTVSS (SEQ ID NO: 324; 20H1); QSLEESGGDLVKPGASLTLTCTASGFSFSSSYSICWVRQAPGKGLEWIACIYAGSSGSTYYA SWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARIEYYSYGDVGYGYNYGMDLWGQGTLV TVSS (SEQ ID NO: 325; 39H2); and

[0010] QSLEESGGDLVKPGASLTLTCTASGFSFSSGYDMCWVRQAPGKGLEWIACRHGGSSGSTHYA TWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDSAAGGYFNLWGQGTLVTVSS (SEQ ID NO: 326; 45H2); and / or b) a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to an amino acid sequence selected from one or more of: ANIVMTQTPASVEVAVGGTVTIKCQASQSISNLLAWYQQKSGQPPKLLIYDSSDLASGVSSR FKGSGSGTQFTLTISGVECADAATYYCQQGWSGSNVNNVFGGGTEVWKGDP (1K2; SEQ ID NO: 28), DVVMTQTPSSVEAAVGGTVTIKCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADIFVFGGGTEVWKGDP (2K1; SEQ ID NO: 29), ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLAWYQQKPGQRPKLLIYGASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYYSSSPDNTFGGGTEWVKGDP (43K2; SEQ ID NO: 30), AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKGDP (15K3; SEQ ID NO: 31), AIEMTQTPFSVSAAVGGTVTINCQASESIYSNLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSAVYSSSADNAFGGGTEWVKGDP (29K1; SEQ ID NO: 32), AAVLTQTPSPVSAAVGGTVSISCQSSKSVYNNNFLSWFQQKPGQPPKLLIYGASTLASGVPS RFKGNGSGTQFTLTISDVQCDDAATYYCAGGYGSSSDRFGFGGGTEWVKGDP (30K3; SEQ ID NO: 33);

[0011] ALVMTQTPSSASEPVGGTVTIKCQAGESISSRLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSESGTEYTLTISDLECDDAATYYCQSVSASGSGDTRAFGGGTEVWK (SEQ ID NO: 327; 5K3);

[0012] ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLGWYQQKPGQPPKLLIYAASYLSSGVPSRF KGSGSGTDFTLTISDLECADAATYYCQSAADSSSGDFFYAFGGGTEWVK (SEQ ID NO: 328; 20K3);

[0013] AQVLTQTPASVEAAVGGTITVNCQASQSIGTDLAWYQQKPGQRPKLLIYAASNLASGVPSRF KGSGSGTQFTLTISDLECADAATYYCQCTYYDSSYGNAFGGGTEWVK (SEQ ID NO: 329; 39K2); and AIEMTQTPFSVSAAVGGTVTINCQASENIYSNLGWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSATYSSGTDRAFGGGTEWVK (SEQ ID NO: 330; 45K2).

[0014] In another aspect, the disclosure features an antibody or an antigen-binding fragment thereof that specifically binds to an anti-cluster of differentiation 7 antibody, or an antigen- binding fragment thereof. In one aspect, the antibody contains a) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSVEESGGRLVTPGTPLTLTCTVSGFSLSDYYMSWVRQAPGKGLEWIGI I YGSGTTYYATWA KGRFTISKTSSTTVDLKMTSLTASDTATYFCARALYADSNYWPLYFNFWGQGTLVTVSS (1H2; SEQ ID NO: 22), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: ANIVMTQTPASVEVAVGGTVTIKCQASQSISNLLAWYQQKSGQPPKLLIYDSSDLASGVSSR FKGSGSGTQFTLTISGVECADAATYYCQQGWSGSNVNNVFGGGTEVWKGDP (1K2; SEQ ID NO: 28). In another aspect, the antibody contains b) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA S WAKGRFT I S KTS S TTVTLQMTS LTAADTATYFC ARS DYTGGNYFNLWGQGTL VTVS S (2H3 ; SEQ ID NO: 23), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: DVVMTQTPSSVEAAVGGTVTIKCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADIFVFGGGTEVWKGDP (2K1; SEQ ID NO: 29). In another aspect, the antibody contains c) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSLEESGGDLVKPGASLTLTCTASGFSFSSSYWMCWVRQAPGKGLEWIACIHAGSSGSIYYA NWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDYHYGGTGYAYNLWGQGTLVTVSS (43H1; SEQ ID NO: 24), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLAWYQQKPGQRPKLLIYGASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYYSSSPDNTFGGGTEWVKGDP (43K2; SEQ ID NO: 30). In another aspect, the antibody contains d) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SS (15H3; SEQ ID NO: 25), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0015] AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKGDP (15K3; SEQ ID NO: 31). In another aspect, the antibody contains e) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0016] QEQLEESGGDLVKPEGSLTLTCTASGFSFSSSYRICWVRQAPGKGLEWIACIYAGNSSYTHY ATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFCARDDTVSFGYPYGYFNLWGQGTLVTVS S (29H3; SEQ ID NO: 26), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0017] AIEMTQTPFSVSAAVGGTVTINCQASESIYSNLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSAVYSSSADNAFGGGTEWVKGDP (29K1; SEQ ID NO: 32). In another aspect, the antibody contains f) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0018] QSLEESGGDLVQPEGSLTLTCTASGSDISGYSLCWVRQAPGKGLEWIACIGNGDGNTYYASW AKGRFT I S KTS S TTVTLQMTS LTAADTATYFC AS DTHDYVGFNLWGQGTL VTVS S (30H3 ; SEQ ID NO: 27), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0019] AAVLTQTPSPVSAAVGGTVSISCQSSKSVYNNNFLSWFQQKPGQPPKLLIYGASTLA SGVPSRFKGNGSGTQFTLTISDVQCDDAATYYCAGGYGSSSDRFGFGGGTEWVKGDP (30K3; SEQ ID NO: 33). In another aspect, the antibody contains g) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QEQLVESGGGLVQPEGSLTLTCTASGFSFSSSYYMCWVRQAPGKGLEWIGCIAIGSGSAYYA NWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFCARDDYAGGGYFNLWGQGTLVTVSS (SEQ ID NO: 323; 5H1), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0020] ALVMTQTPSSASEPVGGTVTIKCQAGESISSRLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSESGTEYTLTISDLECDDAATYYCQSVSASGSGDTRAFGGGTEVWK (SEQ ID NO: 327; 5K3). In another aspect, the antibody contains h) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0021] QSLEESGGDLVKPGASLTLTCTASGFDFSSSYYMCWVRQAPGKGPEWIACIWGGSSGTTYYA NWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDYAGGGYINLRGQGTLVTVSS (SEQ ID NO: 324; 20H1), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0022] ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLGWYQQKPGQPPKLLIYAASYLSSGVPSRF KGSGSGTDFTLTISDLECADAATYYCQSAADSSSGDFFYAFGGGTEWVK (SEQ ID NO: 328; 20K3). In another aspect, the antibody contains i) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0023] QSLEESGGDLVKPGASLTLTCTASGFSFSSSYSICWVRQAPGKGLEWIACIYAGSSGSTYYA SWAKGRFTI SKTSSTTVTLQMTSLTAADTATYFCARI EYYS YGDVGYGYNYGMDLWGQGTLV TVSS (SEQ ID NO: 325; 39H2), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0024] AQVLTQTPASVEAAVGGTITVNCQASQSIGTDLAWYQQKPGQRPKLLIYAASNLASGVPSRF KGSGSGTQFTLTISDLECADAATYYCQCTYYDSSYGNAFGGGTEWVK (SEQ ID NO: 329; 39K2). In another aspect, the antibody contains)) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:

[0025] QSLEESGGDLVKPGASLTLTCTASGFSFSSGYDMCWVRQAPGKGLEWIACRHGGSSGSTHYA TWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDSAAGGYFNLWGQGTLVTVSS (SEQ ID NO: 326; 45H2), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: AI EMTQTPFSVSAAVGGTVTINCQASENIYSNLGWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSATYSSGTDRAFGGGTEWVK (SEQ ID NO: 330; 45K2).

[0026] In another aspect, the disclosure features a polynucleotide encoding the antibody or antigen-binding fragment thereof of any aspect of the disclosure, or embodiments thereof.

[0027] In another aspect, the disclosure features a vector containing the polynucleotide of any aspect of the disclosure, or embodiments thereof.

[0028] In another aspect, the disclosure features a cell containing the antibody or antigen- binding fragment thereof, the polynucleotide, or the vector of any aspect of the disclosure, or embodiments thereof.

[0029] In another aspect, the disclosure features a conjugate containing the antibody or antigen-binding fragment thereof of any aspect of the disclosure, or embodiments thereof, fused to a heterologous moiety.

[0030] In another aspect, the disclosure features a method of producing an antibody or antigen-binding fragment thereof. The method involves expressing the antibody or antigen- binding fragment thereof encoded by the polynucleotide or the vector of of any aspect of the disclosure, or embodiments thereof, in a cell and recovering or isolating the antibody or antigen-binding fragment thereof from the cell.

[0031] In another aspect, the disclosure features a method of producing an antibody or antigen-binding fragment thereof. The method involves culturing the cell of any aspect of the invention, or embodiments thereof, under conditions in which the antibody or antigen- binding fragment thereof is expressed, and recovering or isolating the antibody or antigen- binding fragment thereof from the cell.

[0032] In another aspect, the disclosure features an antibody or antigen-binding fragment thereof produced by the method of any aspect of the disclosure, or embodiments thereof.

[0033] In another aspect, the disclosure features a composition containing the antibody or antigen-binding fragment thereof, the polynucleotide, the vector, the cell, or the conjugate of any aspect of the disclosure, or embodiments thereof.

[0034] In another aspect, the disclosure features a pharmaceutical composition containing the composition of any aspect of the disclosure, or embodiments thereof, and a pharmaceutically acceptable excipient.

[0035] In another aspect, the disclosure features a method for identifying a cell containing an anti-cluster of differentiation (CD7) antibody, or an antigen-binding fragment thereof, on the cell surface in a biological sample. The method involves contacting the biological sample with the antibody or antigen-binding fragment thereof or the conjugate of any aspect of the disclosure, or embodiments thereof, under conditions sufficient for the antibody or antigen- binding fragment thereof or conjugate to bind to the anti-CD7 antibody, or antigen binding fragment thereof, in the biological sample, thereby identifying the cell expressing the anti- CD? antibody or antigen-binding fragment thereof.

[0036] In another aspect, the disclosure features a meso-scale discovery-based anti-drug antibody assay method. The method involves a) contacting an anti-CD7 chimeric antigen receptor (anti-CD7 CAR) polypeptide or antigen-binding fragment thereof bound to an electrode with the antibody or antigen-binding fragment thereof of any aspect of the disclosure, or embodiments thereof, and an anti-CD7 CAR polypeptide, or antigen-binding fragment thereof, labeled using an electrochemiluminescent label under conditions sufficient for the three polypeptides to form a complex. The method also involves b) detecting formation of the complex by applying electricity to the electrode and detecting an electrochemiluminescent signal generated by the electrochemiluminescent label.

[0037] In another aspect, the disclosure features a method of detecting an anti-CD7 antibody or antigen-binding fragment thereof in a biological sample. The method involves a) contacting the biological sample with the antibody or antigen-binding fragment thereof or the conjugate of any aspect of the disclosure, or embodiments thereof, under conditions sufficient for the antibody or antigen-binding fragment thereof or conjugate to bind to the anti-CD7 antibody, or antigen binding fragment thereof, in the biological sample. The method also involves (b) detecting the antibody bound to the anti-CD7 antibody or antigen-binding fragment thereof.

[0038] In another aspect, the disclosure features a method of selecting cells from a cell population. The method involves a) contacting a cell population expressing an anti-CD7 CAR polypeptide with the antibody or antigen-binding fragment thereof or the conjugate of any aspect of the disclosure, or embodiments thereof, under conditions sufficient for the antibody or antigen-binding fragment thereof or conjugate to bind to the anti-CD7 CAR polypeptide, or antigen binding fragment thereof, in the cell population. The method also involves b) selecting cells bound with the antibody or antigen-binding fragment thereof or conjugate.

[0039] In another aspect, the disclosure provides a method of depleting anti-CD7 CAR T cells in a subject. The method involves administering to the subject a composition containing the conjugate of any aspect of the disclosure, or embodiments thereof. The subject has been administered the anti-CD7 CAR T cells. In another aspect, the disclosure features a kit suitable for use in the method of any aspect of the disclosure, or embodiments thereof. The kit contains the antibody or antigen- binding fragment thereof, the polynucleotide, the vector, the cell, or the conjugate of any aspect of the disclosure, or embodiments thereof.

[0040] In another aspect, the disclosure features an antibody or an antigen-binding fragment thereof that specifically binds to an anti-cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof, where the binding polypeptide comprises a heavy chain polypeptide and a light chain polypeptide. In some aspects, a) the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA SWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARSDYTGGNYFNLWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KP KDTLM I S RTP EVTC VWDVSHED PEVKFNWYVDGVEVHNAKTKPRE EQ YNS TYRWS VLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO: 331; 2H3); and the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: DVVMTQTPSSVEAAVGGTVTIKCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADIFVFGGGTEVWKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 337; 2K1). In some aspects, b) the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: QEQLVESGGGLVQPEGSLTLTCTASGFSFSSSYYMCWVRQAPGKGLEWIGCIAIGSGSAYYA NWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFCARDDYAGGGYFNLWGQGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK (SEQ ID NO: 332; 5H1). In some aspects, the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: ALVMTQTPSSASEPVGGTVTIKCQAGESISSRLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSESGTEYTLTISDLECDDAATYYCQSVSASGSGDTRAFGGGTEVWKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 338; 5K3). In some aspects, c) the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 333; 15H3); and the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 339; 15K3). In some aspects, d) the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence:

[0041] QSLEESGGDLVKPGASLTLTCTASGFDFSSSYYMCWVRQAPGKGPEWIACIWGGSSGTTYYA NWAKGRFTISRTSSTTVTLQMTSLTAADTATYFCARDDYAGGGYINLRGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KP KDTLM I S RT PEVTC VWDVSHED PEVKFNWYVDGVEVHNAKTKPRE EQ YNS TYRVVS VLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO: 334; 20H1); and the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLGWYQQKPGQPPKLLIYAASYLSSGVPSRF KGSGSGTDFTLTISDLECADAATYYCQSAADSSSGDFFYAFGGGTEWVKRTVAAPSVFIFP PSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 340; 20K3). In some aspects, e) the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence:

[0042] QSLEESGGDLVKPGASLTLTCTASGFSFSSSYSICWVRQAPGKGLEWIACIYAGSSGSTYYA SWAKGRFTI SKTSSTTVTLQMTSLTAADTATYFCARI EYYS YGDVGYGYNYGMDLWGQGTLV TVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 335; 39H2); and the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence:

[0043] AQVLTQTPASVEAAVGGTITVNCQASQSIGTDLAWYQQKPGQRPKLLIYAASNLASGVPSRF KGSGSGTQFTLTISDLECADAATYYCQCTYYDSSYGNAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 341; 39K2). In some aspects, f) the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence:

[0044] QSLEESGGDLVKPGASLTLTCTASGFSFSSGYDMCWVRQAPGKGLEWIACRHGGSSGSTHYA TWAKGRFTISRTSSTTVTLQMTSLTAADTATYFCARDDSAAGGYFNLWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KP KDTLM I S RTP EVTC VWDVSHED PEVKFNWYVDGVEVHNAKTKPRE EQ YNS TYRWS VLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO: 336; 45H2); and the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: AIEMTQTPFSVSAAVGGTVTINCQASENIYSNLGWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSATYSSGTDRAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 342; 45K2).

[0045] In any aspect of the disclosure, or embodiments thereof, the VH CDR1 amino acid sequence is 8 or 9 amino acids in length, the VH CDR2 amino acid sequence is between 4 and 9 amino acids in length, the VH CDR3 amino acid sequence is between 9 and 23 amino acids in length, the VL CDR1 amino acid sequence is between 6 and 8 amino acids in length, and the VL CDR3 amino acid sequence is between 10 and 16 amino acids in length.

[0046] In any aspect of the disclosure, or embodiments thereof: a) the VH CDR1 contains an amino acid sequence selected from one or more of: GFDFSSSYY (SEQ ID NO: 92), GFDFSSYG (SEQ ID NO: 88), GFIISSSYC (SEQ ID NO: 90), GFSFSGGYD (SEQ ID NO: 89), GFSFSNSYY (SEQ ID NO: 100), GFSFSPSYC (SEQ ID NO: 86), GFSFSSAYW (SEQ IDNO: 102), GFSFSSGYD (SEQ ID NO: 105), GFSFSSGYY (SEQ ID NO: 93), GFSFSSSHY (SEQ ID NO: 99), GFSFSSSYF (SEQ ID NO: 82), GFSFSSSYR (SEQ IDNO: 95), GFSFSSSYS (SEQ ID NO: 103), GFSFSSSYW (SEQ ID NO: 81), GFSFSSSYY (SEQ ID NO: 83), GFSLSDYA (SEQ ID NO: 97), GFSLSDYY (SEQ ID NO: 80), GFSLSSGYD (SEQ ID NO: 101), GFSLSSNA (SEQ ID NO: 84), GFSLSSSYY (SEQ IDNO: 91), GFSLSSYA (SEQ ID NO: 85), GFSLSSYY (SEQ ID NO: 87), GFSLSVYA (SEQ IDNO: 106), GFTISSSYC (SEQ ID NO: 104), GFTISSSYW (SEQ ID NO: 98), GIDFITYYY (SEQ ID NO: 94), and GSDISGYS (SEQ ID NO: 96), b) the VH CDR2 contains an amino acid sequence selected from one or more of: INSDTT (SEQ IDNO: 116), AYGGGSGST (SEQ ID NO: 109), GYAGSSGST (SEQ ID NO: 117), IAIGSGSA (SEQ ID NO: 110), IAPGRSGST (SEQ ID NO: 127), IATADSGST (SEQ IDNO: 121), IDGASSGRT (SEQ ID NO: 138), IDPVHGTT (SEQ ID NO: 120), IDTGGSSV (SEQ IDNO: 113), IFGGVSVRN (SEQ ID NO: 135), IGNGDGNT (SEQ ID NO: 131), IHAGSSGNT (SEQ ID NO: 140), IHAGSSGSI (SEQ ID NO: 144), IHDGSSGST (SEQIDNO: 111), IHGGSSGNT (SEQ ID NO: 108), IHGGSSGST (SEQ IDNO: 139), ILSSGKT (SEQIDNO: 143), ILSSGNT (SEQIDNO: 149), INARIT (SEQIDNO: 133), INTGSGST (SEQIDNO: 129), ISGGSSGST (SEQIDNO: 114), ISGSGST (SEQIDNO: 132), ISNSGPT (SEQ ID NO: 119), ISSSGDT (SEQIDNO: 148), ISSTGST (SEQIDNO: 112), ITSNGRT (SEQIDNO: 126), IVTGTSGST (SEQ IDNO: 137), IWGGSSGTT (SEQIDNO: 125), IYAGGSGNT (SEQIDNO: 136), IYAGNSSYT (SEQ ID NO: 130), I YAGSSGNI (SEQ ID NO: 142), I YAGSSGSN (SEQ IDNO: 147), IYAGSSGST (SEQ ID NO: 134), IYASGST (SEQ ID NO: 115), IYCGVVGT (SEQIDNO: 145), IYGGSSGST (SEQIDNO: 124), IYGSGTT (SEQ ID NO: 107), IYIGDGIT (SEQIDNO: 123), IYVDNSGST (SEQIDNO: 141), RHGGSSGST (SEQIDNO: 146), SGST (SEQ ID NO: 122), THDGSSGST (SEQIDNO: 118), and VYGGSSGST (SEQIDNO: 128), c) the VH CDR3 contains an amino acid sequence selected from one or more of: VRDDGYLDL (SEQ ID NO: 158), AKEDGLVEEFAL

[0047] (SEQ ID NO: 154), ARADDDYGAAPYYFNI (SEQ ID NO: 173), ARADNWNSGWLGAFDP

[0048] (SEQ ID NO: 159), ARADYAGGDYFNL (SEQ ID NO: 160), ARADYTYGYVGYAFDL (SEQ

[0049] ID NO: 176), ARADYTYGYVGYAFNL (SEQ ID NO: 175), ARALYADSNYWPLYFNF (SEQ

[0050] ID NO: 150), ARDDAAYGGYFNL (SEQ ID NO: 187), ARDDAGGGGYFNL (SEQ ID NO:

[0051] 165), ARDDAYSYSGATYAYGTFNL (SEQ ID NO: 168), ARDDAYVYGGADYAYGAFNL

[0052] (SEQ ID NO: 178), ARDDIYGYAGYAYATAFNL (SEQ ID NO: 162), ARDDSAAGGYFNL

[0053] (SEQ ID NO: 188), ARDDSTWGGYFNL (SEQ ID NO: 179), ARDDSYDDYAEGYFNI (SEQ

[0054] ID NO: 185), ARDDTVSFGYPYGYFNL (SEQ ID NO: 171), ARDDYAGGGYFNL (SEQ ID

[0055] NO: 153), ARDDYAGGGYINL (SEQ ID NO: 166), ARDDYAGGGYVNL (SEQ ID NO:

[0056] 180), ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), ARDDYGGVAGYGYAFNL (SEQ ID

[0057] NO: 184), ARDDYHYGGTGYAYNL (SEQ ID NO: 186), ARDEVFTGGDAGYGYALNL (SEQ

[0058] ID NO: 189), ARDEYAGYAGYGYAFNL (SEQ ID NO: 183), ARDGGYDDYGDFDYGMDP

[0059] (SEQ ID NO: 190), AREGGYDDYGDFLNYFNL (SEQ ID NO: 155), ARGDGGMNYAWDL

[0060] (SEQ ID NO: 169), ARGDGYDDYGDPFNL (SEQ ID NO: 156), ARGDSYDDYVDPFNI

[0061] (SEQ ID NO: 167), ARGDYSDAFFNL (SEQ ID NO: 182),

[0062] ARGEGYGYADYAGGRYYYGLDL (SEQ ID NO: 170), ARGEGYSYDDYGDYFLGIYPLDL

[0063] (SEQ ID NO: 163), ARGEGYTYDDYGDYYDAFDP (SEQ ID NO: 157),

[0064] ARIEYYSYGDVGYGYNYGMDL (SEQ ID NO: 181), ARRDSSGPYYFNL (SEQ ID NO:

[0065] 164), ARSDYTGGNYFNL (SEQ ID NO: 151), ARVDGSTGVYTLDL (SEQ ID NO: 174),

[0066] ARVPYSSGWGADDAFDP (SEQ ID NO: 161), ASDTHDYVGFNL (SEQ ID NO: 172), and

[0067] VRDDYAGYAGYGYAFNL (SEQ ID NO: 177), d) the VL CDR1 contains an amino acid sequence selected from one or more of: EDIGTL (SEQ ID NO: 223), EDIYSL (SEQ ID

[0068] NO: 216), EDIYSN (SEQ ID NO: 234), EDIYVN (SEQ ID NO: 208), ENI YSG (SEQ ID

[0069] NO: 230), ENIYSN (SEQ ID NO: 232), ENIYSS (SEQ ID NO: 211), ESIDSH (SEQ ID

[0070] NO: 224), ESIGSN (SEQ ID NO: 219), ESISSR (SEQ ID NO: 204), ESIYGN (SEQ ID

[0071] NO: 212), ESIYSN (SEQ ID NO: 220), ESVGSN (SEQ ID NO: 203), KSVYNNNF (SEQ

[0072] ID NO: 222), QHIYSN (SEQ ID NO: 231), QNIGSN (SEQ ID NO: 233), QNINTY (SEQ

[0073] ID NO: 215), QNIYSG (SEQ ID NO: 209), QNIYSH (SEQ ID NO: 206), QNIYSK (SEQ

[0074] ID NO: 235), QNIYSN (SEQ ID NO: 213), QRINSW (SEQ ID NO: 202), QSIDSS (SEQ

[0075] ID NO: 227), QSIGSN (SEQ ID NO: 217), QSIGTD (SEQ ID NO: 228), QSISGN (SEQ

[0076] ID NO: 214), QSISNL (SEQ ID NO: 201), QSISNY (SEQ ID NO: 226), QSISRY (SEQ ID NO: 205), QSISSY (SEQ ID NO: 221), QSISTA (SEQ ID NO: 229), QSIYSN (SEQ ID NO: 225), QSVANNNC (SEQ ID NO: 210), QSVSNL (SEQ ID NO: 218), and QSVYNNN (SEQ ID NO: 207), e) the VL CDR2 contains an amino acid sequence selected from one or more of: AAS, ATS, DAS, DSS, GAS, KAS, QAS, SAS, TAS, TTS, WAS, and

[0077] YAS, and f) the VL CDR3 contains an amino acid sequence selected from one or more of: AGDYGAYI IS (SEQ ID NO: 242), AGGYGSSSDRFG (SEQ ID NO: 262), AGGYYCGSADCGA (SEQ ID NO: 245), LGVGTYLSADGNA (SEQ ID NO: 279), LGVYNYIGADHA (SEQ ID NO: 243), QCTDSGSSDVSA (SEQ ID NO: 259), QCTYDSYVPDTA (SEQ ID NO: 247), QCTYYDSSYGNA (SEQ ID NO: 270), QCTYYSSSFGVFNV (SEQ ID NO: 263), QGEFNCISADCNA (SEQ ID NO: 265), QGYCVSINPDRWA (SEQ ID NO: 267), QGYYLGSNFEPYNA (SEQ ID NO: 256), QGYYYSNSADTFA (SEQ ID NO: 258), QGYYYSSSADRWA (SEQ ID NO: 257), QQGDSSGWENT (SEQ ID NO: 260), QQGWSGSNVNNV (SEQ ID NO: 236), QQGYDSSFGDNV (SEQ ID NO: 271), QQGYSSSNVEYA (SEQ ID NO: 252), QSAADSSSGDFFYA (SEQ ID NO: 255), QSADYSRGADYA (SEQ ID NO: 280), QSATYSSGTDRA (SEQ ID NO: 277), QSAVYSGSPIWA (SEQ ID NO: 249), QSAVYSSSADNA (SEQ ID NO: 261), QSAYGSTNADIFV (SEQ ID NO: 237), QSAYYGGGTENA (SEQ ID NO: 254), QSAYYSGNTDNV (SEQ ID NO: 238), QSAYYSSSADNT (SEQ ID NO: 278), QSAYYSSSADTYYA (SEQ ID NO: 240), QSAYYSSSAHYA (SEQ ID NO: 274), QSAYYSSSPDNT (SEQ ID NO: 275), QSAYYSSSVART (SEQ ID NO: 246), QSAYYSTNADNFA (SEQ ID NO: 248), QSFYYSSSTDTRA (SEQ ID NO: 253), QSGRYIDSGDNV (SEQ ID NO: 266), QSGYYSSSADFFYA (SEQ ID NO: 269), QSPYYGSITDNA (SEQ ID NO: 273), QSVSASGSGDTRA (SEQ ID NO: 239), QSVYYSSSAHTRA (SEQ ID NO: 276), QSYVHSSGSSYI (SEQ ID NO: 268), QSYYGSSRSSFSPFFA (SEQ ID NO: 241), QSYYVISSSSYGFA (SEQ ID NO: 251), QSYYYGGSSSSDWYA (SEQ ID NO: 264), QSYYYSGSADRGYA (SEQ ID NO: 244), QYGYTYNSGDIA (SEQ ID NO: 250), and QYTYYSSNYNA (SEQ ID NO: 272 ) .

[0078] In any aspect of the disclosure, or embodiments thereof, the antibody or antigen binding fragment thereof contains three VH CDRs containing a set of amino acid sequences selected from one or more of: a) VH CDR1 : GFSLSDYY (SEQ ID NO: 80), VH CDR2: IYGSGTT (SEQ ID NO: 107), and VH CDR3: ARALYADSNYWPLYFNF (SEQ ID NO: 150) ; b) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHGGSSGNT (SEQ ID NO: 108), and VHCDR3: ARSDYTGGNYFNL (SEQ ID NO: 151 ) ; c) VH CDR1: GFSFSSSYF (SEQ ID NO: 82), VH CDR2: AYGGGSGST (SEQ ID NO: 109), and VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152 ) ; d) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VHCDR2: IAIGSGSA (SEQ ID NO: 110), and VH CDR3: ARDDYAGGGYFNL (SEQ ID NO: 153 ) ; e) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VHCDR2: IHDGSSGST (SEQ ID NO: 111), and VH CDR3: ARDDYAGGGYFNL (SEQ ID NO: 153) ; f) VHCDR1: GFSLSSNA (SEQ ID NO: 84), VH CDR2: ISSTGST (SEQ ID NO: 112), and VH CDR3: AKEDGLVEEFAL (SEQ ID NO: 154) ; g) VH CDR1: GFSLSSNA (SEQ ID NO: 84), VHCDR2: ISSTGST (SEQ ID NO: 112), and VH CDR3: AKEDGLVEEFAL (SEQ ID NO: 154 ) ; h) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IDTGGSSV (SEQ ID NO: 113), and VH CDR3: AREGGYDDYGDFLNYFNL (SEQ ID NO: 155 ) ; i) VH CDR1: GFSFSPSYC (SEQ ID NO: 86),VHCDR2: ISGGSSGST (SEQ ID NO: 114), and VH CDR3: ARGDGYDDYGDPFNL (SEQ ID NO: 156);j)VH CDR1: GFSLSSYA (SEQ ID NO: 85),VHCDR2: IYASGST (SEQ ID NO: 115), and VH CDR3: ARGEGYTYDDYGDYYDAFDP (SEQ ID NO: 157) ; k) VH CDR1: GFSLSSYY (SEQ ID NO: 87),VHCDR2: INSDTT (SEQ ID NO: 116), and VH CDR3: VRDDGYLDL (SEQ ID NO: 158) ; 1) VH CDR1: GFSFSSSYW (SEQ ID NO: 81),VHCDR2: GYAGSSGST (SEQ ID NO: 117), and VH CDR3: ARADNWNSGWLGAFDP (SEQ ID NO: 159) ;m)VHCDRl: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), and VHCDR3: ARADYAGGDYFNL (SEQ ID NO: 160) ; n) VH CDR1: GFSLSSYA (SEQIDNO: 85), VHCDR2: ISNSGPT (SEQ ID NO: 119), and VH CDR3: ARVPYSSGWGADDAFDP (SEQ ID NO: 161 ) ; o) VH CDR1: GFDFSSYG (SEQIDNO: 88), VH CDR2: IDPVHGTT (SEQ ID NO: 120), and VH CDR3: ARDDIYGYAGYAYATAFNL (SEQ ID NO: 162 ) ; p) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VHCDR2: IATADSGST (SEQIDNO: 121), and VH CDR3: ARGEGYSYDDYGDYFLGIYPLDL (SEQ ID NO: 163 ) ; q) VH CDR1: GFSFSGGYD (SEQ ID NO: 89), VH CDR2: SGST (SEQ ID NO: 122), and VH CDR3: ARRDSSGPYYFNL (SEQIDNO: 164) ; r) VH CDR1: GFIISSSYC (SEQIDNO: 90), VHCDR2: IYIGDGIT (SEQIDNO: 123), and VH CDR3: ARDDAGGGGYFNL (SEQ ID NO: 165 ) ; s)VHCDRl: GFSLSSSYY (SEQIDNO: 91),VHCDR2: IYGGSSGST (SEQIDNO: 124), and VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152 ) ; t) VH CDR1: GFDFSSSYY (SEQIDNO: 92), VHCDR2: IWGGSSGTT (SEQIDNO: 125), and VH CDR3: ARDDYAGGGYINL (SEQ ID NO: 166 ) ; u) VH CDR1: GFSLSSYA (SEQIDNO: 85), VHCDR2: ITSNGRT (SEQIDNO: 126), and VH CDR3: ARGDSYDDYVDPFNI (SEQIDNO: 167) ; v) VH CDR1: GFSFSSGYY (SEQIDNO: 93),VHCDR2: IAPGRSGST (SEQIDNO: 127), and VHCDR3: ARDDAYSYSGATYAYGTFNL (SEQ ID NO: 168 ) ; w) VH CDR1: GFSFSSSYY (SEQIDNO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), and VH CDR3: ARADYAGGDYFNL (SEQ ID NO: 160) ; x) VH CDR1: GIDFITYYY (SEQIDNO: 94), VH CDR2: VYGGSSGST (SEQIDNO: 128), and VH CDR3: ARGDGGMNYAWDL (SEQ ID NO: 169 ) ; y) VH CDR1: GFSFSSSYW (SEQIDNO: 81), VH CDR2: INTGSGST (SEQ ID NO: 129), and VH CDR3: ARGEGYGYADYAGGRYYYGLDL (SEQ ID NO: 170) ; z) VH CDR1: GFSFSSSYR (SEQ ID NO: 95), VHCDR2: IYAGNSSYT (SEQIDNO: 130), and VH CDR3:

[0079] ARDDTVSFGYPYGYFNL (SEQ ID NO: 171 ) ; aa) VH CDR1: GSDISGYS (SEQIDNO: 96), VH CDR2: IGNGDGNT (SEQ ID NO: 131), and VH CDR3: ASDTHDYVGFNL (SEQ ID NO: 172) ; ab) VHCDR1: GFSLSDYA (SEQIDNO: 97),VHCDR2: ISGSGST (SEQ ID NO: 132), and VH CDR3: ARADDDYGAAPYYFNI (SEQ ID NO: 173 ) ; ac) VH CDR1: GFTISSSYW (SEQIDNO: 98), VHCDR2: INARIT (SEQ ID NO: 133), and VH CDR3: ARVDGSTGVYTLDL (SEQ ID NO: 174 ) ; ad) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VHCDR2: IYAGSSGST (SEQ ID NO: 134), and VH CDR3 : ARAD YTYGYVGYAFNL (SEQIDNO: 175) ; ae) VH CDR1: GFSFSSSYY (SEQIDNO: 83),VHCDR2: IYAGSSGST (SEQ ID NO: 134), and VH CDR3: ARADYTYGYVGYAFDL (SEQ ID NO: 176) ;af) VHCDR1: GFSFSSSHY (SEQ ID NO: 99), VH CDR2: IFGGVSVRN (SEQ ID NO: 135), and VH CDR3: VRDDYAGYAGYGYAFNL (SEQ ID NO: 177) ; ag) VH CDR1: GFSFSNSYY (SEQ ID NO: 100), VH CDR2: IYAGGSGNT (SEQ ID NO: 136), and VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152 ) ; ah) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VHCDR2: IVTGTSGST (SEQIDNO: 137), and VH CDR3:

[0080] ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178) ; ai) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VHCDR2: IVTGTSGST (SEQIDNO: 137), and VH CDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178) ; aj) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VHCDR2: IYAGNSSYT (SEQIDNO: 130), and VH CDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171 ) ; ak) VH CDR1: GFSLSSGYD (SEQIDNO: 101), VHCDR2: IDGASSGRT (SEQIDNO: 138), and VH CDR3: ARDDSTWGGYFNL (SEQIDNO: 179) ; al) VH CDR1: GFSFSSAYW (SEQIDNO: 102),VHCDR2: IHGGSSGST (SEQIDNO: 139), and VHCDR3: ARDDYAGGGYVNL (SEQIDNO: 180) ; am) VHCDR1: GFSFSSSYS (SEQ ID NO: 103), VH CDR2: IYAGSSGST (SEQ ID NO: 134), and VH CDR3: ARIEYYSYGDVGYGYNYGMDL (SEQIDNO: 181);an)VH CDR1: GFSFSSSYS (SEQIDNO: 103), VHCDR2: IYAGSSGST (SEQ ID NO: 134), and VHCDR3: ARIEYYSYGDVGYGYNYGMDL (SEQIDNO: 181) ; ao) VH CDR1: GFSFSSAYW (SEQ ID NO: 102), VH CDR2: IHAGSSGNT (SEQ ID NO: 140), and VH CDR3: ARGDYSDAFFNL (SEQ ID NO: 182 ) ; ap) VH CDR1: GFSFSSSYY (SEQIDNO: 83), VHCDR2: IYVDNSGST (SEQIDNO: 141), and VH CDR3:

[0081] ARDEYAGYAGYGYAFNL (SEQ ID NO: 183 ) ; aq) VH CDR1 : GFSFSSS YW (SEQ ID NO: 81), VHCDR2: IYAGSSGNI (SEQIDNO: 142), and VH CDR3:

[0082] ARDDYGGVAGYGYAFNL (SEQ ID NO: 184 ) ; ar) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VHCDR2: ILSSGKT (SEQIDNO: 143), and VH CDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185 ) ; as) VH CDR1 : GFSFSSS YW (SEQ ID NO: 81), VH CDR2: IHAGSSGSI (SEQ ID NO: 144), and VH CDR3: ARDDYHYGGTGYAYNL (SEQ ID NO: 186) ; at) VHCDR1: GFTISSSYC (SEQ ID NO: 104), VH CDR2: IYCGWGT (SEQ ID NO: 145), and VHCDR3: ARDDAAYGGYFNL (SEQIDNO: 187) ; an) VH CDR1: GFSFSSGYD (SEQIDNO: 105), VHCDR2: RHGGSSGST (SEQIDNO: 146), and VH CDR3: ARDDSAAGGYFNL (SEQ ID NO: 188 ) ; av) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VHCDR2: IYAGSSGSN (SEQIDNO: 147), and VH CDR3:

[0083] ARDEVFTGGDAGYGYALNL (SEQ ID NO: 189 ) ; aw) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VHCDR2: ISSSGDT (SEQIDNO: 148), and VH CDR3: ARDGGYDDYGDFDYGMDP (SEQ ID NO: 190) ; and ax) VH CDR1: GFSLSVYA (SEQ ID NO: 106), VHCDR2: ILSSGNT (SEQIDNO: 149), and VH CDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185) .

[0084] In any aspect of the disclosure, or embodiments thereof, the antibody or an antigen- binding fragment thereof contains three VL CDRs containing a set of amino acid sequences selected from one or more of: a) VLCDR1: QSISNL (SEQIDNO: 201), VLCDR2: DSS, and VL CDR3: QQGWSGSNVNNV (SEQ ID NO: 236 ) ; b) VL CDR1: QRINSW (SEQ ID NO: 202), VLCDR2: YAS, and VL CDR3: QSAYGSTNADIFV (SEQIDNO: 237) ;c)VL CDR1: ESVGSN (SEQIDNO: 203), VLCDR2: TTS, and VL CDR3: QSAYYSGNTDNV (SEQIDNO: 238) ; d) VL CDR1: ESISSR (SEQIDNO: 204), VL CDR2: AAS, and VL CDR3: QSVSASGSGDTRA (SEQ ID NO: 239 ) ; e) VL CDR1: QSISRY (SEQIDNO: 205), VLCDR2: ATS, and VL CDR3: QSAYYSSSADTYYA (SEQIDNO: 240) ; f) VL CDR1: QNIYSH (SEQIDNO: 206),VLCDR2: KAS, and VL CDR3:

[0085] QSYYGSSRSSFSPFFA (SEQ ID NO: 241) ; g) VL CDR1: QSVYNNN (SEQ ID NO: 207), VL CDR2: QAS, and VL CDR3: AGDYGAYI IS (SEQ ID NO: 242 ) ; h) VL CDR1: EDIYVN (SEQ ID NO: 208), VL CDR2: DAS, and VL CDR3: LGVYNYIGADHA (SEQ ID NO: 243) ; i) VLCDR1: QNIYSG (SEQIDNO: 209),VLCDR2: GAS, and VL CDR3: QSYYYSGSADRGYA (SEQ ID NO: 244 ) ; j) VL CDR1: QSVANNNC (SEQ ID NO: 210), VL CDR2: WAS, and VL CDR3: AGGYYCGSADCGA (SEQ ID NO: 245 ) ; k) VL CDR1: ENIYSS (SEQ ID NO: 211), VL CDR2: DAS, and VL CDR3: QSAYYSSSVART (SEQ ID NO: 246) ; 1) VLCDR1: ESIYGN (SEQIDNO: 212),VLCDR2: SAS, and VL CDR3: QCTYDSYVPDTA (SEQ ID NO: 247 ) ; m) VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAYYSTNADNFA (SEQ ID NO: 248 ) ; n) VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAVYSGSPIWA (SEQ ID NO: 249) ; o) VL CDR1: QSISGN (SEQIDNO: 214),VLCDR2: SAS, and VL CDR3: QYGYTYNSGDIA (SEQ ID NO: 250 ) ; p) VL CDR1: QNINTY (SEQ ID NO: 215), VL CDR2: YAS, and VL CDR3: QSYYVISSSSYGFA (SEQ ID NO: 251) ; q) VL CDR1: EDIYSL (SEQ ID NO: 216), VL CDR2: DAS, and VL CDR3: QQGYSSSNVEYA (SEQ ID NO: 252) ; r) VLCDR1: QNIYSN (SEQIDNO: 213), VLCDR2: GAS, and VL CDR3: QSFYYSSSTDTRA (SEQ ID NO: 253 ) ; s) VL CDR1: QSIGSN (SEQ ID NO: 217), VL CDR2: TAS, and VL CDR3: QSAYYGGGTENA (SEQIDNO: 254 ) ; t) VL CDR1: QNIYSN (SEQIDNO: 213), VL CDR2: AAS, and VL CDR3: QSAADSSSGDFFYA (SEQIDNO: 255) ; u) VL CDR1: QSVSNL (SEQIDNO: 218),VLCDR2: YAS, and VL CDR3: QGYYLGSNFEPYNA (SEQ ID NO: 256 ) ; v) VL CDR1: ESIGSN (SEQ ID NO: 219), VL CDR2: GAS, and VL CDR3: QGYYYSSSADRWA (SEQ ID NO: 257) ; w) VL CDR1: ESIYSN (SEQ ID NO: 220), VL CDR2: YAS, and VL CDR3: QGYYYSNSADTFA (SEQ ID NO: 258) ; x) VLCDR1: QNIYSN (SEQIDNO: 213), VL CDR2: AAS, and VL CDR3: QCTDSGSSDVSA (SEQ ID NO: 259 ) ; y) VL CDR1: QSISSY (SEQIDNO: 221), VLCDR2: GAS, and VL CDR3: QQGDSSGWENT (SEQIDNO: 260);z)VL CDR1: ESIYSN (SEQIDNO: 220), VL CDR2: AAS, and VL CDR3: QSAVYSSSADNA (SEQ ID NO: 261) ; aa) VL CDR1: KSVYNNNF (SEQ ID NO: 222), VL CDR2: GAS, and VL CDR3: AGGYGSSSDRFG (SEQ ID NO: 262 ) ; ab) VL CDR1: EDIGTL (SEQIDNO: 223), VLCDR2: GAS, and VL CDR3: QCTYYSSSFGVFNV (SEQIDNO: 263);ac)VL CDR1: QSIGSN (SEQIDNO: 217), VLCDR2: DAS, and VL CDR3: QSYYYGGSSSSDWYA (SEQ ID NO: 264 ) ; ad) VL CDR1: ESIDSH (SEQ ID NO: 224), VLCDR2: SAS, and VL CDR3: QGEFNCISADCNA (SEQIDNO: 265) ; ae) VL CDR1: ESIDSH (SEQ ID NO: 224), VL CDR2: SAS, and VL CDR3: QGEFNCISADCNA (SEQ ID NO: 265) ; af) VL CDR1: QSIYSN (SEQIDNO: 225),VLCDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQ ID NO: 266 ); ag) VL CDR1: QSIYSN (SEQIDNO: 225), VL CDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQ ID NO: 266) ; ah) VL CDR1: QSISNY (SEQIDNO: 226), VLCDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQIDNO: 267) ; ai) VL CDR1: QSISNY (SEQIDNO: 226), VLCDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQ ID NO: 267 ) ; aj) VL CDR1: QSISNL (SEQIDNO: 201), VL CDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268 ) ; ak) VL CDR1: QSISNL (SEQIDNO: 201), VLCDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQIDNO: 268) ; al) VL CDR1: QSIDSS (SEQIDNO: 227), VLCDR2: GAS, and VL CDR3: QSGYYSSSADFFYA (SEQ ID NO: 269 ) ; am) VL CDR1: QSIGSN (SEQIDNO: 217), VL CDR2: AAS, and VL CDR3: QCTYYDSSYGNA (SEQ ID NO: 270) ; an) VL CDR1: QSIGTD (SEQ ID NO: 228), VL CDR2: AAS, and VL CDR3: QCTYYDSSYGNA (SEQIDNO: 270) ; ao) VL CDR1: QSISTA (SEQIDNO: 229), VL CDR2: AAS, and VL CDR3: QQGYDSSFGDNV (SEQ ID NO: 271 ) ; ap) VL CDR1 : EDI YSL (SEQIDNO: 216), VLCDR2: SAS, and VL CDR3: QYTYYSSNYNA (SEQIDNO: 272);aq)VL CDR1: ENIYSG (SEQIDNO: 230), VLCDR2: TAS, and VL CDR3: QSPYYGSITDNA (SEQIDNO: 273) ; ar) VL CDR1: ESISSR (SEQIDNO: 204), VL CDR2: AAS, and VL CDR3: QSAYYSSSAHYA (SEQ ID NO: 274) ; as) VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAYYSSSPDNT (SEQ ID NO: 275) ; at) VL CDR1: QHIYSN (SEQIDNO: 231), VLCDR2: GAS, and VL CDR3: QSVYYSSSAHTRA (SEQIDNO: 276) ; an) VL CDR1: ENIYSN (SEQIDNO: 232), VLCDR2: AAS, and VL CDR3: QSATYSSGTDRA (SEQ ID NO: 277 ) ; av) VL CDR1 : QNIGSN (SEQIDNO: 233), VL CDR2: GAS, and VL CDR3: QSAYYSSSADNT (SEQ ID NO: 278) ; aw) VL CDR1: EDIYSN (SEQIDNO: 234), VLCDR2: QAS, and VL CDR3: LGVGTYLSADGNA (SEQIDNO: 279) ; and ax) VL CDR1: QNIYSK (SEQIDNO: 235), VL CDR2: AAS, and VL CDR3: QSADYSRGADYA (SEQ ID NO: 280) . In any aspect of the disclosure, or embodiments thereof, the antibody or an antigen- binding fragment thereof contains three VH CDRs and three VL CDRs containing a set of amino acid sequences selected from one or more of: a) VH CDR1: GFSLSDYY (SEQ ID NO: 80), VH CDR2: IYGSGTT (SEQ ID NO: 107), VH CDR3: ARAL YADSNYWPLYFNF (SEQ ID NO: 150), VL CDR1: QSI SNL (SEQ ID NO: 201), VL CDR2: DSS, and VL CDR3: QQGWSGSNVNNV (SEQ ID NO: 236 ) ; b) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHGGSSGNT (SEQ ID NO: 108), VH CDR3: ARSDYTGGNYFNL (SEQ ID NO: 151), VL CDR1: QRINSW (SEQ ID NO: 202), VL CDR2: YAS, and VL CDR3: QSAYGSTNADIFV (SEQ ID NO: 237 ) ; c) VH CDR1: GFSFSSSYF (SEQ ID NO: 82), VH CDR2: AYGGGSGST (SEQ ID NO: 109), VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), VL CDR1: ESVGSN (SEQ ID NO: 203), VL CDR2: TTS, and VL CDR3: QSAYYSGNTDNV (SEQ ID NO: 238 ) ; d) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IAIGSGSA (SEQ ID NO: 110), VH CDR3: ARDDYAGGGYFNL (SEQ ID NO:

[0086] 153), VL CDR1: ESI SSR (SEQ ID NO: 204), VL CDR2: AAS, and VL CDR3: QSVSASGSGDTRA (SEQ ID NO: 239 ) ; e) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHDGSSGST (SEQ ID NO: 111), VH CDR3: ARDDYAGGGYFNL (SEQ ID NO: 153), VL CDR1: QSI SRY (SEQ ID NO: 205), VL CDR2: ATS, and VL CDR3: QSAYYSSSADTYYA (SEQ ID NO: 240 ) ; f) VH CDR1: GFSLSSNA (SEQ ID NO: 84), VH CDR2: I SSTGST (SEQ ID NO: 112), VH CDR3: AKEDGLVEEFAL (SEQ ID NO:

[0087] 154), VL CDR1: QNIYSH (SEQ ID NO: 206), VL CDR2: KAS, and VL CDR3: QSYYGSSRSSFSPFFA (SEQ ID NO: 241 ) ; g) VH CDR1: GFSLSSNA (SEQ ID NO: 84), VH CDR2: ISSTGST (SEQ ID NO: 112), VH CDR3: AKEDGLVEEFAL (SEQ ID NO: 154), VL CDR1: QSVYNNN (SEQ ID NO: 207), VL CDR2: QAS, and VL CDR3: AGDYGAYI I S (SEQ ID NO: 242 ) ; h) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IDTGGSSV (SEQ ID NO: 113), VH CDR3: AREGGYDDYGDFLNYFNL (SEQ ID NO: 155), VL CDR1: EDIYVN (SEQ ID NO: 208), VL CDR2: DAS, and VL CDR3: LGVYNYIGADHA (SEQ ID NO: 243 ) ; i) VH CDR1: GFSFSPSYC (SEQ ID NO: 86), VH CDR2: ISGGSSGST (SEQ ID NO: 114), VH CDR3: ARGDGYDDYGDPFNL (SEQ ID NO: 156), VL CDR1: QNIYSG (SEQ ID NO: 209), VL CDR2: GAS, and VL CDR3: QSYYYSGSADRGYA (SEQ ID NO: 244 ) ; j) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IYASGST (SEQ ID NO: 115), VH CDR3: ARGEGYTYDDYGDYYDAFDP (SEQ ID NO: 157), VL CDR1: QSVANNNC (SEQ ID NO: 210), VL CDR2: WAS, and VL CDR3: AGGYYCGSADCGA (SEQ ID NO: 245 ) ; k) VH CDR1: GFSLSSYY (SEQ ID NO: 87), VH CDR2: INSDTT (SEQ ID NO: 116), VH CDR3: VRDDGYLDL (SEQ ID NO: 158), VL CDR1: ENIYSS (SEQ ID NO: 211), VL CDR2: DAS, and VL CDR3: QSAYYSSSVART (SEQ ID NO: 246 ) ; 1) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: GYAGSSGST (SEQ ID NO: 117), VH CDR3: ARADNWNSGWLGAFDP (SEQ ID NO: 159), VL CDR1: ESIYGN (SEQ ID NO: 212), VL CDR2: SAS, and VL CDR3: QCTYDSYVPDTA (SEQ ID NO: 247 ) ; m) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), VH CDR3: ARADYAGGDYFNL (SEQ ID NO: 160), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAYYSTNADNFA (SEQ ID NO: 248 ) ; n) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ISNSGPT (SEQ ID NO: 119), VH CDR3: ARVPYSSGWGADDAFDP (SEQ ID NO: 161), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAVYSGSPIWA (SEQ ID NO: 249 ) ; o) VH CDR1: GFDFSSYG (SEQ ID NO: 88), VH CDR2: IDPVHGTT (SEQ ID NO: 120), VH CDR3: ARDDIYGYAGYAYATAFNL (SEQ ID NO: 162), VL CDR1: QS ISGN (SEQ ID NO: 214), VL CDR2: SAS, and VL CDR3: QYGYTYNSGDIA (SEQ ID NO: 250 ) ; p) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IATADSGST (SEQ ID NO: 121), VH CDR3: ARGEGYSYDDYGDYFLGIYPLDL (SEQ ID NO: 163), VL CDR1: QNINTY (SEQ ID NO: 215), VL CDR2: YAS, and VL CDR3: QSYYVISSSSYGFA (SEQ ID NO: 251 ) ; q) VH CDR1: GFSFSGGYD (SEQ ID NO: 89), VH CDR2: SGST (SEQ ID NO: 122), VH CDR3: ARRDSSGPYYFNL (SEQ ID NO: 164), VL CDR1: EDIYSL (SEQ ID NO: 216), VL CDR2: DAS, and VL CDR3: QQGYSSSNVEYA (SEQ ID NO: 252 ) ; r) VH CDR1: GFI I SSSYC (SEQ ID NO: 90), VH CDR2: IYIGDGIT (SEQ ID NO: 123), VH CDR3: ARDDAGGGGYFNL (SEQ ID NO: 165), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSFYYSSSTDTRA (SEQ ID NO: 253 ) ; s) VH CDR1: GFSLSSSYY (SEQ ID NO: 91), VH CDR2: IYGGSSGST (SEQ ID NO: 124), VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), VL CDR1: QSIGSN (SEQ ID NO: 217), VL CDR2: TAS, and VL CDR3: QSAYYGGGTENA (SEQ ID NO: 254 ) ; t) VH CDR1: GFDFSSSYY (SEQ ID NO: 92), VH CDR2: IWGGSSGTT (SEQ ID NO: 125), VH CDR3: ARDDYAGGGYINL (SEQ ID NO: 166), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: AAS, and VL CDR3: QSAADSSSGDFFYA (SEQ ID NO: 255 ) ; u) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ITSNGRT (SEQ ID NO: 126), VH CDR3: ARGDSYDDYVDPFNI (SEQ ID NO: 167), VL CDR1: QSVSNL (SEQ ID NO: 218), VL CDR2: YAS, and VL CDR3: QGYYLGSNFEPYNA (SEQ ID NO: 256 ) ; v) VH CDR1: GFSFSSGYY (SEQ ID NO: 93), VH CDR2: IAPGRSGST (SEQ ID NO: 127), VH CDR3: ARDDAYSYSGATYAYGTFNL (SEQ ID NO: 168), VL CDR1: ESIGSN (SEQ ID NO: 219), VL CDR2: GAS, and VL CDR3: QGYYYSSSADRWA (SEQ ID NO: 257 ) ; w) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), VH CDR3: ARAD YAGGDYFNL (SEQ ID NO: 160), VL CDR1: ESIYSN (SEQ ID NO: 220), VL CDR2: YAS, and VL CDR3: QGYYYSNSADTFA (SEQ ID NO: 258 ) ; x) VH CDR1: GIDFITYYY (SEQ ID NO:

[0088] 94), VH CDR2: VYGGSSGST (SEQ ID NO: 128), VH CDR3: ARGDGGMNYAWDL (SEQ ID NO: 169), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: AAS, and VL CDR3: QCTDSGSSDVSA (SEQ ID NO: 259 ) ; y) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: INTGSGST (SEQ ID NO: 129), VH CDR3: ARGEGYGYADYAGGRYYYGLDL (SEQ ID NO: 170), VL CDR1: QSI SSY (SEQ ID NO: 221), VL CDR2: GAS, and VL CDR3: QQGDSSGWENT (SEQ ID NO: 260 ) ; z) VH CDR1: GFSFSSSYR (SEQ ID NO:

[0089] 95), VH CDR2: IYAGNSSYT (SEQ ID NO: 130), VH CDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171), VL CDR1: ESIYSN (SEQ ID NO: 220), VL CDR2: AAS, and VL CDR3: QSAVYSSSADNA (SEQ ID NO: 261 ) ; aa) VH CDR1: GSDI SGYS (SEQ ID NO:

[0090] 96), VH CDR2: IGNGDGNT (SEQ ID NO: 131), VH CDR3: ASDTHDYVGFNL (SEQ ID NO: 172), VL CDR1: KSVYNNNF (SEQ ID NO: 222), VL CDR2: GAS, and VL CDR3: AGGYGSSSDRFG (SEQ ID NO: 262 ) ; ab) VH CDR1: GFSLSDYA (SEQ ID NO: 97), VH CDR2: ISGSGST (SEQ ID NO: 132), VH CDR3: ARADDDYGAAPYYFNI (SEQ ID NO:

[0091] 173), VL CDR1: EDIGTL (SEQ ID NO: 223), VL CDR2: GAS, and VL CDR3: QCTYYSSSFGVFNV (SEQ ID NO: 263 ) ; ac) VH CDR1: GFTISSSYW (SEQ ID NO: 98), VH CDR2: INARIT (SEQ ID NO: 133), VH CDR3: ARVDGSTGVYTLDL (SEQ ID NO:

[0092] 174), VL CDR1: QSIGSN (SEQ ID NO: 217), VL CDR2: DAS, and VL CDR3: QSYYYGGSSSSDWYA (SEQ ID NO: 264 ) ; ad) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2 : IYAGSSGST (SEQ ID NO: 134), VH CDR3: ARADYTYGYVGYAFNL (SEQ ID NO: 175), VL CDR1: ESIDSH (SEQ ID NO: 224), VL CDR2: SAS, and VL CDR3: QGEFNCI SADCNA (SEQ ID NO: 265 ) ; ae) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGST (SEQ ID NO: 134), VH CDR3: ARADYTYGYVGYAFDL (SEQ ID NO: 176), VL CDR1: ESIDSH (SEQ ID NO: 224), VL CDR2: SAS, and VL CDR3: QGEFNCI SADCNA (SEQ ID NO: 265) ; af) VH CDR1: GFSFSSSHY (SEQ ID NO: 99), VHCDR2: IFGGVSVRN (SEQIDNO: 135),VHCDR3: VRDDYAGYAGYGYAFNL (SEQ ID NO: 177), VL CDR1: QSIYSN (SEQ ID NO: 225), VL CD R2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQIDNO: 266) ; ag) VH CDR1: GFSFSNSYY (SEQ ID NO: 100), VH CDR2: IYAGGSGNT (SEQ ID NO: 136), VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), VL CDR1: QSIYSN (SEQ ID NO: 225), VLCDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQIDNO: 266);ah)VH CDR1: GFSFSSSYW (SEQIDNO: 81), VHCDR2: IVTGTSGST (SEQIDNO: 137), VH CDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178), VL CDR1: QSISNY (SEQ ID NO: 226), VLCDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQIDNO: 267) ; ai) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IVTGTSGST (SEQ ID NO: 137), VH CDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178), VL CDR1: QSISNY (SEQ ID NO: 226), VL CDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQ ID NO: 267) ; aj) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IYAGNSSYT (SEQ ID NO: 130), VH CDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171), VL CDR1: QSISNL (SEQ ID NO: 201), VL CDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268 ) ; ak) VH CDR1: GFSLSSGYD (SEQIDNO: 101), VHCDR2: IDGASSGRT (SEQIDNO: 138), VHCDR3: ARDDSTWGGYFNL (SEQ ID NO: 179), VL CDR1: QSISNL (SEQIDNO: 201), VL CDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268 ) ; al) VH CDR1: GFSFSSAYW (SEQIDNO: 102), VHCDR2: IHGGSSGST (SEQIDNO: 139), VHCDR3: ARDDYAGGGYVNL (SEQ ID NO: 180), VL CDR1: QSIDSS (SEQIDNO: 227), VLCDR2: GAS, and VL CDR3: QSGYYSSSADFFYA (SEQIDNO: 269);am)VH CDR1: GFSFSSSYS (SEQIDNO: 103), VHCDR2: IYAGSSGST (SEQ ID NO: 134), VHCDR3: ARIEYYSYGDVGYGYNYGMDL (SEQ ID NO: 181), VL CDR1: QSIGSN (SEQ ID NO: 217), VL CDR2: AAS, and VL CDR3: QCTYYDSSYGNA (SEQ ID NO: 270) ; an) VHCDR1: GFSFSSSYS (SEQ ID NO: 103), VH CDR2: IYAGSSGST (SEQIDNO: 134), VH CDR3: ARIEYYSYGDVGYGYNYGMDL (SEQ ID NO: 181), VL CDR1: QSIGTD (SEQ ID NO: 228), VL CDR2: AAS, and VL CDR3: QCTYYDSSYGNA (SEQ ID NO: 270) ; ao)VHCDRl: GFSFSSAYW (SEQIDNO: 102), VHCDR2: IHAGSSGNT (SEQIDNO: 140), VH CDR3: ARGDYSDAFFNL (SEQIDNO: 182),VLCDR1: QSISTA (SEQ ID NO: 229), VL CDR2: AAS, and VL CDR3: QQGYDSSFGDNV (SEQ ID NO: 271) ; ap) VHCDR1: GFSFSSSYY (SEQIDNO: 83), VHCDR2: IYVDNSGST (SEQIDNO: 141), VH CDR3: ARDEYAGYAGYGYAFNL (SEQIDNO: 183),VLCDR1: EDIYSL (SEQ ID NO: 216), VL CDR2: SAS, and VL CDR3: QYTYYSSNYNA (SEQ ID NO: 272 ) ; aq) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IYAGSSGNI (SEQ ID NO: 142), VH CDR3: ARDDYGGVAGYGYAFNL (SEQ ID NO: 184), VL CDR1: ENIYSG (SEQ ID NO: 230), VL CDR2: TAS, and VL CDR3: QSPYYGS ITDNA (SEQ ID NO: 273 ) ; ar) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ILSSGKT (SEQ ID NO: 143), VH CDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185), VL CDR1: ESI SSR (SEQ ID NO: 204), VL CDR2: AAS, and VL CDR3: QSAYYSSSAHYA (SEQ ID NO:

[0093] 274 ) ; as) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHAGSSGSI (SEQ ID NO: 144), VH CDR3: ARDDYHYGGTGYAYNL (SEQ ID NO: 186), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAYYSSSPDNT (SEQ ID NO:

[0094] 275 ) ; at) VH CDR1: GFTISSSYC (SEQ ID NO: 104), VH CDR2: IYCGWGT (SEQ ID NO: 145), VH CDR3: ARDDAAYGGYFNL (SEQ ID NO: 187), VL CDR1: QHIYSN (SEQ ID NO: 231), VL CDR2: GAS, and VL CDR3: QSVYYSSSAHTRA (SEQ ID NO: 276 ) ; an) VH CDR1: GFSFSSGYD (SEQ ID NO: 105), VH CDR2: RHGGSSGST (SEQ ID NO:

[0095] 146), VH CDR3: ARDDSAAGGYFNL (SEQ ID NO: 188), VL CDR1: ENIYSN (SEQ ID NO: 232), VL CDR2: AAS, and VL CDR3: QSATYSSGTDRA (SEQ ID NO: 277 ) ; av) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGSN (SEQ ID NO: 147), VH CDR3: ARDEVFTGGDAGYGYALNL (SEQ ID NO: 189), VL CDR1: QNIGSN (SEQ ID NO: 233), VL CDR2: GAS, and VL CDR3: QSAYYSSSADNT (SEQ ID NO: 278 ) ; aw) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: I SSSGDT (SEQ ID NO: 148), VH CDR3: ARDGGYDDYGDFDYGMDP (SEQ ID NO: 190), VL CDR1: EDIYSN (SEQ ID NO: 234), VL CDR2: QAS, and VL CDR3: LGVGTYLSADGNA (SEQ ID NO: 279 ) ; and ax) VH CDR1: GFSLSVYA (SEQ ID NO: 106), VH CDR2: ILSSGNT (SEQ ID NO: 149), VH CDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185), VL CDR1: QNIYSK (SEQ ID NO: 235), VL CDR2: AAS, and VL CDR3: QSADYSRGADYA (SEQ ID NO: 280 ) .

[0096] In any aspect of the disclosure, or embodiments thereof, the antibody or antigen-binding fragment thereof contains: a) a VH framework region 1 (VH FR1) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: QEQLKESGGGLVLPGGSLKLSCKAS (SEQ ID NO: 36 ) ;

[0097] QSVEESGGRLVTPGTPLTLTCTVS (SEQ ID NO: 37 ) ; QSLEESGGDLVQPEGSLTLTCTAS (SEQ ID NO: 38 ) ; QEQLEESGGDLVKPEGSLTLTCTAS (SEQ ID NO: 39 ) ;

[0098] QSLEESGGDLVKSGASLTLTCTAS (SEQ ID NO: 40 ) ; QSLEESGGDLVKPGASLTLTCTAS (SEQ ID NO: 41 ) ; and QEQLVESGGGLVQPEGSLTLTCTAS (SEQ ID NO: 294); b) a VH framework region 2 (VH FR2) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: MNWVRQAPGKGLEWIGY (SEQ ID NO: 42 ) ; MSWVRQAPGKGLEWIGI (SEQ ID NO: 43 ) ; LCWVRQAPGKGLEWIAC (SEQ ID NO:

[0099] 44 ) ; ICWVRQAPGKGLEWIAC (SEQ ID NO: 45 ) ; MCWVRQAPGKGLEWIAC (SEQ ID NO:

[0100] 46 ) ; MCWVRQAPGKGLEWIGC (SEQ ID NO: 298); MCWVRQAPGKGPEWIAC (SEQ ID NO:

[0101] 299); and CWVRQAPGKGLEWIAC (SEQ ID NO: 300); c) a VH framework region 3 (VH

[0102] FR3) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: YYANWVNGRFTISSHNVQKKLYLQLNSLTAADTATYFC (SEQ

[0103] ID NO: 47 ) ; YYATWAKGRFTISKTSSTTVDLKMTSLTASDTATYFC (SEQ ID NO: 48 ) ;

[0104] YYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 49 ) ;

[0105] HYATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFC (SEQ ID NO: 50 ) ;

[0106] AYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 51 ) ;

[0107] YYANWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 52 ) ;

[0108] YYANWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFC (SEQ ID NO: 302);

[0109] YYANWAKGRFTISRTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 303); and HYATWAKGRFTISRTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 305); d) a VH framework region 4 (VH FR4) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: WGQGTLVTVSS (SEQ ID NO: 53 ) ; and RGQGTLVTVSS (SEQ ID NO: 307); e) a VL framework region 1 (VL FR1) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: AAVLTQTPSPVSAAVGGTVSISCQSS (SEQ ID NO: 54 ) ;

[0110] ANIVMTQTPASVEVAVGGTVTIKCQAS (SEQ ID NO: 55 ) ;

[0111] DVVMTQTPSSVEAAVGGTVTIKCQAS (SEQ ID NO: 56); ALVMTQTPSSVSAAVGGTVTINCQAS (SEQ ID NO: 57); AQVLTQTPASVSAAVGGTVTIKCQAS (SEQ ID NO: 58); AIEMTQTPFSVSAAVGGTVTINCQAS (SEQ ID NO: 59); ALVMTQTPSSASEPVGGTVTIKCQAG (SEQ ID NO: 310); and AQVLTQTPASVEAAVGGTITVNCQAS (SEQ ID NO: 312); f) a VL framework region 1 (VL FR2) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: LSWFQQKPGQPPKLLIY (SEQ ID NO: 60 ) ;

[0112] LAWYQQKSGQPPKLLIY (SEQ ID NO: 61 ) ; LAWYQQKPGQPPKLLI Y (SEQ ID NO: 62 ) ; and LAWYQQKPGQRPKLLIY (SEQ ID NO: 63 ) ; g) a VL framework region 3 (VL FR3) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: TLASGVPSRFKGNGSGTQFTLTISDVQCDDAATYYC (SEQ ID NO: 287 ) ; DLASGVSSRFKGSGSGTQFTLTI SGVECADAATYYC (SEQ ID NO: 64 ) ;

[0113] NLESGVPSRFKGSGSGTEYTLTI SDLECDDAATYYC (SEQ ID NO: 65 ) ;

[0114] TLASGVPSRFKGSGSGTEYTLTI SGVQCADAATYYC (SEQ ID NO: 66 ) ;

[0115] YLASGVPSRFKGSGSGTEYTLTI SGVQCADAATYYC (SEQ ID NO: 67 ) ;

[0116] YLASGVPSRFKGSESGTEYTLTI SDLECDDAATYYC (SEQ ID NO: 318);

[0117] YLSSGVPSRFKGSGSGTDFTLTI SDLECADAATYYC (SEQ ID NO: 319); and NLASGVPSRFKGSGSGTQFTLTI SDLECADAATYYC (SEQ ID NO: 320); and h) a VL framework region 4 (VL FR4) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following: FGGGTEWVKGDP (SEQ ID NO: 68) and FGGGTEVWK (SEQ ID NO: 322)..

[0118] In any aspect of the disclosure, or embodiments thereof, the antibody contains a heavy chain constant region containing an Fc region or a portion of the Fc region containing CH2 and CH3 domains and / or a light chain constant region containing a constant light chain (CL) domain.

[0119] In any aspect of the disclosure, or embodiments thereof, the CH2 and / or CH3 domain is derived from an immunoglobulin G (IgG). In any aspect of the disclosure, or embodiments thereof, the CL domain contains a kappa light chain or a lambda light chain.

[0120] In any aspect of the disclosure, or embodiments thereof, the antibody or an antigen-binding fragment thereof further contains a heavy chain (HC) constant domain fused to the C- terminus of the variable heavy chain (VH) domain and contains an amino acid sequence with at least about 85% amino acid sequence identity to a sequence selected from:

[0121] GQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGL YSLSSWSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGGPSVFIFPPKPK DTLMISRTPEVTCVWDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRWSTLPITH QDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGF YPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYNKLSVPTSEWQRGDVFTCSVMHEALHN HYTQKSI SRSPGK (SEQ ID NO: 285); and

[0122] ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK (SEQ ID NO: 355).

[0123] In any aspect of the disclosure, or embodiments thereof, the antibody or an antigen- binding fragment thereof further contains a light chain (LC) constant domain (CL) fused to the C-terminus of the variable light chain (VL) domain and contains an amino acid sequence with at least about 85% amino acid sequence identity to a sequence selected from: VAPTVL I F P PAADQVATGTVT I VCVANKYF PDVTVTWEVDGTTQTTG I ENS KT PQNS ADCTY NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC (SEQ ID NO: 35); and RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 356).

[0124] In any aspect of the disclosure, or embodiments thereof, the antibody or antigen- binding fragment thereof competes with CD7 for binding to the anti-CD7 antibody, or antigen-binding fragment thereof. In any aspect of the disclosure, or embodiments thereof, the antibody or antigen-binding fragment thereof has a dissociation constant (kdis) calculated over 60 seconds for binding to the anti-CD7 antibody that is less than about 0.002 or less than about 2E-3. In any aspect of the disclosure, or embodiments thereof, the antibody or antigen- binding fragment thereof has a dissociation constant (kdis) calculated over 60 seconds for binding to the anti-CD7 antibody that is less than about IE-5. In any aspect of the disclosure, or embodiments thereof, the antibody or antigen-binding fragment thereof has a dissociation constant (kdis) (1 / s) calculated over 60 seconds for binding to the anti-CD7 antibody that is less than about IE-7.

[0125] In any aspect of the disclosure, or embodiments thereof, the antibody or antigen- binding fragment thereof is a full-length antibody. In any aspect of the disclosure, or embodiments thereof, the antigen-binding fragment is selected from among Fab fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, an scFv, and a single domain antibody.

[0126] In any aspect of the disclosure, or embodiments thereof, the anti-CD7 antibody binds a human CD7 polypeptide.

[0127] In any aspect of the disclosure, or embodiments thereof, the anti-CD7 antibody, or antigen binding fragment thereof, is an scFv. In some embodiments, the scFv is fused to a chimeric antigen receptor (CAR) polypeptide.

[0128] In any aspect of the disclosure, or embodiments thereof, the antibody or antigen- binding fragment thereof is humanized. In any aspect of the disclosure, or embodiments thereof, the heterologous moiety is a detectable label. In some embodiments, the detectable label is selected from one or more of a fluorescent dye, a fluorescent protein, a radioisotope, a chromophore, a metal ion, a gold particle, a silver particle, a magnetic particle, a polypeptide, an enzyme, a streptavidin, a biotin, a luminescent compound and an oligonucleotide. In any aspect of the disclosure, or embodiments thereof, the heterologous moiety is a cytotoxic polypeptide, cytotoxic polynucleotide, or cytotoxic small molecule.

[0129] In any aspect of the disclosure, or embodiments thereof, the conjugate is an antibody- drug conjugate.

[0130] In any aspect of the disclosure, or embodiments thereof, binding is detected using a direct or indirect detection method. In any aspect of the disclosure, or embodiments thereof, binding is detected using fluorescence activated flow cytometry. In any aspect of the disclosure, or embodiments thereof, binding is detected using fluorescence microscopy.

[0131] In any aspect of the disclosure, or embodiments thereof, the biological sample is a tissue sample or a blood sample. In any aspect of the disclosure, or embodiments thereof, the biological sample is from a subject that has been administered anti-CD7 CAR T cells.

[0132] In any aspect of the disclosure, or embodiments thereof, the subject is being treated for a neoplasia. In some embodiments, the neoplasia is a leukemia or a lymphoma.

[0133] In any aspect of the disclosure, or embodiments thereof, the method further involves identifying one or more of the following cell types in the biological sample using flow cytometry: a) CD4+ T cells; b) CD8+ T cells; c) CD4+ or CD8+ T cells surface expressing one or more of LAG3, PD-1, TIM3, and TIGIT; d) CD3- T cells; e) CD4+ Tregcells; f) CD4+ or CD8+ naive T cells; g) CD4+ or CD8+ memory T cells; h) CD4+ or CD8+ central memory T cells; i) CD4+ or CD8+ stem cell memory T cells; j) CD4+ or CD8+ effector memory re-expressing CD45RA T cells; k) CD4+ or CD8+ HLA-DR+ T cells; 1) CD4+ or CD8+ effector memory T cells; and m) NK cells; n) NK cells surface expressing high or low levels of CD16 and / or CD56. O) NK cells surface expressing one or more of CD38, NKG2A, NKG2D, KIR2DL1, KIR2DL3, KIR3DL1, and KIR3DL2.

[0134] In any aspect of the disclosure, or embodiments thereof, the cells are anti-CD7 CAR T cells. In any aspect of the disclosure, or embodiments thereof, the cells are in vitro or ex vivo.

[0135] In any aspect of the disclosure, or embodiments thereof, the electrochemiluminescent label is a SULFO-TAG. In any aspect of the disclosure, or embodiments thereof, the anti-CD7 CAR polypeptide or antigen-binding fragment thereof is bound to the electrode using a biotin- streptavidin bridge.

[0136] In any aspect of the disclosure, or embodiments thereof, the detecting is direct or indirect.

[0137] In any aspect of the disclosure, or embodiments thereof, detecting binding involves fluorescence activated flow cytometry.

[0138] In any aspect of the disclosure, or embodiments thereof, the method further involves characterizing the persistence of CAR-T cells in the subject.

[0139] In any aspect of the disclosure, or embodiments thereof, the cells bound with the antibody or antigen-binding fragment thereof or conjugate are selected by immunoaffinity- based separation. In any aspect of the disclosure, or embodiments thereof, the cells bound with the antibody or antigen-binding fragment thereof or conjugate are selected by flow cytometry.

[0140] In any aspect of the disclosure, or embodiments thereof, the cell population contains T cells. In any aspect of the disclosure, or embodiments thereof, the cell population contains T cells expressing the anti-CD7 CAR polypeptide have been engineered to knock out expression of one or more polypeptides selected from one or more of CD7, TRAC, CD62, PD-1, CD3 -epsilon, and CD3 -gamma.

[0141] In any aspect of the disclosure, or embodiments thereof, the polynucleotide has at least 85% sequence identity to a sequence selected from one or more of the following: CAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGTCTGGGGCATCCCTGACACTCACCTG CACAGCTTCTGGATTCTCCTTCAGTAGCAGCTACTGGATATGCTGGGTCCGCCAGGCTCCAG GGAAGGGGCTGGAGTGGATCGCATGCATTCATGGTGGTAGTAGTGGTAACACTGCCTACGCG AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAAT GACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCAAGATCTGATTATACTGGTG GTAATTATTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAA GGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCT TGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCT TGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGT AGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCA TAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACA CCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCT AAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGT GTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACG

[0142] CTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACT

[0143] GTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCT

[0144] GCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGT

[0145] ACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTT

[0146] AAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAA CTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCA CCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCC CTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 343);

[0147] CAGGAGCAGCTGGTGGAGTCCGGGGGAGGCCTGGTCCAGCCTGAGGGATCCCTGACACTCAC

[0148] CTGCACAGCTTCTGGATTCTCCTTCAGTAGCAGCTACTACATGTGCTGGGTCCGCCAGGCTC

[0149] CAGGGAAGGGGCTGGAGTGGATCGGATGCATTGCTATTGGTAGTGGTAGCGCTTACTACGCG

[0150] AACTGGGCGAAGGGCCGATTCACCATCACCAGAAGCACCAGCCTAAACACGGTGACTCTGCA

[0151] ACTGAACAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATTATGCTG

[0152] GTGGTGGTTACTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACA

[0153] AAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGC

[0154] TCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCG

[0155] CCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTC

[0156] AGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAA

[0157] TCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACAC

[0158] ACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCT

[0159] CCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGA

[0160] CGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACA

[0161] ACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTG

[0162] ACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGC

[0163] CCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGG

[0164] TGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTG

[0165] GTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAA

[0166] CAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAAC

[0167] TCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAG

[0168] GCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 344); CAGGAGCAACTGAAGGAGTCCGGGGGAGGCCTGGTCCTGCCGGGGGGATCCCTGAAACTCTC

[0169] CTGCAAAGCCTCTGGATTTGACTTCAGTAGCTATGGAATGAACTGGGTCCGCCAGGCTCCAG

[0170] GGAAGGGGCTGGAGTGGATCGGATACATTGATCCTGTTCATGGTACCACATACTACGCGAAC

[0171] TGGGTGAATGGCCGATTCACCATCTCCAGCCACAACGTCCAGAAAAAGCTGTATCTGCAACT

[0172] CAACAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATATTTATGGTT

[0173] ATGCTGGTTATGCTTATGCTACGGCCTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTC

[0174] TCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAG

[0175] TGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTT

[0176] CATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGT

[0177] GGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTA

[0178] TATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAAT

[0179] CATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGC

[0180] GTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCAC

[0181] TTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACG

[0182] GGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGG

[0183] GTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAA

[0184] GGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAAC

[0185] CTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTC

[0186] TCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAA

[0187] TGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCT

[0188] TCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGT

[0189] TCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGG

[0190] AAAGTGA (SEQ ID NO: 345);

[0191] CAGTCGTTGGAGGAGTCCGGGGGAGACCTAGTCAAGCCTGGGGCATCCCTGACACTCACCTG

[0192] CACAGCCTCTGGATTCGACTTCAGTAGCAGCTATTACATGTGCTGGGTCCGCCAGGCTCCAG

[0193] GGAAGGGGCCGGAGTGGATCGCATGCATTTGGGGTGGTAGTAGTGGTACCACTTATTACGCG

[0194] AACTGGGCGAAAGGCCGATTCACCATCTCCAGAACCTCGTCGACCACGGTGACTCTGCAAAT

[0195] GACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATTATGCTGGTG

[0196] GTGGTTATATCAACTTGAGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAA

[0197] GGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCT

[0198] TGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCT

[0199] TGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGT

[0200] AGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCA

[0201] TAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACA CCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCT

[0202] AAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGT

[0203] GTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACG

[0204] CTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACT

[0205] GTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCT

[0206] GCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGT

[0207] ACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTT

[0208] AAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAA

[0209] CTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCA

[0210] CCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCC

[0211] CTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 346);

[0212] CAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTG

[0213] CACAGCCTCTGGATTCTCCTTCAGTAGCAGCTACTCGATATGCTGGGTCCGCCAGGCTCCAG

[0214] GGAAGGGGCTGGAGTGGATCGCATGCATTTATGCTGGTAGTAGTGGTAGCACTTACTACGCG

[0215] AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAAT

[0216] GACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAATTGAATACTATAGTT

[0217] ATGGTGATGTTGGTTATGGTTATAACTACGGCATGGACCTCTGGGGCCAGGGCACCCTGGTC

[0218] ACCGTCTCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAG

[0219] TACCAGTGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCA

[0220] CTGTTTCATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAG

[0221] TCAAGTGGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACA

[0222] AACTTATATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAAC

[0223] CAAAATCATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGG

[0224] CCCAGCGTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGA

[0225] AGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATG

[0226] TTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACC

[0227] TACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAA

[0228] GTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAG

[0229] GTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAAC

[0230] CAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGA

[0231] GTCTAATGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGAT

[0232] CTTTCTTCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTC AGCTGTTCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAG

[0233] TCCAGGAAAGTGA (SEQ ID NO: 347);

[0234] CAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTG

[0235] CACAGCCTCTGGATTCTCCTTCAGTAGCGGCTACGACATGTGCTGGGTCCGCCAGGCTCCAG

[0236] GGAAGGGGCTGGAGTGGATCGCATGCAGACATGGTGGTAGTAGTGGTAGTACGCACTACGCG

[0237] ACCTGGGCGAAAGGCCGATTCACCATCTCCAGAACCTCGTCGACCACGGTGACTCTACAAAT

[0238] GACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATAGTGCTGCTG

[0239] GTGGTTACTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAA

[0240] GGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCT

[0241] TGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCT

[0242] TGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGT

[0243] AGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCA

[0244] TAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACA

[0245] CCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCT

[0246] AAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGT

[0247] GTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACG

[0248] CTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACT

[0249] GTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCT

[0250] GCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGT

[0251] ACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTT

[0252] AAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAA

[0253] CTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCA

[0254] CCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCC

[0255] CTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 348);

[0256] GATGTTGTGATGACCCAGACTCCATCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCAT

[0257] CAAGTGCCAGGCCAGTCAGAGGATTAACAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGC

[0258] AGCCTCCCAAGCTCCTGATCTATTATGCATCCAATCTAGAATCTGGGGTCCCATCGCGGTTC

[0259] AAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGACGATGC

[0260] TGCTACTTACTACTGTCAAAGTGCTTATGGTAGTACTAATGCTGATATTTTTGTTTTCGGCG

[0261] GAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCA

[0262] TCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCC

[0263] CCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGA

[0264] GCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCT AAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTC

[0265] CCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 349);

[0266] GCCCTTGTGATGACCCAGACTCCATCTTCCGCGTCTGAACCTGTGGGAGGCACAGTCACCAT

[0267] CAAGTGCCAGGCCGGTGAGAGTATTAGTAGTAGATTAGCCTGGTATCAGCAGAAACCAGGGC

[0268] AGCCTCCCAAGCTCCTGATCTATGCTGCATCCTATCTGGCATCTGGGGTCCCATCGCGGTTC

[0269] AAAGGCAGTGAATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGATGATGC

[0270] TGCCACTTACTACTGTCAAAGTGTTTCTGCCAGTGGGAGTGGTGATACGCGGGCTTTCGGCG

[0271] GAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCA

[0272] TCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCC

[0273] CCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGA

[0274] GCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCT

[0275] AAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTC

[0276] CCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 350);

[0277] GCCCAAGTGCTGACCCAGACTCCAGCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCAT

[0278] CAAGTGCCAGGCCAGTCAGAGCATTAGTGGCAACTTAGCCTGGTATCAGCAGAAACCAGGGC

[0279] AGCCTCCCAAACTCCTGATCTATTCTGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTC

[0280] AAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGGCGTGCAGTGTGCCGATGC

[0281] TGCCACTTACTACTGTCAGTATGGTTATACTTATAATAGTGGTGATATTGCTTTCGGCGGAG

[0282] GGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCA

[0283] GATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCG

[0284] GGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCG

[0285] TGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAG

[0286] GCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCC

[0287] TGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: (SEQ ID NO: 351);

[0288] GCCCTTGTGATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCAT

[0289] CAATTGCCAGGCCAGTCAGAACATTTACAGCAATTTAGGCTGGTATCAGCAGAAACCAGGGC

[0290] AGCCTCCCAAGCTCCTGATCTATGCTGCATCCTATCTGTCATCTGGGGTCCCATCACGGTTC

[0291] AAAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGC

[0292] AGCCACTTACTACTGTCAAAGCGCTGCTGATAGTAGTAGTGGTGATTTTTTTTATGCTTTCG

[0293] GCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCA

[0294] CCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTA

[0295] TCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGG

[0296] AGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTG TCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTC TTCCCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 352);

[0297] GCGCAAGTGCTGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAATCACCGT CAATTGCCAAGCCAGTCAGAGCATTGGTACCGACTTAGCCTGGTATCAGCAGAAACCAGGGC AGCGTCCCAAGCTCCTGATCTATGCTGCATCCAATCTGGCATCTGGGGTCCCATCGCGGTTC AAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGC TGCCACTTACTACTGTCAATGTACTTATTATGATAGTAGTTATGGGAATGCTTTCGGCGGAG GGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCA GATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCG GGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCG TGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAG GCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCC TGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 353); and GCCATCGAAATGACCCAGACTCCATTCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCAT CAATTGCCAGGCCAGTGAGAACATTTATAGTAATTTAGGCTGGTATCAGCAGAAACCAGGGC AGCCTCCCAAGCTCCTGATCTATGCTGCATCCTATCTGGCATCTGGGGTCCCATCACGGTTC AAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGGCGTGCAGTGTGCCGATGC AGCCACTTACTACTGTCAAAGTGCTACTTATAGTAGTGGTACTGATAGGGCTTTCGGCGGAG GGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCA GATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCG GGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCG TGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAG GCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCC TGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 354).

[0298] In any aspect of the disclosure, or embodiments thereof, contacting the biological sample with the antibody or antigen-binding fragment thereof or conjugate involves preparing a mixture containing the biological sample and from about 2 pg / ml to about 3 pg / ml of the antibody or antigen-binding fragment thereof or conjugate. In any aspect of the disclosure, or embodiments thereof, contacting the biological sample with the antibody or antigen-binding fragment thereof or conjugate involves preparing a mixture containing the biological sample and the antibody or antigen-binding fragment thereof or conjugate, where the mixture contains human serum. In any aspect of the disclosure, or embodiments thereof, the biological sample is added to the mixture at a dilution ratio of from about 1: 10 and 1 :40. In any aspect of the disclosure, or embodiments thereof, the method further involves contacting the biological sample a goat anti-human secondary antibody capable of specifically binding IgGl antibodies and conjugated to a detectable label. In any aspect of the disclosure, or embodiments thereof, the detectable label is Alexa Fluor 647.

[0299] In any aspect of the disclosure, or embodiments thereof, the antibody or antigen- binding fragment thereof or conjugate contains a heavy chain polypeptide and a light chain polypeptide, where: the heavy chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 333; 15H3); and the light chain polypeptide contains an amino acid sequence with at least about 90% identity to the following sequence: AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 339; 15K3).

[0300] Definitions

[0301] Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which the aspects and embodiments described herein belong. The following references provide one of skill with a general definition of many of the terms used in the described aspects and embodiments: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nded. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5thEd., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them below, unless specified otherwise. By “agent” is meant a small compound, polypeptide, nucleic acid molecule or a fragment thereof. In one embodiment, the agent is an anti-idiotypic antibody capable of specifically binding an anti-CD7 antibody or antigen-binding fragment thereof

[0302] By “protein tag,” is meant a peptide that is fused to a protein to facilitate purification or detection of that protein. In embodiments, the peptide is fused to a recombinant protein, a binding polypeptide or an antibody. Such tags, which may be fused to either or both the N (aroino)-termmus or the C (carboxy)-terminus, are typically removable by chemical or enzymatic agents, such as proteolysis or intein splicing. If the tag is inserted into the coding sequence of the protein of interest, it is termed an internal tag.

[0303] Another embodiment of a protein tag is a detectable tag. Fluorescence tags, such as green fluorescent protein (GFP) and known variants of GFP, provide a visual readout, e.g., via fluorescence. Affinity tags may allow specific enzymatic modification (such as biotinylation by biotin ligase) or chemical modification (such as reaction with FlAsH-EDT2, a pro-fluorescent, membrane-permeable biarsenical compound that binds covalently to a tetracysteine sequence (CCPGCC (SEQ ID NO: 8)), for fluorescence imaging).

[0304] As used herein, the term “antibody” (Ab) refers to a polypeptide, or antigen-binding fragment thereof, having immunogen binding ability. The polypeptide may be an immunoglobulin. Exemplary antibodies include polyclonal, monoclonal, genetically and molecularly engineered and otherwise modified forms of antibodies, including, but not limited to, chimeric antibodies, humanized antibodies, heteroconjugate antibodies (e.g., bi- tri- and quad-specific antibodies, diabodies, triabodies, and tetrabodies), and antigen-binding fragments of antibodies, including e.g., Fab’, F(ab’)2, Fab, Fv, rlgG, and scFv fragments. In embodiments, an antibody (e.g., immunoglobulin polypeptide) comprises two heavy chains linked together by disulfide bonds, and two light chains, with each light chain being linked to a respective heavy chain by disulfide bonds in a “Y” shaped configuration. Each heavy chain comprises a variable domain (VH) and a number of constant domains (CH). Each light chain comprises a variable domain (VL) and a constant domain (CL). The variable domain of the light chain (VL) is aligned with the variable domain of the heavy chain (VL), and the light chain constant domain (CL) is aligned with the first constant domain of the heavy chain (CHI). The variable domains of each pair of light and heavy chains form the antigen-binding site. The isotype of the heavy chain (gamma, alpha, delta, epsilon or mu) determines the immunoglobulin class (IgG, IgA, IgD, IgE or IgM, respectively). The light chain is either of two isotypes (kappa (K) or lambda (X)) found in all antibody classes. The terms “antibody” or “antibodies” include intact or full-length antibodies, such as polyclonal antibodies or monoclonal antibodies (mAbs), as well as proteolytic portions or fragments thereof, such as the Fab or F(ab')2 fragments, that are capable of specifically binding to a target protein. Antibodies may include chimeric antibodies; recombinant and engineered antibodies, and antigen-binding fragments thereof.

[0305] Exemplary functional antibody fragments comprising whole or essentially whole variable regions of both the light and heavy chains are defined as follows: (i) Fv, defined as a genetically engineered fragment consisting of the variable region of the light chain and the variable region of the heavy chain expressed as two chains; (ii) single-chain Fv (“scFv”), a genetically engineered single-chain molecule including the variable region of the light chain and the variable region of the heavy chain, linked by a suitable polypeptide linker; (iii) Fab, a fragment of an antibody molecule containing a monovalent antigen-binding fragment of an antibody molecule, obtained by treating an intact antibody with the enzyme papain to yield the intact light chain and the Fd fragment of the heavy chain, which consists of the variable and CHI domains thereof; (iv) Fab’, a fragment of an antibody molecule containing a monovalent antigen-binding fragment of an antibody molecule, obtained by treating an intact antibody with the enzyme pepsin, followed by reduction (two Fab’ fragments are generated per antibody molecule); and (v) F(ab’)2, a fragment of an antibody molecule containing a monovalent antigen-binding fragment of an antibody molecule, obtained by treating an intact antibody with the enzyme pepsin (i.e., a dimer of Fab’ fragments held together by two disulfide bonds). Exemplary anti-idiotypic antibodies are described herein and are useful in the various aspects and embodiments described herein. Without intending to be limiting, the antibodies described herein provide the ability to recognize and bind specifically to an anti- CD? antibody (e.g., to an idiotype of the CI)7 antibody or a portion thereof).

[0306] By “anti-cluster of differentiation 7 (anti-CD7) antibody polypeptide” is meant a polypeptide or antigen-binding fragment thereof that is capable of specifically binding a CD7 antigen, and has at least about 85% amino acid sequence identity to a Variable Heavy Chain (VH) Complementarity Determining Region (CDR) and / or a Variable Light Chain (VL) CDR of the anti-CD7 antibody VH and VL amino acid sequence provided below, where the CDR sequences are shown in bold and the framework reagions are shown in plain text. >Anti-CD7 antibody VH ammo acid sequence (locations of CDRs are shown in bold and the locations of framework regions are shown in plain text) QVKLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGGSYTYYPD SVKGRFT I S RDNAKNTL YLQMS SLRSEDTAMYY C ARQDGYYPGWFANWGQGTTVTVS S ( SEQ ID NO: 9)

[0307] >Anti-CD7 antibody VL amino acid sequence (locations of CDRs are shown in bold and the locations of framework regions are shown in plain text)

[0308] DIELTQSPAIMSASLGEEITLTCSASSSVSYMHWYQQKSGTSPKLLIYSTSNIASGVPSRFS GSGSGTFYSLTISSVEAEDAADYYCHQWSSYTFGGGTKLEIKR (SEQ ID NO: 10)

[0309] In embodiments, the anti-CD7 antibody comprises VL CDR1, VL CDR2, and VL CDR3. In embodiments, the anti-CD7 antibody comprises VL CDR1, VL CDR2, VL CDR3, and one or more of VL FR1, VL FR2, VL FR3, and VL FR4 amino acid sequences. In embodiments, the anti-CD7 antibody or antigen-binding fragment thereof has at least about 85%, 90%, 95%, or 100% amino acid sequence identity to SEQ ID NO: 10,

[0310] In embodiments, the anti-CD7 antibody comprises VH CDR1, VH CDR2, and VH CDR3. In embodiments, the anti-CD7 antibody comprises VH CDR1, VH CDR2, VH CDR3, and one or more of VH FR1, VH FR2, VH FR3, and VH FR4 amino acid sequences. In embodiments, the anti-CD7 antibody or antigen-binding fragment thereof has at least about 85%, 90%, 95%, or 100% amino acid sequence identity to SEQ ID NO. 9.

[0311] In embodiments, the anti-CD? antibody further comprises a protein tag (e.g., affinity tag, epitope tag, detectable tag). In an embodiment, the tag is fused to the N- or C-terminus of the anti-CD7 antibody or antigen-binding fragment thereof. In embodiments, the peptide comprises a His-tag, an Avi peptide, and / or an mFc peptide. In embodiments, the His-tag comprises the amino acid sequence HHHHHH (SEQ ID NO: 1 1). In some embodiments, the .Avi peptide comprise the amino acid sequence GLNDIFEAQKIEWHE (SEQ ID NO: 12). In some cases, the mFc peptide comprises an ammo acid sequence with at least about 85% sequence identity to the following sequence: VPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCWVDISKDDPEVQFSWFVDDV EVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPK APQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFV YSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK (SEQ ID NO: 13).

[0312] In various instances, the anti-CD7 antibody is an scFv comprising a VH and a VL domain fused to one another by a linker. In embodiments, the linker is a (GGGGS)n (SEQ I D NO: 14) linker, where n is an integer between I and 10, such as a linker comprising or consisting of the amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO: 15). In some cases, an anti-CD7 antibody comprises a sequence having at least about 85% amino acid sequence identity to one of the following sequences: >7CAR scFv-Hinge-His MALPVTALLLPLALLLHAARPGSDIELTQSPAIMSASLGEEITLTCSASSSVSYMHWYQQKS GTSPKLLIYSTSNLASGVPSRFSGSGSGTFYSLTISSVEAEDAADYYCHQWSSYTFGGGTKL EIKRGGGGSGGGGSGGGGSQVKLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEK RLEWVATISSGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARQDGYYPG WFANWGQGTTVTVSSAAATTTPAPRPPTPAPTIASQPLSLRPEA.CRPAAGGAVHTRGLDbAC DHHHHHH (SEQ ID NO: 16).

[0313] >7CAR scFv-Hmge-His-Avi MALPVTALLLPLALLLHAARPGSDI ELTQSPAIMSASLGEEITLTCSASSSVSYMHWYQQKS GTSPKLLIYSTSNLASGVPSRFSGSGSGTFYSLTISSVEAEDAADYYCHQWSSYTFGGGTKL EIKRGGGGSGGGGSGGGGSQVKLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEK RLEWVATISSGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARQDGYYPG WFAWGQGTTVTVSSAAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC DHHHHHHGLNDIFEAQKIEWHE (SEQ ID NO: 17).

[0314] >7CAR scFv-Hinge-mFc MALPVTALLLPLALLLHAARPGSDIELTQSPAIMSASLGEEITLTCSASSSVSYMHWYQQKS GTSPKLLIYSTSNLASGVPSRFSGSGSGTFYSLTISSVEAEDAADYYCHQWSSYTFGGGTKL EIKRGGGGSGGGGSGGGGSQVKLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEK RLEWVATISSGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARQDGYYPG WFANWGQGTTVTVSSAAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC DVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVWDISKDDPEVQFSWFVDD VEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRP

[0315] KAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYF VYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK (SEQ ID NO: 18).

[0316] By “anti -cluster of differentiation 7 (CD7) chimeric antigen receptor (CAR) (7CAR) polypeptide” is meant a protein having at least about 85% amino acid sequence identity to an exemplary 7CAR polypeptide sequence provided below, or a fragment thereof, capable of mediating an immune response in an immune effector cell surface-expressing the protein when the protein binds a CD7 antigen. An exemplar}' CD7 CAR amino acid sequence is provided below, where a signal peptide sequence is indicated by bold text, an scFv domain is indicated by underlined text, a CD8a hinge domain is indicated by bold-underlined text, a CD8a transmembrane domain is indicated by doubl e-underl ined text, a CD28 co-stimulatory domain is indicated by bold-italic text, and a CD3ȗ (CD3z) signaling domain is indicated by plain text. An exemplary 7CAR polypeptide sequence is provided below: >7CAR MALPVTALLLPLALLLHAARPGSDIELTQSPAIMSASLGEEITLTCSASSSVSYMHWYQQKS GTSPKLLIYSTSNLASGVPSRFSGSGSGTFYSLTISSVEAEDAADYYCHQWSSYTFGGGTKL EIKRGGGGSGGGGSGGGGSQVKLQESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEK RLEWVATISSGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLRSEDTAMYYCARQDGYYPG WFANWGQGTTVTVSSAAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC DIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFA AYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGL YNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO: 19). In one embodiment, a fragment of a 7CAR polypeptide is used in the immunization of an animal to produce an anti-idiotypic antibody capable of specifically binding a 7CAR. In another embodiment, the anti-idiotypic antibody binds an scFv domain of a 7CAR. In another embodiment, a fragment for immunizing an animal to generate anti-idiotypic antibody comprises the following sequence: >7CAR fragment DIELTQSPAIMSASLGEEITLTCSASSSVSYMHWYQQKSGTSPKLLIYSTSNLASGVPSRFS GSGSGTFYSLTISSVEAEDAADYYCHQWSSYTFGGGTKLEIKRGGGGSGGGGSGGGGSQVKL QESGGGLVKPGGSLKLSCAASGFTFSSYAMSWVRQTPEKRLEWVATISSGGSYTYYPDSVKG RFTISRDNAKNTLYLQMSSLRSEDTAMYYCARQDGYYPGWFANWGQGTTVTVSSAAATTTPA PRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD (SEQ ID NO: 20). In an embodiment, the 7CAR fragment comprises a poly histidine tag. By “anti-cluster of differentiation 7 (CD7) chimeric antigen receptor (CAR) (7CAR) polynucleotide” is meant a nucleic acid molecule encoding a 7CAR polypeptide, as well as the introns, exons, 3ƍ untranslated regions, 5ƍ untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, a 7CAR polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for 7CAR expression. An exemplary 7CAR nucleotide sequence is provided below. >7CAR ATGGCGCTCCCCGTGACTGCGCTGCTGCTCCCTCTGGCCCTGCTCCTGCATGCCGCCAGACC GGGATCCGACATCGAGCTTACCCAGTCCCCGGCCATTATGTCCGCCTCGTTGGGGGAAGAAA TCACCCTGACCTGTTCCGCGTCCTCCTCCGTGTCCTACATGCACTGGTACCAGCAAAAGAGC GGCACTTCGCCGAAGCTGCTGATCTACTCGACGTCCAATCTCGCCTCTGGAGTGCCCAGCCG CTTCAGCGGATCCGGCTCAGGGACCTTCTACTCCCTGACTATTTCCTCCGTGGAAGCCGAAG ATGCCGCCGACTACTACTGCCACCAATGGTCGAGCTACACCTTCGGCGGCGGAACCAAGCTC GAGATTAAGCGCGGTGGTGGAGGATCAGGGGGTGGAGGGTCTGGCGGTGGAGGTTCCCAAGT CAAGCTGCAGGAATCCGGTGGCGGATTGGTCAAGCCCGGCGGATCCTTGAAGCTCTCTTGCG CGGCATCCGGCTTCACCTTCTCATCGTACGCCATGTCGTGGGTTCGGCAGACCCCCGAAAAA CGGCTCGAATGGGTGGCCACCATCTCCAGTGGTGGATCCTACACTTACTATCCCGACTCCGT GAAAGGGCGATTCACTATCTCGCGCGACAACGCCAAGAACACCCTGTACCTTCAAATGTCGT CACTGCGGTCCGAGGACACCGCCATGTACTACTGCGCAAGACAGGACGGATACTACCCTGGC TGGTTCGCCAACTGGGGACAGGGAACCACCGTGACCGTGTCATCAGCCGCCGCGACAACTAC GCCTGCACCTAGGCCTCCGACTCCTGCCCCAACCATCGCGTCCCAGCCTCTGTCGCTCCGGC CTGAAGCCTGTAGACCAGCTGCTGGCGGAGCAGTCCACACCCGGGGTCTGGACTTTGCCTGC GATATCTACATTTGGGCTCCTCTAGCGGGCACCTGTGGTGTCCTGCTGTTGTCCCTGGTCAT CACGCTCTATTGTCGGAGCAAGCGGAGCAGGCTGCTGCATTCGGATTACATGAACATGACCC CAAGGAGGCCTGGTCCGACTCGGAAGCACTACCAGCCCTATGCCCCGCCTCGCGATTTCGCC GCCTACCGCTCACGCGTGAAGTTCAGCAGATCGGCTGACGCTCCAGCGTATCAACAGGGCCA GAACCAGCTTTACAACGAGCTGAATCTGGGTCGGAGGGAGGAATACGACGTGCTGGACAAGC GGAGGGGACGGGATCCAGAAATGGGAGGGAAGCCCAGACGCAAGAACCCTCAGGAGGGCCTG TACAATGAGCTGCAGAAGGATAAGATGGCCGAGGCGTACAGCGAGATCGGCATGAAGGGAGA ACGCAGACGCGGAAAGGGCCACGATGGGCTGTACCAGGGACTCTCGACTGCCACAAAGGACA CCTACGACGCCCTGCACATGCAGGCACTGCCACCTAGA (SEQ ID NO: 21).

[0317] By “anti -idiotypic antibody” or “anti -idiotypic polypeptide” is meant an antibody or antigen-binding fragment thereof that specifically binds the idiotype of a different antibody. An idiotype is a specific region within an antibody’s Fv region that binds to the paratope (i.e., antigenic epitope binding site) of a different antibody. In embodiments, the specific idiotype is a cluster of differentiation 7 (CD7) binding idiotype.

[0318] By “anti-cluster of differentiation 7 (CD7) antibody-binding anti-idiotypic polypeptide” or “anti -idiotypic antibody capable of binding an anti-CD7 antibody” is meant a polypeptide or fragment thereof that is capable of specifically binding an antigen-binding fragment of a polypeptide that is capable of binding a CD7 antigen, and has at least 85% amino acid sequence identity to a Variable Heavy Chain (VH) Complementarity Determining Regions (CDRs) and / or a Variable Light Chain (VL) CDRs selected from those listed in Tables 1A-1K and / or Tables 2A-2F. In embodiments, the polypeptide capable of binding a CD7 antigen is an anti-CD7 antibody or an anti-CD7 chimeric antigen receptor (7CAR).

[0319] In embodiments, an anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a Variable Heavy Chain (VH) amino acid sequence having at least about 85% amino acid sequence identity to 1H2, 2H3, 43H1, 15H3, 29H3, or 30H3. Amino acid sequences of the VH domains of the anti -idiotypic polypeptide capable of binding an anti- CD7 antibody (e.g., 1H2, 2H3, 43H1, 15H3, 29H3, and 30H3) are provided below. CDRs are provided herein below.

[0320] >1H2:

[0321] QSVEESGGRLVTPGTPLTLTCTVSGFSLSDYYMSWVRQAPGKGLEWIGI I YGSGTTYYATWA KGRFTISKTSSTTVDLKMTSLTASDTATYFCARALYADSNYWPLYFNFWGQGTLVTVSS (SEQ ID NO: 22)

[0322] >2H3:

[0323] QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA S WAKGRFT I S KTS S TTVTLQMTS LTAADTATYFC ARS DYTGGNYFNLWGQGTL VTVS S (SEQ ID NO: 23)

[0324] >43H1:

[0325] QSLEESGGDLVKPGASLTLTCTASGFSFSSSYWMCWVRQAPGKGLEWIACIHAGSSGSIYYA NWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDYHYGGTGYAYNLWGQGTLVTVSS (SEQ ID NO: 24)

[0326] >15H3:

[0327] QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SS (SEQ ID NO: 25)

[0328] >29H3:

[0329] QEQLEESGGDLVKPEGSLTLTCTASGFSFSSSYRICWVRQAPGKGLEWIACIYAGNSSYTHY ATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFCARDDTVSFGYPYGYFNLWGQGTLVTVS S (SEQ ID NO: 26)

[0330] >30H3:

[0331] QSLEESGGDLVQPEGSLTLTCTASGSDISGYSLCWVRQAPGKGLEWIACIGNGDGNTYYASW AKGRFTISKTSSTTVTLQMTSLTAADTATYFCASDTHDYVGFNLWGQGTLVTVSS (SEQ ID NO: 27) In embodiments, an anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a Variable Light Chain (VL) amino acid sequence having at least about 85% amino acid sequence identity to 1K2, 2K1, 43K2, 15K3, 29K1, or 30K3. Amino acid sequences of the VL domains of the anti -idiotypic polypeptide capable of binding an anti- CD? antibody (e.g., 1K2, 2K1, 43K2, 15K3, 29K1, and 30K3) are provided below. CDRs are provided herein below.

[0332] >1K2:

[0333] ANIVMTQTPASVEVAVGGTVTIKCQASQSI SNLLAWYQQKSGQPPKLLIYDSSDLASGVSSR FKGSGSGTQFTLTI SGVECADAATYYCQQGWSGSNVNNVFGGGTEVWKGDP (SEQ ID NO:

[0334] 28) >2K1: DVVMTQTPSSVEAAVGGTVTI KCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADI FVFGGGTEVWKGDP (SEQ ID NO:

[0335] 29)

[0336] >43K2:

[0337] ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLAWYQQKPGQRPKLLIYGASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYYSSSPDNTFGGGTEWVKGDP (SEQ ID NO:

[0338] 30)

[0339] >15K3:

[0340] AQVLTQTPASVSAAVGGTVTI KCQASQS ISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKGDP (SEQ ID NO:

[0341] 31)

[0342] >29K1:

[0343] AI EMTQTPFSVSAAVGGTVTINCQASES IYSNLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSAVYSSSADNAFGGGTEWVKGDP (SEQ ID NO:

[0344] 32)

[0345] >30K3:

[0346] AAVLTQTPSPVSAAVGGTVSI SCQSSKSVYNNNFLSWFQQKPGQPPKLLIYGASTLASGVPS RFKGNGSGTQFTLTISDVQCDDAATYYCAGGYGSSSDRFGFGGGTEWVKGDP (SEQ ID NO: 33)

[0347] In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a heavy chain (HC) constant domain fused to the C-terminus of a variable heavy chain (VH) domain provided herein. In embodiments, the HC constant domain of the anti-idiotypic polypeptide comprises an amino acid sequence having at least about 85% sequence identity to the following amino acid sequence: GQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGL YSLSSWSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGGPSVFIFPPKPK DTLMISRTPEVTCVWDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRWSTLPITH QDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGF YPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYNKLSVPTSEWQRGDVFTCSVMHEALHN HYTQKSISRSPGK (SEQ ID NO: 34).

[0348] In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a light chain (LC) constant domain fused to the C-terminus of a variable light chain (VL) domain provided herein. In embodiments, the LC constant domain of the anti-idiotypic polypeptide comprises an amino acid sequence having at least about 85% sequence identity to the following amino acid sequence: VAPTVL I F P PAADQVATGTVT I VCVANKYF PDVTVTWEVDGTTQTTG I ENS KT PQNS ADCTY NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC (SEQ ID NO: 35).

[0349] In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises VH CDR1, CDR2, and CDR3 sequences listed in Table 1A. In some embodiments, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VH CDR1 that is 8 or 9 amino acids in length, a VH CDR2 that is 4 to 9 amino acids in length, and / or a VH CDR3 that is 9 to 23 amino acids in length. In some cases, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VH CDR1 having a sequence described in Tables IB or 1C. In some cases, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VH CDR2 having a sequence described in Tables ID- IF. In some cases, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VH CDR3 having a sequence described in Tables 1G-1K.

[0350] In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises VL CDR1, CDR2, and CDR3 sequences listed in Table 2A. In some embodiments, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VL CDR1 that is 6 to 8 amino acids in length, a VL CDR2 that is 3 amino acids in length, and / or a VL CDR3 that is 10 to 16 amino acids in length. In some cases, the anti- idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VL CDR1 having a sequence described in table 2B. In some cases, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VL CDR2 having a sequence described in Table 2C. In some cases, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VL CDR3 having a sequence described in Tables 2D-2F.

[0351] VH and VL framework regions (FR) are provided herein. In an embodiment, a FR has at least about 85% amino acid sequence identity to one of the following sequences. VH FR1:

[0352] QEQLKESGGGLVLPGGSLKLSCKAS (SEQ ID NO: 36);

[0353] QSVEESGGRLVTPGTPLTLTCTVS (SEQ ID NO: 37);

[0354] QSLEESGGDLVQPEGSLTLTCTAS (SEQ ID NO: 38);

[0355] QEQLEESGGDLVKPEGSLTLTCTAS (SEQ ID NO: 39);

[0356] QSLEESGGDLVKSGASLTLTCTAS (SEQ ID NO: 40); and

[0357] QSLEESGGDLVKPGASLTLTCTAS (SEQ ID NO: 41).

[0358] VH FR2:

[0359] MNWVRQAPGKGLEWIGY (SEQ ID NO: 42);

[0360] MSWVRQAPGKGLEWIGI (SEQ ID NO: 43);

[0361] LCWVRQAPGKGLEWIAC (SEQ ID NO: 44);

[0362] ICWVRQAPGKGLEWIAC (SEQ ID NO: 45); and

[0363] MCWVRQAPGKGLEWIAC (SEQ ID NO: 46).

[0364] VH FR3:

[0365] YYANWVNGRFTISSHNVQKKLYLQLNSLTAADTATYFC (SEQ ID NO: 47);

[0366] YYATWAKGRFTISKTSSTTVDLKMTSLTASDTATYFC (SEQ ID NO: 48);

[0367] YYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 49);

[0368] HYATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFC (SEQ ID NO: 50);

[0369] AYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 51); and YYANWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 52).

[0370] VH FR4:

[0371] WGQGTLVTVSS (SEQ ID NO: 53).

[0372] VL FR1:

[0373] AAVLTQTPSPVSAAVGGTVS ISCQSS (SEQ ID NO: 54);

[0374] ANIVMTQTPASVEVAVGGTVTIKCQAS (SEQ ID NO: 55);

[0375] DVVMTQTPSSVEAAVGGTVTIKCQAS (SEQ ID NO: 56);

[0376] ALVMTQTPSSVSAAVGGTVTINCQAS (SEQ ID NO: 57);

[0377] AQVLTQTPASVSAAVGGTVTIKCQAS (SEQ ID NO: 58); and AI EMTQTPFSVSAAVGGTVTINCQAS (SEQ ID NO: 59).

[0378] VL FR2:

[0379] LSWFQQKPGQPPKLLIY (SEQ ID NO: 60);

[0380] LAWYQQKSGQPPKLLIY (SEQ ID NO: 61);

[0381] LAWYQQKPGQPPKLLIY (SEQ ID NO: 62); and

[0382] LAWYQQKPGQRPKLLIY (SEQ ID NO: 63).

[0383] VL FR3:

[0384] TLASGVPSRFKGNGSGTQFTLTI SDVQCDDAATYYC (SEQ ID NO: 287);

[0385] DLASGVSSRFKGSGSGTQFTLTI SGVECADAATYYC (SEQ ID NO: 64);

[0386] NLESGVPSRFKGSGSGTEYTLTI SDLECDDAATYYC (SEQ ID NO: 65);

[0387] (SEQ ID NO: TLASGVPSRFKGSGSGTEYTLTISGVQCADAATYYC (SEQ ID NO: 66); and YLASGVPSRFKGSGSGTEYTLTI SGVQCADAATYYC (SEQ ID NO: 67).

[0388] VL FR4:

[0389] FGGGTEVWKGDP (SEQ ID NO: 68).

[0390] In embodiments, the FR comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid substitutions to one of the FR sequences provided herein above. In other embodiments, the FR is located on either side of a VH or VL CDR.

[0391] In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises one or more signal peptides. In one embodiment, the signal peptide is fused at an N-terminus of a light chain or heavy chain. In some cases, the signal peptide comprises the amino acid sequence METGLRWLLLVAVLKGVQC (SEQ ID NO: 69), or the amino acid sequence MDTRAPTQLLGLLLLWLP (SEQ ID NO: 70), or an amino acid sequence corresponding to one of these two sequences and having 1, 2, 3, 4, or 5 amino acid alterations.

[0392] In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VH having at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% amino acid sequence identity to one of the VH sequences provided herein (see, e.g., those VH sequences listed in Table 5). In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody comprises a VL having at least about 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% amino acid sequence identity to one of the VL sequences provided herein (see, e.g., those VL sequences listed in Table 5). In embodiments the VH comprises from N-terminus to C-terminus: VH FR1, VH CDR1, VH FR2, VH CDR2, VH FR3, VH CDR3, and VH FR4. In embodiments the VL comprises from N- terminus to C-terminus: VL FR1, VL CDR1, VL FR2, VL CDR2, VL FR3, VL CDR3, and VL FR4. In embodiments, the anti -idiotypic polypeptide capable of binding an anti-CD7 antibody is a humanized polypeptide. In some instances, the anti-idiotypic polypeptide capable of binding an anti-CD7 antibody comprises from N-terminus to C-terminus the VL and the VH or the VH and the VL. In some cases, the LC and HC are linked to one another by a linker sequence, such as a (GGGGS)n (SEQ ID NO: 71) sequence (e.g., GGGGSGGGGSGGGGS (SEQ ID NO: 15)).

[0393] By “anti-cluster of differentiation 7 (CD7) antibody-binding anti-idiotypic polynucleotide” or “anti -idiotypic antibody capable of binding an anti-CD7 antibody polynucleotide” is meant a nucleic acid molecule encoding an anti-idiotypic antibody capable of binding an anti-CD7 antibody polypeptide, as well as the introns, exons, 3' untranslated regions, 5' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, an anti -idiotypic antibody capable of binding an anti- CD7 antibody polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for anti -idiotypic antibody capable of binding an anti-CD7 antibody expression.

[0394] By “alteration” is meant a change (increase or decrease) in the structure, expression levels or activity of a gene or polypeptide as detected by standard art known methods such as those described herein. As used herein, an alteration includes a 10% change in expression or activity levels, a 25% change, a 40% change, and a 50% or greater change in expression or activity levels. In embodiments, an alteration is a change in the sequence of a polypeptide or polynucleotide relative to a reference sequence. In some embodiments, the activity is antibody-binding activity.

[0395] The term "antigen-binding fragment,” as used herein, refers to one or more portions or fragments of an antibody that retain the ability to specifically bind to a target antigen. In an embodiment, the target antigen is an anti-CD7 antibody (e.g., an idiotype of the anti-CD7 antibody). The antigen-binding function of an antibody can be performed by fragments of a full-length antibody. The antibody fragments can be a Fab, F(ab’)2, scFv, SMIP, diabody, a triabody, an affibody, a nanobody, an aptamer, or a domain antibody. Examples of binding fragments encompassed by the term “antigen-binding fragment” of an antibody include, but are not limited to: (i) a Fab fragment, a monovalent fragment co’sisting of the VL, VH, CL, and CHI domains; (ii) a F(ab’)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CHI domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb including VH and VL domains; (vi) a dAb fragment (Ward et al., Nature 341:544-546, 1989), which consists of a VH domain; (vii) a dAb which consists of a VH or a VL domain; (viii) an isolated complementarity determining region (CDR); and (ix) a combination of two or more isolated CDRs which may optionally be joined by a synthetic linker. Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single-chain Fv (scFv); see, e.g., Bird et al., Science 242:423-426, 1988, and Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883, 1988). Such antibody fragments can be obtained using conventional techniques known to those of skill in the art, and the fragments can be screened for utility in the same manner as intact antibodies. Antigen-binding fragments can be produced by recombinant DNA techniques, enzymatic or chemical cleavage of intact immunoglobulins, or, in some cases, by chemical peptide synthesis procedures known in the art. In some embodiments, antigen-binding fragments (e.g., .g., Fab’, F(ab’)2, Fab, scFab, Fv, rlgG, and scFv fragments) of an anti-idiotypic antibody, which are joined by a synthetic linker, are encompassed herein.

[0396] The terms "antigen of interest" or "target protein” are used herein interchangeably and refer generally to the agent recognized and specifically bound by an antibody. In an embodiment, such an antigen of interest or target protein is an anti-CD7 antibody, or an antigen-binding fragment thereof.

[0397] By “analog” is meant a molecule that is not identical but has analogous functional or structural features. For example, a polypeptide analog retains the biological activity of a corresponding naturally-occurring polypeptide, while having certain biochemical modifications that enhance the analog’s function relative to a naturally occurring polypeptide. Such biochemical modifications could increase the analog’s protease resistance, membrane permeability, or half-life, without altering, for example, ligand binding. An analog may include an unnatural amino acid.

[0398] A “binding polypeptide” refers to a polypeptide, or an antigen-binding fragment thereof, that has specificity for and specifically binds a target polypeptide. In embodiments, the target polypeptide is an anti-CD7 antibody. In embodiments, the binding polypeptide specifically binds an idiotype of an anti-CD7 antibody. In an embodiment, a binding polypeptide is an anti -idiotypic antibody capable of binding an anti-CD7 antibody or an antigen-binding fragment thereof. As used herein, and without intending to be limiting, a cell preparation, or a tissue or organ preparation, refers to a cell lysate, homogenate, extract (e.g., fluid extract), supernatant, and the like that results after treating the cell, tissue, or organ with an agent or agents that disrupt the cell membrane such that the internal contents of the cell are available for assay. Disruption of the integrity of the cell membrane may occur by chemical, enzymatic, or physical means, e g,, strong detergents, homogenization, or high-energy sound waves, A fluid containing the contents of lysed cells is called a lysate. Cell lysis is used to break open cells to avoid shear forces that would denature or degrade sensitive proteins and DNA. Cell lysis is used (e.g., in western and Southern blotting) to analyze and assess specific proteins, lipids, and / or nucleic acids, as well as in reporter assays, immunoassays, and protein purification methods. Depending upon the detergent used, either all or some membranes in cells are lysed. It will be understood that tissue and organ preparations contain cells that comprise them.

[0399] By “chimeric antigen receptor” or “CAR” is meant a synthetic or engineered receptor comprising an extracellular antigen-binding domain joined to one or more intracellular signaling domains (e.g., T cell signaling domain) that confers specificity for an antigen onto an immune effector cell (e.g., a T-cell, an NK cell, or a macrophage). In embodiments, the CAR is a SUPRA CAR, an anti-tag CAR, a TCR-CAR, or a TCR-like CAR (see, e.g., Guedan, et al. “Engineering and Design of Chimeric Antigen Receptors,” Methods and Clinical Development, 12: 145-156 (2019); Poorebrahim, et al., “TCR-like CARs and TCR- CARs targeting neoepitopes: an emerging potential,” Cancer Gene Therapy, 28:581-589 (2021); and Minutolo, et al. “The Emergence of Universal Immune Receptor T Cell Therapy for Cancer,” Front Oncol., 9: 176 (2019), the disclosures of which are incorporated herein by reference in their entireties for all purposes).

[0400] By “chimeric antigen receptor (CAR) T cell” or “CAR-T cell” is meant a T cell expressing a CAR that has antigen specificity determined by the antibody-derived targeting domain of the CAR. As used herein, “CAR-T cells” includes T cells, regulatory T cells (TREG), or NK cells. As used herein, “CAR-T cells” include cells engineered to express a CAR or a T cell receptor (TCR, sometimes referred to as TCR-CARs or TCR-like CARs). Methods of making CARs (e.g., for treatment of cancer) are publicly available (see, e.g., Park et al., Trends Biotechnol., 29:550-557, 2011; Grupp et al., N Engl J Med., 368: 1509-1518, 2013; Han et al., J. Hematol Oncol. 6:47, 2013; Haso et al., (2013) Blood, 121, 1165-1174; Mohseni, et al., (2020) Front. Immunol., 11, art. 1608, doi: 10.3389 / fimmu.2020.01608; Eggenhuizen, et al. Int. J. Mol. Sci. (2020), 21:7015, doi: 10.3390 / ijms21197015; Poorebrahim, et al., Cancer Gene Ther 28, 581-589 (2021), doi.org / 10.1038 / s41417-021- 00307-7, PCT Pubs. WO2012 / 079000, WO2013 / 059593; and U.S. Pub. 2012 / 0213783, the disclosure of each of which is incorporated herein by reference herein in its entirety).

[0401] By “cluster of differentiation 7 (CD7) polypeptide” is meant a protein having at least about 85% amino acid sequence identity to NCBI Reference Sequence: NP_006128.1, which is provided below, or a fragment thereof having immunomodulatory activity.

[0402] >NP_006128.1 T-cell antigen CD7 precursor [Homo sapiens]

[0403] MAGPPRLLLLPLLLALARGLPGALAAQEVQQSPHCTTVPVGASVNITCSTSGGLRGIYLRQL GPQPQDI IYYEDGVVPTTDRRFRGRIDFSGSQDNLTITMHRLQLSDTGTYTCQAITEVNVYG SGTLVLVTEEQSQGWHRCSDAPPRASALPAPPTGSALPDPQTASALPDPPAASALPAALAVI SFLLGLGLGVACVLARTQIKKLCSWRDKNSAACVVYEDMSHSRCNTLSSPNQYQ (SEQ ID NO: 72).

[0404] By “cluster of differentiation 7 (CD7) polynucleotide” is meant a nucleic acid molecule encoding a CD7 polypeptide, as well as the introns, exons, 3' untranslated regions, 5' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, a CD7 polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for CD7 expression. An exemplary CD7 nucleotide sequence from Homo Sapiens is provided below (NCBI Ref. Seq.: NM_006137.7). >NM_006137.7 Homo sapiens CD7 molecule (CD7), mRNA CTCTCTGAGCTCTGAGCGCCTGCGGTCTCCTGTGTGCTGCTCTCTGTGGGGTCCTGTAGACC CAGAGAGGCTCAGCTGCACTCGCCCGGCTGGGAGAGCTGGGTGTGGGGAACATGGCCGGGCC TCCGAGGCTCCTGCTGCTGCCCCTGCTTCTGGCGCTGGCTCGCGGCCTGCCTGGGGCCCTGG CTGCCCAAGAGGTGCAGCAGTCTCCCCACTGCACGACTGTCCCCGTGGGAGCCTCCGTCAAC ATCACCTGCTCCACCAGCGGGGGCCTGCGTGGGATCTACCTGAGGCAGCTCGGGCCACAGCC CCAAGACATCATTTACTACGAGGACGGGGTGGTGCCCACTACGGACAGACGGTTCCGGGGCC GCATCGACTTCTCAGGGTCCCAGGACAACCTGACTATCACCATGCACCGCCTGCAGCTGTCG GACACTGGCACCTACACCTGCCAGGCCATCACGGAGGTCAATGTCTACGGCTCCGGCACCCT GGTCCTGGTGACAGAGGAACAGTCCCAAGGATGGCACAGATGCTCGGACGCCCCACCAAGGG CCTCTGCCCTCCCTGCCCCACCGACAGGCTCCGCCCTCCCTGACCCGCAGACAGCCTCTGCC CTCCCTGACCCGCCAGCAGCCTCTGCCCTCCCTGCGGCCCTGGCGGTGATCTCCTTCCTCCT CGGGCTGGGCCTGGGGGTGGCGTGTGTGCTGGCGAGGACACAGATAAAGAAACTGTGCTCGT GGCGGGATAAGAATTCGGCGGCATGTGTGGTGTACGAGGACATGTCGCACAGCCGCTGCAAC ACGCTGTCCTCCCCCAACCAGTACCAGTGACCCAGTGGGCCCCTGCACGTCCCGCCTGTGGT CCCCCCAGCACCTTCCCTGCCCCACCATGCCCCCCACCCTGCCACACCCCTCACCCTGCTGT CCTCCCACGGCTGCAGCAGAGTTTGAAGGG961CCCAGCCGTGCCCAGCTCCAAGCAGACAC ACAGGCAGTGGCCAGGCCCCACGGTGCTTCTCAGTGGACAATGATGCCTCCTCCGGGAAGCC TTCCCTGCCCAGCCCACGCCGCCACCGGGAGGAAGCCTGACTGTCCTTTGGCTGCATCTCCC GACCATGGCCAAGGAGGGCTTTTCTGTGGGATGGGCCTGGGCACGCGGCCCTCTCCTGTCAG TGCCGGCCCACCCACCAGCAGGCCCCCAACCCCCAGGCAGCCCGGCAGAGGACGGGAGGAGA CCAGTCCCCCACCCAGCCGTACCAGAAATAAAGGCTTCTGTGCTTCC(SEQ ID NO: 73).

[0405] By “Cluster of Differentiation 52 (CD52) polypeptide” is meant a protein having at least about 85% amino acid sequence identity to NCBI Accession No. NP_001794.2 (SEQ ID NO: 74), or a fragment thereof having immunomodulatory activity.

[0406] By “Cluster of Differentiation 52 (CD52) polynucleotide” is meant a nucleic acid molecule encoding a CD52 polypeptide, as well as the introns, exons, 3' untranslated regions, 5' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, a CD52 polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for CD52 expression. An exemplary CD52 polynucleotide has at least about 85% nucleic acid sequence identity to NCBI Accession No. NM_001803.3 (SEQ ID NO: 75), or a fragment thereof.

[0407] As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended. This wording indicates that specified elements, features, components, and / or method steps are present, but does not exclude the presence of other elements, features, components, and / or method steps. Any embodiments specified as “comprising” a particular component(s) or element(s) are also contemplated as “consisting of’ or “consisting essentially of’ the particular component(s) or element(s) in some embodiments. It is contemplated that any embodiment discussed in this specification can be implemented with respect to any method or composition of the present disclosure, and vice versa. Furthermore, compositions of the present disclosure can be used to achieve methods of the present disclosure.

[0408] As used herein, the term “complementarity determining region” (CDR) refers to a hypervariable region found both in the light chain and the heavy chain variable domains ((VL and VH domains, respectively). The more highly conserved portions of variable domains are called the framework regions (FRs). As is appreciated in the art, the amino acid positions that delineate a hypervariable region of an antibody can vary, depending on the context and the various definitions known in the art. Some positions within a variable domain may be viewed as hybrid hypervariable positions in that these positions can be deemed to be within a hypervariable region under one set of criteria while being deemed to be outside a hypervariable region under a different set of criteria. One or more of these positions can also be found in extended hypervariable regions. The variable domains of native heavy and light chains each comprise four framework regions (FR1, FR2, FR3, FR4) that primarily adopt a beta-sheet configuration, connected by three CDRs (CDR1, CDR2, CDR3), which form loops that connect, and, in some cases, form part of, the beta-sheet structure. The CDRs in each chain are held together in close proximity by the FR regions in the order FR1-CDR1-FR2- CDR2-FR3-CDR3-FR4 and the CDRs in each antibody chain contribute to the formation of the target binding site of antibodies (see Kabat et al, Sequences of Proteins of Immunological Interest (National Institute of Health, Bethesda, Md. 1987; incorporated herein by reference). As used herein, numbering of immunoglobulin amino acid residues is done according to the immunoglobulin amino acid residue numbering system of Kabat et al., unless otherwise indicated.

[0409] “Detect” refers to identifying the presence, absence or amount of the analyte to be detected. In some embodiments, the analyte is an antigen, epitope, or fragment thereof. In one embodiment, the term “detect” refers to detecting antibody binding to an agent of interest, such as an anti-CD7 antibody, antigen binding fragment thereof, or anti-CD7 CAR (7CAR).

[0410] By “detectable label” is meant a composition that when linked to a molecule of interest renders the latter detectable, via spectroscopic, photochemical, biochemical, immunochemical, or chemical means. For example, useful labels include radioactive isotopes, magnetic beads, metallic beads, colloidal particles, fluorescent dyes, electron-dense reagents, enzymes (for example, as commonly used in an ELISA), biotin, digoxigenin, or haptens. In some embodiments, an antibody as described herein is directly or indirectly linked to a detectable label.

[0411] By “disease” is meant any condition or disorder that damages or interferes with the normal function of a cell, tissue, or organ. Examples of diseases include neoplasias, such as tumors or cancers. In some embodiments, the disease is a T-cell leukemia / lymphoma, such as a T-cell acute lymphoblastic leukemia (T-ALL) or a T-cell lymphoblastic lymphoma (T-LL). T-ALL is an immunophenotypically heterogenous acute leukemia that originates in immature cells that would normally develop into T-cell lymphocytes. T-LL has overlapping morphologic and immunophenotypic characteristics with T-ALL, with less prominent or no bone marrow involvement.

[0412] The term "Fc region" herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl -terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5thEd. Public Health Service, National Institutes of Health, Bethesda, MD, 1991.

[0413] The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a native antibody structure or having heavy chains that contain an Fc region as defined herein.

[0414] As used herein, the term “framework region” or “FR region” includes amino acid residues that are adjacent to the CDRs. FR region residues may be present in, for example, human antibodies, rodent-derived antibodies (e.g., murine antibodies), rabbit-derived antibodies, humanized antibodies, primatized antibodies, chimeric antibodies, antibody fragments (e.g., Fab fragments), single-chain antibody fragments (e.g., scFv fragments), antibody domains, and bispecific antibodies, among others.

[0415] By “fragment” is meant a portion of a polypeptide or nucleic acid molecule. This portion contains, preferably, at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. A fragment may contain less than 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. A fragment may contain at least 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. A fragment may contain an antigen-binding portion of a polypeptide. A fragment may contain a domain of a polypeptide (e.g., an extracellular domain, an intracellular domain, a transmembrane domain, an antigen-binding domain).

[0416] As used herein, the term “human antibody” or “humanized antibody” refers to an antibody in which substantially every part of the protein (e.g., CDR, framework, CL, CH domains (e.g., CHI, CH2, CJB), hinge, (VL, VH)) is substantially non-immunogenic in humans, with only minor sequence changes or variations. A human antibody can be produced in a human cell (e.g., by recombinant expression), or by a non-human animal or a prokaryotic or eukaryotic cell (e.g., yeast) that is capable of expressing functionally rearranged human immunoglobulin (e.g., heavy chain and / or light chain) genes. Further, when a human antibody is a single-chain antibody, it can include a linker peptide that is not found in native human antibodies. For example, an Fv can comprise a linker peptide, such as two to about eight glycine or other amino acid residues, which connects the variable region of the heavy chain and the variable region of the light chain. Such linker peptides are considered to be of human origin. Human antibodies can be made by a variety of methods known in the art including phage display methods using antibody libraries derived from human immunoglobulin sequences. See U.S. Pat. Nos. 4,444,887 and 4,716,111; and PCT publications WO 1998 / 46645; WO 1998 / 50433; WO 1998 / 24893; WO 1998 / 16654; WO 1996 / 34096; WO 1996 / 33735; and WO 1991 / 10741; incorporated herein by reference. Human antibodies can also be produced using transgenic mice that are incapable of expressing functional endogenous immunoglobulins, but which can express human immunoglobulin genes. See, e.g., PCT publications WO 98 / 24893; WO 92 / 01047; WO 96 / 34096; WO 96 / 33735; U.S. Pat. Nos. 5,413,923; 5,625,126; 5,633,425; 5,569,825; 5,661,016; 5,545,806; 5,814,318; 5,885,793; 5,916,771; and 5,939,598; incorporated by reference herein.

[0417] As used herein, the term “humanized” antibodies also refers to forms of non-human (e.g., rabbit) antibodies that are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2 or other target-binding subdomains of antibodies) which contain minimal sequences derived from non-human immunoglobulin. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin. All or substantially all of the FR regions may also be those of a human immunoglobulin sequence. The humanized antibody can also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin consensus sequence. Methods of antibody humanization are known in the art. See, e.g., Riechmann et al., Nature 332:323-7, 1988; U.S. Pat. Nos. 5,530,101; 5,585,089; 5,693,761; 5,693,762; and U.S. Pat. No. 6,180,370 to Queen et al; EP239400; PCT publication WO 91 / 09967; U.S. Pat. No. 5,225,539; EP592106; and EP519596; incorporated herein by reference. By “idiotype” is meant the portion(s) of an antigen-binding polypeptide that determine the antigen-binding specificity thereof. In embodiments, the idiotype is a cluster of differentiation 7 (CD7) binding idiotype. In various embodiments, an idiotype comprises one or more complementarity determining regions (CDRs) of an antigen-binding polypeptide (e.g., an scFv, a CAR, or an antibody).

[0418] By “immune cell” is meant a cell of the immune system capable of generating an immune response. Exemplary immune cells include, but are not limited to, T cells, NK cells, B cells, macrophages, hematopoietic stem cells, or precursors thereof. In embodiments, an immune cell is allogeneic to a subject to whom the cell is to be administered. In embodiments, an immune cell is from a donor and is allogeneic to a subject to which the immune cell will be administered after being modified according to the methods provided herein. The invention of the disclosure features methods for preparing modified allogeneic immune cells with improved characteristics (e.g., increased persistence in a subject) as well as the cells produced by these methods.

[0419] By “immune effector cell” is meant a lymphocyte, once activated, capable of effecting an immune response upon a target cell. In some embodiments, immune effector cells are effector T cells. In some embodiments, the effector T cell is a naive CD8+T cell, a cytotoxic T cell, a natural killer T (NKT) cell, a natural killer (NK) cell, or a regulatory T (Treg) cell. In some embodiments, immune effector cells are effector NK cells. In some embodiments, the effector T cells are thymocytes, immature T lymphocytes, mature T lymphocytes, resting T lymphocytes, or activated T lymphocytes. In some embodiments the immune effector cell is a CD4+CD8+T cell or a CD4" CD8" T cell. In some embodiments the immune effector cell is a T helper cell. In some embodiments the T helper cell is a T helper 1 (Thl), a T helper 2 (Th2) cell, or a helper T cell expressing CD4 (CD4+ T cell).

[0420] By “immunomodulatory activity” is meant increasing, decreasing, or sustaining an immune response.

[0421] The terms “protein,” “peptide,” “polypeptide,” and their grammatical equivalents are used interchangeably herein, and refer to a polymer of amino acid residues linked together by peptide (amide) bonds. The terms refer to a protein, peptide, or polypeptide of any size, structure, or function. Typically, a protein, peptide, or polypeptide will be at least three amino acids long. A protein, peptide, or polypeptide can refer to an individual protein or a collection of proteins. One or more of the amino acids in a protein, peptide, or polypeptide can be modified, for example, by the addition of a chemical entity such as a carbohydrate group, a hydroxyl group, a phosphate group, a famesyl group, an isofamesyl group, a fatty acid group, a linker for conjugation, functionalization, or other modifications, etc. A protein, peptide, or polypeptide can also be a single molecule or can be a multi-molecular complex. A protein, peptide, or polypeptide can be just a fragment of a naturally occurring protein or peptide. A protein, peptide, or polypeptide can be naturally occurring, recombinant, or synthetic, or any combination thereof.

[0422] The terms "isolated," "purified,” or “biologically pure” refer to material that is free to varying degrees from components which normally accompany it as found in its native state. “Isolate” denotes a degree of separation from original source or surroundings. “Purify” denotes a degree of separation that is higher than isolation. A “purified” or “biologically pure” protein is sufficiently free of other materials such that any impurities do not materially affect the biological properties of the protein or cause other adverse consequences. That is, a nucleic acid or peptide of some aspects and embodiments is purified if it is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high performance liquid chromatography. The term “purified” can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified.

[0423] “Neoplasia” refers to cells or tissues exhibiting abnormal growth or proliferation. In some embodiments, the neoplasia is a hematological cancer. In some embodiments, the hematological cancer is leukemia, myeloma, and / or lymphoma. In some embodiments, the hematological cancer is a B cell cancer. In some embodiments, the B cell cancer is a lymphoma or a leukemia. In some cases, the leukemia comprises a pre-leukemia. In some cases, the leukemia is an acute leukemia. Acute leukemias include, for example, an acute myeloid leukemia (AML). Acute leukemias also include, for example, an acute lymphoid leukemia or an acute lymphocytic leukemia (ALL); ALL includes B-lineage ALL; T-lineage ALL; and T-cell acute lymphocytic leukemia (T-ALL).

[0424] As used herein, the term “operatively linked” in the context of a polynucleotide fragment is intended to mean that the two polynucleotide fragments are joined such that the amino acid sequences encoded by the two polynucleotide fragments remain in-frame. By “programmed cell death 1 (PD1; PDCD1) polypeptide” is meant a protein having at least about 85% amino acid sequence identity to GenBank Accession No. AJS10360.1 (SEQ ID NO: 76), or a fragment thereof having immunomodulatory activity.

[0425] By “programmed cell death 1 (PD1; PDCD1) polynucleotide” is meant a nucleic acid molecule encoding a PD1 polypeptide, as well as the introns, exons, 3' untranslated regions, 5' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. An exemplary PD1 polynucleotide sequence is provided at GenBank Accession No. KJ865861.1 (SEQ ID NO: 77). An exemplary PD1 polynucleotide sequence is also provided at Ensenbl accession no: ENSG00000188389.

[0426] The term "recombinant" as used herein in the context of proteins or nucleic acids refers to proteins or nucleic acids that do not occur in nature but are the product of human engineering. For example, in some embodiments, a recombinant protein or nucleic acid molecule comprises an amino acid or nucleotide sequence that comprises at least one, at least two, at least three, at least four, at least five, at least six, or at least seven mutations as compared to any naturally occurring sequence.

[0427] By “reduces” is meant a negative alteration of at least 5%, 10%, 25%, 50%, 75%, 80%, 90%, 95%, or 100%.

[0428] By “reference” is meant a standard or control condition. In an embodiment, the reference is a T cell that does not express a chimeric antigen receptor (CAR). In some cases, the reference is a T cell that expresses a CAR that does not comprise an antigen-binding domain bound by an anti-idiotypic antibody of interest. A further non-limiting example of a reference is an antibody that does not bind an idiotype of an antibody. In other embodiments and without limitation, a reference is an untreated cell that is not subjected to a test condition, or is subjected to a normal saline, medium, buffer, and / or a control vector that does not harbor a polynucleotide or produce a polypeptide of interest. In some cases, a reference is a cell or population of cells that has not been contacted with an anti-idiotypic antibody of interest.

[0429] A "reference sequence" is a defined sequence used as a basis for sequence comparison. A reference sequence may be a subset of or the entirety of a specified sequence; for example, a segment of a full-length cDNA or gene sequence, or the complete cDNA or gene sequence. For polypeptides, the length of the reference polypeptide sequence will generally be at least about 16 amino acids, at least about 20 amino acids, more at least about 25 amino acids, and even more preferably about 35 amino acids, about 50 amino acids, or about 100 amino acids. For nucleic acids, the length of the reference nucleic acid sequence will generally be at least about 50 nucleotides, at least about 60 nucleotides, at least about 75 nucleotides, and about 100 nucleotides or about 300 nucleotides or any integer thereabout or therebetween. In some embodiments, a reference sequence is a wild-type sequence of a protein of interest. In other embodiments, a reference sequence is a polynucleotide sequence encoding a wild-type protein.

[0430] A “sample” or “biological sample” refers to specimen obtained, taken, generated, or derived from a subject or individual, such as a patient. The specimen may be a body fluid, such as blood, plasma, serum, saliva, sputum, tears, urine; other body fluids, e.g., bronchial fluid, lavage fluid, central nervous system (CNS) fluid; stool; cells; tissues; organs; and the like. In an embodiment, the sample is an blood sample. In embodiments, the sample is collected from a subject administered a chimeric antigen receptor (CAR) T cell of the disclosure (e.g., a 7CAR-T cell). In an embodiment, the cell is a human cell. In embodiments, the cells are primary cells or are cultured cells.

[0431] As used herein, the term “scFv” refers to a single-chain Fv antibody in which the variable domains of the heavy chain and the light chain from an antibody have been joined to form one chain. scFv fragments contain a single polypeptide chain that includes the variable region of an antibody light chain (VL) (e.g., CDR-L1, CDR-L2, and / or CDR-L3) and the variable region of an antibody heavy chain (VH) (e.g., CDR-H1, CDR-H2, and / or CDR-H3) separated by a linker. The linker that joins the VL and VH regions of a scFv fragment can be a peptide linker composed of proteinogenic amino acids. Alternative linkers can be used to so as to increase the resistance of the scFv fragment to proteolytic degradation (e.g., linkers containing D-amino acids), in order to enhance the solubility of the scFv fragment (e.g., hydrophilic linkers such as polyethylene glycol-containing linkers or polypeptides containing repeating glycine and serine residues), to improve the biophysical stability of the molecule (e.g., a linker containing cysteine residues that form intramolecular or intermolecular disulfide bonds), or to attenuate the immunogenicity of the scFv fragment (e.g., linkers containing glycosylation sites). scFv molecules are known in the art and are described, e.g., in U.S. Pat. No. 5,892,019, Flo et al., (Gene 77:51, 1989); Bird et al., (Science 242:423, 1988); Pantoliano et al., (Biochemistry 30: 10117, 1991); Milenic et al., (Cancer Research 51:6363, 1991); and Takkinen et al., (Protein Engineering 4:837, 1991). The VL and VH domains of a scFv molecule can be derived from one or more antibody molecules. It will also be understood by one of ordinary skill in the art that the variable regions of the scFv molecules of some aspects and embodiments herein can be modified such that they vary in amino acid sequence from the antibody molecule from which they were derived. For example, in one embodiment, nucleotide or amino acid substitutions leading to conservative substitutions or changes at amino acid residues can be made (e.g., in CDR and / or framework residues). Alternatively, or in addition, mutations are made to CDR amino acid residues to optimize antigen binding using art recognized techniques. scFv fragments are described, for example, in WO 2011 / 084714; incorporated herein by reference.

[0432] By “specifically binds” is meant a polypeptide or antibody, or antigen-binding fragment or portion thereof, that recognizes and binds to a polypeptide (antigen) of interest (e.g., an anti-CD7 antibody or antigen-binding fragment and / or idiotype thereof), but which does not substantially recognize and bind to other molecules in a sample. In some cases, and without intending to be limiting, an antibody or antigen-binding fragment thereof that specifically binds to an antigen will bind to the antigen with a KD of less than 100 nM. For example, an antibody or antigen-binding fragment thereof that specifically binds to an antigen will bind to the antigen with a KD of up to 100 nM (e.g., between 1 pM and 100 nM). An antibody or antigen-binding fragment thereof that does not exhibit specific binding to a particular antigen or epitope thereof will exhibit a KD of greater than 100 nM (e.g., greater than 500 nm, 1 uM, 100 uM, 500 uM, or 1 mM) for that particular antigen or epitope thereof. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein or carbohydrate. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein or carbohydrate. See, Harlow & Lane, Antibodies, A Laboratory Manual, Cold Spring Harbor Press, New York (1988) and Harlow & Lane, Using Antibodies, A Laboratory Manual, Cold Spring Harbor Press, New York (1999), for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity.

[0433] Nucleic acid molecules (polynucleotides) in some aspects and embodiments herein include any nucleic acid molecule that encodes a polypeptide of some aspects and embodiments herein or a fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence but will typically exhibit substantial identity. Polynucleotides having “substantial identity” to an endogenous sequence are typically capable of hybridizing with at least one strand of a double-stranded nucleic acid molecule. Nucleic acid molecules useful in the methods of some aspects and embodiments herein include any nucleic acid molecule that encodes a polypeptide of some aspects and embodiments herein, or a fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence but will typically exhibit substantial identity. Polynucleotides having “substantial identity” to an endogenous sequence are typically capable of hybridizing with at least one strand of a double-stranded nucleic acid molecule. By “hybridize” is meant pair to form a double-stranded molecule between complementary polynucleotide sequences (e.g., a gene described herein), or portions thereof, under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol . 152:399; Kimmel, A. R. (1987) Methods Enzymol . 152:507).

[0434] By “substantially identical” is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In one embodiment, such a sequence is at least 60%, 80% or 85%, 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison.

[0435] Sequence identity is typically measured using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BUAST, BESTFIT, GAP, or PIEEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. Amino acids generally can be grouped according to the following common side- chain properties:

[0436] (1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, He;

[0437] (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin;

[0438] (3) acidic: Asp, Glu;

[0439] (4) basic: His, Lys, Arg;

[0440] (5) residues that influence chain orientation: Gly, Pro;

[0441] (6) aromatic: Trp, Tyr, Phe.

[0442] In some embodiments, conservative substitutions can involve the exchange of a member of one of these classes for another member of the same class. In some embodiments, non-conservative amino acid substitutions can involve exchanging a member of one of these classes for another class.

[0443] By “subject” or “patient” is meant a mammal, including, but not limited to, a human or non-human mammal. In embodiments, the mammal is a bovine, equine, canine, ovine, rabbit, rodent, nonhuman primate, or feline. In an embodiment, “patient” refers to a mammalian subject with a higher than average likelihood of developing a disease or a disorder. Exemplary patients can be humans, non-human primates, cats, dogs, pigs, cattle, cats, horses, camels, llamas, goats, sheep, rodents (e.g., mice, rabbits, rats, or guinea pigs) and other mammalians that can benefit from the therapies disclosed herein. Exemplary human patients can be male and / or female.

[0444] By “T cell receptor alpha chain (TRAC) polypeptide” is meant a protein having at least about 85% amino acid sequence identity to GenBank Accession No.: AAO72258.1 (SEQ ID NO: 78), or a fragment thereof having immunomodulatory activity.

[0445] By “T cell receptor alpha chain (TRAC) polynucleotide” is meant a polynucleotide encoding a TRAC polypeptide, as well as the introns, exons, 3 ' untranslated regions, 5 ' untranslated regions, and regulatory sequences associated with its expression, or fragments thereof. In embodiments, a TRAC polynucleotide is the genomic sequence, cDNA, mRNA, or gene associated with and / or required for TRAC expression. An exemplary TRAC nucleic acid sequence is provided at GenBank Accession No. AY247834. 1 (SEQ ID NO: 79).

[0446] An exemplary TRAC gene sequence is provided at ENSEMBL Accession No. ENSG00000277734.

[0447] Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

[0448] The term "transfecting" or “transfection” is used synonymously and according to some aspects and embodiments herein means the introduction of heterologous nucleic acid (DNA / RNA) into a eukaryotic cell, in particular yeast cells.

[0449] According to some aspects and embodiments herein, antibody fragments are understood as meaning functional parts of antibodies, such as Fc, Fab, Fab’, Fv, F(ab’)2, scFv. According to some aspects and embodiments herein, corresponding biologically active fragments are to be understood as meaning those parts of antibodies which are capable of binding to an antigen, such as Fab, Fab’, Fv, F(ab’)2, and scFv.

[0450] As used herein the term “variable region complementarity determining region (CDR)” includes amino acids in a CDR or complementarity determining region as identified using sequence or structure based methods. As used herein, the term “CDR” or “complementarity determining region” refers to the noncontiguous antigen-binding sites found within the variable regions of both heavy and light chain polypeptides. These particular regions have been described by Kabat et al., J. Biol. Chem. 252:6609-6616, 1977 and Kabat, et al., Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242, 1991; by Chothia et al., (J. Mol. Biol. 196:901-917, 1987), and by MacCallum et al., (J. Mol. Biol. 262:732-745, 1996) where the definitions include overlapping or subsets of amino acid residues when compared against each other. In certain embodiments, the term “CDR” is a CDR as defined by Kabat based on sequence comparisons. The boundaries of a given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based structural alignments, while the Chothia scheme is based on structural information. Numbering for both the Kabat (Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5thEd. Public Health Service, National Institutes of Health, Bethesda, MD, the disclosure of which is incorporated herein by reference in its entirety for all purposes) and Chothia (Al-Lazikani et al., (1997) JMB 273,927-948, the disclosure of which is incorporated herein by reference in its entirety for all purposes) schemes is based upon the most common antibody region sequence lengths, with insertions accommodated by insertion letters, for example, “30a,” and deletions appearing in some antibodies. The two schemes place certain insertions and deletions (“indels”) at different positions, resulting in differential numbering. The Contact scheme is based on analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme.

[0451] As used herein, the term “vector” refers to a means of introducing a nucleic acid sequence into a cell, resulting in a transformed cell. Vectors include plasmids, transposons, phages, viruses, liposomes, lipid nanoparticles, and episomes. “Expression vectors” are nucleic acid sequences comprising the nucleotide sequence to be expressed in the recipient cell. Expression vectors contain a polynucleotide sequence as well as additional nucleic acid sequences to promote and / or facilitate the expression of the introduced sequence, such as start, stop, enhancer, promoter, and secretion sequences, into the genome of a mammalian cell.

[0452] As used herein, the term “VH” refers to the variable region of an immunoglobulin heavy chain of an antibody, including the heavy chain of an Fv, scFv, or Fab. References to “VL” refer to the variable region of an immunoglobulin light chain, including the light chain of an Fv, scFv, dsFv or Fab. Antibodies (Abs) and immunoglobulins (Igs) are glycoproteins having the same structural characteristics. While antibodies exhibit binding specificity to a specific target, immunoglobulins include both antibodies and other antibody-like molecules which lack target specificity. Native antibodies and immunoglobulins are usually heterotetrameric glycoproteins of about 150,000 Daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each heavy chain of a native antibody has at the amino terminus a variable domain (VH) followed by a number of constant domains at the carboxy terminus. Each light chain of a native antibody has a variable domain at the amino terminus (VL) and a constant domain at the carboxy terminus.

[0453] Unless specifically stated or obvious from context, as used herein, the term “or” is understood to be inclusive. Unless specifically stated or obvious from context, as used herein, the terms “a”, “an”, and “the” are understood to be singular or plural.

[0454] The term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, z.e., the limitations of the measurement system.

[0455] Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

[0456] Reference in the specification to “some embodiments,” “an embodiment,” “one embodiment” or “other embodiments” means that a particular feature, structure, or characteristic described in connection with the embodiments is included in at least some embodiments, but not necessarily all embodiments, of the present disclosures.

[0457] The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable or aspect herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof.

[0458] Any compositions or methods provided herein can be combined with one or more of any of the other compositions and methods provided herein.

[0459] BRIEF DESCRIPTION OF THE DRAWINGS

[0460] FIGs. 1A to 1AZ provide flow cytometry histograms showing specific binding of the indicated antibodies to anti-cluster of differentiation 7 (CD7) chimeric antigen receptor- expressing (7CAR) T cells (7CAR-T cells). In FIGs. 1A to 1AZ, the following terminology is used to identify each antibody evaluated: VH / VL (e.g., 1H2 / 1K2), where “VH” (e.g., 1H2) identifies the heavy chain variable region of the antibody and “VL” identifies the light chain variable region of the antibody (e.g., 1K2) (see Tables 1A-5 for antibody amino acid sequences). In each of FIGs. 1A to 1AY, the leftmost plots represent measurements of immunostaining of 7CAR-T cells (i.e., “Transduced CAR-T cells) and the rightmost plots represent measurements of immunostaining of the T cells used to prepare the 7CAR-T cells but that do not express any chimeric antigen receptor (CAR) (i.e., “Untransduced T-cells”), the negative control in each plot represents cells stained only with a secondary antibody. In FIG. 1AY, cells were stained using a CD7 polypeptide linked to the fluorescent compound phycoerythrin (PE). FIG. 1AZ presents measurements taken for a negative control corresponding to supernatants that were collected from HEK293 cells that did not contain antibody expressing plasmids (i.e., mock transfected cells). In FIGs. 1A to 1AZ, the term “BL2-H” represents the channel used for gathering flow cytometry fluorescence measurements, and a higher “BL2-H” value represents higher staining with the indicated antibody. The X-axis in each of FIGs. 1A to 1AZ represents the number of events counted for each “BL2-H” fluorescence measurement.

[0461] FIGs. 2A-2C provide a schematic diagram and two plots demonstrating the generation of highly specific rabbit recombinant anti-idiotypic antibodies against anti-CD7 scFv polypeptides (i.e., a purified His-tagged ectodomain of an anti-CD7 chimeric antigen receptor (CAR) polypeptide). FIG. 2A provides a schematic diagram summarizing an experimental protocol for the production of recombinant anti-idiotypic antibodies capable of binding an anti-CD7 scFv antigen. In FIG. 2A, “PBMC” indicates “peripheral blood mononuclear cells.” FIG. 2B provides a plot showing rabbit serum enzyme-linked immunosorbent assay (ELISA) data showing that rabbits immunized using an anti-CD7 scFv polypeptide generated antibodies capable of binding an anti-CD7 chimeric antigen receptor antigen. Pre- and post-immunized serum samples (“Pre-immune” and “Immune Sera,” respectively) were analyzed. FIG. 2C provides a plot showing ELISA data demonstrating that recombinant monoclonal antibodies identified using the method shown in FIG. 2A were capable of binding an anti-CD7 CAR polypeptide antigen.

[0462] FIGs. 3A-3G provide plots and charts showing flow cytometry data demonstrating that rabbits immunized using a His-tagged anti-CD7 scFv polypeptide generated anti- idiotypic antibodies capable of binding T cells expressing an anti-CD7 chimeric antigen receptor (anti-CD7 CAR-T cells). Anti-CD7 CAR-T cells were immunostained using serum from rabbits immunized using the anti-CD7 scFv polypeptide (“Serum” or “Immune Sera”) and from the rabbits prior to immunization (“Preimmune” or “Pre-immune”). In each of FIGs. 3A-3D, “BL2-H” represents the BL2-H channel on a flow cytometer used to measure PE fluorescence. FIG. 3A provides a plot summarizing flow cytometry measurements for anti-CD7 CAR expressing T cells stained shortly after thawing using serum from two post- and pre-immunized rabbits (rabbit identities were Rb #38450 and Rb #38451). FIG. 3B provides a plot summarizing flow cytometry measurements for anti-CD7 CAR expressing T cells stained following an overnight incubation at 37 °C using serum from two post- and pre- immunized rabbits (rabbit identities were Rb #38450 and Rb #38451). FIG. 3C provides a plot summarizing flow cytometry measurements for T cells not expressing any CAR that were stained shortly after thawing using serum from two post- and pre-immunized rabbits (rabbit identities were Rb #38450 and Rb #38451). FIG. 3D provides a plot summarizing flow cytometry measurements for T cells not expressing any CAR that were stained following an overnight incubation at 37 °C using serum from two post- and pre-immunized rabbits (rabbit identities were Rb #38450 and Rb #38451). FIG. 3E provides charts presenting data corresponding to FIG. 3A (top chart of FIG. 3E) and FIG. 3B (bottom chart of FIG. 3E). FIG. 3F provides a chart presenting data corresponding to FIG. 3C (top chart of FIG. 3F) and FIG. 3D (bottom chart of FIG. 3F). FIG. 3G provides charts showing the ratio of staining of transduced cells to untransduced cells for cells stained shortly after thawing (top chart of FIG. 3G) and after an overnight incubation at 37 °C (bottom chart of FIG. 3G). In FIGs. 3A-3G, “Transduced cells” or “scFv Transduced cells” indicates T cells expressing an anti-CD7 CAR, and “Un-transduced cells” or “scFv Untransduced Cells” indicates T cells that do not express the anti-CD7 CAR. In each of FIGs. 3E-3G, row “F” corresponds to unstained cells and row “E” corresponds to the positive control.

[0463] FIGs. 4A-4C provide schematic diagrams showing assay orientation schematics for an offrate assay (FIG. 4A), a sandwich assay (FIG. 4B), and a reverse sandwich assay (FIG. 4C). “ProA” indicates a ProA biosensor (Sartorius, cat#18-5010) and SAX indicates a streptavidin biosensor (Sartorius, cat#18-5117).

[0464] FIG. 5 provides a plot showing full sensograms of a reverse sandwich assay (a competition assay) showing that anti-idiotypic antibodies of the disclosure (“rabbit Abs”) were unable to bind an anti-CD7 scFv polypeptide when the scFv polypeptide was bound by CD7. The plot of FIG. 5 shows an overlay of data gathered from 32 different anti-idiotypic antibodies including 30H3 / 30K2 and 48H1 / 48K2. In FIG. 5, the buffer control (i.e., sample with no administration of an anti-idiotypic antibody) is indicated by an arrow. In FIG. 5, “ProA” indicates a ProA biosensor (Sartorius, cat#18-5010) and SAX indicates a streptavidin biosensor (Sartorius, cat#18-5117). FIGs. 6A-6F provide plots showing kinetics for dissociation of an anti-CD7 scFv polypeptide (“CD7 CAR” in FIGs. 6A-6F) from the anti-idiotypic antibodies 01H2 / 1K2 (FIG. 6A), 11H3 / 11K2 (FIG. 6B), 15H3 / 15K3 (FIG. 6C), 29H3 / 29K1 (FIG. 6D), 30H3 / 30K3 (FIG. 6E), and 43H1 / 43K2 (FIG. 6F) as measured using bio-layer interferometry- (BLI) based offrate assay (see FIG. 4A). The offrate binding assay was carried out using an Octed® Red96 platform.

[0465] FIG. 7 provides a phylogenetic tree comparing the sequences of anti-idiotypic antibodies of the disclosure.

[0466] FIG. 8 provides a series of flow cytometry histograms showing that anti-idiotypic antibodies of the disclosure were capable of binding anti-CD7 CAR expressing CCRF 2.2 cells. As a negative control, cells were stained using only a PE-labeled donkey anti-rabbit antibody. As a positive control, cells were stained using serum from an immunized rabbit as a primary antibody. The cells were stained using goat anti-rabbit antibodies as a secondary antibody.

[0467] FIG. 9 provides an overlay of flow cytometry histograms showing a flow cytometry profde for the anti-idiotypic antibody 15H3-15K3.

[0468] FIG. 10 provides a schematic diagram containing a series of flow cytometry scatter plots demonstrating the ability of a flow cytometry assay to characterize in a single step cells in a sample containing anti-CD7 CAR-T cells and peripheral blood mononuclear cells (PBMCs). In FIG. 10, the “dump channel” is a channel used to dispose of non-T cells.

[0469] FIG. 11 provides a plot showing a linear correlation between the number of anti-CD7 CAR-T cells spiked into a population of peripheral blood mononuclear cells (PBMCs) (“spiked cell count”) and the number of cells counted (“retrieved cell count”) using a pharmacodynamic flow cytometry-based assay of the disclosure.

[0470] FIG. 12 provides a schematic diagram showing a representative embodiment of a meso scale discovery- (MSD) based anti-drug antibody (ADA) assay of the disclosure.

[0471] FIG. 13 provides a schematic diagram showing a representative embodiment of an immunohistochemistry (IHC) based assay for the detection of CAR-T cells in tissue biopsies.

[0472] FIGs. 14A to 14F provide flow cytometry histograms showing results from flow- cytometry screening of humanized antibodies. Six primary humanized antibodies were screened: 02H3 / 2K1, 05H1 / 5K3, 15H3 / 15K3, 20H1 / 20K3, 39H2 / 39K2, and 45H2 / 45K2. Binding of humanized antibodies to anti-CD7 CAR-T cells (FIGs. 14A to 14C) was compared to that of their respective parental rabbit antibodies (FIGs. 14D to 14F). FIGs. 15A and 15B provide a flow cytometry histogram and a plot presenting data relating to the optimization of concentrations of the humanized antibody 15H3 / 15K3 for flow cytometry. Different concentrations of humanized 15H3 / 15K3 antibody were tested to find the optimal staining concentration for one million anti-CD7 CAR-expressing cells. 15H3 / 15K3 antibody stained one million cells optimally at 2.5 mg / ml concentration.

[0473] FIGs. 16A to 16D present flow cytometry histograms and plots demonstrating that humanized antibody 15H3 / 15K3 bound to anti-CD7 CAR-expressing cells in human serum matrix. The humanized antibody 15H3 / 15K3 bound anti-CD7 CAR-expressing cells optimally at 2.5 mg / ml at 1:20 diluted human serum matrix. Binding was evaluated at human serum dilutions of 1: 10 (FIGs. 16A and 16B) and 1:20 (FIGs. 16C and 16D).

[0474] FIGs. 17A and 17B provide a flow cytometry histogram and a plot showing that binding of humanized 15H3 / 15K3 antibody to anti-CD7 CAR-expressing CAR cells in human serum matrix was inhibited by the parental rabbit 15H3 / 15K3 antibody in a dose- dependent manner.

[0475] FIGs. 18A to 18C provide flow cytometry histograms and plots presenting data showing the minimal required dilution (MRD) of biological matrix (serum) necessary for the detection of anti-drug antibodies in the biological matrix with least interference using surrogate positive control (SPC) antibody (15H3 / 15K3). To determine MRD, pooled healthy human serum samples were diluted to 1:8 (FIG. 18A), 1: 10 (FIG. 18B), and 1: 12 (FIG. 18C) to achieve different serum backgrounds and spiked with different concentrations of SPC antibody. Among the pooled human serum dilutions tested, a dilution of 1 : 10 was found to be the optimal MRD.

[0476] FIG. 19 provides a plot showing linearity and sensitivity of an assay for detecting anti-CD7 CAR polypeptides using the SPC antibody (15H3 / 15K3). The linearity of the assay was reproducibly observed within a range of 11.71 to 375 ng / mL SPC.

[0477] DETAILED DESCRIPTION

[0478] Featured and described herein are binding polypeptides, such as anti-idiotypic antibodies, or antigen-binding fragments thereof, that specifically bind to an anti-cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof, compositions or articles of manufacture comprising the same, and methods of using such binding polypeptides and antibodies, such as for specifically binding to and identifying, selecting for, depleting, and / or stimulating cells that express on their surface an anti-CD7 antigen-binding domain (e.g., an anti-CD7 chimeric antigen receptor (CAR)-T cell). In an embodiment, the binding polypeptide is an antibody or an antigen-binding fragment thereof. In an embodiment, the binding polypeptide is a monoclonal antibody or an antigen-binding fragment thereof.

[0479] The invention of the disclosure is based, at least in part, on the discovery of anti- idiotypic antibodies capable of binding an anti-CD7 antibody or antigen-binding fragment thereof. The anti-idiotypic antibodies of the disclosure can be used in any of the methods provided herein, such as methods to detect (e.g., a pharmacokinetic assay, and / or an assay as depicted in FIG. 10) or select for or sort anti-CD7 CAR (7CAR) T cells in a sample, methods to inactivate or deplete 7CAR T cells in a subject (e.g., when 7CAR T cells previously administered to a subject are associated with harm to the subject), methods for stimulating 7CAR T cells, immunohistochemistry methods (e.g., FIG. 13), immunophenotypic assays), and meso scale discovery-based anti-drug antibody assays (e.g., FIG. 12) for characterization of a subject’s immune response to 7CAR T cells.

[0480] In some embodiments, the provided anti-idiotypic antibodies can be used for specific identification and / or selection of various anti-CD7 chimeric antigen receptors (CARs), such as CARs bound to or expressed on a cell surface, and can also be used to specifically activate cells expressing target CARs, such as CAR-T cells. In some embodiments, provided herein are antibodies that are specific to an anti-CD7 antibody, or an antibody fragment derived therefrom, including antibodies and CARs containing variable regions derived from such antibodies, and / or an antibody containing an idiotype contained therein.

[0481] In some aspects, the provided anti-idiotypic antibodies offer advantages compared to conventional reagents for detecting, identifying, manipulating and / or affecting and / or engineering cells that express a CAR, and in particular a CAR containing an anti-CD7 antibody scFv extracellular domain or one containing the recognized idiotype. In certain available methods, detection of the presence or absence or amount of CAR or CAR- expressing cells (and / or stimulation or manipulation of the CAR), in a sample (e.g., biological sample, such as a blood sample), is carried out by assessing the presence or absence or amount of the CAR using the anti-idiotypic antibody described herein.

[0482] The anti-idiotypic antibodies described herein provide advantages over available methods where, for example, detection is carried out using a generic antibody reagent and / or a reagent that is not specific for the particular CAR assessed, e.g., as compared to other CARs that may have similar or identical domains other than the antigen-binding region; for example, such antibodies may include anti- species antibodies recognizing spacer or other domains from the species from which a CAR domain was derived, and / or antibodies recognizing particular components used in spacer regions of the target and also other chimeric receptors; or in methods designed to detect the presence or absence of CARs, where detection is carried out using an agent recognizing a CAR constant region; or where CAR cells are stimulated through the use of general reagents, such as anti-CD3 / CD28 recognizing agents. Certain methods use a recombinant ligand of the CAR (e.g., CD7-Fc). Such methods in certain contexts may not be entirely satisfactory and / or have certain limitations. In some cases, CAR ligands, such as CD7, may not always be entirely effective, e.g., for use in complex flow cytometry panels. The anti-idiotypic antibodies address these limitations because they provide for improved sensitivity and / or selectivity.

[0483] The provided anti-idiotypic antibodies and antigen-binding fragments overcome challenges of low binding affinity associated with target antibody ligands and non-specific binding associated with antibody reagents directed to target antibody constant regions, providing a reagent with both high affinity and specificity for its target antibody or antigen- binding fragment thereof.

[0484] Furthermore, anti-idiotypic antibodies and antigen-binding fragments may be selected as agonists or antagonists of chimeric receptors comprising their target antibodies or antigen- binding fragments, allowing for selective detection, isolation, ablation and / or depletion (for example, killing via antibody-dependent cell-mediated cytotoxicity, ADCC), and / or stimulation or activation of cells with such chimeric receptors bound to or expressed on their surface. Provided herein are anti -idiotypic antibody agonists that exhibit activity to stimulate, such as activate, a CAR containing an extracellular binding domain derived from anti-CD7 antibody. In some aspects, such antibodies can be used in methods of stimulating and expanding specific CAR-expressing cells, including in processes for generating and preparing the CAR-expressing cells.

[0485] Anti-Idiotypic Antibodies that Bind an Anti-CD7 Antibody

[0486] The disclosure provides binding polypeptides, such as anti-idiotypic antibodies or antigen-binding fragments thereof, that specifically recognize a target anti-CD7 antibody, or an antigen-binding fragment thereof.

[0487] Complementarity determining region 1-3 (CDR1-3) sequences, Framework region 1-4 (FR1-4) sequences, Heavy chain variable region (VH), and Light chain variable region (VL) amino acid sequences of representative anti -idiotypic antibody capable of binding an anti- CD7 antibody (generated from hybridoma clones) are provided in the following Tables 1A-5: Table 1A. Variable heavy chain (VH) complementarity determining regions (CDRs 1-3) for anti-idiotypic antibodies. The CDRs provided in the table were determined using the Kabat definition of CDRs. Table IB. Variable heavy chain (VH) 9 amino acid complementarity determining region 1 (CDR1) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR. Table 1C. Variable heavy chain (VH) 8 amino acid complementarity determining region

[0488] 1 (CDR1) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0489] Table ID. Variable heavy chain (VH) 9 amino acid complementarity determining region 2 (CDR2) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0490] Table IE. Variable heavy chain (VH) 8 amino acid complementarity determining region

[0491] 2 (CDR2) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0492] Table IF. Variable heavy chain (VH) 7 amino acid complementarity determining region 2 (CDR2) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0493] Table 1G. Variable heavy chain (VH) 20 amino acid complementarity determining region 3 (CDR3) consensus sequence (SEQ ID NO: 196) for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR. Table 1H. Variable heavy chain (VH) 17 amino acid complementarity determining region 3 (CDR3) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0494] Table II. Variable heavy chain (VH) 16 amino acid complementarity determining region 3 (CDR3) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR. Table 1J. Variable heavy chain (VH) 13 amino acid complementarity determining region 3 (CDR3) consensus sequence (SEQ ID NO: 199) for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0495] Table IK. Variable heavy chain (VH) 12 amino acid complementarity determining region 3 (CDR3) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0496] Table 2A. Variable light chain (VL) complementarity determining regions (CDRs 1-3) for anti-idiotypic antibodies.

[0497] Table 2B. Variable light chain (VL) 6 amino acid complementarity determining region 1 (CDR1) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0498] Table 2C. Variable light chain (VL) 3 amino acid complementarity determining region 2 (CDR2) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR. Table 2D. Variable light chain (VL) 14 amino acid complementarity determining region 3 (CDR3) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR. Table 2E. Variable light chain (VL) 13 amino acid complementarity determining region 3 (CDR3) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR. Table 2F. Variable light chain (VL) 12 amino acid complementarity determining region

[0499] 3 (CDR3) consensus sequence for anti-idiotypic antibodies. The top row indicates the amino acid position within the CDR.

[0500] Table 3. Variable heavy chain (VH) framework regions for anti-idiotypic antibodies.

[0501] Table 4. Variable light chain (VL) framework regions for anti-idiotypic antibodies.

[0502] 1In some embodiments, the FR4 region lacks the “GDP” shown in parenthesis.

[0503] Table 5. Variable heavy chain (VH) and variable light chain (VL) amino acid sequences for anti-idiotypic antibodies.

[0504] In various embodiments, the VH CDR1 contains the following amino acid sequence:

[0505] GX2X3X4X5X6X7X8X9, wherein

[0506] X2 is F, I, or S, X3is D, I, S, or T,

[0507] X4 is F, I, or L,

[0508] Xs is I or S,

[0509] Xe is G, N, null, P, S, or T,

[0510] X7is A, D, G, S, V, orY, X8is H, N, or Y, and

[0511] X9is A, C, D, F, G, R, S, W, or Y.

[0512] In various embodiments, the VH CDR2 contains the following amino acid sequence:

[0513] X10X11X12X13X14X15X16X17X18, where

[0514] Xio is A, G, I, null, R, T, or V, Xi 1 is A, D, F, G, H, N, null, S, V, W, or Y,

[0515] X12 is A, C, D, G, I, N, null, P, T, or V,

[0516] X13 is A, D, G, I, L, null, R, S, T, or V,

[0517] X14 is D, G, I, N, null, R, S, T, or V, Xis is D, H, N, S, T, or V,

[0518] Xi6 is D, G, null, S, or V,

[0519] X17 is D, I, K, N, null, P, R, S, T, V, or Y, and

[0520] Xis is A, I, N, null, or T.

[0521] In various embodiments, the VH CDR3 contains the following amino acid sequence:

[0522] X19X20X21X22X23X24X25X26X27X28X29X30X31X32X33X34X35X36X37X38X39X40X

[0523] 41X42, where

[0524] X19 is A or V,

[0525] X20 is K, R, or S,

[0526] X21 is A, D, E, G, I, R, S, or V,

[0527] X22 is D, E, G, L, P, or T,

[0528] X23 is A, D, G, I, N, null, S, T, V, or Y,

[0529] X24 is A, D, F, G, H, L, null, S, V, W, or Y,

[0530] X25 is D, G, N, null, S, T, or V,

[0531] X26 is A, D, E, F, G, null, S, V, or Y,

[0532] X27 is A, D, E, G, N, null, S, T, V, W, or Y,

[0533] X28 is A, D, G, null, V, W, or Y,

[0534] X29 is D, null, or Y,

[0535] X30 is A, D, E, F, G, L, M, null, S, T, V, W, or Y,

[0536] X31 is A, D, G, L, N, null, P, or T,

[0537] X32 is A, D, G, L, N, null, or V,

[0538] X33 is A, F, null, R, or Y,

[0539] X34 is F or null,

[0540] X35 is A, G, L, or null,

[0541] X36 is G, Y, or null,

[0542] X37 is G, I, N, null, T, or Y,

[0543] X38 is A, D, null, T, or Y,

[0544] X39 is A, G, null, P, or T,

[0545] X40 is F, I, L, M, V, W, or Y,

[0546] X41 is A, D, orN, and

[0547] X42is F, I, L, or P.

[0548] In various embodiments, the VL CDR1 contains the following amino acid sequence:

[0549] X43X44X45X46X47X48X49X50, where

[0550] X43 is E or Q, X44 is D, H, N, R, or S, X45 is I or V,

[0551] X46is A, D, G, N, S, or Y, X47 is G, N, R, S, T, or V, X48 is A, D, G, H, K, L, N, R, S, W, or Y, X49 is N or null, and X50 is C, F, or null.

[0552] In various embodiments, the VL CDR2 contains the following amino acid sequence: X51X52S, where

[0553] X51 is A, D, G, K, Q, S, T, W, or Y, and X52 is A, S, or T.

[0554] In various embodiments, the VL CDR3 contains the following amino acid sequence: X54X55X56X57X58X59X60X61X62X63X64X65X66X67X68X69X70X71, where X54 is A, L, or Q, X55 is C, G, Q, S, or Y, X56is A, D, E, F, G, P, T, V, orY, X57 is A, C, D, F, G, R, S, T, V, W, orY, X58 is A, D, G, H, L, N, S, T, V, or Y, X59 is G or null, Xeo is G or null, X6iis A, C, D, G, I, S, or Y, X62 is D, G, I, L, N, R, S, T, orY, X63is F, G, I, N, R, S, or V, X64is A, D, F, G, I, P, S, T, V, or Y, X65is A, D, E, G, H, I, N, R, S, or V, X66 is A, C, F, G, H, I, N, null, P, R, S, T, V, W, or Y, X67 is A, F, G, I, N, null, R, S, T, V, W, or Y, X68is A, F, N, null, P, V, or Y, X69 is A, F, null, or V, X70 is F or null, and X71 is A or null.

[0555] In various embodiments a VH polypeptide of the disclosure is fused to a human IgGl framework polypeptide containing an amino acid sequence with at least 85% identity to the following sequence: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK (SEQ ID NO: 355). Representative amino acid and nucleotide sequences for VH polypeptides fused to an IgGl framework polypeptide are provided in Tables 16A and 16C.

[0556] In various embodiments a VL polypeptides of the disclosure is fused to a human IgGl framework polypeptide containing an amino acid sequence with at least 85% identity to the following sequence: RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 356). Representative amino acid and nucleotide sequences for VL polypeptides fused to an IgGl framework polypeptide are provided in Tables 16B and 16D.

[0557] Variants

[0558] In certain embodiments, the anti-idiotypic antibodies of the disclosure include one or more amino acid variations, e.g., substitutions, deletions, insertions, and / or mutations, compared to the sequence of an anti-idiotypic antibody described herein. Exemplary variants include those designed to improve the binding affinity and / or other biological properties of the anti-idiotypic antibody. Amino acid sequence variants of an anti-idiotypic antibody may be prepared by introducing appropriate modifications into the nucleotide sequence encoding the anti-idiotypic antibody, or by peptide synthesis. Such modifications include, for example, deletions from, and / or insertions into and / or substitutions of residues within the amino acid sequences of the anti-idiotypic antibody. Any combination of deletion, insertion, and substitution can be made to arrive at the final construct, provided that the final construct possesses the desired characteristics, e.g., antigen -binding.

[0559] In certain embodiments, the anti-idiotypic antibodies include one or more amino acid substitutions, e.g., as compared to an anti-idiotypic antibody sequence described herein. Sites of interest for substitutional mutagenesis include the CDRs and FRs. Amino acid substitutions may be introduced into an anti-idiotypic antibody of interest and the products screened for a desired activity, e.g., retained / improved antigen binding, decreased immunogenicity, improved half-life, and / or improved effector function, such as the ability to promote antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). In some embodiments, the variant anti -idiotypic antibody exhibits retained or improved binding to a target anti-CD7 antibody or fragment thereof. For example, in some embodiments, the variant anti-idiotypic antibody exhibits an increase in binding affinity to the target anti-CD7 antibody of at least about 10% (such as at least about any of 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 1000% or more) as compared to the unmodified anti-idiotypic antibody. In some embodiments, an anti-idiotypic antibody has at least about 85, 90, 95, 96, 97, 98, 99, or 100% amino acid identity to a CDR, VH, or VL domain described herein.

[0560] In some embodiments, one or more residues within a CDR of a parent antibody (e.g., a humanized or human antibody) is / are substituted. In some embodiments, the substitution is made to revert a sequence or position in the sequence to a germline sequence, such as an antibody sequence found in the germline (e.g., human germline), for example, to reduce the likelihood of immunogenicity, e.g., upon administration to a human individual.

[0561] In some embodiments, alterations are made in CDR “hotspots,” residues encoded by codons that undergo mutation at high frequency during the somatic maturation process (see, e.g., Chowdhury, Methods Mol. Biol. 207: 179-196 (2008)), and / or residues that contact antigen, with the resulting variant VH or VL being tested for binding affinity. Affinity maturation by constructing and reselecting from secondary libraries has been described, e.g., in Hoogenboom et al. in Methods in Molecular Biology 178: 1-37 (O’Brien et al., ed., Human Press, Totowa, NJ, (2001)). In some embodiments of affinity maturation, diversity is introduced into the variable genes chosen for maturation by any of a variety of methods (e.g., error-prone PCR, chain shuffling, or oligonucleotide-directed mutagenesis). A secondary library is then created. The library is then screened to identify any antibody variants with the desired affinity. Another method to introduce diversity involves CDR-directed approaches, in which several CDR residues (e.g., 4-6 residues at a time) are randomized. CDR residues involved in antigen binding may be specifically identified, e.g., using alanine scanning mutagenesis or modeling. CDR-H3 and CDR-L3 in particular are often targeted.

[0562] In certain embodiments, substitutions, insertions, or deletions may occur within one or more CDRs so long as such alterations do not substantially reduce the ability of the antibody to bind antigen. For example, conservative alterations (e.g., conservative substitutions as provided herein) that do not substantially reduce binding affinity may be made in CDRs. Such alterations may, for example, be outside of antigen contacting residues in the CDRs. In certain embodiments of the variant VH and VL sequences provided above, each CDR either is unaltered, or contains no more than one, two or three amino acid substitutions.

[0563] Amino acid sequence insertions include amino- and / or carboxyl-terminal fusions ranging in length from one residue to polypeptides containing a hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Examples of terminal insertions include an antibody with an N-terminal methionyl residue. Other insertional variants of the antibody molecule include the fusion to the N- or C-terminus of the antibody to an enzyme or a polypeptide which increases the serum half-life of the antibody.

[0564] Modifications

[0565] In certain embodiments, an anti-idiotypic antibody of the disclosure is altered to increase or decrease the extent to which the antibody is glycosylated, for example, by removing or inserting one or more glycosylation sites by altering the amino acid sequence and / or by modifying the oligosaccharide(s) attached to the glycosylation sites, e.g., using certain cell lines.

[0566] Exemplary modifications, variants, and cell lines are described, e.g., in Patent Application Publications No. US 2003 / 0157108, US 2004 / 0093621, US 2003 / 0157108; WO 2000 / 61739; WO 2001 / 29246; US 2003 / 0115614; US 2002 / 0164328; US 2004 / 0093621; US 2004 / 0132140; US 2004 / 0110704; US 2004 / 0110282; US 2004 / 0109865; WO 2003 / 085119; WO 2003 / 084570; WO 2005 / 035586; WO 2005 / 035778; W02005 / 053742;

[0567] W02002 / 031140; Okazaki et al. J. Mol. Biol. 336: 1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004). Ripka et al. Arch. Biochem. Biophys. 249: 533-545 (1986); US Pat Appl No US 2003 / 0157108 Al, Presta, L; and WO 2004 / 056312 Al, Yamane-Ohnuki et al. Biotech. Bioeng. 87: 614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4): 680-688 (2006); and W02003 / 085107); WO 2003 / 011878 (Jean-Mairet et al.); U.S. Patent No. 6,602,684 (Umana et al.); and US 2005 / 0123546 (Umana et al.); WO 1997 / 30087 (Patel et al.); WO 1998 / 58964 (Raju, S.); and WO 1999 / 22764 (Raju, S.).

[0568] Among the modified antibodies contemplated herein are those having one or more amino acid modifications in the Fc region, such as those having a human Fc region sequence or other portion of a constant region (e.g., a human IgGl, IgG2, IgG3 or IgG4 Fc region) comprising an amino acid modification (e.g., a substitution) at one or more amino acid positions. Such modifications can be made, e.g., to improve half-life, alter binding to one or more types of Fc receptors, and / or alter effector functions.

[0569] In certain embodiments, an anti-idiotypic antibody contains all or a portion of a modified Fc region having an altered (e.g., decreased) binding to an Fc receptor relative to that of an unmodified Fc region. Non-limiting examples of Fc modifications that alter binding to the Fc receptors are described, for example, in U.S. Pat. Nos. 7,217,797 and 7,732,570; and U.S. Application Nos. US 2010 / 0143254 and 2010 / 0143254, the disclosures of each of which are incorporated herein by reference in their entireties for all purposes.

[0570] Also among the variants are cysteine engineered antibodies such as “thioMAbs” and other cysteine engineered variants, in which one or more residues of an antibody are substituted with cysteine residues, in order to generate reactive thiol groups at accessible sites, e.g., for use in conjugation of agents and linker- agents, to produce immunoconjugates. Cysteine engineered antibodies are described, e.g., in U.S. Patent Nos. 7,855,275 and 7,521,541.

[0571] In some embodiments, the antibodies are modified to contain additional nonproteinaceous moieties, including water soluble polymers. Exemplary polymers include, but are not limited to, polyethylene glycol (PEG), copolymers of ethylene glycol / propylene glycol, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1, 3- dioxolane, poly-l,3,6-trioxane, ethylene / maleic anhydride copolymer, polyaminoacids (either homopolymers or random copolymers), and dextran or poly(n-vinyl pyrrolidone)polyethylene glycol, propropylene glycol homopolymers, prolypropylene oxide / ethylene oxide co- polymers, polyoxyethylated polyols (e.g., glycerol), polyvinyl alcohol, and mixtures thereof. Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water. The polymer may be of any molecular weight and may be branched or unbranched. The number of polymers attached to the antibody may vary, and if more than one polymer is attached, they can be the same or different molecules. In general, the number and / or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of the antibody to be improved, whether the antibody derivative will be used in a therapy under defined conditions, etc. Chimeric Antigen Receptors (CARs) and CAR-T Cells

[0572] The invention provides anti-idiotypic antibodies specifically binding the antigen- binding domain of a target chimeric antigen receptor (CAR) that targets a CD7 antigen. Such anti-idiotypic antibodies are useful, for example, to characterize the persistence of infused CAR-T cells in a subject and / or to retrieve CAR-T cells from the subject.

[0573] Modification of immune cells to express a chimeric antigen receptor can enhance an immune cell’s immunoreactive activity, wherein the chimeric antigen receptor has an affinity for an epitope on an antigen, wherein the antigen is associated with an altered fitness of an organism. For example, the chimeric antigen receptor can have an affinity for an epitope (e.g., a CD7 epitope) on a protein expressed in a neoplastic cell. Because the CAR-T cells can act independently of major histocompatibility complex (MHC), activated CAR-T cells can kill the neoplastic cell expressing the antigen. The direct action of the CAR-T cell evades neoplastic cell defensive mechanisms that have evolved in response to MHC presentation of antigens to immune cells. Exemplary chimeric antigen receptors, modified immune cells, and methods for preparing the same are described in PCT Applications No. PCT / US2020 / 013964, PCT / US2020 / 052822, PCT / US2020 / 018178, PCT / US2021 / 52035, and PCT / US2022 / 075021, or in Hardke-Wolenski, et al., Biomedicines 10: 1493 (2022), the disclosures of which are incorporated herein by reference in their entirety for all purposes.

[0574] In some embodiments, a CAR-T cell of the disclosure is prepared by transducing a T cell with a lentiviral vector (LVV) encoding a chimeric antigen receptor (e.g., an anti-CD7 CAR) polypeptide.

[0575] In embodiments, the CAR-T cells have been engineered to knock out expression of one or more polypeptides. For example, in some embodiments, the CAR-T cells have been engineered to knock out expression of one or more polypeptides selected from TRAC, CD7, CD52, CD3 (e.g., CD3-epsilon or CD3-gamma), and PDCD1. In some cases, the CAR-T cells have been engineered to knock out expression of TRAC, CD7, CD52, and PDCD1. In some cases, the CAR-T cells have been engineered to knock out expression of TRAC, CD7, CD52, PDCD1, and CD3. It can be advantageous to knock out expression of CD7 in an anti- CD7 CAR-T cell to prevent fratricidal anti-CD7 CAR-T cell activity. It can be advantageous to knock out expression of TRAC in a CAR-T cell to prevent induction of graft-versus-host disease (GVHD) in a subject administered the CAR-T cells. It can be advantageous to knock out expression of CD52 in a CAR-T cell to reduce host rejection of allogeneic CAR-T cells in a subject (e.g., in the context of alemtuzumab-mediated patient lymphodepletion). It can also be advantageous to knock out expression of PDCD1 in a CAR-T cell to reduce PD-L1- mediated immunosuppression of the CAR-T cells in a subject. A variety of methods familiar to the skilled practitioner are available in the art for knocking out expression of a polypeptide in a cell.

[0576] Some embodiments comprise autologous immune cell immunotherapy, wherein immune cells are obtained from a subject having a disease or altered fitness characterized by cancerous or otherwise altered cells expressing a surface marker. The obtained immune cells are genetically modified to express a chimeric antigen receptor and are effectively redirected against specific antigens. Thus, in some embodiments, immune cells are obtained from a subject in need of CAR-T immunotherapy. In some embodiments, these autologous immune cells are cultured and modified shortly after they are obtained from the subject. In other embodiments, the autologous cells are obtained and then stored for future use. This practice may be advisable for individuals who may be undergoing parallel treatment that will diminish immune cell counts in the future. In allogeneic immune cell immunotherapy, immune cells can be obtained from a donor other than the subject who will be receiving treatment. In some embodiments, immune cells are obtained from a healthy subject or donor and are genetically modified to express a chimeric antigen receptor and are effectively redirected against specific antigens. The immune cells, after modification to express a chimeric antigen receptor, are administered to a subject for treating a neoplasia (e.g. , T- or NK-cell malignancy). In some embodiments, immune cells to be modified to express a chimeric antigen receptor can be obtained from pre-existing stock cultures of immune cells.

[0577] Immune cells and / or immune effector cells can be isolated or purified from a sample collected from a subject or a donor using standard techniques known in the art. For example, immune effector cells can be isolated or purified from a whole blood sample by lysing red blood cells and removing peripheral mononuclear blood cells by centrifugation. The immune effector cells can be further isolated or purified using a selective purification method that isolates the immune effector cells based on cell-specific markers such as CD25, CD3, CD4, CD8, CD28, CD45RA, or CD45RO. In one embodiment, CD4+is used as a marker to select T cells. In one embodiment, CD8+is used as a marker to select T cells. In one embodiment, CD4+and CD8+are used as a marker to select regulatory T cells.

[0578] The immune effector cells contemplated are effector T cells or NK cells. In some embodiments, the effector T cell is a naive CD8+T cell, a cytotoxic T cell, a natural killer T (NKT) cell, a natural killer (NK) cell, or a regulatory T (Treg) cell. In some embodiments, the effector T cells are thymocytes, immature T lymphocytes, mature T lymphocytes, resting T lymphocytes, or activated T lymphocytes. In some embodiments the immune effector cell is a CD4+CD8+T cell or a CD4" CD8" T cell. In some embodiments the immune effector cell is a T helper cell. In some embodiments the T helper cell is a T helper 1 (Thl), a T helper 2 (Th2) cell, or a helper T cell expressing CD4 (CD4+ T cell). In some embodiments, immune effector cells are effector NK cells. In some embodiments, the immune effector cell is any other subset of T cells.

[0579] Chimeric antigen receptors of the disclose comprise an extracellular binding domain, a transmembrane domain, and an intracellular domain. Binding of an antigen to the extracellular binding domain can activate the CAR-T cell and generate an effector response, which includes CAR-T cell proliferation, cytokine production, and other processes that lead to the death of the antigen expressing cell. In some embodiments, the chimeric antigen receptor further comprises a linker. In some embodiments, the linker is a (GGGGS)n linker (SEQ ID NO: 71). In some embodiments, the linker is a (GGGGS)s linker (SEQ ID NO: 15). In some embodiments, a CAR of the present invention includes a leader peptide sequence (e.g., N-terminal to the antigen-binding domain). An exemplary leader peptide amino acid sequence is: METDTLLLWVLLLWVPGSTG (SEQ ID NO: 293).

[0580] In various embodiments, the CAR-T specifically targets a cluster of differentiation 7 (CD 7) polypeptide.

[0581] Extracellular Binding Domain

[0582] The chimeric antigen receptors of the disclosure include an extracellular binding domain. The extracellular binding domain of a chimeric antigen receptor contemplated herein comprises an amino acid sequence of an antibody, or an antigen-binding fragment thereof, that has an affinity for a specific antigen. In some embodiments, the antigen is a cluster of differentiation 7 (CD7) polypeptide, or a fragment thereof.

[0583] In some embodiments the chimeric antigen receptor comprises an amino acid sequence of an antibody. In some embodiments, the chimeric antigen receptor comprises the amino acid sequence of an antigen-binding fragment of an antibody. The antibody (or fragment thereof) portion of the extracellular binding domain recognizes and binds to an epitope of an antigen. In some embodiments, the antibody fragment portion of a chimeric antigen receptor is a single chain variable fragment (scFv). An scFv comprises the light and variable fragments of a monoclonal antibody. In other embodiments, the antibody fragment portion of a chimeric antigen receptor is a multichain variable fragment, which comprises more than one extracellular binding domains and therefore bind to more than one antigen simultaneously. In a multiple chain variable fragment embodiment, a hinge region may separate the different variable fragments, providing necessary spatial arrangement and flexibility.

[0584] In some embodiments, the extracellular binding domain is an anti-CD7 scFv.

[0585] In other embodiments, the antibody portion of a chimeric antigen receptor comprises at least one heavy chain and at least one light chain. In some embodiments, the antibody portion of a chimeric antigen receptor comprises two heavy chains, joined by disulfide bridges and two light chains, wherein the light chains are each joined to one of the heavy chains by disulfide bridges. In some embodiments, the light chain comprises a constant region and a variable region. Complementarity determining regions residing in the variable region of an antibody are responsible for the antibody’s affinity for a particular antigen. Thus, antibodies that recognize different antigens comprise different complementarity determining regions. Complementarity determining regions reside in the variable domains of the extracellular binding domain, and variable domains (z.e., the variable heavy and variable light) can be linked with a linker or, in some embodiments, with disulfide bridges. In some embodiments, the variable heavy chain and variable light chain are linked by a (GGGGS)n linker (SEQ ID NO: 14), wherein the n is an integer from 1 to 10. In some embodiments, the linker is a (GGGGSjs linker (SEQ ID NO: 15).

[0586] Antibody-antigen interactions are noncovalent interactions resulting from hydrogen bonding, electrostatic or hydrophobic interactions, or from van der Waals forces. The affinity of extracellular binding domain of the chimeric antigen receptor for an antigen can be calculated with the following formula:

[0587] KA = [Antibody-Antigen] / [Antibody] [Antigen], wherein

[0588] [Ab] = molar concentration of unoccupied binding sites on the antibody;

[0589] [Ag] = molar concentration of unoccupied binding sites on the antigen; and [Ab-Ag] = molar concentration of the antibody-antigen complex.

[0590] The antibody-antigen interaction can also be characterized based on the dissociation of the antigen from the antibody. The dissociation constant (KD) is the ratio of the association rate to the dissociation rate and is inversely proportional to the affinity constant. Thus, KD = 1 / KA. Those skilled in the art will be familiar with these concepts and will know that traditional methods, such as ELISA assays, can be used to calculate these constants.

[0591] Transmembrane Domain The chimeric antigen receptors of the disclosure include a transmembrane domain. The transmembrane domain of the chimeric antigen receptors described herein spans the CAR-T cell’s lipid bilayer cellular membrane and separates the extracellular binding domain and the intracellular signaling domain. In some embodiments, this domain is derived from other receptors having a transmembrane domain, while in other embodiments, this domain is synthetic.

[0592] Transmembrane domains for use in the disclosed CARs can include at least the transmembrane region(s) of) the alpha, beta or zeta chain of the T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. In some embodiments, the transmembrane domain is derived from CD4, CD8a, CD28 and CD3^

[0593] The chimeric antigen receptor is designed, in some embodiments, to comprise a spacer between the transmembrane domain and the extracellular domain, the intracellular domain, or both. Such spacers can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids in length.

[0594] Intracellular Signaling Domain

[0595] The chimeric antigen receptors of the disclosure include an intracellular signaling domain. The intracellular signaling domain is the intracellular portion of a protein expressed in a T cell that transduces a T cell effector function signal (e.g. , an activation signal) and directs the T cell to perform a specialized function. T cell activation can be induced by a number of factors, including binding of cognate antigen to the T cell receptor on the surface of T cells and binding of cognate ligand to costimulatory molecules on the surface of the T cell. A T cell co-stimulatory molecule is a cognate binding partner on a T cell that specifically binds with a co-stimulatory ligand, thereby mediating a co-stimulatory response by the T cell, such as, but not limited to, proliferation. Co-stimulatory molecules include but are not limited to an MHC class I molecule. Activation of a T cell leads to immune response, Such as T cell proliferation and differentiation (see, e.g., Smith-Garvin et al., Annu. Rev. Immunol., 27:591-619, 2009). Exemplary T cell signaling domains are known in the art. Non-limiting examples include the CD3^, CD8, CD28, CD27, CD154, GITR (TNFRSF18), CD134 (0X40), and CD137 (4-1BB) signaling domains. Methods and Use

[0596] In some embodiments, provided herein are methods involving the use of one or more anti-idiotypic antibodies. For example, the anti-idiotypic antibodies of the disclosure can be used in any of the methods provided herein, such as methods to detect (e.g., a pharmacokinetic assay, and / or an assay as depicted in FIG. 10) or select for or sort anti-CD7 CAR (7CAR) T cells in a sample, methods to inactivate or deplete 7CAR T cells in a subject (e.g., when 7CAR T cells previously administered to a subject are associated with harm to the subject), methods for stimulating 7CAR T cells, immunohistochemistry methods (e.g., FIG. 13), immunophenotypic assays), and meso scale discovery-based anti -drug antibody assays (e.g., FIG. 12) for characterization of a subject’s immune response to 7CAR T cells.

[0597] In some aspects, provided herein are methods for measuring or detecting a target polypeptide, such as a chimeric antigen receptor (CAR) (e.g., a 7CAR) or a cell expressing a 7CAR (e.g., a CAR-T cell), and methods for modifying the activity of the target polypeptide, such as the activity of a CAR or the activity of a cell expressing a CAR. In certain embodiments, the one or more anti-idiotypic antibodies bind, detect, identify, and / or quantify the CAR and / or cells expressing the CAR. In some embodiments, the methods provided herein provide one or more steps of contacting and / or incubating the one or more anti- idiotypic antibodies with a cell or a sample containing or thought to be containing cells that express a chimeric antigen receptor (CAR). In some embodiments, the anti-idiotypic antibody is treated, incubated, and / or contacted with the composition or sample under conditions that allow for the formation of a complex (e.g., a non-covalent complex) between the anti- idiotypic antibody and a target polypeptide, e.g., the CAR. In some aspects, the complex may be utilized for the purposes of detecting, isolating, and / or measuring the CAR. In some embodiments, the formation of the complex modifies the activity of the target polypeptide, e.g., the CAR, such as by stimulating receptor signaling activity, or in some embodiments, antagonizing the activity of the target polypeptide, e.g., the CAR, by preventing the association of the CAR with an antigen.

[0598] Methods for use of the anti-idiotypic antibodies disclosed herein include those uses of anti-idiotypic antibodies describe in, for example, U.S. Patent Application Publication No. 2023 / 0028050 and / or in PCT Application Publications No. 2021 / 178695 and / or 2018 / 023100, the full disclosures of which are hereby incorporated by reference in their entireties for all purposes. Detection / Selection

[0599] In some embodiments, there are provided methods involving use of one or more of the anti-idiotypic antibodies, and / or molecules (such as conjugates and complexes) containing one or more of such anti-idiotypic antibodies, for detecting, binding, and / or isolating a polypeptide, e.g., a target antibody. In embodiments, an anti-idiotypic antibody of the disclosure is used in a meso scale discovery (MSD) assay (e.g., an MSD-based anti-drug antibody (ADA) assay, such as that depicted in FIG. 12), in an immunohistochemistry (IHC) based assay for detection of CAR T-cells in tissue biopsies (see, e.g., FIG. 13), in an immunophenotypic assay (see, e.g., FIG. 10), in a pharmacokinetics assay, and / or in a pharmacodynamics assay (see, e.g., FIG. 10).

[0600] In certain embodiments, the methods provide one or more steps of contacting, incubating, and / or exposing the one or more anti-idiotypic antibodies to a sample (e.g., biological sample, such as a blood sample) and / or composition. In some embodiments, the sample and / or composition has, is likely to have, and / or is suspected of having a target polypeptide (e.g., an antibody) and / or antigen-binding fragment thereof that is bound by and / or recognized by the one or more anti-idiotypic antibodies. In certain embodiments, the antibody or antigen-binding fragment thereof that is bound by or recognized by the one or more anti-idiotypic antibodies contains one or more fusion domains and / or is a fusion protein. In certain embodiments, the target polypeptide and / or antigen-binding fragment thereof is a CAR. In certain embodiments, the anti-idiotypic antibody, binds to and / or recognizes an anti- CD? antibody, or an antigen-binding fragment thereof, including a chimeric molecule or conjugate including a CAR, containing such anti-CD7 antibody (e.g., antibody fragment).

[0601] Provided herein are methods for assessing the presence or absence of a molecule in a sample that binds to a chimeric antigen receptor (CAR), such as the extracellular domain of a CAR, or to a portion thereof containing an antigen-binding domain. In some embodiments, the methods can be used to assess the presence or absence of a humoral response or antibody response in a subject to an administered cell therapy comprising a chimeric antigen receptor (CAR). In some embodiments, the chimeric antigen receptor comprises an anti-CD7 antigen- binding domain. In some embodiments, an anti-idiotypic antibody or antigen-binding fragment thereof specific to the extracellular domain of the CAR, such as any described herein, can be used as a positive control in the method.

[0602] In particular embodiments, the method includes contacting a biologic sample with an anti-idiotypic antibody or antigen-binding fragment thereof or conjugate capable of binding an anti-CD7 antibody at a concentration of between 10 ng / ml and 100 pg / ml, between 100 ng / ml and 1.0 gg / ml, between 250 ng / ml and 10 gg / ml, between 250 ng / ml andAg / ml, between 1 gg / ml and 10 gg / ml, between 250 ng and 2.5 gg / ml, or between 1 gg / ml and 10 gg / ml of the anti-idiotypic antibody, antigen-binding fragment thereof, or conjugate. In some embodiments, the concentration is between 250 ng / ml and 10 gg / ml. In certain embodiments, the concentration of the anti-idiotypic antibody, fragment thereof, or conjugate is about or at least about 0.1 gg / ml, 0.25 gg / ml , 0.5 gg / ml, 1.0 gg / ml, 1.25 gg / ml, 2 gg / ml, 2.5 gg / ml, 3 gg / ml, 3.5 gg / ml, 4 gg / ml, or 5 gg / ml of the anti -idiotypic antibody, antigen-binding fragment thereof, or conjugate. In some embodiments, the concentration is between 250 ng / ml and 10 gg / ml. In certain embodiments, the concentration of the anti-idiotypic antibody, fragment thereof, or conjugate is less than about 0.25 gg / ml , 0.5 gg / ml, 1.0 gg / ml, 1.25 gg / ml, 2 gg / ml, 2.5 gg / ml, 3 gg / ml, 3.5 gg / ml, 4 gg / ml, or 5 gg / ml of the anti-idiotypic antibody, antigen-binding fragment thereof, or conjugate. In some cases, the biological sample comprises a CAR-T cell and the anti-idiotypic antibody, antigen-binding fragment thereof, or conjugate is specific to the extracellular domain of the CAR.

[0603] In some instances, the biological sample contains serum, such as human blood serum. In some cases, the biological sample is diluted at a ratio of about or at least about 1:5, 1:6, 1:7, 1:8, 1:9, 1: 10, 1: 11, 1: 12, 1: 13, 1: 14, 1: 15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, or 1:50 prior to being contacted with the anti -idiotypic antibody, antigen-binding fragment thereof, or conjugate. In some instances, the biological sample contains serum, such as human blood serum. In some cases, the biological sample is diluted at a ratio of less than about 1:5, 1:6, 1:7, 1:8, 1:9, 1: 10, 1: 11, 1: 12, 1: 13, 1: 14, 1: 15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, or 1:50 prior to being contacted with the anti -idiotypic antibody, antigen-binding fragment thereof, or conjugate.

[0604] In some aspects, adoptive cell therapy may be associated with development of an immune response in the subject to the cells and / or construct administered. For example, in some cases, exposure to a chimeric antigen receptor may be limited by host immune responses against the recombinant receptors expressed by the administered cells, which may prematurely eliminate the cells. It is observed that even in certain subjects having B cell malignancies, who often are immunocompromised, immune responses can be detected that are specific for regions of CARs expressed by cells administered in adoptive cell therapy. For example, subjects, e.g., human subjects, administered cells genetically engineered with a CAR can develop a specific immune response to an immunogenic region of the chimeric region, including regions that may contain non-human sequences (e.g., murine scFv) and or to a region containing the junction between two domains or portions of the chimeric receptor, e.g., the transmembrane and costimulatory domain of the CAR.

[0605] In some embodiments (e.g., in a meso scale discovery assay, such as that depicted in FIG. 12 or in a histochemistry assay, such as that depicted in FIG. 13), there are provided methods that involve contacting or incubating a capture polypeptide (e.g., a polypeptide containing a target antigen, such as a CAR, to which an anti-idiotypic antibody of the disclosure is capable of binding) with a sample from a subject having been administered a cell therapy comprising a cell engineered with a chimeric antigen receptor (e.g., a 7CAR T cell). Such embodiments can be useful, for example, in an assay for detecting anti-7CAR antibodies generated in a subject, and anti -idiotypic antibodies of the disclosure may be used as a positive control in such an assay. In embodiments the capture polypeptide is a protein that includes the extracellular domain of the CAR or a portion thereof containing a target antibody or an antigen-binding fragment thereof. In some embodiments, the methods further include detecting whether a complex is formed between the capture polypeptide and a molecule, e.g., binding molecule, such as an antibody, present in the sample, and / or detecting the presence or absence or level of such binding. In certain embodiments, the contacting or incubating is under conditions permissive for binding of the capture polypeptide to a molecule present in the sample from the subject. In certain aspects, the method can be further carried out on a positive control sample containing an anti-idiotypic antibody of the disclosure or antigen-binding fragment thereof specific for the CAR (e.g., specific for an antigen-binding domain of the CAR). In some embodiments, determining the presence, absence or level of binding of the molecule to the capture polypeptide can include comparison of the binding or detection to the binding or detection of the positive control sample to the capture polypeptide.

[0606] In some embodiments, the cell therapy is or comprises genetically engineered cells expressing an anti-CD7 CAR. In some embodiments, the positive control includes an anti- idiotypic antibody of the disclosure (see, e.g., Tables 1A to 5).

[0607] In some embodiments, the methods include detecting whether a complex is formed between the capture polypeptide and a molecule (see, e.g., the complex of FIG. 12 or of FIG. 13), e.g., binding molecule, such as an antibody, or antigen-binding fragment thereof, present in the sample, and / or detecting the presence or absence or level of such binding. In certain embodiments, the contacting or incubating is under conditions permissive for binding of the capture polypeptide to a molecule present in the sample from the subject. In some aspects, the complex is detected by an immunoassay, optionally a sandwich or bridge assay (e.g., FIGs. 4B or 4C). For example, the immunoassay may be an enzyme-linked immunosorbent assay (ELISA), chemiluminescent, electrochemiluminescent (e.g., in a meso scale discovery assay), surface plasmon resonance (SPR)-based biosensor (e.g., BIAcore), flow cytometry, or Western blot. In some embodiments, the immunoassay is or includes meso scale discovery (MSD).

[0608] Anti-drug antibodies (ADAs) induced by biologic therapeutics often impact drug pharmacokinetics, pharmacodynamics response, clinical efficacy, and patient safety. It is critical to assess the immunogenicity risk of potential biotherapeutics in producing neutralizing and nonneutralizing anti-drug antibodies, especially in clinical phases of drug development. Different assay methodologies have been used to detect all anti -drug antibodies, including ELISA, radioimmunoassay, surface plasmon resonance, and electrochemiluminescence-based technologies. The most commonly used method is a bridging assay, performed in an ELISA or using a meso scale discovery assay.

[0609] In some embodiments, the immunoassay is a meso scale discovery (MSD) assay, such as an MSD-based anti-drug antibody (ADA) assay (see, e.g., FIG. 12). A chimeric antigen receptor (CAR) ADA assay facilitates the monitoring of a CAR-specific humor immune response in a subject administered a T cell or NK cell expressing the CAR (e.g., an anti-CD7 CAR). ADA assays are mandated by some regulatory agencies. An MSD-based bridging assay (FIG. 12) is a species agnostic highly sensitive and specific method for detecting a CAR specific ADA in a subject. The anti-idiotypic antibodies of the disclosure may be used as a positive control in a MSD assay, such as an MSD-based ADA assay for detecting antibodies generated by a subject in response to a CAR administered to the subject.

[0610] In various embodiments, an MSD assay involves binding a CAR protein to a working electrode (e.g., binding a biotinylated CAR protein to a working electrode containing streptavidin), allowing an anti-idiotypic antibody to bind to the CAR, and allowing a SULFO-TAG labeled CAR protein to bind to the anti -idiotypic antibody, thereby forming a complex. The SULFO-TAG is an electrochemiluminescent label that allows for sensitive detection of complexes bound to the working electrode when electricity is applied to the working electrode. The SULFO-TAG of the complex emits light when an electric field is applied to the working electrode.

[0611] In some embodiments, the immunoassay is an immunohistochemistry (IHC) assay (see, e.g., FIG. 13). In various embodiments, the anti-idiotypic antibodies of the disclosure are used in an IHC assay to detect the presence of anti-CD7 CAR T cells in a tissue sample (e.g., a biopsy containing a tumor sample). Immunohistochemistry assay methods are known in the art, such as those described in Emmanuel, T., et al., “Quantification of hnmunohistochemically Stained Cells in Skin Biopsies,” Dermatopathology 9:82-93 (2022), or in Hasic, E. (2022). Immunohistochemistry Fundamentals. In T. Nguyen (Ed.), Immunohistochemistry: A Technical Guide to Current Practices (pp. 1-23). Cambridge: Cambridge University Press. Doi: 10.1017 / 9781009106924.002, the disclosures of which are herein incorporated by reference for all purposes.

[0612] Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Another way to describe the difference between the 2 disciplines is to say that pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” When prescribing medications, physicians must take into account both the drug’s pharmacodynamics and its pharmacokinetics to determine the correct dosage and to ensure the appropriate effect.

[0613] In embodiments, the anti-idiotypic antibodies of the disclosure may be used in a pharmacokinetic assay or a pharmacodynamic assay. For example, in a pharmacokinetic assay, the anti-idiotypic antibodies of the disclosure may be used to detect the proliferation, persistence, tumor-uptake, killing, distribution, and the like of CAR-T cells in a subject. In a pharmacodynamics assay, the anti-idiotypic antibodies of the disclosure maybe used to measure the dynamics of binding of a CAR-T cell to a target antigen (e.g., a CD7 antigen) and / or a target cell.

[0614] In some aspects, the immunoassay is a sandwich assay or a bridge assay. In a sandwich or bridge assay, detecting the presence or absence of a molecule or a complex (e.g., a complex containing an antibody bound to a 7CAR) comprising a molecule includes contacting the complex formed between the capture polypeptide and molecule (e.g., an antibody, such as an anti-idiotypic antibody of the disclosure, or antigen-binding fragment thereof capable of binding a 7 CAR, or an antigen-binding domain thereof) with a detection polypeptide in which the detection polypeptide (see, e.g., the detectably labeled CAR protein of FIG. 12) is an agent that is able to bind to the same or similar molecule as the capture polypeptide. In some embodiments, the detection polypeptide comprises the extracellular domain of the CAR or a portion thereof. In some aspects, the extracellular domain of the CAR or portion thereof of the capture polypeptide and the detection polypeptide is the same or substantially the same. In some embodiments, the capture or detection polypeptide, is detectably labeled or is capable of producing a detectable signal. The capture or detection polypeptide may be linked, directly or indirectly, to a detectable label. In some embodiments, the detectable label is or includes a fluorescent label, a chemiluminescent label, an electroluminescent label, a colorimetric label, a bioluminescent label or a radiolabel. In some embodiments, the capture or detection polypeptide, is linked, directly or indirectly, to a detectable label. In some embodiments, at least one of the capture and detection polypeptides is detectably labeled or is capable of producing a detectable signal and the other of the capture and detection polypeptides is attached or immobilized to a solid support. In some aspects, the capture polypeptide is attached or immobilized to a solid support or capable of being attached or immobilized to a solid support. Methods for directly or indirectly attaching a capture polypeptide to a solid support are well known in the art. Methods of attachment generally include non-specific adsorption of the capture polypeptide to the solid support or covalent attachment of the capture polypeptide, typically through a free amine group, to a chemically reactive group on the solid support, such as an activated carboxyl, hydroxyl, or aldehyde group. Methods of attachment also include indirect attachment of the capture polypeptide to the solid support such as by coating the solid support with a capture reagent, such as streptavidin, and adding affinity labeled capture polypeptides, such as biotin-labeled reagents, to the solid support so that the interaction between the affinity label (e.g., biotin) and capture reagent (e.g., streptavidin) link the capture polypeptide to the solid support. In some embodiments, the capture polypeptide is linked, directly or indirectly, to a biotin. In some examples, the capture polypeptide is bound to a solid support coated with streptavidin. In some embodiments, the detection polypeptide is linked, directly or indirectly, to a detectable label.

[0615] In particular embodiments, the sample is contacted with a capture polypeptide that is attached, bound, coated, and / or conjugated to a solid surface or support, e.g., a plate or a well. In certain embodiments, the capture polypeptide has been attached, bound, coated, and / or conjugated to the solid surface or support by indirect attachment of the capture polypeptide to the solid support such as by coating the solid support with a capture reagent, such as streptavidin, and adding affinity labeled capture polypeptides, such as biotin-labeled reagents, to the solid support so that the interaction between the affinity label (e.g., biotin) and capture reagent (e.g., streptavidin) link the capture polypeptide to the solid support. In some embodiments, the sample is contacted with a detection polypeptide that is linked, directly or indirectly, to a detectable label. In particular embodiments, the capture and / or detection polypeptide is used at a concentration of between 10 ng / ml and 100 pg / ml, between 100 ng / ml and 1.0 pg / ml, between 250 ng / ml and 10 pg / ml, between 250 ng / ml andAg / ml, between 1 pg / ml and 10 pg / ml, between 250 ng and 2.5 pg / ml, or between 1 pg / ml and 10 pg / ml the anti-idiotypic antibody. In some embodiments, the solid surface or support is incubated with between 250 ng / ml and 10 pg / ml. In certain embodiments, the solid surface or support is incubated with or with about 0.25 pg / ml , 0.5 pg / ml, 1.0 pg / ml, 1.25 pg / ml, 2 pg / ml, 2.5 pg / ml, 5 pg / ml or 10 pg / ml.

[0616] In some embodiments, the sample from a subject having been administered a cell therapy comprising cell engineered with a chimeric antigen receptor is or comprises any bodily fluid or tissue sample from the subject. In some aspects, the sample is or comprises whole blood, serum or plasma. In some embodiments, the sample is obtained from the subject within or about within 1 hour to 1 year after initiation of administration of the cell therapy or dose of cells, such as within or about within 6 hours, 12 hours, 24 hours, one week, two weeks, three weeks, one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months or twelve months. In some aspects, the sample is obtained from the subject from or from about 1 month to 6 months of initiation of administration of the cell therapy, such as 2 months to 6 months or 2 months to 4 months, for example, about or approximately 2 months, 3 months, 4 months, 5 months or 6 months after initiation of administration of the cell therapy.

[0617] The methods in some embodiments include incubating, treating, and / or contacting a sample and / or a composition containing or suspected of containing the target polypeptide with the anti-idiotypic antibody. In certain embodiments, the incubating is under conditions permissive for binding of the anti-idiotypic antibody to the target polypeptide present in the composition, for example to form a complex containing the anti-idiotypic antibody and the target polypeptide.

[0618] In some embodiments, the sample and / or composition contains or is suspected of containing the target polypeptide, e.g., a CAR or antibody. In certain embodiments, the sample and / or composition contains or is suspected of containing cells that express the target polypeptide, e.g., a CAR. In certain embodiments, the sample is a biological sample. In particular embodiments, the sample is a serum sample or a blood sample. In some embodiments, the biological sample contains one or more immune cells. In some embodiments, the biological sample is or is derived from a tissue, such as connective tissue, muscle tissue, nervous tissue, or epithelial tissue. In particular embodiments, the biological sample is or is derived from heart, vasculature, salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines, colon, rectum, hypothalamus, pituitary gland, pineal gland, thyroid, parathyroid, adrenal gland, kidney, ureter, bladder, urethra, lymphatic system, skin, muscle, brain, spinal cord, nerves, ovaries, uterus, testes, prostate, pharynx, larynx, trachea, bronchi, lungs, diaphragm, bone, cartilage, ligaments, or tendons. In particular embodiments, the biological sample is taken, collected, and / or obtained from a human subject. In certain embodiments, the sample contains cells that are live and / or intact. In some embodiments, the sample is or contains a homogenate and / or cells that have been disrupted and / or lysed. In some embodiments, the biological sample contains proteins and / or antibodies, or antigen- binding fragments thereof, that have been isolated from blood, serum, and / or a tissue.

[0619] In particular embodiments, the anti-idiotypic antibody forms or is capable of forming a complex with a target polypeptide, e.g., a CAR. In particular embodiments, the complex is detected, measured, quantified, and / or assessed, for example, to allow for the detection, identification, measurement, and / or quantification of the target polypeptide, for example in a composition or a sample. In certain embodiments, the methods include detecting whether a complex is formed between the anti-idiotypic antibody and the target polypeptide in the sample, and / or detecting the presence or absence or level of such binding. In some embodiments, the complex contains a detectable label. In particular embodiments, the anti- idiotypic antibody is an immunoconjugate that contains a detectable label. In certain embodiments, the anti-idiotypic antibody contains, is conjugated with, bound to, and / or attached to the detectable label. In some embodiments, the complex contains an antibody that binds to and / or recognizes the anti-idiotypic antibody, e.g., a secondary antibody, that in conjugated with, bound to, and / or attached to a detectable label. In some embodiment, the secondary antibody is a goat anti-human antibody. In some cases, the secondary antibody is capable of specifically binding IgGl antibodies (e.g., human IgGl antibodies). In some embodiments, the detectable label is Alexa Fluor 647.

[0620] In some embodiments, methods for detecting, quantifying, detecting, and / or assessing a target polypeptide, for example in a sample or composition, includes detecting a complex of the target polypeptide and the anti-idiotypic antibody. In some embodiments, the complex contains a detectable label. In certain embodiments, the complex is probed and / or contacted with a detectable label. In some embodiments, the complex is detected by any suitable method or means, such as but not limited to flow cytometry, immunocytochemistry, immunohistochemistry, western blot analysis, and ELISA.

[0621] In some embodiments, the target polypeptide or antigen-binding fragment is bound to a cell or expressed on the surface of a cell. In particular embodiments, target polypeptide, e.g., the CAR, is not bound or contained within a cell, for example, in some embodiments, the target polypeptide is secreted. In certain embodiments, the polypeptide has been detached, removed, and / or lysed from the surface of a cell.

[0622] In some embodiments, the target polypeptide or antigen-binding fragment is contained in a chimeric antigen receptor (CAR), such as a CAR expressed on the surface of a cell. In some embodiments, the cell is a stem cell, e.g., an iPSC, or an immune cell. In some embodiments, the immune cell is a T cell, e.g., a CD4+ T cell, a CD8+ T cell, naive T (TN) cell, effector T cell (TEFF), memory T cell, tumor-infiltrating lymphocyte (TIL), immature T cell, mature T cell, helper T cells, cytotoxic T cell, mucosa-associated invariant T (MAIT) cell, naturally occurring and adaptive regulatory T (Treg) cell, helper T cell, such as a TH1 cell, TH2 cell, TH3 cell, TH 17 cell, TH9 cell, TH22 cell, follicular helper T cell, alpha / beta T cell, and / or a delta / gamma T cells.

[0623] In some embodiments, the target polypeptide is an anti-CD7 antibody.

[0624] In some embodiments, there is provided a method of detecting a target antibody, such as an anti-CD7 antibody, or an antigen-binding fragment thereof (and / or chimeric molecules comprising an antigen-binding fragment of the anti-CD7 antibody, such as a CAR), comprising contacting a composition comprising the target antibody or antigen-binding fragment with an anti-idiotypic antibody or antigen-binding fragment thereof or an anti- idiotypic antibody immunoconjugate described herein, and detecting the anti-idiotypic antibody bound to the target antibody or antigen-binding fragment thereof. In some embodiments, the method further includes detecting whether a complex is formed between the anti-idiotypic antibody and the target antibody, or antigen-binding fragment thereof, in the composition, such as detecting the presence or absence or level of such binding. In some embodiments, the target antibody or antigen-binding fragment thereof is bound to a cell or expressed on the surface of a cell and the detecting comprises detecting cells bound with the anti-idiotypic antibody. In some embodiments, the anti-idiotypic antibody or antigen-binding fragment thereof is directly or indirectly labeled for detection.

[0625] In some embodiments, there is provided a method of isolating a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof (and / or chimeric molecules comprising such antibody or antigen-binding fragment, such as a CAR), comprising contacting a composition and / or a sample containing or suspected of containing the target polypeptide or antigen-binding fragment with an anti-idiotypic antibody or antigen- binding fragment thereof or an anti-idiotypic antibody immunoconjugate described herein, and isolating complexes comprising the anti-idiotypic antibody bound to the target polypeptide or antigen-binding fragment. In certain embodiments, the target polypeptide is isolated with an anti-idiotypic antibody or antigen-binding fragment thereof is an immunoconjugate. In some embodiments, the target polypeptide or antigen-binding fragment is bound to a cell or expressed on the surface of a cell and the isolating comprises isolating cells bound with the anti-idiotypic antibody. In some embodiments, the complexes comprising the anti-idiotypic antibody are isolated by affinity-based separation. In some embodiments, the affinity-based separation is selected from the group consisting of immunoaffinity-based separation, magnetic-based separation, and affinity chromatography.

[0626] In some embodiments, there is provided a method of detecting a cell expressing a CAR comprising a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, comprising contacting the cell expressing the CAR with an anti-idiotypic antibody or antigen-binding fragment thereof or an anti-idiotypic antibody immunoconjugate described herein, and detecting cells bound with the anti-idiotypic antibody. In some embodiments, the anti-idiotypic antibody or antigen-binding fragment thereof is directly or indirectly labeled for detection.

[0627] In certain embodiments, the methods for detecting a target polypeptide with an anti- idiotypic antibody described herein are used to assess the target polypeptide in a subject. For example, in some embodiments, provided herein are methods of use for the anti-idiotypic antibody for assessing, measuring, and / or quantifying the in vivo pharmacokinetics, expansion, and / or persistence of a CAR expressing cells of a therapeutic cell composition. In some embodiments, the in vivo pharmacokinetics, expansion, and / or persistence of the cells, and / or changes in cell phenotypes or functional activity of cells, such as CAR expressing cells administered for immunotherapy, e.g., CAR-T cell therapy, in the methods provided herein, can be measured with the anti-idiotypic antibodies provided herein. In some embodiments, the pharmacokinetics, expansion, and / or persistence of the CAR expressing cells are measured, assessed by detecting the presence and / or amount of cells expressing the CAR in the subject and / or in sample obtained from the subject following the administration of the therapeutic cell composition during and / or after the administration of the therapy with an anti-idiotypic antibody provided herein.

[0628] In some aspects, an anti-idiotypic antibody of the disclosure is used with flow cytometry to assess the quantity of cells expressing a recombinant receptor (e.g., CAR- expressing cells administered for T cell based therapy) in a blood, serum, organ, or tissue sample (e.g., disease site, e.g., tumor sample) of a subject. In some aspects, persistence is quantified as the number of CAR- expressing cells per microliter of the sample, e.g., of blood or serum, or per total number of peripheral blood mononuclear cells (PBMCs) or white blood cells or T cells per microliter of the sample. In certain aspects, expansion is quantified as the increase in the number of CAR- expressing cells per microliter between samples, e.g., of blood or serum, or per total number of peripheral blood mononuclear cells (PBMCs) or white blood cells or T cells per microliter of the samples over time. In some embodiments, the pharmacokinetics, expansion, and / or persistence are measured or assessed by detecting the amount of CAR expressing cells in the subject and / or in samples collected from the subject at multiple time points. In certain embodiments, the one or more samples are collected, obtained, and / or taken from the subject within 24 hours, 48 hours, 72 hours, 4 days, 5 days, 6 days, 7 days, 10 days, 14 days, 21 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3 months, 4 months, 6 months, one year, or over one year after the therapeutic cell composition is administered.

[0629] In some embodiments, there is provided a method of selecting cells expressing a CAR containing a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, involving contacting a population of cells comprising cells expressing the CAR with an anti-idiotypic antibody or antigen-binding fragment thereof or an anti-idiotypic antibody immunoconjugate described herein, and selecting cells bound with the anti-idiotypic antibody. In some embodiments, the cells bound with the anti-idiotypic antibody are selected by affinity-based separation. In some embodiments, the affinity-based separation is selected from the group consisting of immunoaffinity-based separation, flow cytometry, magnetic - based separation, and affinity chromatography. In some embodiments, the anti-idiotypic antibody or antigen-binding fragment thereof or anti-idiotypic antibody immunoconjugate is reversibly bound or immobilized to a support or a stationary phase.

[0630] In some embodiments, there is provided a method of validating a CAR comprising a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, involving a) incubating a sample comprising T cells transduced with the CAR with an anti- idiotypic antibody or antigen-binding fragment thereof targeting the CAR; b) determining the percent of cells bound with the anti-idiotypic antibody or antigen-binding fragment thereof; and c) validating the CAR based on the percent of anti-idiotypic antibody-bound T cells. In some embodiments, the anti-idiotypic antibody is labeled, and anti-idiotypic antibody-bound T cells are assayed by flow cytometry.

[0631] Also provided are methods involving use of the provided anti-idiotypic antibodies, and molecules (such as conjugates and complexes) containing one or more of such anti- idiotypic antibodies, for informing treatment decisions in an individual, such as by the detection of CARs recognized by the anti-idiotypic antibody, such as CARs comprising a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof. In some embodiments, the methods are for informing treatment decisions in an individual in association with a therapy comprising administration of CAR-T cells, such as anti-CD7 CAR-T cells. The methods in some embodiments include incubating and / or probing a biological sample with the anti-idiotypic antibody and / or administering the anti-idiotypic antibody to the individual. In certain embodiments, a biological sample includes a cell or tissue or portion thereof, such as tumor or cancer tissue or biopsy or section thereof. In certain embodiments, the incubating is under conditions permissive for binding of the anti- idiotypic antibody to CARs present in the sample. In some embodiments, the methods further include detecting whether a complex is formed between the anti-idiotypic antibody and CARs in the sample, such as detecting the presence or absence or level of such binding. Such a method may be an in vitro or in vivo method.

[0632] In one embodiment, an anti-idiotypic antibody is used to determine whether adjustment to a CAR-T cell therapy in an individual is necessary, e.g., where low levels of the CAR-T cells in the individual indicate the need to adjust the therapy.

[0633] In some embodiments, there is provided a method of evaluating a CAR-T cell therapy in an individual, wherein the CAR comprises a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, comprising incubating a sample from the individual with an anti-idiotypic antibody or antigen-binding fragment thereof targeting the CAR and determining the amount of T cells bound with the anti -idiotypic antibody, and determining the potential therapeutic benefit of the therapy based on the amount of anti- idiotypic antibody- bound T cells. In some embodiments, the anti-idiotypic antibody is labeled, and anti-idiotypic antibody-bound T cells are assayed by flow cytometry. In some embodiments, the sample is a blood-derived sample, or is or is derived from an apheresis or leukapheresis product.

[0634] In some embodiments, there is provided a method of evaluating a CAR-T cell therapy in an individual. In some aspects, the CAR comprises a target polypeptide, such as an ani- CD7 antibody or an antigen-binding fragment thereof. In some embodiments, the method includes administering an anti-idiotypic antibody or antigen-binding fragment thereof targeting the CAR (e.g., targeting the antibody, e.g., antibody fragment, of the CAR) to the individual. In some aspects, the administration is carried out following initiation of a first dose of the therapy. The method can comprise determining the presence of the anti-idiotypic antibody in one or more tissues / organs in the individual. In some aspects, the method includes determining the potential therapeutic benefit of the therapy based on the presence of the anti-idiotypic antibody in at least one of the one or more tissues / organs. In some embodiments, the anti-idiotypic antibody is labeled, and presence of the anti-idiotypic antibody in the individual is determined by imaging in the individual to detect the label. In some embodiments, determining the presence of the anti-idiotypic antibody in one or more tissues / organs in the individual includes or is carried out by determining a level of the anti- idiotypic antibody or binding thereof in the one or more tissues / organs.

[0635] In some embodiments, the method further comprises administering the anti-idiotypic antibody to the individual following initiation of a second or subsequent dose of the therapy and / or determining the presence of the anti-idiotypic antibody in the one or more tissues / organs in the individual. In some aspects, the method further involves determining the potential therapeutic benefit of the therapy based on the difference in the level of the anti- idiotypic antibody in at least one of the one or more tissue / organs in the individual between the first and second anti-idiotypic antibody administrations.

[0636] In some embodiments, there is provided a method of adjusting a CAR-T cell therapy in an individual, wherein the CAR comprises a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof. In some aspects, the method includes incubating or contacting a sample from the individual with an anti-idiotypic antibody or antigen- binding fragment thereof targeting the CAR. In some aspects, the method includes determining the amount of T cells bound with or to the anti-idiotypic antibody. In some aspects, the method includes adjusting the therapy based on the amount of anti-idiotypic antibody-bound T cells. In some embodiments, the anti -idiotypic antibody is labeled directly or indirectly. In some aspects of such embodiments, the anti-idiotypic antibody-bound T cells are imaged in vivo or ex vivo, such as, in some cases, by assaying a sample, from the subject administered the CAR-T cells and anti-idiotypic antibody, by flow cytometry. In some embodiments, the sample is a blood-derived sample, and / or is or is derived from an apheresis or leukapheresis product.

[0637] In some embodiments, there is provided a method of adjusting a CAR-T cell therapy in an individual. In some aspects, such a method is carried out for a CAR-T cell therapy where the CAR comprises a target polypeptide, such as an anti-CD7 antibody, or an antigen- binding fragment thereof. The method in some embodiments comprises administering, to the individual, an anti-idiotypic antibody or antigen-binding fragment thereof that targets or binds the CAR following initiation of administration of a first dose of the therapy and determining the presence, absence or level of the anti-idiotypic antibody in one or more tissues / organs in the individual. In some aspects, the method includes adjusting the therapy based on the presence, absence or level of the anti-idiotypic antibody in at least one of the one or more tissues / organs. In some embodiments, the anti -idiotypic antibody is labeled directly or indirectly, and in some such embodiments the presence of the anti-idiotypic antibody in the individual is determined by imaging in the individual to detect the label. In some embodiments, determining the presence of the anti-idiotypic antibody in one or more tissues / organs in the individual comprises determining a level of or for the anti-idiotypic antibody in the one or more tissues / organs or binding thereof. In some embodiments, the method further comprises administering the anti-idiotypic antibody to the individual after initiation of a second or subsequent dose of administration of the therapy and in some aspects determining the presence, absence or level of the anti-idiotypic antibody in the one or more tissues / organs in the individual, and / or adjusting the therapy based on the observations such as based on the difference in the level of the anti-idiotypic antibody in at least one of the one or more tissue / organs in the individual between the first and second anti-idiotypic antibody administrations.

[0638] In some aspects, the therapy is adjusted (i) if the number of cells of the T cell therapy detectable in the blood or other biological sample, after having been detectable, is not detectable or is reduced, optionally reduced compared to a preceding time point after administration of the T cell therapy; (ii) the number of cells of the T cell therapy detectable in the blood or other biological sample is decreased by or more than 1.5-fold, 2.0-fold, 3.0-fold, 4.0-fold, 5.0-fold, 10-fold or more the peak or maximum number cells of the T cell therapy detectable in the blood or the biological sample of the subject after initiation of administration of the T cell therapy, optionally the first, second or subsequent dose; (iii) at a time after a peak or maximum level of the cells of the T cell therapy are detectable in the blood of the subject, the number of cells of or derived from the T cells detectable in the blood from the subject is less than less than 10%, less than 5%, less than 1% or less than 0. 1% of total peripheral blood mononuclear cells (PBMCs) in the blood of the subject; and / or (iv) if the number of CD3+ or CD8+ cells of the cell therapy detectable in the blood is less than 20 cells per pL-, 15 cells per pL, 10 cells per pL, less than 5 cells per pL- or less than per 1 cells per pL. In some embodiments, the therapy is adjusted by administered one or more additional doses of the CAR-T cell therapy, administered an increased dose of the CAR-T cell therapy, administering an alternative CAR-T cell therapy specific for the same or different antigen, administering one or more immunomodulatory agent or other agent for promoting or increasing expansion or persistence of the CAR-T cells. Various methods known in the art for detecting specific antibody- antigen binding can be used. Exemplary immunoassays include fluorescence polarization immunoassay (FPIA), fluorescence immunoassay (FIA), enzyme immunoassay (EIA), nephelometric inhibition immunoassay (NIA), enzyme linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). An indicator moiety, or label group, can be attached to the anti -idiotypic antibodies and is selected so as to meet the needs of various uses of the method which are often dictated by the availability of assay equipment and compatible immunoassay procedures. Exemplary labels include radionuclides (e.g.,1251,1311,35S,3H, or32P and / or chromium (51Cr), cobalt (57Co), fluorine (18F), gadolinium (153Gd,159Gd), germanium (68Ge), holmium (166Ho), indium (115In,113In,112In,mIn), iodine (125I,123I,121I), lanthanium (140La), lutetium (177Lu), manganese (54Mn), molybdenum ( 99 Mo), palladium ( 103 Pd), phosphorous ( 32 P), praseodymium ( 142 Pr), promethium (149Pm), rhenium (186Re, 188Re), rhodium (105Rh), rutheroium (97Ru), samarium (153Sm), scandium (47Sc), selenium (75Se), (85Sr), sulphur (35S), technetium ("Tc), thallium (201Ti), tin (113Sn,117Sn), tritium (3H), xenon (133Xe), ytterbium (169Yb,175Yb), yttrium (90Y),), enzymes (e.g., alkaline phosphatase, horseradish peroxidase, luciferase, or p-glactosidase), fluorescent moieties or proteins (e.g., fluorescein, rhodamine, phycoerythrin, GFP, or BFP), or luminescent moieties (e.g., Qdot™ nanoparticles supplied by the Quantum Dot Corporation, Palo Alto, Calif.). Various general techniques to be used in performing the various immunoassays noted above are known.

[0639] In some embodiments, anti-idiotypic antibodies need not be labeled, and the presence thereof can be detected using a labeled antibody which binds to any of the anti-idiotypic antibodies.

[0640] The anti-idiotypic antibodies provided herein can be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays. Zola, Monoclonal Antibodies: A Manual of Techniques, pp. 147- 158 (CRC Press, Inc. 1987).

[0641] The anti-idiotypic antibodies can also be used for in vivo diagnostic assays, such as in vivo imaging. Generally, the anti-idiotypic antibody is labeled with a radionuclide (such asluIn,99Tc,14C,1311,125I, or3H) so that the cells or tissue of interest can be localized in vivo following administration to an individual.

[0642] In some embodiments, the anti-idiotypic antibody or antigen-binding fragment is immobilized or bound to a solid support, wherein one or more target cells comprising CAR-T cells are contacted with the solid support. In some embodiments, the solid support is a bead. In some embodiments, the solid support is the surface of a well or plate, e.g., a cell culture plate. In some embodiments, the solid support is a resin or matrix present in or contained within a chromatography column, for example, to permit chromatographic isolation or selection of CAR+ T cells. In some embodiments, the anti-idiotypic antibody or antigen - binding fragment is or is capable of being reversibly bound to a solid support. In some embodiments, the solid support is an affinity chromatography matrix comprising one or more binding sites capable of binding, e.g., reversibly binding, to a binding partner present in the anti-idiotypic antibody. In one exemplary embodiment, the anti-idiotypic antibody comprises a streptavidin-binding peptide or other streptavidin binding moiety capable of binding to a streptavidin or streptavidin mutein molecule present on or immobilized on the solid support, which, in some cases, can be dissociated in the presence of a competition substance, such as biotin. Exemplary of such systems include those described in U.S. Patent Application Publication No. 20150024411.

[0643] In some aspects, the anti-idiotypic antibodies provided herein can be expressed on the surface of a cell. In some aspects, a cell-expressed anti -idiotypic antibody can be used to induce or stimulate a CAR-expressing cell, such as part of a system for selectively growing CAR cells. In some aspects, the anti-idiotypic antibody or antigen-binding fragment thereof is expressed on an artificial antigen presenting cell (aAPC). The anti -idiotypic-antibody- expressing aAPCs may be used as reagents for stimulation or expansion of CAR-T cell populations.

[0644] Methods for preparing or generating aAPCs include those describe in, e.g., U.S. Pats. No. 6,225,042; 6,355,479; 6,362,001; 6,790,662; 7,754,482; U.S. Patent Application Publications No. 2009 / 0017000 and 2009 / 0004142; and International Publication No. W02007 / 103009. Various aAPCs are known in the art, see e.g., U.S. Patent No. 8,722,400, U.S. Patent Application Publication No. US2014 / 0212446; Butler and Hirano (2014) Immunol Rev., 257(1): 10. 111 l / imr.12129; Suhoshki et al. (2007) Mol. Then, 15:981-988). aAPCs include features of natural antigen-presenting cells (APCs), including expression of a major histocompatibility complex (MHC) molecule, stimulatory and costimulatory molecule(s), Fc receptor, adhesion molecule(s) and / or the ability to produce or secrete cytokines (e.g., IE-2). Normally, an aAPC is produced from a cell line that lacks expression of one or more of these features, and the aAPC is produced by introduction (e.g., by transfection or transduction) of one or more of the missing features necessary for stimulation of a target cell, e.g., a CAR-T cell.

[0645] In some embodiments, cells selected to be used in the production of aAPCs have deficiencies in intracellular antigen-processing, intracellular peptide trafficking, and / or intracellular MHC Class I or Class II molecule -peptide loading. In some aspects, such cells also lack the ability to express an MHC Class I or Class II molecule and / or molecules involve in or related to antigen processing. Exemplary aAPCs either constitute or are derived from a transporter associated with antigen processing (TAP) -deficient cell line, such as an insect cell line. An exemplary cell line is a Drosophila cell line, such as a Schneider 2 cell line (see, e.g., Schneider, J. Embryol. Exp. Morph. 1972 Vol 27, pp. 353-365). Illustrative methods for the preparation, growth, and culture of Schneider 2 cells, are provided in U.S. Pat. Nos. 6,225,042, 6,355,479, and 6,362,001.

[0646] In some embodiments, the cell is a K652 cell or a K562-derived cell. In some embodiments, the cell is the cell line available at ATCC No. CCL-243.

[0647] In some aspects, the aAPC is further engineered to express a further molecule to enhance, potentiate or augment stimulation of a CAR-expressing T cell.

[0648] In some embodiments, because the anti-idiotypic antibody is capable of delivering a signal through the CAR, the aAPC does not express a stimulatory ligand that specifically binds with a TCR / CD3 complex. In some embodiments, the aAPC does not express a costimulatory molecule.

[0649] In some embodiments, the anti-idiotypic antibody is expressed as a single chain fragment (scFv) for display on the surface of the cell. The nucleic acid encoding the scFv can be fused to DNA sequences encoding a transmembrane domain. Transmembrane regions of particular use include those derived from the transmembrane region(s) of the alpha, beta or zeta chain of the T- cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, CD154. Alternatively, the transmembrane domain may be synthetic, in which case it will comprise predominantly hydrophobic residues such as leucine and valine. In some cases, a triplet of phenylalanine, tryptophan and valine will be found at each end of a synthetic transmembrane domain. Exemplary transmembrane domain include those derived from CD8 or CD28.

[0650] Cell Inactivation / Depletion

[0651] In some embodiments, the provided anti-idiotypic antibodies or antigen-binding fragments thereof are antagonists and / or exhibit specific activity to inhibit, ablate, and / or deplete (for example, kill via antibody-dependent cell-mediated cytotoxicity, ADCC) cells expressing a target polypeptide (e.g., an anti-CD7 antibody), or antigen-binding fragment thereof. Also provided are methods involving use of the provided anti-idiotypic antibodies, and molecules (such as conjugates, such as antibody-drug conjugates, and complexes) containing one or more of such anti-idiotypic antibodies, for inactivation, ablation, and / or depletion of CAR-T cells, wherein the CAR comprises a target polypeptide, such as an anti- CD? antibody, or an antigen-binding fragment thereof. It can be advantageous to kill 7CAR cells in a subject if the subject has an adverse reaction to the 7CAR cells.

[0652] The methods in some embodiments include treating, contacting, and / or incubating a composition and / or a sample comprising T cells transduced with a CAR with the anti- idiotypic antibody. In certain embodiments, the methods further include detecting whether the CAR-T cells are inactivated, such as by assessing the viability, proliferation, and / or expression of activation markers in the CAR-T cells. In some embodiments, the methods are in association with a therapy comprising administration of CAR-T cells. The methods in some embodiments include administering the anti-idiotypic antibody to an individual. In one embodiment, an anti-idiotypic antibody or conjugate is used to ablate and / or deplete (such as kill) CAR-T cells in an individual. In some embodiments, the target polypeptide is an anti- CD? antibody, or an antigen-binding fragment thereof.

[0653] In some embodiments, the anti-idiotypic antibody is administered to deplete, reduce, and / or decrease the number of CAR expressing cells in a subject. In particular embodiments, administration of the anti-idiotypic antibody depletes, reduces, and / or decreases the amount of CAR expressing cells, e.g., circulating CAR-T cells, by at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, at least 99.9%, 100% or about 100%. In certain embodiments, the depletion, reduction, and / or decrease is in relation to an amount of CAR expressing cells in the subject prior to the administration of the anti-idiotypic antibody. In particular embodiments, the depletion, reduction, and / or decrease is in relation to an amount of CAR expressing cells in a subject that is not administered the anti-idiotypic antibody. In some embodiments, CAR expressing cells are not detectable in the subject following administration of the anti-idiotypic antibody. In particular embodiments, the anti-idiotypic antibody is a human or humanized antibody.

[0654] In some embodiments, there is provided a method of inactivating CAR-T cells, wherein the CAR comprises a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, comprising incubating a sample comprising the CAR-T cells with an antagonistic anti-idiotypic antibody or antigen-binding fragment thereof targeting the CAR, thereby inactivating the CAR-T cells in the sample. In some embodiments, the anti-idiotypic antibody is used in an amount sufficient to attenuate the activation of the CAR-T cells in the sample. In some embodiments, the anti -idiotypic antibody is used in an amount sufficient to substantially inactivate the CAR-T cells in the sample. In some embodiments, incubation with the anti-idiotypic antibody results in ablation and / or depletion of CAR-T cells in the sample. In some embodiments, the anti -idiotypic antibody is used in an amount sufficient to result in clearance of the CAR-T cells in the sample.

[0655] In some embodiments, the anti-idiotypic antibody is administered to deplete, reduce, and / or decrease the activity of the CAR and / or the CAR expressing cells in a subject. In particular embodiments, administration of the anti-idiotypic antibody reduces and / or decreases stimulation and / or activation of the CAR and / or the CAR expressing cell by at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, at least 99.9%, 100% or about 100%. In certain embodiments, the reduction and / or decrease is in relation to the stimulation and / or activity of the CAR and / or CAR expressing cells in the subject prior to the administration of the anti-idiotypic antibody. In particular embodiments, the reduction and / or decrease is in relation to stimulation and / or activity of the CAR and / or CAR expressing cells in a subject that is not administered the anti-idiotypic antibody. In some embodiments, the activity and / or stimulation refers to one or more aspects of CAR receptor or CAR-T cell activity and may be assessed by any suitable known means, including by any means provided herein. In some embodiments, activity and / or stimulation of the CAR and / or CAR expressing cells are not detectable in the subject following administration of the anti-idiotypic antibody. In particular embodiments, the anti-idiotypic antibody is a human or humanized antibody.

[0656] In some embodiments, the anti-idiotypic antibody is administered to prevent, reduce, and / or decrease the binding and / or the ability of the CAR and / or the CAR expressing cells to bind to the antigen. In particular embodiments, administration of the anti-idiotypic antibody reduces and / or decreases antigen binding of the CAR and / or the CAR expressing cell by at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, at least 99.9%, 100% or about 100%. In certain embodiments, the reduction and / or decrease is in relation to the antigen binding and / or the ability of the CAR and / or CAR expressing cells to bind to the antigen in the subject prior to the administration of the anti- idiotypic antibody. In particular embodiments, the reduction, and / or decrease is in relation to antigen binding and / or the ability to bind the antigen of the CAR and / or CAR expressing cells in a subject that is not administered the anti-idiotypic antibody. In particular embodiments, the anti-idiotypic antibody is a human or humanized antibody. In some embodiments, there is provided a method of ablating and / or depleting (such as killing) CAR-T cells, wherein the CAR comprises a target polypeptide, such as an anti- CD? antibody, or an antigen-binding fragment thereof, comprising incubating a sample comprising the CAR-T cells with an anti-idiotypic antibody or antigen-binding fragment thereof targeting the CAR, thereby ablating and / or depleting CAR-T cells in the sample. In some embodiments, the ablating and / or depleting is by antibody-dependent cell-mediated cytotoxicity (ADCC). In some embodiments, the ablating and / or depleting is mediated by an agent (e.g., a chemotherapeutic drug) to which the anti-idiotypic antibody is conjugated (e.g., an antibody-drug conjugate). In some embodiments, the anti-idiotypic antibody is used in an amount sufficient to result in ablation and / or depletion of substantially all of the CAR-T cells in the sample.

[0657] In some embodiments, there is provided a method of adjusting a CAR-T cell therapy in an individual, wherein the CAR comprises a target antibody, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, comprising administering an antagonistic anti-idiotypic antibody or antigen-binding fragment thereof targeting the CAR to the individual, thereby inactivating the CAR-T cells. In some embodiments, the anti -idiotypic antibody is administered in an amount sufficient to attenuate the activation of the CAR-T cells in the individual. In some embodiments, the anti-idiotypic antibody is administered in an amount sufficient to substantially inactivate the CAR-T cells in the individual. In some embodiments, administration of the anti-idiotypic antibody results in ablation and / or depletion of CAR-T cells in the individual. In some embodiments, the anti-idiotypic antibody is administered in an amount sufficient to result in clearance of the CAR-T cells in the individual.

[0658] In some embodiments, there is provided a method of adjusting a CAR-T cell therapy in an individual, wherein the CAR comprises a target polypeptide, such as an anti-CD7 antibody, or an antigen-binding fragment thereof, comprising administering an anti-idiotypic antibody immunoconjugate targeting the CAR to the individual, wherein the anti-idiotypic antibody immunoconjugate comprises a cytotoxic agent. In some embodiments, the anti- idiotypic antibody immunoconjugate is administered in an amount sufficient to attenuate the CAR-T cell therapy in the individual. In some embodiments, the anti-idiotypic antibody immunoconjugate is administered in an amount sufficient to substantially stop the CAR-T cell therapy in the individual. In some embodiments, the anti -idiotypic antibody immunoconjugate is administered in an amount sufficient to result in clearance of the CAR-T cells in the individual. In some embodiments, the cytotoxic agent is selected from the group consisting of chemotherapeutic agents or drugs, growth inhibitory agents, toxins (e.g., protein toxins, enzymatically active toxins of bacterial, fungal, plant, or animal origin, or fragments thereof), and radioactive isotopes.

[0659] Immun oconj ugates

[0660] In some embodiments, an anti-idiotypic antibody of the disclosure is or is part of an immunoconjugate (“ anti-idiotypic antibody immunoconjugate”), in which the anti-idiotypic antibody is conjugated to one or more heterologous molecule(s), such as, but not limited to, a cytotoxic or an imaging agent. The fusion of the cytotoxic agent with the anti-idiotypic antibody may have therapeutic value. Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At211, 1131, 1125, Y90, Rel86, Rel88, Sml53, Bi212, P32, Pb212and radioactive isotopes of Lu); chemotherapeutic agents (e.g., maytansinoids, taxanes, methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitory agents; enzymes and fragments thereof such as nucleolytic enzymes; antibiotics; toxins such as small molecule toxins or enzymatically active toxins. In some embodiments, the antibody is conjugated to one or more cytotoxic agents, such as chemotherapeutic agents or drugs, growth inhibitory agents, toxins (e.g., protein toxins, enzymatically active toxins of bacterial, fungal, plant, or animal origin, or fragments thereof), or radioactive isotopes.

[0661] Among the anti-idiotypic antibody immunoconjugates are antibody-drug conjugates (ADCs), in which an anti-idiotypic antibody is conjugated to one or more drugs, including but not limited to a maytansinoid (see U.S. Patent Nos. 5,208,020, 5,416,064 and European Patent EP 0 425 235 B 1); an auristatin such as monomethylauristatin drug moieties DE and DF (MMAE and MMAF) (see U.S. Patent Nos. 5,635,483 and 5,780,588, and 7,498,298); a dolastatin; a calicheamicin or derivative thereof (see U.S. Patent Nos. 5,712,374, 5,714,586, 5,739,116, 5,767,285, 5,770,701, 5,770,710, 5,773,001, and 5,877,296; Hinman et al., Cancer Res. 53: 3336-3342 (1993); and Lode et al, Cancer Res. 58: 2925-2928 (1998)); an anthracycline such as daunomycin or doxorubicin (see Kratz et al., Current Med. Chem. 13: 477- 523 (2006); Jeffrey et al., Bioorganic & Med. Chem. Letters 16: 358-362 (2006); Torgov et al., Bioconj. Chem. 16: 717-721 (2005); Nagy et al, Proc. Natl. Acad. Sci. USA 97: 829-834 (2000); Dubowchik et al, Bioorg. & Med. Chem. Letters 12: 1529-1532 (2002); King et al, J. Med. Chem. 45: 4336-4343 (2002); and U.S. Patent No. 6,630,579); methotrexate; vindesine; a taxane such as docetaxel, paclitaxel, larotaxel, tesetaxel, and ortataxel; a trichothecene; and CC1065.

[0662] Also among the anti-idiotypic antibody immunoconjugates are those in which the antibody is conjugated to an enzymatically active toxin or fragment thereof, including but not limited to diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes.

[0663] Also among the anti-idiotypic antibody immunoconjugates are those in which the anti-idiotypic antibody is conjugated to a radioactive atom to form a radioconjugate. Exemplary radioactive isotopes include At211, 1131, 1125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212and radioactive isotopes of Lu.

[0664] Conjugates of an anti-idiotypic antibody and cytotoxic agent may be made using any of a number of known protein coupling agents, e.g., linkers, (see Vitetta et al., Science 238: 1098 (1987)). The linker may“be a "cleavable ’’inker" facilitating release of a cytotoxic drug in the cell, such as acid-labile linkers, peptidase- sensitive linkers, photolabile linkers, dimethyl linkers, and disulfide-containing linkers (Chari et al., Cancer Res. 52: 127-131 (1992); U.S. Patent No. 5,208,020).

[0665] Also provided are anti-idiotypic antibody immunoconjugates comprising an anti- idiotypic antibody attached to a label, e.g., a detectable label, which can generate a detectable signal, indirectly or directly. These anti-idiotypic antibody immunoconjugates can be used for research or diagnostic applications. The label is preferably capable of producing, either directly or indirectly, a detectable signal. For example, the label may be radio-opaque or a radioisotope, such as3H,14C,32P,35S,1231,1251,131I; a fluorescent (fluorophore) or chemiluminescent (chromophore) compound, such as fluorescein isothiocyanate, rhodamine or luciferin; an enzyme, such as alkaline phosphatase, P-galactosidase or horseradish peroxidase; an imaging agent; or a metal ion. In some embodiments, the label is a radioactive atom for scintigraphic studies, for example99Tc or123I, or a spin label for nuclear magnetic resonance (NMR) imaging (also known as magnetic resonance imaging, MRI), such as zirconium-89, iodine- 123, iodine- 131, indium-i l l, fluorine-19, carbon-13, nitrogen-15, oxygen- 17, gadolinium, manganese or iron. Zirconium-89 may be complexed to various metal chelating agents and conjugated to antibodies, e.g., for PET imaging (WO 2011 / 056983). Examples of detectable labels include but are not limited to radionucleotides, enzymes, coenzymes, fluorescers, chemiluminescers, chromogens, enzyme substrates or co- factors, enzyme inhibitors, prosthetic group complexes, free radicals, particles, dyes, and the like. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, P- galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin, coumarin, Alexa488, Oregon green 488, rhodamine green, Alexa 532, Cy3, Bodipy 588 / 586, Alexa586, TAMRA, Rox, Alexa 594, Texas red, Bodipy 630 / 650, Cy5, Alexa647, IR Dye 680, IR Dye 680, IR Dye 700 DX, Cy5.5, Alexa 750, IR Dye 800CW, IR Dye 800, Atto 532, and Atto 465.

[0666] In some embodiments, the anti-idiotypic antibody immunoconjugate is detectable indirectly. For example, a secondary antibody that is specific for the anti-idiotypic antibody immunoconjugate and contains a detectable label can be used to detect the anti-idiotypic antibody immunoconjugate.

[0667] Generation and Screening of Antibodies

[0668] Antibodies, including recombinantly produced antibodies, that specifically bind to an anti-cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof are provided and described herein. In embodiments, the antibodies are selected from those described in Tables 1A-5, or antigen-binding fragments thereof.

[0669] Methods for generating antibodies against a protein or peptide of interest are known and practiced in the art. When animals are immunized with antigens they respond by generating a polyclonal antibody response comprised of many individual monoclonal antibody specificities. It is the sum of these individual specificities that make polyclonal antibodies useful in so many different assays. Individual monoclonal antibodies were originally isolated by immortalizing individual B cells using hybridoma technology (Kohler and Milstein, Nature 256, 495, 2011), in which B cells from an immunized animal are fused with a myeloma cell. With the advent of molecular biology, in vitro methods to generate antibodies against proteins of interest, such as an anti-CD7 antibody or an antigen-binding fragment thereof, have been developed.

[0670] An antibody is a polypeptide chain-containing molecular structure with a specific shape that specifically binds an epitope (e.g., the idiotype of an anti-CD7 antibody), where one or more non-covalent binding interactions stabilize the complex between the molecular structure and the epitope. In one embodiment, an antibody molecule is an immunoglobulin (e.g., IgG, IgM, IgA, IgE, IgD). Antibodies from a variety of sources, e.g., human, rodent, rabbit, cow, sheep, pig, dog, or fowl are consi“ered "antib”dies." Numerous antibody coding sequences have been described; and others may be raised by methods well-known in the art.

[0671] For example, antibodies or antigen-binding fragments may be produced by genetic engineering. Antibody coding sequences of interest include those encoded by native sequences, as well as nucleic acids that, by virtue of the degeneracy of the genetic code, are not identical in sequence to a wild-type nucleic acid sequence. Variant polypeptides can include amino acid (aa) substitutions, additions or deletions. The amino acid substitutions can be conservative amino acid substitutions or substitutions to eliminate non-essential amino acids, such as to alter a glycosylation site, or to minimize misfolding by substitution or deletion of one or more cysteine residues that are not necessary for function. Variants can be designed so as to retain or have enhanced biological activity of a particular region of the protein (e.g., a functional domain, catalytic amino acid residues). Variants also include fragments of the polypeptides disclosed herein, particularly biologically active fragments and / or fragments corresponding to functional domains. Techniques for in vitro mutagenesis of cloned genes are known. Also included in some aspects and embodiments herein are polypeptides that have been modified using ordinary molecular biological techniques so as to improve their resistance to proteolytic degradation or to optimize solubility properties or to render them more suitable as a therapeutic agent.

[0672] Chimeric antibodies may be made by recombinant means by combining the variable light and heavy chain regions obtained from antibody producing cells of one species with the constant light and heavy chain regions from another. Typically, chimeric antibodies utilize rodent or rabbit variable regions and human constant regions, in order to produce an antibody with predominantly human domains. The production of such chimeric antibodies is well known in the art and may be achieved by standard means (as described, e.g., in U.S. Pat. No. 5,624,659, incorporated fully herein by reference).

[0673] Humanized antibodies are engineered to contain even more human-like immunoglobulin domains and incorporate only the complementarity-determining regions of the animal-derived antibody. This is accomplished by carefully examining the sequence of the hyper-variable loops of the variable regions of the monoclonal antibody and fitting them to the structure of the human antibody chains. Although apparently complex, the process is straightforward in practice. See, e.g., U.S. Patent No. 6,187,287, incorporated fully herein by reference.

[0674] In addition to entire immunoglobulins (or their recombinant counterparts), immunoglobulin fragments comprising the epitope binding site (e.g’, Fab” F(ab')2, or other fragments) may be synthesi“ed. "Fra”ment," or minimal immunoglobulins may be designed utilizing recombinant immunoglobulin techniques. For inst“nc”, "Fv" immunoglobulins for use in some aspects and embodiments herein may be produced by synthesizing a variable light chain region and a variable heavy chain region. Combinations of antibodies are also of interest, e.g., diabodies, which comprise two distinct Fv specificities.

[0675] Immunoglobulins may be modified post-translationally, e.g., to add chemical linkers, detectable moieties, such as fluorescent dyes, enzymes, substrates, chemiluminescent moieties and the like, or specific binding moieties, such as streptavidin, avidin, or biotin, and the like may be utilized in the methods and compositions of some aspects and embodiments herein.

[0676] Screening of Libraries of Antibodies

[0677] Methods for high throughput screening of polypeptide (e.g., antibody or antigen- binding antibody fragment) libraries for molecules capable of binding to the anti-CD7 antibody, or antigen-binding fragments thereof, include, without limitation, display techniques including phage display, bacterial display, yeast display, mammalian display, ribosome display, mRNA display, and cDNA display. The use of phage display to isolate ligands that bind biologically relevant molecules has been reviewed, e.g., in Felici et al. (Biotechnol. Annual Rev. 1: 149-183, 1995), Katz (Annual Rev. Biophys. Biomol. Struct. 26:27-45, 1997), and Hoogenboom et al. (Immunotechnology 4: 1-20, 1998). Several randomized combinatorial peptide libraries have been constructed to select for polypeptides that bind different targets, e.g., cell surface receptors or DNA (reviewed by Kay (Perspect. Drug Discovery Des. 2, 251-268, 1995), Kay et al., (Mol. Divers. 1: 139-140, 1996)). Proteins and multimeric proteins have been successfully phage-displayed as functional molecules (see. e.g., EP 0349578A, EP 4527839A, EP 0589877A; Chiswell and McCafferty (Trends Biotechnol. 10, 80-84 1992)). In addition, functional antibody fragments (e.g., Fab, single-chain Fv [scFv]) have been expressed as reported by McCafferty et al. (Nature 348: 552-554, 1990), Barbas et al. (Proc. Natl. Acad Sci. USA 88:7978-7982, 1991), and Clackson et al. (Nature 352:624-628, 1991). These references are hereby incorporated by reference in their entirety.

[0678] In addition to generating anti-idiotypic antibodies capable of binding an anti-CD7 antibody of some aspects and embodiments herein, in vitro display techniques, which are known and practiced in the art, also provide methods for improving the affinity of an anti- idiotypic antibody capable of binding an anti-CD7 antibody, or antigen-binding fragments thereof. For instance, rather than screening libraries of antibodies and fragments thereof containing completely randomized hypervariable regions, narrower libraries of antibodies and antigen-binding fragments thereof that feature targeted mutations at specific sites within hypervariable regions can be screened. This can be accomplished, for example, by assembling libraries of polynucleotides encoding antibodies or antigen-binding fragments thereof that encode random mutations only at particular sites within hypervariable regions. These polynucleotides can then be expressed in, e.g., filamentous phage, bacterial cells, yeast cells, mammalian cells, or in vitro using, e.g., ribosome display, mRNA display, or cDNA display techniques in order to screen for antibodies or antigen-binding fragments thereof that specifically bind to the anti-CD7 antibody, or antigen-binding fragments thereof, with improved binding affinity. Yeast display, for instance, is well-suited for affinity maturation, and has been used previously to improve the affinity of a single-chain antibody to a KD of 48 fM (Boder et al. (Proc Natl Acad Sci USA 97: 10701, 2000)).

[0679] Additional in vitro techniques that can be used for the generation and affinity maturation of anti-idiotypic antibodies capable of binding an anti-CD7 antibody, and antigen- binding fragments thereof (e.g., single-chain polypeptides, antibodies, and antigen-binding fragments thereof) of some aspects and embodiments herein include the screening of combinatorial libraries of antibodies or antigen-binding fragments thereof for functional molecules capable of specifically binding to peptides derived from an anti-CD7 antibody. Combinatorial antibody libraries can be obtained, e.g., by expression of polynucleotides encoding randomized hypervariable regions of an antibody or antigen-binding fragment thereof in a eukaryotic or prokaryotic cell. This can be achieved, e.g., using gene expression techniques described herein or known in the art. Heterogeneous mixtures of antibodies can be purified, e.g., by Protein A or Protein G selection, sizing column chromatography), centrifugation, differential solubility, and / or by any other standard technique for the purification of proteins. Libraries of combinatorial libraries thus obtained can be screened, e.g., by incubating a heterogeneous mixture of these antibodies with a peptide(s) derived from the anti-CD7 antibody that has been immobilized to a surface for a period of time sufficient to allow antibody-antigen binding. Non-binding antibodies or fragments thereof can be removed by washing the surface with an appropriate buffer (e.g., a solution buffered at physiological pH (approximately 7.4) and containing physiological salt concentrations and ionic strength, and optionally containing a detergent, such as TWEEN-20®). Antibodies that remain bound can subsequently be detected, e.g., using an ELISA-based detection protocol (see, e.g., U.S. Patent No. 4,661,445; incorporated herein by reference).

[0680] Additional techniques for screening combinatorial libraries of polypeptides (e.g., antibodies, and antigen-binding fragments thereof) for those that specifically bind to anti- CD7-derived peptides include the screening of one-bead-one-compound libraries of antibody fragments. Antibody fragments can be chemically synthesized on a solid bead (e.g., using established split-and-pool solid phase peptide synthesis protocols) composed of a hydrophilic, water-swellable material such that each bead displays a single antibody fragment. Heterogeneous bead mixtures can then be incubated with an anti-CD7 antibody- derived peptide that is optionally labeled with a detectable moiety (e.g., a fluorescent dye) or that is conjugated to an epitope tag (e.g., biotin, avidin, FLAG tag, HA tag) that can later be detected by treatment with a complementary tag (e.g., avidin, biotin, anti-FLAG antibody, anti-HA antibody, respectively). Beads containing antibody portions or fragments that specifically bind to an anti-CD7 antibody-derived peptide can be identified by analyzing the fluorescent properties of the beads following incubation with a fluorescently-labeled antigen or complementary tag (e.g., by confocal fluorescent microscopy or by fluorescence-activated bead sorting; see, e.g., Muller et al. (J. Biol. Chem., 16500-16505, 1996); incorporated herein by reference in its entirety for all purposes). Beads containing antibody fragments that specifically bind to anti-CD7 antibody-derived peptides can thus be separated from those that do not contain high-affinity antibody fragments. The sequence of an antibody fragment that specifically binds to an anti-CD7 antibody-derived peptide can be determined by techniques known in the art, including, e.g., Edman degradation, tandem mass spectrometry, matrix- assisted laser-desorption time-of-flight mass spectrometry (MALDI-TOF MS), nuclear magnetic resonance (NMR), and 2D gel electrophoresis, among others (see, e.g., WO 2004 / 062553; incorporated herein by reference).

[0681] Methods of Identifying Antibodies and Ligands

[0682] Methods for high throughput screening of antibody, antibody fragment, and ligand libraries for molecules capable of binding an anti-CD7 antibody or antigen-binding fragments thereof can be used to identify antibodies suitable for the uses as described herein. Such methods include in vitro display techniques known in the art, such as phage display, bacterial display, yeast display, mammalian cell display, ribosome display, mRNA display, and cDNA display, among others. The use of phage display to isolate ligands that bind biologically relevant molecules has been reviewed, for example, in Felici et al., Biotechnol. Annual Rev. 1: 149-183, 1995; Katz, Annual Rev. Biophys. Biomol. Struct. 26:27-45, 1997; and Hoogenboom et al., Immunotechnology 4: 1-20, 1998, the disclosures of each of which are incorporated herein by reference in their entireties for all purposes. Randomized combinatorial peptide libraries have been constructed to select for polypeptides that bind cell surface antigens as described in Kay, Perspect. Drug Discovery Des . 2:251-268, 1995 and Kay et al., Mol. Divers. 1 : 139-140, 1996, the disclosures of each of which are incorporated herein by reference in their entireties for all purposes. Proteins, such as multimeric proteins, have been successfully phage-displayed as functional molecules (see, for example, EP 0349578; EP 4527839; and EP 0589877, as well as Chiswell and McCafferty, Trends Biotechnol. 10:80-84 1992, the disclosures of each of which are incorporated herein by reference in their entireties for all purposes). In addition, functional antibody fragments, such as Fab and scFv fragments, have been expressed in in vitro display formats (see, for example, McCafferty et al., Nature 348:552-554, 1990; Barbas et al., Proc. Natl. Acad. Sci. USA 88:7978-7982, 1991; and Clackson et al., Nature 352:624-628, 1991, the disclosures of each of which are incorporated herein by reference in their entireties for all purposes). These techniques, among others, can be used to identify and improve the affinity of antibodies that bind to the anti-CD7 antibody, or antigen-binding fragments thereof.

[0683] Producing Antibodies

[0684] Mammalian cells can be co-transfected with polynucleotides encoding the antibodies of some aspects and embodiments herein, which are expressed as recombinant polypeptides, and assembled into anti -idiotypic antibodies capable of binding an anti-CD7 antibody by the host cell. In one embodiment, a mammalian cell is co-transfected with polynucleotides encoding the heavy and light chains of an anti-idiotypic antibody capable of binding an anti- CD7 antibody, which are expressed in the cell and assembled as the anti-idiotypic antibody capable of binding an anti-CD7 antibody.

[0685] It is possible to express antibodies or antigen-binding fragments thereof in either prokaryotic or eukaryotic host cells. In certain embodiments, expression of polypeptides or antigen-binding fragments thereof is performed in eukaryotic cells, e.g., mammalian host cells, for optimal secretion of a properly folded and immunologically active antibody. Exemplary, nonlimiting mammalian host cells for expressing the recombinant antibodies or antigen-binding fragments thereof of some aspects and embodiments herein include Chinese Hamster Ovary (CHO cells) (including DHFR CHO cells, described in Urlaub and Chasin (1980, Proc. Natl. Acad. Set. USA 77:4216-4220), used with a DHFR selectable marker, e.g., as described in Kaufman and Sharp (1982, Mol. Biol. 159:601-621), NSO myeloma cells, COS cells, HEK293T cells, SP2 / 0, NIH3T3, and BaF3 cells. Additional, nonlimiting cell types that may be useful for the expression of antibodies and fragments thereof include bacterial cells, such as BL-21(DE3) E. colt cells, which can be transformed with vectors containing foreign DNA according to established protocols. Additional eukaryotic cells that may be useful for expression of antibodies include yeast cells, such as auxotrophic strains of .S', cerevisiae. which can be transformed and selectively grown in incomplete medium according to established procedures known in the art. When recombinant expression vectors encoding antibody genes are introduced into mammalian host cells, the antibodies are produced by culturing the host cells for a period of time sufficient to allow for expression of the antibody protein in the host cells or secretion of the antibody into the culture medium in which the host cells are grown.

[0686] Polypeptides (e.g., antibodies or antigen-binding fragments thereof) can be recovered from the culture medium using standard protein purification methods. Host cells can also be used to produce portions of intact antibodies, such as Fab fragments or scFv molecules. Also included in some aspects and embodiments herein are methods in which the above procedure is varied according to established protocols known in the art. For example, it may be desirable to transfect a host cell with DNA encoding either the light chain or the heavy chain (but not both) of an anti-idiotypic antibody capable of binding an anti-CD7 antibody of some aspects and embodiments herein in order to produce an antigen-binding fragment of the antibody.

[0687] Once an anti-idiotypic antibody capable of binding an anti-CD7 antibody of some aspects and embodiments herein has been produced by recombinant expression, it can be purified by any method known in the art, such as a method useful for purification of an immunoglobulin molecule, for example, by chromatography (e.g., ion exchange, affinity, affinity for antigen (e.g., an anti-CD7 antibody or antigen-binding fragment thereof) after Protein A or Protein G selection, and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for the purification of proteins. Further, an anti-idiotypic antibody capable of binding an anti-CD7 antibody, or an antigen- binding fragment thereof, can be fused to heterologous polypeptide sequences as known in the art, for example, to facilitate purification, e.g., a histidine tag, a detectable / detectably labeled marker, and the like.

[0688] Once isolated, an anti -idiotypic antibody capable of binding an anti-CD7 antibody, or antigen-binding fragment thereof can, if desired, be further purified, e.g., by high performance liquid chromatography (see, e.g., Fisher, Laboratory Techniques in Biochemistry and Molecular Biology (Work and Burdon, eds., Elsevier, 1980); incorporated herein by reference), or by gel filtration chromatography, such as on a Superdex.TM. 75 column (Pharmacia Biotech AB, Uppsala, Sweden).

[0689] Compositions

[0690] In some aspects, the disclosure provides a composition (e.g., a pharmaceutical composition) comprising 7CAR-T cells prepared according to the methods provided herein (e.g., isolated, stimulated, or characterized using the anti-idiotypic antibodies), anti-idiotypic antibodies, or antigen-binding fragments thereof, polynucleotides encoding such antibodies, or vectors comprising the polynucleotides as described herein.

[0691] The compositions of the present invention can be prepared in accordance with known techniques. See, e.g., Remington, The Science And Practice of Pharmacy(21st ed. 2005). In general, the cell, or population thereof is admixed with a suitable carrier prior to use or storage, and in some embodiments, the composition further comprises a pharmaceutically acceptable carrier or excipient. Suitable carriers generally comprise inert substances that aid in administering a composition to a subject or cell, aid in processing the compositions into preparations ready for use, or aid in storing the composition prior to use. Acceptable carriers can include agents that can stabilize, optimize or otherwise alter the form, consistency, viscosity, pH, pharmacokinetics, solubility of the composition. Such agents include buffering agents, wetting agents, emulsifying agents, diluents, encapsulating agents, and skin penetration enhancers. For example, carriers can include, but are not limited to, saline, buffered saline, dextrose, arginine, sucrose, water, glycerol, ethanol, sorbitol, dextran, sodium carboxymethyl cellulose, and combinations thereof.

[0692] In some embodiments, the composition is formulated for delivery to a subject. Suitable routes of administrating the composition described herein include, without limitation: topical, subcutaneous, transdermal, intradermal, intralesional, intraarticular, intraperitoneal, intravesical, transmucosal, gingival, intradental, intracochlear, transtympanic, intraorgan, epidural, intrathecal, intramuscular, intravenous, intravascular, intraosseus, periocular, intratumoral, intracerebral, and intracerebroventricular administration.

[0693] In some embodiments, the composition described herein is administered locally to a diseased site. In some embodiments, the pharmaceutical composition described herein is administered to a subject by injection, by means of a catheter, by means of a suppository, or by means of an implant, the implant being of a porous, non-porous, or gelatinous material, including a membrane, such as a sialastic membrane, or a fiber.

[0694] In some embodiments, any of the cells (e.g., 7CAR-T cells), anti-idiotypic antibodies, or antigen-binding fragments thereof, polynucleotides, or vectors are provided as part of a composition (e.g., a pharmaceutical composition). In some embodiments, the composition comprises any of the cells (e.g., 7CAR-T cells), anti-idiotypic antibodies, or antigen-binding fragments thereof, polynucleotides, or vectors provided herein. Pharmaceutical compositions can optionally comprise one or more additional therapeutically active substances.

[0695] The compositions, as described above, can be administered in effective amounts. The effective amount will depend upon the mode of administration, the particular use, and / or the desired outcome. It may also depend upon the stage of the condition, the age and physical condition of the subject, the nature of therapy, and like factors well-known to the medical practitioner. For therapeutic applications, it is that amount sufficient to achieve a medically desirable result.

[0696] In some embodiments, compositions in accordance with the present disclosure can be used in the treatment of any of a variety of diseases, disorders, and / or conditions.

[0697] The compositions can also be lyophilized. The compositions can contain auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH buffering agents, gelling or viscosity enhancing additives, preservatives, colors, and the like. Standard texts may in some aspects be consulted to prepare suitable preparations.

[0698] The formulations to be used for in vivo administration are generally sterile. Sterility may be readily accomplished, e.g., by fdtration through sterile fdtration membranes.

[0699] Articles of Manufacture or Kits

[0700] Also provided are articles of manufacture or kits containing anti-idiotypic antibodies that bind an anti-CD7 antibody or antigen-binding fragment thereof, antigen-binding fragments thereof, conjugates, and / or compositions that suitable for use in any of the methods provided herein. In some aspects, a conjugate (e.g., an anti-idiotypic antibody conjugated to a detectable labe or to a drugl) containing the anti-idiotypic antibodies described herein are provided in the articles of manufacture or kits.

[0701] In some embodiments (e.g., a kit for use in a meso scale discovery anti-drug antibody assay; see, e.g,, FIG. 12 or FIG. 13), the kit or article of manufacture includes the anti- idiotypic antibody or antigen-binding fragment thereof and a capture polypeptide containing the extracellular domain, or portion of an extracellular domain of a chimeric antigen receptor (CAR) to which the anti -idiotypic antibody binds. In some embodiments, the extracellular domain of the CAR is or includes an anti-CD7 antibody or an antigen-binding fragment thereof. In embodiments, these kits are useful in detecting anti-7CAR antibodies present in the blood of a subject, where, in some cases, the antibodies are generated as part of an immune response to 7CAR cells administered to the subject.

[0702] In some embodiments, the kit or article of manufacture additionally includes a detection polypeptide (e.g., a detectably labeled anti-CD7 antibody or 7CAR, or an antigen- binding fragment thereof), such as for use in a meso scale discovery assay (e.g., FIG. 12). In such examples, the detection polypeptide (e.g., a detectably labeled 7CAR, or a detectably labeled antigen-binding fragment thereof) is an agent that is able to bind to the same or similar molecule (e.g., CD7 and / or an anti -idiotypic antibody of the disclosure) as the capture polypeptide (see, e.g., FIG. 12). In some embodiments, the detection polypeptide comprises the extracellular domain of the CAR or a portion thereof. In some aspects, the extracellular domain of the CAR or portion thereof of the capture polypeptide and the detection polypeptide is the same or substantially the same.

[0703] In some embodiments, the capture and / or detection polypeptide, is attached to a label (e.g., detectable label) such as a label described herein. In some embodiments, at least one of the capture and / or detection polypeptide is attached to a solid support or capable of being attached to a solid support (see, e.g., FIG. 12). In some aspects, one of the capture and detection polypeptide is detectably labeled or is capable of producing a detectable signal and the other of the capture and detection polypeptide is attached or immobilized to the solid support. In some embodiments, the capture and detection polypeptides are provided as a kit or as part of a system as described elsewhere herein for use in connection with an immunoassay (e.g., sandwich or bridge assay). In some embodiments, the capture polypeptide is bound to a solid support, optionally a streptavidin coated solid support (e.g., FIG. 12). In some embodiments, the detection polypeptide is linked directly or indirectly to a detectable label. In some embodiments, the anti-idiotypic antibody or antigen-binding fragment thereof is provided as a positive control sample. In some examples, the positive control sample forms a complex with the capture and detection polypeptides or reagents which contains regions of the extracellular domain of a chimeric antigen receptor (CAR) comprising an anti-CD7 antibody or an antigen-binding fragment thereof.

[0704] In some embodiments, the kit or article of manufacturer comprises reagents or components for carrying out any of the provided methods. In some embodiments, the article of manufacture or kit comprises one or more reagent or other materials desirable from a commercial, therapeutic, and / or user standpoint including secondary antibodies, affinity labels, capture reagents, buffers, diluents, signal detection agents, filters, needles, syringes, capillary tubes, and package inserts with instructions for use.

[0705] In some embodiments, the kits can be provided as articles of manufacture that include packing materials for the packaging of the polypeptides or compositions thereof or the one or more additional reagents, e.g., capture and detection polypeptides, or components thereof. For example, the kits may contain containers, bottles, tubes, vial and any packaging material suitable for separating or organizing the components of the kit.

[0706] In some embodiments, the kit includes one or more containers. Suitable containers include, for example, bottles, vials (e.g., dual chamber vials), syringes (such as single or dual chamber syringes) and test tubes. The one or more containers may be formed from a variety of materials such as glass or plastic. The one or more containers hold a composition comprising an antibody or other reagents, e.g., capture and / or detection polypeptides, for use in the methods. The article of manufacture or kit herein may comprise the polypeptides (e.g., anti-idiotypic antibodies) or reagents in separate containers or in the same container. In some embodiments, the one or more containers holding the composition may be a single-use vial or a multi-use vial, which, in some cases, may allow for repeat use of the reconstituted composition.

[0707] In some embodiments, the article of manufacture or kit may further comprise a second container comprising a suitable diluent. The article of manufacture or kit may further include other materials desirable from a commercial, therapeutic, and user standpoint, including other buffers, diluents, filters, needles, syringes, therapeutic agents and / or package inserts with instructions for use.

[0708] The articles of manufacture may include a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, etc. The containers may be formed from a variety of materials such as glass or plastic. The container in some embodiments holds a composition containing an anti-idiotypic antibody or antigen-binding fragment thereof as provided herein which is by itself or is combined with another composition effective for treating, preventing and / or diagnosing a disease or condition. In some embodiments, the container has a sterile access port. Exemplary containers include an intravenous solution bags, vials, including those with stoppers pierceable by a needle for injection. The article of manufacture may include a first container with a composition contained therein, wherein the composition includes the anti- idiotypic antibody. Alternatively, or additionally, the article of manufacture may further include another or the same container comprising an acceptable buffer. It may further include other materials such as oth...

Claims

CLAIMSWhat is claimed is:

1. An antibody or an antigen-binding fragment thereof that specifically binds to an anti- cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof, wherein the binding polypeptide comprises one or more complementarity determining regions (CDRs) selected from the group consisting of heavy chain variable region (VH) CDR1, VH CDR2, VH CDR3, light chain variable region (VL) CDR1, VL CDR2, and VL CDR3, wherein a) the VH CDR1 comprises the following amino acid sequence:GX2X3X4X5X6X7X8X9, whereinX2 is F, I, or S,X3 is D, I, S, or T,X4 is F, I, or L,Xs is I or S,Xe is G, N, null, P, S, or T,X7is A, D, G, S, V, or Y,Xs is H, N, or Y, andX9is A, C, D, F, G, R, S, W, or Y; b) the VH CDR2 comprises the following amino acid sequence:X10X11X12X13X14X15X16X17X18, wherein Xio is A, G, I, null, R, T, or V,Xn is A, D, F, G, H, N, null, S, V, W, or Y,X12 is A, C, D, G, I, N, null, P, T, or V,X13 is A, D, G, I, L, null, R, S, T, or V,X14 is D, G, I, N, null, R, S, T, or V,X15 is D, H, N, S, T, or V,Xi6 is D, G, null, S, or V,X17 is D, I, K, N, null, P, R, S, T, V, or Y, andXis is A, I, N, null, or T; c) the VH CDR3 comprises the following amino acid sequence:X19X20X21X22X23X24X25X26X27X28X29X30X31X32X33X34X35X36X37X38X39X40X41X42, whereinX19 is A or V,X20 is K, R, or S,X21 is A, D, E, G, I, R, S, or V,X22 is D, E, G, L, P, or T,X23 is A, D, G, I, N, null, S, T, V, or Y,X24 is A, D, F, G, H, L, null, S, V, W, or Y,X25 is D, G, N, null, S, T, or V,X26 is A, D, E, F, G, null, S, V, or Y,X27 is A, D, E, G, N, null, S, T, V, W, or Y,X28is A, D, G, null, V, W, or Y,X29 is D, null, or Y,X30 is A, D, E, F, G, L, M, null, S, T, V, W, or Y,X31 is A, D, G, L, N, null, P, or T,X32 is A, D, G, L, N, null, or V,X33 is A, F, null, R, or Y,X34 is F or null,X35 is A, G, L, or null,X36 is G, Y, or null,X37 is G, I, N, null, T, orY,X38 is A, D, null, T, or Y,X39 is A, G, null, P, or T,X40 is F, I, L, M, V, W, orY,X41 is A, D, orN, andX42is F, I, L, or P; d) the VL CDR1 comprises the following amino acid sequence:X43X44X45X46X47X48X49X50, whereinX43 is E or Q,X44 is D, H, N, R, or S,X45 is I or V,X46is A, D, G, N, S, orY,X47 is G, N, R, S, T, or V,X48 is A, D, G, H, K, L, N, R, S, W, or Y,X49 is N or null, andX50 is C, F, or null;e) the VL CDR2 comprises the following amino acid sequence:X51X52S, whereinX51 is A, D, G, K, Q, S, T, W, or Y, andX52 is A, S, or T; and f) the VL CDR3 comprises the following amino acid sequence:X54X55X56X57X58X59X60X61X62X63X64X65X66X67X68X69X70X71, wherein X54 is A, L, or Q, X55 is C, G, Q, S, or Y, X56 is A, D, E, F, G, P, T, V, or Y, X57 is A, C, D, F, G, R, S, T, V, W, or Y, X58 is A, D, G, H, L, N, S, T, V, or Y, X59 is G or null, Xeo is G or null, X6iis A, C, D, G, I, S, or Y, X62 is D, G, I, L, N, R, S, T, orY, X63is F, G, I, N, R, S, or V, X64is A, D, F, G, I, P, S, T, V, or Y, X65is A, D, E, G, H, I, N, R, S, or V,X66 is A, C, F, G, H, I, N, null, P, R, S, T, V, W, or Y,X67 is A, F, G, I, N, null, R, S, T, V, W, or Y,X68is A, F, N, null, P, V, or Y,X69 is A, F, null, or V,X70 is F or null, andX71 is A or null.

2. The antibody or antigen-binding fragment thereof of claim 1, wherein the VH CDR1 amino acid sequence is 8 or 9 amino acids in length, the VH CDR2 amino acid sequence is between 4 and 9 amino acids in length, the VH CDR3 amino acid sequence is between 9 and 23 amino acids in length, the VL CDR1 amino acid sequence is between 6 and 8 amino acids in length, and the VL CDR3 amino acid sequence is between 10 and 16 amino acids in length.

3. The antibody or an antigen-binding fragment thereof of claim 1, wherein:a) the VH CDR1 comprises an amino acid sequence selected from the group consisting of: GFDFSSSYY (SEQIDNO: 92), GFDFSSYG (SEQ ID NO: 88), GFIISSSYC (SEQ IDNO: 90), GFSFSGGYD (SEQ ID NO: 89), GFSFSNSYY (SEQ ID NO: 100), GFSFSPSYC (SEQ ID NO: 86), GFSFSSAYW (SEQ ID NO: 102), GFSFSSGYD (SEQ ID NO: 105), GFSFSSGYY (SEQ ID NO: 93), GFSFSSSHY (SEQ IDNO: 99), GFSFSSSYF (SEQ ID NO: 82), GFSFSSSYR (SEQ ID NO: 95), GFSFSSSYS (SEQ IDNO: 103), GFSFSSSYW (SEQ ID NO: 81), GFSFSSSYY (SEQ IDNO: 83), GFSLSDYA (SEQ ID NO: 97), GFSLSDYY (SEQ ID NO: 80), GFSLSSGYD (SEQ IDNO: 101), GFSLSSNA (SEQ ID NO: 84), GFSLSSSYY (SEQ ID NO: 91), GFSLSSYA (SEQ IDNO: 85), GFSLSSYY (SEQ ID NO: 87), GFSLSVYA (SEQIDNO: 106), GFTISSSYC (SEQ ID NO: 104), GFTISSSYW (SEQ ID NO: 98), GIDFITYYY (SEQ ID NO: 94), and GSDISGYS (SEQ ID NO: 96), b) the VH CDR2 comprises an amino acid sequence selected from the group consisting of: INSDTT (SEQ ID NO: 116), AYGGGSGST (SEQ ID NO: 109), GYAGSSGST (SEQIDNO: 117), IAIGSGSA (SEQIDNO: 110), IAPGRSGST (SEQ IDNO: 127), IATADSGST (SEQIDNO: 121), IDGASSGRT (SEQIDNO: 138), IDPVHGTT (SEQIDNO: 120), IDTGGSSV (SEQ ID NO: 113), IFGGVSVRN (SEQ ID NO: 135), IGNGDGNT (SEQIDNO: 131), IHAGSSGNT (SEQIDNO: 140), IHAGSSGSI (SEQ IDNO: 144), IHDGSSGST (SEQ ID NO: 111), IHGGSSGNT (SEQ IDNO: 108), IHGGSSGST (SEQIDNO: 139), ILSSGKT (SEQIDNO: 143), ILSSGNT (SEQIDNO: 149), INARIT (SEQ ID NO: 133), INTGSGST (SEQIDNO: 129), ISGGSSGST (SEQIDNO: 114), ISGSGST (SEQIDNO: 132), ISNSGPT (SEQ IDNO: 119), ISSSGDT (SEQIDNO: 148), ISSTGST (SEQIDNO: 112), ITSNGRT (SEQIDNO: 126), IVTGTSGST (SEQIDNO: 137), IWGGSSGTT (SEQIDNO: 125), IYAGGSGNT (SEQ ID NO: 136), I YAGNSSYT (SEQ ID NO: 130), I YAGSSGNI (SEQ IDNO: 142), IYAGSSGSN (SEQIDNO: 147), IYAGSSGST (SEQIDNO: 134), IYASGST (SEQIDNO: 115), IYCGVVGT (SEQ ID NO: 145), I YGGSSGST (SEQ ID NO: 124), IYGSGTT (SEQIDNO: 107), IYIGDGIT (SEQIDNO: 123), IYVDNSGST (SEQIDNO: 141), RHGGSSGST (SEQIDNO: 146), SGST (SEQIDNO: 122), THDGSSGST (SEQ ID NO: 118), and VYGGSSGST (SEQ ID NO: 128), c) the VH CDR3 comprises an amino acid sequence selected from the group consisting of: VRDDGYLDL (SEQ ID NO: 158), AKEDGLVEEFAL (SEQ ID NO: 154),ARADDDYGAAPYYFNI (SEQ ID NO: 173), ARADNWNSGWLGAFDP (SEQ ID NO: 159),ARADYAGGDYFNL (SEQ ID NO: 160), ARADYTYGYVGYAFDL (SEQ ID NO: 176),ARADYTYGYVGYAFNL (SEQ ID NO: 175), ARALYADSNYWPLYFNF (SEQ ID NO: 150),ARDDAAYGGYFNL (SEQ ID NO: 187), ARDDAGGGGYFNL (SEQ ID NO: 165),ARDDAYSYSGATYAYGTFNL (SEQ ID NO: 168), ARDDAYVYGGADYAYGAFNL (SEQ IDNO: 178), ARDDIYGYAGYAYATAFNL (SEQ ID NO: 162), ARDDSAAGGYFNL (SEQ IDNO: 188), ARDDSTWGGYFNL (SEQ ID NO: 179), ARDDSYDDYAEGYFNI (SEQ ID NO:185), ARDDTVSFGYPYGYFNL (SEQ ID NO: 171), ARDDYAGGGYFNL (SEQ ID NO:153), ARDDYAGGGYINL (SEQ ID NO: 166), ARDDYAGGGYVNL (SEQ ID NO: 180),ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), ARDDYGGVAGYGYAFNL (SEQ ID NO:184), ARDDYHYGGTGYAYNL (SEQ ID NO: 186), ARDEVFTGGDAGYGYALNL (SEQ IDNO: 189), ARDEYAGYAGYGYAFNL (SEQ ID NO: 183), ARDGGYDDYGDFDYGMDP (SEQID NO: 190), AREGGYDDYGDFLNYFNL (SEQ ID NO: 155), ARGDGGMNYAWDL (SEQID NO: 169), ARGDGYDDYGDPFNL (SEQ ID NO: 156), ARGDSYDDYVDPFNI (SEQ IDNO: 167), ARGDYSDAFFNL (SEQ ID NO: 182), ARGEGYGYADYAGGRYYYGLDL (SEQID NO: 170), ARGEGYSYDDYGDYFLGIYPLDL (SEQ ID NO: 163),ARGEGYTYDDYGDYYDAFDP (SEQ ID NO: 157), ARIEYYSYGDVGYGYNYGMDL (SEQID NO: 181), ARRDSSGPYYFNL (SEQ ID NO: 164), ARSDYTGGNYFNL (SEQ ID NO:151), ARVDGSTGVYTLDL (SEQ ID NO: 174), ARVPYSSGWGADDAFDP (SEQ ID NO:161), ASDTHDYVGFNL (SEQ ID NO: 172), and VRDDYAGYAGYGYAFNL (SEQ ID NO:177), d) the VL CDR1 comprises an amino acid sequence selected from the group consisting of: EDIGTL (SEQ ID NO: 223), EDIYSL (SEQ ID NO: 216), EDIYSN (SEQID NO: 234), EDIYVN (SEQ ID NO: 208), ENIYSG (SEQ ID NO: 230), ENI YSN (SEQID NO: 232), ENIYSS (SEQ ID NO: 211), ESIDSH (SEQ ID NO: 224), ESIGSN (SEQID NO: 219), ESISSR (SEQ ID NO: 204), ESIYGN (SEQ ID NO: 212), ESIYSN (SEQID NO: 220), ESVGSN (SEQ ID NO: 203), KSVYNNNF (SEQ ID NO: 222), QHIYSN(SEQ ID NO: 231), QNIGSN (SEQ ID NO: 233), QNINTY (SEQ ID NO: 215), QNIYSG(SEQ ID NO: 209), QNI YSH (SEQ ID NO: 206), QNIYSK (SEQ ID NO: 235), QNIYSN(SEQ ID NO: 213), QRINSW (SEQ ID NO: 202), QSIDSS (SEQ ID NO: 227), QSIGSN(SEQ ID NO: 217), QSIGTD (SEQ ID NO: 228), QSISGN (SEQ ID NO: 214), QSISNL(SEQ ID NO: 201), QSISNY (SEQ ID NO: 226), QSISRY (SEQ ID NO: 205), QSISSY(SEQ ID NO: 221), QSISTA (SEQ ID NO: 229), QSIYSN (SEQ ID NO: 225), QSVANNNC (SEQ ID NO: 210), QSVSNL (SEQ ID NO: 218), and QSVYNNN (SEQ ID NO: 207), e) the VL CDR2 comprises an amino acid sequence selected from the group consisting of: AAS, ATS, DAS, DSS, GAS, KAS, QAS, SAS, TAS, TTS, WAS, and YAS, and f) the VL CDR3 comprises an amino acid sequence selected from the group consisting of: AGDYGAYI IS (SEQ ID NO: 242), AGGYGSSSDRFG (SEQ ID NO: 262), AGGYYCGSADCGA (SEQ ID NO: 245), LGVGTYLSADGNA (SEQ ID NO: 279), LGVYNYIGADHA (SEQ ID NO: 243), QCTDSGSSDVSA (SEQ ID NO: 259), QCTYDSYVPDTA (SEQ ID NO: 247), QCTYYDSSYGNA (SEQ ID NO: 270), QCTYYSSSFGVFNV (SEQ ID NO: 263), QGEFNCISADCNA (SEQ ID NO: 265), QGYCVSINPDRWA (SEQ ID NO: 267), QGYYLGSNFEPYNA (SEQ ID NO: 256), QGYYYSNSADTFA (SEQ ID NO: 258), QGYYYSSSADRWA (SEQ ID NO: 257), QQGDSSGWENT (SEQ ID NO: 260), QQGWSGSNVNNV (SEQ ID NO: 236), QQGYDSSFGDNV (SEQ ID NO: 271), QQGYSSSNVEYA (SEQ ID NO: 252), QSAADSSSGDFFYA (SEQ ID NO: 255), QSADYSRGADYA (SEQ ID NO: 280), QSATYSSGTDRA (SEQ ID NO: 277), QSAVYSGSPIWA (SEQ ID NO: 249), QSAVYSSSADNA (SEQ ID NO: 261), QSAYGSTNADIFV (SEQ ID NO: 237), QSAYYGGGTENA (SEQ ID NO: 254), QSAYYSGNTDNV (SEQ ID NO: 238), QSAYYSSSADNT (SEQ ID NO: 278), QSAYYSSSADTYYA (SEQ ID NO: 240), QSAYYSSSAHYA (SEQ ID NO: 274), QSAYYSSSPDNT (SEQ ID NO: 275), QSAYYSSSVART (SEQ ID NO: 246), QSAYYSTNADNFA (SEQ ID NO: 248), QSFYYSSSTDTRA (SEQ ID NO: 253), QSGRYIDSGDNV (SEQ ID NO: 266), QSGYYSSSADFFYA (SEQ ID NO: 269), QSPYYGSITDNA (SEQ ID NO: 273), QSVSASGSGDTRA (SEQ ID NO: 239), QSVYYSSSAHTRA (SEQ ID NO: 276), QSYVHSSGSSYI (SEQ ID NO: 268), QSYYGSSRSSFSPFFA (SEQ ID NO: 241), QSYYVISSSSYGFA (SEQ ID NO: 251), QSYYYGGSSSSDWYA (SEQ ID NO: 264), QSYYYSGSADRGYA (SEQ ID NO: 244), QYGYTYNSGDIA (SEQ ID NO: 250), and QYTYYSSNYNA (SEQ ID NO: 272 ) .

4. The antibody or an antigen-binding fragment thereof of claim 1, comprising three VH CDRs comprising a set of amino acid sequences selected from the group consisting of:a) VHCDR1: GFSLSDYY (SEQ ID NO: 80), VH CDR2: IYGSGTT (SEQIDNO:107), and VHCDR3: ARAL YADSNYWPLYFNF (SEQIDNO: 150) ; b) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHGGSSGNT (SEQ ID NO: 108), andVHCDR3: ARSDYTGGNYFNL (SEQIDNO: 151) ; c) VHCDR1: GFSFSSSYF (SEQ ID NO: 82), VH CDR2: AYGGGSGST (SEQ ID NO: 109), and VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152 ) ; d) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IAIGSGSA (SEQ ID NO: 110), andVHCDR3: ARDDYAGGGYFNL (SEQIDNO: 153) ; e)VHCDRl: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHDGSSGST (SEQ ID NO: 111), andVHCDR3: ARDDYAGGGYFNL (SEQIDNO: 153) ; f) VHCDR1: GFSLSSNA (SEQ ID NO: 84), VH CDR2: ISSTGST (SEQIDNO: 112), and VHCDR3: AKEDGLVEEFAL (SEQIDNO: 154) ; g)VHCDRl: GFSLSSNA (SEQ ID NO: 84), VH CDR2: ISSTGST (SEQIDNO: 112), and VHCDR3: AKEDGLVEEFAL (SEQIDNO: 154) ; h) VHCDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IDTGGSSV (SEQ ID NO: 113), andVHCDR3: AREGGYDDYGDFLNYFNL (SEQIDNO: 155) ; i) VHCDR1: GFSFSPSYC (SEQ ID NO: 86), VH CDR2: ISGGSSGST (SEQ ID NO: 114), andVHCDR3: ARGDGYDDYGDPFNL (SEQIDNO: 156) ; j)VHCDRl: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IYASGST (SEQIDNO:115), and VHCDR3: ARGEGYTYDDYGDYYDAFDP (SEQIDNO: 157) ; k) VHCDR1: GFSLSSYY (SEQ ID NO: 87), VH CDR2: INSDTT (SEQIDNO:116), and VHCDR3: VRDDGYLDL (SEQIDNO: 158) ; l) VH CDR1 : GFSFSSSYW (SEQ ID NO: 81), VH CDR2: GYAGSSGST (SEQ ID NO: 117), andVHCDR3: ARADNWNSGWLGAFDP (SEQIDNO: 159) ; m) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), andVHCDR3: ARADYAGGDYFNL (SEQIDNO: 160) ; n)VHCDRl: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ISNSGPT (SEQIDNO: 119), and VHCDR3: ARVPYSSGWGADDAFDP (SEQIDNO: 161) ; o) VHCDR1: GFDFSSYG (SEQ ID NO: 88), VH CDR2: IDPVHGTT (SEQ ID NO: 120), andVHCDR3: ARDDIYGYAGYAYATAFNL (SEQIDNO: 162) ; p)VHCDRl: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IATADSGST (SEQ ID NO: 121), andVHCDR3: ARGEGYSYDDYGDYFLGIYPLDL (SEQIDNO: 163) ;q) VH CDR1 : GFSFSGGYD (SEQ ID NO: 89), VH CDR2: SGST (SEQ ID NO: 122), and VHCDR3: ARRDSSGPYYFNL (SEQ ID NO: 164) ; r) VHCDR1: GFIISSSYC (SEQ ID NO: 90), VH CDR2: IYIGDGIT (SEQ ID NO: 123), andVHCDR3: ARDDAGGGGYFNL (SEQ ID NO: 165) ; s) VHCDR1: GFSLSSSYY (SEQ ID NO: 91), VH CDR2: IYGGSSGST (SEQ ID NO: 124), and VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152 ) ; t) VHCDR1: GFDFSSSYY (SEQ ID NO: 92), VH CDR2: IWGGSSGTT (SEQ ID NO: 125), and VH CDR3: ARDDYAGGGYINL (SEQ ID NO: 166) ; u) VHCDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ITSNGRT (SEQ ID NO:126), and VHCDR3: ARGDSYDDYVDPFNI (SEQ ID NO: 167) ; v) VHCDR1: GFSFSSGYY (SEQ ID NO: 93), VH CDR2: IAPGRSGST (SEQ ID NO: 127), and VH CDR3: ARDDAYSYSGATYAYGTFNL (SEQ ID NO: 168) ; w) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), andVHCDR3: ARADYAGGDYFNL (SEQ ID NO: 160) ; x) VH CDR1: GIDFITYYY (SEQ ID NO: 94), VH CDR2: VYGGSSGST (SEQ ID NO: 128), andVHCDR3: ARGDGGMNYAWDL (SEQ ID NO: 169) ; y) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: INTGSGST (SEQ ID NO: 129), andVHCDR3: ARGEGYGYADYAGGRYYYGLDL (SEQ ID NO: 170) ; z) VHCDR1: GFSFSSSYR (SEQ ID NO: 95), VH CDR2: I YAGNSSYT (SEQ ID NO: 130), andVHCDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171) ; aa) VHCDR1: GSDISGYS (SEQ ID NO: 96), VH CDR2: IGNGDGNT (SEQ ID NO: 131), andVHCDR3: ASDTHDYVGFNL (SEQ ID NO: 172) ; ab) VHCDR1: GFSLSDYA (SEQ ID NO: 97), VH CDR2: ISGSGST (SEQ ID NO: 132), and VHCDR3: ARADDDYGAAPYYFNI (SEQ ID NO: 173) ; ac) VHCDR1: GFTISSSYW (SEQ ID NO: 98), VH CDR2: INARIT (SEQ ID NO:133), and VHCDR3: ARVDGSTGVYTLDL (SEQ ID NO: 174) ; ad) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGST (SEQ ID NO: 134), and VHCDR3: ARADYTYGYVGYAFNL (SEQ ID NO: 175 ) ; ae)VHCDRl: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGST (SEQ ID NO: 134), andVHCDR3: ARADYTYGYVGYAFDL (SEQ ID NO: 176) ; af) VHCDR1: GFSFSSSHY (SEQ ID NO: 99), VH CDR2: IFGGVSVRN (SEQ ID NO: 135), andVHCDR3: VRDDYAGYAGYGYAFNL (SEQ ID NO: 177) ;ag) VHCDR1: GFSFSNSYY (SEQ ID NO: 100), VH CDR2: IYAGGSGNT (SEQ ID NO: 136), and VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152) ; ah) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IVTGTSGST (SEQ ID NO: 137), and VH CDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178) ; ai)VHCDRl: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IVTGTSGST (SEQ ID NO: 137), and VHCDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178) ; aj)VHCDRl: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IYAGNSSYT (SEQ ID NO: 130), and VH CDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171) ; ak) VHCDR1: GFSLSSGYD (SEQ ID NO: 101), VH CDR2: IDGASSGRT (SEQ ID NO: 138), and VHCDR3: ARDDSTWGGYFNL (SEQ ID NO: 179) ; al) VHCDR1: GFSFSSAYW (SEQ ID NO: 102), VH CDR2: IHGGSSGST (SEQ ID NO: 139), and VH CDR3: ARDDYAGGGYVNL (SEQ ID NO: 180) ; am) VHCDR1: GFSFSSSYS (SEQ ID NO: 103), VH CDR2: IYAGSSGST (SEQ ID NO: 134),, and VHCDR3: ARIEYYSYGDVGYGYNYGMDL (SEQ ID NO: 181) ; an) VHCDR1: GFSFSSSYS (SEQ ID NO: 103), VHCDR2: IYAGSSGST (SEQ ID NO: 134), and VHCDR3: ARIEYYSYGDVGYGYNYGMDL (SEQ ID NO: 181) ; ao)VHCDRl: GFSFSSAYW (SEQ ID NO: 102), VH CDR2: IHAGSSGNT (SEQ ID NO: 140), and VHCDR3: ARGDYSDAFFNL (SEQ ID NO: 182) ; ap) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYVDNSGST (SEQ ID NO: 141), andVHCDR3: ARDEYAGYAGYGYAFNL (SEQ ID NO: 183) ; aq)VHCDRl: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IYAGSSGNI (SEQ ID NO: 142), and VH CDR3: ARDDYGGVAGYGYAFNL (SEQ ID NO: 184 ) ; ar) VHCDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ILSSGKT (SEQ ID NO: 143), and VHCDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185) ; as) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHAGSSGSI (SEQ ID NO: 144), andVHCDR3: ARDDYHYGGTGYAYNL (SEQ ID NO: 186) ; at) VHCDR1: GFTISSSYC (SEQ ID NO: 104), VH CDR2: IYCGVVGT (SEQ ID NO: 145), andVHCDR3: ARDDAAYGGYFNL (SEQ ID NO: 187) ; an) VHCDR1: GFSFSSGYD (SEQ ID NO: 105), VH CDR2: RHGGSSGST (SEQ ID NO: 146), and VHCDR3: ARDDSAAGGYFNL (SEQ ID NO: 188) ;av) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGSN (SEQ ID NO: 147), and VH CDR3: ARDEVFTGGDAGYGYALNL (SEQ ID NO: 189) ; aw) VHCDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ISSSGDT (SEQ ID NO: 148), andVHCDR3: ARDGGYDDYGDFDYGMDP (SEQ ID NO: 190) ; and ax) VHCDR1: GFSLSVYA (SEQ ID NO: 106), VH CDR2: ILSSGNT (SEQ ID NO: 149), andVHCDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185) .

5. The antibody or an antigen-binding fragment thereof of claim 1, comprising three VLCDRs comprising a set of amino acid sequences selected from the group consisting of: a) VLCDR1: QSISNL (SEQ ID NO: 201), VLCDR2: DSS, and VL CDR3:QQGWSGSNVNNV (SEQ ID NO: 236 ) ; b)VLCDRl: QRINSW (SEQ ID NO: 202), VLCDR2: YAS, and VL CDR3: QSAYGSTNADIFV (SEQ ID NO: 237 ) ; c) VLCDR1: ESVGSN (SEQ ID NO: 203), VLCDR2: TTS, and VL CDR3: QSAYYSGNTDNV (SEQ ID NO: 238) ; d)VLCDRl: ESISSR (SEQ ID NO: 204), VL CDR2: AAS, and VL CDR3:QSVSASGSGDTRA (SEQ ID NO: 239 ) ; e)VLCDRl: QSISRY (SEQ ID NO: 205), VL CDR2: ATS, and VL CDR3: QSAYYSSSADTYYA (SEQ ID NO: 240 ) ; f) VLCDR1: QNIYSH (SEQ ID NO: 206), VLCDR2: KAS, and VL CDR3: QSYYGSSRSSFSPFFA (SEQ ID NO: 241 ) ; g) VL CDR1: QSVYNNN (SEQ ID NO: 207), VL CDR2: QAS, and VL CDR3: AGDYGAYIIS (SEQ ID NO: 242 ) ; h)VLCDRl: EDIYVN (SEQ ID NO: 208), VLCDR2: DAS, and VL CDR3: LGVYNYIGADHA (SEQ ID NO: 243 ) ; i)VLCDRl: QNIYSG (SEQ ID NO: 209), VLCDR2: GAS, and VL CDR3: QSYYYSGSADRGYA (SEQ ID NO: 244 ) ; j)VLCDRl: QSVANNNC (SEQ ID NO: 210), VLCDR2: WAS, and VL CDR3: AGGYYCGSADCGA (SEQ ID NO: 245 ) ; k)VLCDRl: ENIYSS (SEQ ID NO: 211), VLCDR2: DAS, and VL CDR3: QSAYYSSSVART (SEQ ID NO: 246 ) ;l)VLCDR1: ESIYGN (SEQIDNO: 212),VLCDR2: SAS, and VL CDR3: QCTYDS YVPDTA (SEQ ID NO: 247 ) ; m) VL CDR1: QNIYSN (SEQIDNO: 213), VL CDR2: GAS, and VL CDR3:QSAYYSTNADNFA (SEQ ID NO: 248) ; n)VLCDRl: QNIYSN (SEQIDNO: 213), VLCDR2: GAS, and VL CDR3: QSAVYSGSPIWA (SEQ ID NO: 249 ) ; o)VLCDRl: QSISGN (SEQIDNO: 214), VLCDR2: SAS, and VL CDR3: QYGYTYNSGDI A (SEQ ID NO: 250 ) ; p) VL CDR1: QNINTY (SEQ ID NO: 215), VL CDR2: YAS, and VL CDR3: QSYYVISSSSYGFA (SEQ ID NO: 251 ) ; q)VLCDRl: EDIYSL (SEQIDNO: 216), VLCDR2: DAS, and VL CDR3: QQGYSSSNVEYA (SEQ ID NO: 252) ; r) VLCDR1: QNIYSN (SEQIDNO: 213), VLCDR2: GAS, and VL CDR3: QSFYYSSSTDTRA (SEQ ID NO: 253 ) ; s)VLCDRl: QSIGSN (SEQIDNO: 217), VLCDR2: TAS, and VL CDR3:QSAYYGGGTENA (SEQ ID NO: 254) ;QVLCDRl: QNIYSN (SEQIDNO: 213), VL CDR2: AAS, and VL CDR3: QSAADSSSGDFFYA (SEQ ID NO: 255 ) ; u) VL CDR1: QSVSNL (SEQ ID NO: 218), VL CDR2: YAS, and VL CDR3: QGYYLGSNFEPYNA (SEQ ID NO: 256) ; v)VLCDRl: ESIGSN (SEQIDNO: 219), VLCDR2: GAS, and VL CDR3: QGYYYSSSADRWA (SEQ ID NO: 257) ; w) VLCDR1: ESIYSN (SEQIDNO: 220), VLCDR2: YAS, and VL CDR3: QGYYYSNSADTFA (SEQ ID NO: 258 ) ; x)VLCDRl: QNIYSN (SEQIDNO: 213), VL CDR2: AAS, and VL CDR3: QCTDSGSSDVSA (SEQ ID NO: 259 ) ; y)VLCDRl: QSISSY (SEQIDNO: 221), VLCDR2: GAS, and VL CDR3:QQGDSSGWENT (SEQ ID NO: 260) ; z)VLCDRl: ESIYSN (SEQIDNO: 220), VL CDR2: AAS, and VL CDR3:QSAVYSSSADNA (SEQ ID NO: 261) ; aa) VL CDR1: KSVYNNNF (SEQ ID NO: 222), VL CDR2: GAS, and VL CDR3: AGGYGSSSDRFG (SEQ ID NO: 262 ) ;ab) VLCDR1: EDIGTL (SEQIDNO: 223),VLCDR2: GAS, and VL CDR3: QCTYYSSSFGVFNV (SEQ ID NO: 263 ) ; ac) VLCDR1: QSIGSN (SEQIDNO: 217), VL CDR2: DAS, and VL CDR3: QSYYYGGSSSSDWYA (SEQIDNO: 264) ; ad)VLCDRl: ESIDSH (SEQIDNO: 224),VLCDR2: SAS, and VL CDR3:QGEFNCISADCNA (SEQ ID NO: 265) ; ae)VLCDRl: ESIDSH (SEQIDNO: 224),VLCDR2: SAS, and VL CDR3:QGEFNCISADCNA (SEQ ID NO: 265) ; af)VLCDRl: QSIYSN (SEQIDNO: 225), VLCDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQ ID NO: 266 ) ; ag) VLCDR1: QSIYSN (SEQIDNO: 225),VLCDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQ ID NO: 266 ) ; ah) VLCDR1: QSISNY (SEQIDNO: 226),VLCDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQ ID NO: 267 ) ; ai) VL CDR1: QSISNY (SEQ ID NO: 226), VL CDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQ ID NO: 267 ) ; aj) VLCDR1: QSISNL (SEQIDNO: 201), VLCDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268 ) ; ak) VLCDR1: QSISNL (SEQIDNO: 201),VLCDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268 ) ; al) VL CDR1: QSIDSS (SEQ ID NO: 227), VL CDR2: GAS, and VL CDR3:QSGYYSSSADFFYA (SEQ ID NO: 269 ) ; am)VLCDRl: QSIGSN (SEQIDNO: 217), VLCDR2: AAS, and VL CDR3:QCTYYDSSYGNA (SEQ ID NO: 270) ; an)VLCDRl: QSIGTD (SEQIDNO: 228), VL CDR2: AAS, and VL CDR3:QCTYYDSSYGNA (SEQ ID NO: 270) ; ao)VLCDRl: QSISTA (SEQIDNO: 229), VL CDR2: AAS, and VL CDR3:QQGYDSSFGDNV (SEQ ID NO: 271) ; ap)VLCDRl: EDIYSL (SEQIDNO: 216),VLCDR2: SAS, and VL CDR3: QYTYYSSNYNA (SEQIDNO: 272) ; aq) VLCDR1: ENIYSG (SEQIDNO: 230),VLCDR2: TAS, and VL CDR3: QSPYYGSITDNA (SEQ ID NO: 273 ) ;ar)VLCDRl: ESISSR (SEQIDNO: 204), VL CDR2: AAS, and VL CDR3: QSAYYSSSAHYA (SEQ ID NO: 274) ; as) VLCDR1: QNIYSN (SEQIDNO: 213), VLCDR2: GAS, and VL CDR3: QSAYYSSSPDNT (SEQ ID NO: 275) ; at) VL CDR1: QHIYSN (SEQ ID NO: 231), VL CDR2: GAS, and VL CDR3: QSVYYSSSAHTRA (SEQ ID NO: 276 ) ; au)VLCDRl: ENIYSN (SEQIDNO: 232), VL CDR2: AAS, and VL CDR3: QSATYSSGTDRA (SEQ ID NO: 277 ) ; av) VL CDR1: QNIGSN (SEQ ID NO: 233), VL CDR2: GAS, and VL CDR3: QSAYYSSSADNT (SEQ ID NO: 278 ) ; aw) VLCDR1: EDIYSN (SEQIDNO: 234), VLCDR2: QAS, and VL CDR3: LGVGTYLSADGNA (SEQ ID NO: 279 ) ; and ax)VLCDRl: QNIYSK (SEQIDNO: 235), VL CDR2: AAS, and VL CDR3: QSADYSRGADYA (SEQ ID NO: 280) .

6. The antibody or an antigen-binding fragment thereof of claim 1, comprising three VH CDRs and three VL CDRs comprising a set of amino acid sequences selected from the group consisting of: a) VHCDR1: GFSLSDYY (SEQ ID NO: 80), VH CDR2: IYGSGTT (SEQIDNO:107), VH CDR3: ARALYADSNYWPLYFNF (SEQ ID NO: 150), VL CDR1: QSISNL (SEQ ID NO: 201), VL CDR2: DSS, and VL CDR3: QQGWSGSNVNNV (SEQ ID NO: 236) ; b) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHGGSSGNT (SEQ ID NO: 108), VHCDR3: ARSDYTGGNYFNL (SEQIDNO: 151), VLCDR1: QRINSW (SEQ ID NO: 202), VL CDR2: YAS, and VL CDR3: QSAYGSTNADIFV (SEQ ID NO: 237) ; c) VHCDR1: GFSFSSSYF (SEQ ID NO: 82), VH CDR2: AYGGGSGST (SEQ ID NO: 109), VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), VL CDR1: ESVGSN (SEQ ID NO: 203), VL CDR2: TTS, and VL CDR3: QSAYYSGNTDNV (SEQ ID NO: 238) ; d) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IAIGSGSA (SEQ ID NO: 110), VHCDR3: ARDDYAGGGYFNL (SEQIDNO: 153), VLCDR1: ESISSR(SEQ ID NO: 204), VL CDR2: AAS, and VL CDR3: QSVSASGSGDTRA (SEQ ID NO: 239 ) ; e) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHDGSSGST (SEQ ID NO: 111), VH CDR3: ARDDYAGGGYFNL (SEQ ID NO: 153), VL CDR1: QSISRY (SEQ ID NO: 205), VL CDR2: ATS, and VL CDR3: QSAYYSSSADTYYA (SEQ ID NO: 240 ) ; f) VH CDR1: GFSLSSNA (SEQ ID NO: 84), VH CDR2: ISSTGST (SEQ ID NO: 112), VH CDR3: AKEDGLVEEFAL (SEQ ID NO: 154), VL CDR1: QNIYSH(SEQ ID NO: 206), VL CDR2: KAS, and VL CDR3: QSYYGSSRSSFSPFFA (SEQ ID NO: 241 ) ; g) VH CDRl: GFSLSSNA (SEQ ID NO: 84), VH CDR2: ISSTGST (SEQ ID NO: 112), VH CDR3: AKEDGLVEEFAL (SEQ ID NO: 154), VL CDR1: QSVYNNN (SEQ ID NO: 207), VL CDR2: QAS, and VL CDR3: AGDYGAYI I S (SEQ ID NO: 242 ) ; h) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IDTGGSSV (SEQ ID NO: 113), VH CDR3: AREGGYDDYGDFLNYFNL (SEQ ID NO: 155), VL CDR1: EDIYVN (SEQ ID NO: 208), VL CDR2: DAS, and VL CDR3: LGVYNYIGADHA (SEQ ID NO: 243 ) ; i) VH CDR1: GFSFSPSYC (SEQ ID NO: 86), VH CDR2: ISGGSSGST (SEQ ID NO: 114), VH CDR3: ARGDGYDDYGDPFNL (SEQ ID NO: 156), VL CDR1:QNIYSG (SEQ ID NO: 209), VL CDR2: GAS, and VL CDR3: QSYYYSGSADRGYA (SEQ ID NO: 244 ) ; j) VH CDRl: GFSLSSYA (SEQ ID NO: 85), VH CDR2: IYASGST (SEQ ID NO:115), VH CDR3: ARGEGYTYDDYGDYYDAFDP (SEQ ID NO: 157), VL CDR1: QSVANNNC (SEQ ID NO: 210), VL CDR2: WAS, and VL CDR3:AGGYYCGSADCGA (SEQ ID NO: 245 ) ; k) VH CDR1: GFSLSSYY (SEQ ID NO: 87), VH CDR2: INSDTT (SEQ ID NO:116), VH CDR3: VRDDGYLDL (SEQ ID NO: 158), VL CDR1: ENIYSS (SEQ ID NO: 211), VL CDR2: DAS, and VL CDR3: QSAYYSSSVART (SEQ ID NO: 246 ) ; l) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: GYAGSSGST (SEQ ID NO: 117), VH CDR3: ARADNWNSGWLGAFDP (SEQ ID NO: 159), VL CDR1:ES IYGN (SEQ ID NO: 212), VL CDR2: SAS, and VL CDR3: QCTYDSYVPDTA (SEQ ID NO: 247 ) ; m) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), VH CDR3: ARAD YAGGDYFNL (SEQ ID NO: 160), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAYYSTNADNFA (SEQ ID NO: 248 ) ; n) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ISNSGPT (SEQ ID NO: 119), VH CDR3: ARVPYSSGWGADDAFDP (SEQ ID NO: 161), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAVYSGSPIWA (SEQ ID NO: 249 ) ; o) VH CDR1: GFDFSSYG (SEQ ID NO: 88), VH CDR2: IDPVHGTT (SEQ ID NO: 120), VH CDR3: ARDDIYGYAGYAYATAFNL (SEQ ID NO: 162), VL CDR1: QS ISGN (SEQ ID NO: 214), VL CDR2: SAS, and VL CDR3: QYGYTYNSGDIA (SEQ ID NO: 250 ) ; p) VH CDRl: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IATADSGST (SEQ ID NO: 121), VH CDR3: ARGEGYSYDDYGDYFLGIYPLDL (SEQ ID NO: 163), VL CDR1: QNINTY (SEQ ID NO: 215), VL CDR2: YAS, and VL CDR3: QSYYVI SSSSYGFA (SEQ ID NO: 251 ) ; q) VH CDR1 : GFSFSGGYD (SEQ ID NO: 89), VH CDR2: SGST (SEQ ID NO: 122), VH CDR3: ARRDSSGPYYFNL (SEQ ID NO: 164), VL CDR1: EDIYSL (SEQ ID NO: 216), VL CDR2: DAS, and VL CDR3: QQGYSSSNVEYA (SEQ ID NO: 252 ) ; r) VH CDR1: GFI ISSSYC (SEQ ID NO: 90), VH CDR2: IYIGDGIT (SEQ ID NO: 123), VH CDR3: ARDDAGGGGYFNL (SEQ ID NO: 165), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSFYYSSSTDTRA (SEQ ID NO: 253 ) ; s) VH CDR1: GFSLSSSYY (SEQ ID NO: 91), VH CDR2: IYGGSSGST (SEQ ID NO: 124), VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), VL CDR1: QS IGSN (SEQ ID NO: 217), VL CDR2: TAS, and VL CDR3: QSAYYGGGTENA (SEQ ID NO: 254 ) ; t) VH CDR1: GFDFSSSYY (SEQ ID NO: 92), VH CDR2: IWGGSSGTT (SEQ ID NO: 125), VH CDR3: ARDDYAGGGYINL (SEQ ID NO: 166), VL CDR1: QNIYSN(SEQ ID NO: 213), VL CDR2: AAS, and VL CDR3: QSAADSSSGDFFYA (SEQ ID NO: 255 ) ; u) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ITSNGRT (SEQ ID NO: 126), VH CDR3: ARGDSYDDYVDPFNI (SEQ ID NO: 167), VL CDR1: QSVSNL (SEQ ID NO: 218), VL CDR2: YAS, and VL CDR3: QGYYLGSNFEPYNA (SEQ ID NO: 256 ) ; v) VH CDR1: GFSFSSGYY (SEQ ID NO: 93), VH CDR2: IAPGRSGST (SEQ ID NO: 127), VH CDR3: ARDDAYSYSGATYAYGTFNL (SEQ ID NO: 168), VL CDR1: ES IGSN (SEQ ID NO: 219), VL CDR2: GAS, and VL CDR3: QGYYYSSSADRWA (SEQ ID NO: 257 ) ; w) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: THDGSSGST (SEQ ID NO: 118), VH CDR3: ARAD YAGGDYFNL (SEQ ID NO: 160), VL CDR1: ESIYSN (SEQ ID NO: 220), VL CDR2: YAS, and VL CDR3: QGYYYSNSADTFA (SEQ ID NO: 258 ) ; x) VH CDR1: GIDFITYYY (SEQ ID NO: 94), VH CDR2: VYGGSSGST (SEQ ID NO: 128), VH CDR3: ARGDGGMNYAWDL (SEQ ID NO: 169), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: AAS, and VL CDR3: QCTDSGSSDVSA (SEQ ID NO: 259 ) ; y) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: INTGSGST (SEQ ID NO: 129), VH CDR3: ARGEGYGYADYAGGRYYYGLDL (SEQ ID NO: 170), VL CDR1: QS ISSY (SEQ ID NO: 221), VL CDR2: GAS, and VL CDR3: QQGDSSGWENT (SEQ ID NO: 260 ) ; z) VH CDR1: GFSFSSSYR (SEQ ID NO: 95), VH CDR2: IYAGNSSYT (SEQ ID NO: 130), VH CDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171), VL CDR1: ES IYSN (SEQ ID NO: 220), VL CDR2: AAS, and VL CDR3: QSAVYSSSADNA (SEQ ID NO: 261 ) ; aa) VH CDR1: GSDISGYS (SEQ ID NO: 96), VH CDR2: IGNGDGNT (SEQ ID NO: 131), VH CDR3: ASDTHDYVGFNL (SEQ ID NO: 172), VL CDR1: KSVYNNNF (SEQ ID NO: 222), VL CDR2: GAS, and VL CDR3: AGGYGSSSDRFG (SEQ ID NO: 262 ) ; ab) VH CDR1: GFSLSDYA (SEQ ID NO: 97), VH CDR2: ISGSGST (SEQ ID NO: 132), VH CDR3: ARADDDYGAAPYYFNI (SEQ ID NO: 173), VL CDR1: EDIGTL(SEQ ID NO: 223), VL CDR2: GAS, and VL CDR3: QCTYYSSSFGVFNV (SEQ ID NO: 263 ) ; ac) VH CDR1: GFTISSSYW (SEQ ID NO: 98), VH CDR2: INARIT (SEQ ID NO: 133), VH CDR3: ARVDGSTGVYTLDL (SEQ ID NO: 174), VL CDR1: QSIGSN (SEQ ID NO: 217), VL CDR2: DAS, and VL CDR3: QSYYYGGSSSSDWYA (SEQ ID NO: 264 ) ; ad) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2 : IYAGSSGST (SEQ ID NO: 134), VH CDR3: ARADYTYGYVGYAFNL (SEQ ID NO: 175), VL CDR1: ES IDSH (SEQ ID NO: 224), VL CDR2: SAS, and VL CDR3: QGEFNCI SADCNA (SEQ ID NO: 265 ) ; ae) VH CDRl: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGST (SEQ ID NO: 134), VH CDR3: ARAD YTYGYVGYAFDL (SEQ ID NO: 176), VL CDR1: ES IDSH (SEQ ID NO: 224), VL CDR2: SAS, and VL CDR3: QGEFNCI SADCNA (SEQ ID NO: 265 ) ; af) VH CDR1: GFSFSSSHY (SEQ ID NO: 99), VH CDR2: IFGGVSVRN (SEQ ID NO: 135), VH CDR3: VRDDYAGYAGYGYAFNL (SEQ ID NO: 177), VL CDR1: QS IYSN (SEQ ID NO: 225), VL CDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQ ID NO: 266 ) ; ag) VH CDR1: GFSFSNSYY (SEQ ID NO: 100), VH CDR2: IYAGGSGNT (SEQ ID NO: 136), VH CDR3: ARDDYAGYAGYGYAFNL (SEQ ID NO: 152), VL CDR1: QS IYSN (SEQ ID NO: 225), VL CDR2: TAS, and VL CDR3: QSGRYIDSGDNV (SEQ ID NO: 266 ) ; ah) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IVTGTSGST (SEQ ID NO: 137), VH CDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178), VL CDR1: QS ISNY (SEQ ID NO: 226), VL CDR2: SAS, and VL CDR3: QGYCVS INPDRWA (SEQ ID NO: 267 ) ; ai) VH CDRl: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IVTGTSGST (SEQ ID NO: 137), VH CDR3: ARDDAYVYGGADYAYGAFNL (SEQ ID NO: 178), VL CDR1: QS ISNY (SEQ ID NO: 226), VL CDR2: SAS, and VL CDR3: QGYCVSINPDRWA (SEQ ID NO: 267 ) ; aj) VH CDRl: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IYAGNSSYT (SEQ ID NO: 130), VH CDR3: ARDDTVSFGYPYGYFNL (SEQ ID NO: 171), VL CDR1:QSISNL (SEQIDNO: 201), VLCDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268) ; ak) VHCDR1: GFSLSSGYD (SEQ ID NO: 101), VH CDR2: IDGASSGRT (SEQ ID NO: 138), VH CDR3: ARDDSTWGGYFNL (SEQ ID NO: 179), VL CDR1: QSISNL (SEQIDNO: 201), VLCDR2: GAS, and VL CDR3: QSYVHSSGSSYI (SEQ ID NO: 268) ; al) VHCDR1: GFSFSSAYW (SEQ ID NO: 102), VH CDR2: IHGGSSGST (SEQ ID NO: 139), VH CDR3: ARDDYAGGGYVNL (SEQ ID NO: 180), VL CDR1: QSIDSS (SEQIDNO: 227), VLCDR2: GAS, and VL CDR3: QSGYYSSSADFFYA (SEQ ID NO: 269) ; am)VHCDRl: GFSFSSSYS (SEQIDNO: 103), VHCDR2: IYAGSSGST (SEQ ID NO: 134), VH CDR3: ARIEYYSYGDVGYGYNYGMDL (SEQIDNO: 181), VL CDR1: QSIGSN (SEQIDNO: 217), VLCDR2: AAS, and VL CDR3: QCTYYDSSYGNA (SEQ ID NO: 270 ) ; an) VHCDR1: GFSFSSSYS (SEQ ID NO: 103), VH CDR2: IYAGSSGST (SEQ ID NO: 134), VHCDR3: ARIEYYSYGDVGYGYNYGMDL (SEQ ID NO: 181), VL CDR1: QSIGTD (SEQIDNO: 228), VL CDR2: AAS, and VL CDR3: QCTYYDSSYGNA (SEQ ID NO: 270) ; ao)VHCDRl: GFSFSSAYW (SEQ ID NO: 102), VH CDR2: IHAGSSGNT (SEQ ID NO: 140), VHCDR3: ARGDYSDAFFNL (SEQIDNO: 182),VLCDR1: QSISTA (SEQ ID NO: 229), VL CDR2: AAS, and VL CDR3: QQGYDSSFGDNV (SEQ ID NO: 271) ; ap) VHCDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYVDNSGST (SEQ ID NO: 141), VH CDR3: ARDEYAGYAGYGYAFNL (SEQ ID NO: 183), VL CDR1: EDIYSL (SEQ ID NO: 216), VL CDR2: SAS, and VL CDR3: QYTYYSSNYNA (SEQ ID NO: 272) ; aq) VHCDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IYAGSSGNI (SEQ ID NO: 142), VH CDR3: ARDDYGGVAGYGYAFNL (SEQ ID NO: 184), VL CDR1: ENIYSG (SEQ ID NO: 230), VL CDR2: TAS, and VL CDR3: QSPYYGSITDNA (SEQ ID NO: 273) ; ar) VHCDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ILSSGKT (SEQIDNO: 143), VH CDR3: ARDDSYDDYAEGYFNI (SEQIDNO: 185), VLCDR1: ESISSR(SEQ ID NO: 204), VL CDR2: AAS, and VL CDR3: QSAYYSSSAHYA (SEQ ID NO: 274 ) ; as) VH CDR1: GFSFSSSYW (SEQ ID NO: 81), VH CDR2: IHAGSSGS I (SEQ ID NO: 144), VH CDR3: ARDDYHYGGTGYAYNL (SEQ ID NO: 186), VL CDR1: QNIYSN (SEQ ID NO: 213), VL CDR2: GAS, and VL CDR3: QSAYYSSSPDNT (SEQ ID NO: 275 ) ; at) VH CDR1: GFTI SSSYC (SEQ ID NO: 104), VH CDR2: IYCGVVGT (SEQ ID NO: 145), VH CDR3: ARDDAAYGGYFNL (SEQ ID NO: 187), VL CDR1: QHIYSN (SEQ ID NO: 231), VL CDR2: GAS, and VL CDR3: QSVYYSSSAHTRA (SEQ ID NO: 276 ) ; an) VH CDR1: GFSFSSGYD (SEQ ID NO: 105), VH CDR2: RHGGSSGST (SEQ ID NO: 146), VH CDR3: ARDDSAAGGYFNL (SEQ ID NO: 188), VL CDR1: ENIYSN (SEQ ID NO: 232), VL CDR2: AAS, and VL CDR3: QSATYSSGTDRA (SEQ ID NO: 277 ) ; av) VH CDR1: GFSFSSSYY (SEQ ID NO: 83), VH CDR2: IYAGSSGSN (SEQ ID NO: 147), VH CDR3: ARDEVFTGGDAGYGYALNL (SEQ ID NO: 189), VL CDR1: QNIGSN (SEQ ID NO: 233), VL CDR2: GAS, and VL CDR3: QSAYYSSSADNT (SEQ ID NO: 278 ) ; aw) VH CDR1: GFSLSSYA (SEQ ID NO: 85), VH CDR2: ISSSGDT (SEQ ID NO: 148), VH CDR3: ARDGGYDDYGDFDYGMDP (SEQ ID NO: 19O), VL CDR1: EDIYSN (SEQ ID NO: 234), VL CDR2: QAS, and VL CDR3: LGVGTYLSADGNA (SEQ ID NO: 279 ) ; and ax) VH CDR1: GFSLSVYA (SEQ ID NO: 106), VH CDR2: ILSSGNT (SEQ ID NO: 149), VH CDR3: ARDDSYDDYAEGYFNI (SEQ ID NO: 185), VL CDR1: QNIYSK (SEQ ID NO: 235), VL CDR2: AAS, and VL CDR3: QSADYSRGADYA (SEQ ID NO: 280 ) .

7. The antibody or antigen-binding fragment thereof of any one of claims 1-6 comprising: a) a VH framework region 1 (VH FR1) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:QEQLKESGGGLVLPGGSLKLSCKAS (SEQ ID NO: 36 ) ;QSVEESGGRLVTPGTPLTLTCTVS (SEQ ID NO: 37 ) ;QSLEESGGDLVQPEGSLTLTCTAS (SEQ ID NO: 38 ) ;QEQLEESGGDLVKPEGSLTLTCTAS (SEQ ID NO: 39 ) ;QSLEESGGDLVKSGASLTLTCTAS (SEQ ID NO: 40 ) ;QSLEESGGDLVKPGASLTLTCTAS (SEQ ID NO: 41 ) ; andQEQLVESGGGLVQPEGSLTLTCTAS (SEQ ID NO: 294); b) a VH framework region 2 (VH FR2) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:MNWVRQAPGKGLEWIGY (SEQ ID NO: 42 ) ;MSWVRQAPGKGLEWIGI (SEQ ID NO: 43 ) ;LCWVRQAPGKGLEWIAC (SEQ ID NO: 44 ) ;ICWVRQAPGKGLEWIAC (SEQ ID NO: 45 ) ;MCWVRQAPGKGLEWIAC (SEQ ID NO: 46 ) ;MCWVRQAPGKGLEWIGC (SEQ ID NO: 298);MCWVRQAPGKGPEWIAC (SEQ ID NO: 299); andCWVRQAPGKGLEWIAC (SEQ ID NO: 300); c) a VH framework region 3 (VH FR3) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:YYANWVNGRFTISSHNVQKKLYLQLNSLTAADTATYFC (SEQ ID NO: 47 ) ;YYATWAKGRFTISKTSSTTVDLKMTSLTASDTATYFC (SEQ ID NO: 48 ) ;YYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 49 ) ;HYATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFC (SEQ ID NO: 50 ) ;AYASWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 51 ) ;YYANWAKGRFTISKTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 52 ) ;YYANWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFC (SEQ ID NO: 302);YYANWAKGRFTISRTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 303); andHYATWAKGRFTISRTSSTTVTLQMTSLTAADTATYFC (SEQ ID NO: 305); d) a VH framework region 4 (VH FR4) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:WGQGTLVTVSS (SEQ ID NO: 53 ) ; andRGQGTLVTVSS (SEQ ID NO: 307);e) a VL framework region 1 (VL FR1) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:AAVLTQTPSPVSAAVGGTVSISCQSS (SEQ ID NO: 54 ) ;ANIVMTQTPASVEVAVGGTVTIKCQAS (SEQ ID NO: 55 ) ;DVVMTQTPSSVEAAVGGTVTIKCQAS (SEQ ID NO: 56 ) ;ALVMTQTPSSVSAAVGGTVTINCQAS (SEQ ID NO: 57 ) ;AQVLTQTPASVSAAVGGTVTIKCQAS (SEQ ID NO: 58 ) ;AIEMTQTPFSVSAAVGGTVTINCQAS (SEQ ID NO: 59 ) ;ALVMTQTPSSASEPVGGTVTIKCQAG (SEQ ID NO: 310); andAQVLTQTPASVEAAVGGTITVNCQAS (SEQ ID NO: 312); f) a VL framework region 1 (VL FR2) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:LSWFQQKPGQPPKLLIY (SEQ ID NO: 60 ) ;LAWYQQKSGQPPKLLIY (SEQ ID NO: 61 ) ;LAWYQQKPGQPPKLLIY (SEQ ID NO: 62 ) ; andLAWYQQKPGQRPKLLIY (SEQ ID NO: 63 ) ; g) a VL framework region 3 (VL FR3) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:TLASGVPSRFKGNGSGTQFTLTI SDVQCDDAATYYC (SEQ ID NO: 287 ) ;DLASGVSSRFKGSGSGTQFTLTI SGVECADAATYYC (SEQ ID NO: 64 ) ;NLESGVPSRFKGSGSGTEYTLTISDLECDDAATYYC (SEQ ID NO: 65 ) ;TLASGVPSRFKGSGSGTEYTLTI SGVQCADAATYYC (SEQ ID NO: 66 ) ;YLASGVPSRFKGSGSGTEYTLTI SGVQCADAATYYC (SEQ ID NO: 67 ) ;YLASGVPSRFKGSESGTEYTLTISDLECDDAATYYC (SEQ ID NO: 318);YLSSGVPSRFKGSGSGTDFTLTISDLECADAATYYC (SEQ ID NO: 319); and NLASGVPSRFKGSGSGTQFTLTISDLECADAATYYC (SEQ ID NO: 320); and h) a VL framework region 4 (VL FR4) having at least about 85% amino acid sequence identity to an amino acid sequence selected from the following:FGGGTEVWKGDP (SEQ ID NO: 68); andFGGGTEVWK (SEQ ID NO: 322).

8. An antibody or an antigen-binding fragment thereof that specifically binds to an anti- cluster of differentiation 7 antibody, or an antigen-binding fragment thereof, comprising: a) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to an amino acid sequence selected from the group consisting of: QSVEESGGRLVTPGTPLTLTCTVSGFSLSDYYMSWVRQAPGKGLEWIGI I YGSGTTYYATWA KGRFTISKTSSTTVDLKMTSLTASDTATYFCARALYADSNYWPLYFNFWGQGTLVTVSS (1H2; SEQ ID NO: 22), QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA SWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARSDYTGGNYFNLWGQGTLVTVSS (2H3; SEQ ID NO: 23), QSLEESGGDLVKPGASLTLTCTASGFSFSSSYWMCWVRQAPGKGLEWIACIHAGSSGSIYYA NWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDYHYGGTGYAYNLWGQGTLVTVSS (43H1; SEQ ID NO: 24), QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SS (15H3; SEQ ID NO: 25), QEQLEESGGDLVKPEGSLTLTCTASGFSFSSSYRICWVRQAPGKGLEWIACIYAGNSSYTHY ATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFCARDDTVSFGYPYGYFNLWGQGTLVTVS S (29H3; SEQ ID NO: 26), QSLEESGGDLVQPEGSLTLTCTASGSDISGYSLCWVRQAPGKGLEWIACIGNGDGNTYYASW AKGRFT I S KTS S TTVTLQMTS LTAADTATYFC AS DTHDYVGFNLWGQGTL VTVS S (30H3 ; SEQ ID NO: 27);QEQLVESGGGLVQPEGSLTLTCTASGFSFSSSYYMCWVRQAPGKGLEWIGCIAIGSGSAYYA NWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFCARDDYAGGGYFNLWGQGTLVTVSS (SEQ ID NO: 323; 5H1);QSLEESGGDLVKPGASLTLTCTASGFDFSSSYYMCWVRQAPGKGPEWIACIWGGSSGTTYYA NWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDYAGGGYINLRGQGTLVTVSS (SEQ ID NO: 324; 20H1);QSLEESGGDLVKPGASLTLTCTASGFSFSSSYSICWVRQAPGKGLEWIACIYAGSSGSTYYA SWAKGRFTI SKTSSTTVTLQMTSLTAADTATYFCARI EYYS YGDVGYGYNYGMDLWGQGTLV TVSS (SEQ ID NO: 325; 39H2); andQSLEESGGDLVKPGASLTLTCTASGFSFSSGYDMCWVRQAPGKGLEWIACRHGGSSGSTHYA TWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDSAAGGYFNLWGQGTLVTVSS (SEQ ID NO: 326; 45H2); and / or b) a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to an amino acid sequence selected from the group consisting of: ANIVMTQTPASVEVAVGGTVTIKCQASQSISNLLAWYQQKSGQPPKLLIYDSSDLASGVSSR FKGSGSGTQFTLTISGVECADAATYYCQQGWSGSNVNNVFGGGTEVWKGDP(1K2; SEQ ID NO: 28),DVVMTQTPSSVEAAVGGTVTIKCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADIFVFGGGTEVWKGDP (2K1; SEQ ID NO: 29), ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLAWYQQKPGQRPKLLIYGASNLESGVPSRFKGSGSGTEYTLTISDLECDDAATYYCQSAYYSSSPDNTFGGGTEWVKGDP (43K2; SEQ ID NO: 30),AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKGDP (15K3; SEQ ID NO: 31),AIEMTQTPFSVSAAVGGTVTINCQASESIYSNLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSAVYSSSADNAFGGGTEWVKGDP (29K1; SEQ ID NO: 32),AAVLTQTPSPVSAAVGGTVSISCQSSKSVYNNNFLSWFQQKPGQPPKLLIYGASTLASGVPS RFKGNGSGTQFTLTISDVQCDDAATYYCAGGYGSSSDRFGFGGGTEWVKGDP (30K3; SEQ ID NO: 33)ALVMTQTPSSASEPVGGTVTIKCQAGESISSRLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSESGTEYTLTISDLECDDAATYYCQSVSASGSGDTRAFGGGTEVWK (SEQ ID NO: 327; 5K3);ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLGWYQQKPGQPPKLLIYAASYLSSGVPSRF KGSGSGTDFTLTISDLECADAATYYCQSAADSSSGDFFYAFGGGTEWVK (SEQ ID NO: 328; 20K3);AQVLTQTPASVEAAVGGTITVNCQASQSIGTDLAWYQQKPGQRPKLLIYAASNLASGVPSRF KGSGSGTQFTLTISDLECADAATYYCQCTYYDSSYGNAFGGGTEWVK (SEQ ID NO: 329; 39K2); andAIEMTQTPFSVSAAVGGTVTINCQASENIYSNLGWYQQKPGQPPKLLIYAASYLASGVPSRFKGSGSGTEYTLTISGVQCADAATYYCQSATYSSGTDRAFGGGTEWVK (SEQ ID NO: 330; 45K2).

9. An antibody or an antigen-binding fragment thereof that specifically binds to an anti- cluster of differentiation 7 antibody, or an antigen-binding fragment thereof, comprising: a) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSVEESGGRLVTPGTPLTLTCTVSGFSLSDYYMSWVRQAPGKGLEWIGI I YGSGTTYYATWA KGRFTISKTSSTTVDLKMTSLTASDTATYFCARALYADSNYWPLYFNFWGQGTLVTVSS (1H2; SEQ ID NO: 22), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:ANIVMTQTPASVEVAVGGTVTIKCQASQSISNLLAWYQQKSGQPPKLLIYDSSDLASGVSSR FKGSGSGTQFTLTISGVECADAATYYCQQGWSGSNVNNVFGGGTEVWKGDP (1K2; SEQ ID NO: 28); b) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA S WAKGRFT I S KTS S TTVTLQMTS LTAADTATYFC ARS DYTGGNYFNLWGQGTL VTVS S (2H3 ; SEQ ID NO: 23), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:DVVMTQTPSSVEAAVGGTVTIKCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADIFVFGGGTEVWKGDP (2K1; SEQ ID NO: 29); c) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSLEESGGDLVKPGASLTLTCTASGFSFSSSYWMCWVRQAPGKGLEWIACIHAGSSGSIYYA NWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARDDYHYGGTGYAYNLWGQGTLVTVSS (43H1; SEQ ID NO: 24), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLAWYQQKPGQRPKLLIYGASNLESGVPSRFKGSGSGTEYTLTISDLECDDAATYYCQSAYYSSSPDNTFGGGTEWVKGDP (43K2; SEQ ID NO: 30); d) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SS (15H3; SEQ ID NO: 25), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKGDP (15K3; SEQ ID NO: 31); e) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QEQLEESGGDLVKPEGSLTLTCTASGFSFSSSYRICWVRQAPGKGLEWIACIYAGNSSYTHY ATWAKGRFTISKTSSTTVTLQMTGLTAADTATYFCARDDTVSFGYPYGYFNLWGQGTLVTVS S (29H3; SEQ ID NO: 26), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:AIEMTQTPFSVSAAVGGTVTINCQASESIYSNLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSAVYSSSADNAFGGGTEWVKGDP (29K1; SEQ ID NO: 32); f) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSLEESGGDLVQPEGSLTLTCTASGSDISGYSLCWVRQAPGKGLEWIACIGNGDGNTYYASW AKGRFT I S KTS STTVTLQMTS LTAADTATYFC AS DTHDYVGFNLWGQGTL VTVS S (30H3 ; SEQ ID NO: 27), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:AAVLTQTPSPVSAAVGGTVSISCQSSKSVYNNNFLSWFQQKPGQPPKLLIYGASTLASGVPS RFKGNGSGTQFTLTISDVQCDDAATYYCAGGYGSSSDRFGFGGGTEWVKGDP (30K3; SEQ ID NO: 33);g) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QEQLVESGGGLVQPEGSLTLTCTASGFSFSSSYYMCWVRQAPGKGLEWIGCIAIGSGSAYYA NWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFCARDDYAGGGYFNLWGQGTLVTVSS (SEQ ID NO: 323; 5H1), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:ALVMTQTPSSASEPVGGTVTIKCQAGESISSRLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSESGTEYTLTISDLECDDAATYYCQSVSASGSGDTRAFGGGTEVWK (SEQ ID NO: 327; 5K3); h) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence: QSLEESGGDLVKPGASLTLTCTASGFDFSSSYYMCWVRQAPGKGPEWIACIWGGSSGTTYYA NWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDYAGGGYINLRGQGTLVTVSS (SEQ ID NO: 324; 20H1), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLGWYQQKPGQPPKLLIYAASYLSSGVPSRF KGSGSGTDFTLTISDLECADAATYYCQSAADSSSGDFFYAFGGGTEWVK (SEQ ID NO: 328; 3); j) i) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:QSLEESGGDLVKPGASLTLTCTASGFSFSSSYSICWVRQAPGKGLEWIACIYAGSSGSTYYA SWAKGRFTI SKTSSTTVTLQMTSLTAADTATYFCARI EYYS YGDVGYGYNYGMDLWGQGTLV TVSS (SEQ ID NO: 325; 39H2), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:AQVLTQTPASVEAAVGGTITVNCQASQSIGTDLAWYQQKPGQRPKLLIYAASNLASGVPSRF KGSGSGTQFTLTISDLECADAATYYCQCTYYDSSYGNAFGGGTEWVK (SEQ ID NO: 329; 39K2); and j) a heavy chain variable domain (VH) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:QSLEESGGDLVKPGASLTLTCTASGFSFSSGYDMCWVRQAPGKGLEWIACRHGGSSGSTHYA TWAKGRFTI SRTSSTTVTLQMTSLTAADTATYFCARDDSAAGGYFNLWGQGTLVTVSS (SEQ ID NO: 326; 45H2), and a light chain variable domain (VL) sequence having at least 85% amino acid sequence identity to the following amino acid sequence:AIEMTQTPFSVSAAVGGTVTINCQASENIYSNLGWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSATYSSGTDRAFGGGTEWVK (SEQ ID NO: 330; 45K2).

10. The antibody or an antigen-binding fragment thereof of any one of claims 1-9, wherein the antibody comprises a heavy chain constant region comprising an Fc region or a portion of the Fc region comprising CH2 and CH3 domains and / or a light chain constant region comprising a constant light chain (CL) domain.

11. The antibody or an antigen-binding fragment thereof of claim 10, wherein the CH2 and / or CH3 domain is derived from an immunoglobulin G (IgG).

12. The antibody or an antigen-binding fragment thereof of claim 10 or claim 11, wherein the CL domain comprises a kappa light chain or a lambda light chain.

13. The antibody or an antigen-binding fragment thereof of any one of claims 1-12, further comprising a heavy chain (HC) constant domain fused to the C-terminus of the variable heavy chain (VH) domain and comprising an amino acid sequence with at least about 85% amino acid sequence identity to a sequence selected from:GQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGL YSLSSWSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGGPSVFIFPPKPK DTLMISRTPEVTCVWDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRWSTLPITH QDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSSRSVSLTCMINGF YPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYNKLSVPTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK (SEQ ID NO: 285); andASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRW SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK (SEQ ID NO: 355).

14. The antibody or an antigen-binding fragment thereof of any one of claims 1-13, further comprising a light chain (LC) constant domain (CL) fused to the C-terminus of the variable light chain (VL) domain and comprising an amino acid sequence with at least about 85% amino acid sequence identity to a sequence selected from:VAPTVL I F P PAADQVATGTVT I VCVANKYF PDVTVTWEVDGTTQTTG I ENS KT PQNS ADCTY NLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC (SEQ ID NO: 35); and RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 356).

15. The antibody or antigen-binding fragment thereof of any one of claims 1-13, wherein the antibody or antigen-binding fragment thereof competes with CD7 for binding to the anti- CD? antibody, or antigen-binding fragment thereof.

16. The antibody or antigen-binding fragment thereof of any one of claims 1-14, wherein the antibody or antigen-binding fragment thereof has a dissociation constant (kdis) calculated over 60 seconds for binding to the anti-CD7 antibody that is less than about 0.002 or less than about 2E-3.

17. The antibody or antigen-binding fragment thereof of any one of claims 1-14, wherein the antibody or antigen-binding fragment thereof has a dissociation constant (kdis) calculated over 60 seconds for binding to the anti-CD7 antibody that is less than about IE-5.

18. The antibody or antigen-binding fragment thereof of any one of claims 1-14, wherein the antibody or antigen-binding fragment thereof has a dissociation constant (kdis) (1 / s) calculated over 60 seconds for binding to the anti-CD7 antibody that is less than about IE-7.

19. The antibody or antigen-binding fragment thereof of any one of claims 1-18, wherein the antibody or antigen-binding fragment thereof is a full-length antibody.

20. The antibody or antigen-binding fragment thereof of any one of claims 1-18, wherein the antigen-binding fragment is selected from among Fab fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, an scFv, and a single domain antibody.

21. The antibody or antigen-binding fragment thereof of any one of claims 1-20, wherein the anti-CD7 antibody binds a human CD7 polypeptide.

22. The antibody or antigen-binding fragment thereof of any one of claims 1-21, wherein the anti-CD7 antibody, or antigen binding fragment thereof, is an scFv.

23. The antibody or antigen-binding fragment thereof of claim 22, wherein the scFv is fused to a chimeric antigen receptor (CAR) polypeptide.

24. The antibody or antigen-binding fragment thereof of any one of claims 1-23, wherein the antibody or antigen-binding fragment thereof is humanized.

25. A polynucleotide encoding the antibody or antigen-binding fragment thereof of any one of claims 1-24.

26. The polynucleotide of claim 25, wherein the polynucleotide has at least 85% sequence identity to a sequence selected from the group consisting of: CAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGTCTGGGGCATCCCTGACACTCACCTGCACAGCTTCTGGATTCTCCTTCAGTAGCAGCTACTGGATATGCTGGGTCCGCCAGGCTCCAG GGAAGGGGCTGGAGTGGATCGCATGCATTCATGGTGGTAGTAGTGGTAACACTGCCTACGCG AGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAAT GACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCAAGATCTGATTATACTGGTG GTAATTATTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAA GGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCT TGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCT TGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGT AGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCA TAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACA CCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCT AAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAA CTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCA CCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCC CTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 343);CAGGAGCAGCTGGTGGAGTCCGGGGGAGGCCTGGTCCAGCCTGAGGGATCCCTGACACTCACCTGCACAGCTTCTGGATTCTCCTTCAGTAGCAGCTACTACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATGCATTGCTATTGGTAGTGGTAGCGCTTACTACGCGAACTGGGCGAAGGGCCGATTCACCATCACCAGAAGCACCAGCCTAAACACGGTGACTCTGCAACTGAACAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATTATGCTGGTGGTGGTTACTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 344);CAGGAGCAACTGAAGGAGTCCGGGGGAGGCCTGGTCCTGCCGGGGGGATCCCTGAAACTCTCCTGCAAAGCCTCTGGATTTGACTTCAGTAGCTATGGAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATACATTGATCCTGTTCATGGTACCACATACTACGCGAACTGGGTGAATGGCCGATTCACCATCTCCAGCCACAACGTCCAGAAAAAGCTGTATCTGCAACTCAACAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATATTTATGGTTATGCTGGTTATGCTTATGCTACGGCCTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 345);CAGTCGTTGGAGGAGTCCGGGGGAGACCTAGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCGACTTCAGTAGCAGCTATTACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCCGGAGTGGATCGCATGCATTTGGGGTGGTAGTAGTGGTACCACTTATTACGCGAACTGGGCGAAAGGCCGATTCACCATCTCCAGAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATTATGCTGGTGGTGGTTATATCAACTTGAGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 346);CAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCTTCAGTAGCAGCTACTCGATATGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCATTTATGCTGGTAGTAGTGGTAGCACTTACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACGGTGACTCTGCAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAATTGAATACTATAGTTATGGTGATGTTGGTTATGGTTATAACTACGGCATGGACCTCTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 347);CAGTCGTTGGAGGAGTCCGGGGGAGACCTGGTCAAGCCTGGGGCATCCCTGACACTCACCTGCACAGCCTCTGGATTCTCCTTCAGTAGCGGCTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGCAGACATGGTGGTAGTAGTGGTAGTACGCACTACGCGACCTGGGCGAAAGGCCGATTCACCATCTCCAGAACCTCGTCGACCACGGTGACTCTACAAATGACCAGTCTGACAGCCGCGGACACGGCCACCTATTTCTGTGCGAGAGATGATAGTGCTGCTGGTGGTTACTTTAACTTGTGGGGCCAGGGCACCCTGGTCACCGTCTCGTCAGCCAGTACAAAAGGTCCAAGTGTGTTCCCTCTTGCTCCCTCATCCAAGAGTACCAGTGGAGGCACCGCCGCTCTTGGCTGCTTGGTTAAGGATTATTTCCCAGAGCCTGTCACTGTTTCATGGAACTCCGGCGCCTTGACATCTGGTGTGCATACCTTTCCAGCCGTGCTGCAGTCAAGTGGCCTCTACAGCCTCAGTAGCGTGGTCACTGTGCCCAGCAGCTCTCTCGGCACACAAACTTATATCTGTAATGTGAATCATAAGCCTTCAAATACCAAGGTGGATAAGAAAGTGGAACCAAAATCATGTGACAAGACACACACCTGCCCTCCTTGTCCAGCCCCCGAACTGCTGGGTGGGCCCAGCGTGTTCCTGTTTCCTCCTAAACCCAAAGACACTCTGATGATTAGTAGGACCCCAGAAGTCACTTGCGTGGTGGTTGACGTGTCACATGAAGATCCCGAGGTCAAGTTCAATTGGTATGTTGACGGGGTCGAAGTTCACAACGCTAAAACTAAACCAAGAGAGGAACAGTATAACTCTACCTACCGGGTGGTGAGTGTTCTGACTGTCCTCCATCAAGACTGGCTGAATGGCAAAGAATACAAGTGTAAGGTGAGCAACAAAGCCCTGCCCGCTCCTATAGAGAAAACAATATCCAAAGCCAAAGGTCAACCTCGCGAGCCACAGGTGTACACCCTCCCACCAAGCCGCGATGAACTTACTAAGAACCAAGTCTCTCTTACTTGCCTGGTTAAGGGGTTCTATCCATCCGACATTGCAGTCGAGTGGGAGTCTAATGGACAGCCTGAGAACAACTACAAAACCACCCCTCCTGTTCTGGATTCTGACGGATCTTTCTTCCTTTATTCTAAACTCACCGTGGATAAAAGCAGGTGGCAGCAGGGCAACGTGTTCAGCTGTTCCGTTATGCATGAGGCCCTGCATAACCATTATACCCAGAAGTCTTTGTCCCTCAGTCCAGGAAAGTGA (SEQ ID NO: 348);GATGTTGTGATGACCCAGACTCCATCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGGATTAACAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATTATGCATCCAATCTAGAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGACGATGCTGCTACTTACTACTGTCAAAGTGCTTATGGTAGTACTAATGCTGATATTTTTGTTTTCGGCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 349);GCCCTTGTGATGACCCAGACTCCATCTTCCGCGTCTGAACCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCGGTGAGAGTATTAGTAGTAGATTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGCTGCATCCTATCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGAATCTGGGACAGAGTACACTCTCACCATCAGCGACCTGGAGTGTGATGATGCTGCCACTTACTACTGTCAAAGTGTTTCTGCCAGTGGGAGTGGTGATACGCGGGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 350);GCCCAAGTGCTGACCCAGACTCCAGCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCCAGTCAGAGCATTAGTGGCAACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAACTCCTGATCTATTCTGCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGGCGTGCAGTGTGCCGATGCTGCCACTTACTACTGTCAGTATGGTTATACTTATAATAGTGGTGATATTGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: (SEQ ID NO: 351);GCCCTTGTGATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGGCCAGTCAGAACATTTACAGCAATTTAGGCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGCTGCATCCTATCTGTCATCTGGGGTCCCATCACGGTTCAAAGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCAGCCACTTACTACTGTCAAAGCGCTGCTGATAGTAGTAGTGGTGATTTTTTTTATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTC TTCCCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 352);GCGCAAGTGCTGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAATCACCGTCAATTGCCAAGCCAGTCAGAGCATTGGTACCGACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTATGCTGCATCCAATCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATCAGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAATGTACTTATTATGATAGTAGTTATGGGAATGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCCTGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 353); andGCCATCGAAATGACCCAGACTCCATTCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGGCCAGTGAGAACATTTATAGTAATTTAGGCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATGCTGCATCCTATCTGGCATCTGGGGTCCCATCACGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATCAGCGGCGTGCAGTGTGCCGATGCAGCCACTTACTACTGTCAAAGTGCTACTTATAGTAGTGGTACTGATAGGGCTTTCGGCGGAGGGACCGAGGTGGTGGTCAAGAGAACTGTCGCAGCACCTTCCGTCTTTATTTTCCCACCATCAGATGAACAGCTGAAATCCGGTACTGCCAGTGTGGTCTGTCTGCTCAATAATTTCTATCCCCGGGAGGCTAAAGTCCAGTGGAAAGTGGATAATGCCCTTCAGTCCGGCAACTCCCAGGAGAGCGTGACCGAGCAGGATTCTAAGGACTCAACATATTCACTGTCATCTACTCTCACCCTGTCTAAGGCTGATTACGAAAAGCACAAGGTGTACGCTTGCGAAGTTACTCATCAGGGCCTCTCTTCCCC TGTGACCAAGAGTTTCAACCGGGGCGAGTGCTGA (SEQ ID NO: 354).

27. A vector comprising the polynucleotide of claim 25 or claim 26.

28. A cell comprising the antibody or antigen-binding fragment thereof of any one of claims 1-24, the polynucleotide of claim 25 or claim 26, or the vector of claim 27.

29. A conjugate comprising the antibody or antigen-binding fragment thereof of any one of claims 1-24 fused to a heterologous moiety.

30. The conjugate of claim 29, wherein the heterologous moiety is a detectable label.

31. The conjugate of claim 30, wherein the detectable label is selected from the group consisting of a fluorescent dye, a fluorescent protein, a radioisotope, a chromophore, a metal ion, a gold particle, a silver particle, a magnetic particle, a polypeptide, an enzyme, a streptavidin, a biotin, a luminescent compound and an oligonucleotide.

32. The conjugate of claim 29, wherein the heterologous moiety is a cytotoxic polypeptide, cytotoxic polynucleotide, or cytotoxic small molecule.

33. The conjugate of claim 29 or claim 32, wherein the conjugate is an antibody-drug conjugate.

34. A method of producing an antibody or antigen-binding fragment thereof, the method comprising expressing the antibody or antigen-binding fragment thereof encoded by the polynucleotide of claim 25 or claim 26 or the vector of claim 27 in a cell and recovering or isolating the antibody or antigen-binding fragment thereof from the cell.

35. A method of producing an antibody or antigen-binding fragment thereof, the method comprising culturing the cell of claim 28 under conditions in which the antibody or antigen- binding fragment thereof is expressed, and recovering or isolating the antibody or antigen- binding fragment thereof from the cell.

36. An antibody or antigen-binding fragment thereof produced by the method of claim 34 or claim 35.

37. A composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1-24 or claim 36, the polynucleotide of claim 25 or claim 26, the vector of claim 27, the cell of claim 28, or the conjugate of any one of claims 29-33.

38. A pharmaceutical composition comprising the composition of claim 37 and a pharmaceutically acceptable excipient.

39. A method for identifying a cell comprising an anti-cluster of differentiation (CD7) antibody, or an antigen-binding fragment thereof, on the cell surface in a biological sample,the method comprising contacting the biological sample with the antibody or antigen-binding fragment thereof of any one of claims 1-24 or 36 or the conjugate of any one of claims 29-31 under conditions sufficient for the antibody or antigen-binding fragment thereof or conjugate to bind to the anti-CD7 antibody, or antigen binding fragment thereof, in the biological sample, thereby identifying the cell expressing the anti-CD7 antibody or antigen-binding fragment thereof.

40. The method of claim 39, wherein binding is detected using a direct or indirect detection method.

41. The method of claim 40, wherein binding is detected using fluorescence activated flow cytometry.

42. The method of claim 40, wherein binding is detected using fluorescence microscopy.

43. The method of any one of claims 39-42, wherein the biological sample is a tissue sample or a blood sample.

44. The method of claim 43, wherein the biological sample is from a subject that has been administered anti-CD7 CAR T cells.

45. The method of claim 44, wherein the subject is being treated for a neoplasia.

46. The method of claim 45, wherein the neoplasia is a leukemia or a lymphoma.

47. The method of any one of claims 39-46, further comprising identifying one or more of the following cell types in the biological sample using flow cytometry: a) CD4+ T cells; b) CD8+ T cells; c) CD4+ or CD8+ T cells surface expressing one or more of LAG3, PD-1, TIM3, and TIGIT; d) CD3- T cells; e) CD4+ Treg cells; f) CD4+ or CD8+ naive T cells; g) CD4+ or CD8+ memory T cells;h) CD4+ or CD8+ central memory T cells; i) CD4+ or CD8+ stem cell memory T cells; j) CD4+ or CD8+ effector memory re-expressing CD45RA T cells; k) CD4+ or CD8+ HLA-DR+ T cells; l) CD4+ or CD8+ effector memory T cells; and m) NK cells; n) NK cells surface expressing high or low levels of CD16 and / or CD56. o) NK cells surface expressing one or more of CD38, NKG2A, NKG2D, KIR2DL1, KIR2DL3, KIR3DL1, and KIR3DL2.

48. The method of any one of claims 39-47, wherein the cells are anti-CD7 CAR T cells.

49. The method of any one of claims 39-48, wherein the cells are in vitro or ex vivo.

50. The method of claim 39, wherein contacting the biological sample with the antibody or antigen-binding fragment thereof or conjugate comprises preparing a mixture comprising the biological sample and from about 2 pg / ml to about 3 pg / ml of the antibody or antigen- binding fragment thereof or conjugate.

51. The method of claim 39, wherein contacting the biological sample with the antibody or antigen-binding fragment thereof or conjugate comprises preparing a mixture comprising the biological sample and the antibody or antigen-binding fragment thereof or conjugate, wherein the mixture comprises human serum.

52. The method of claim 51, wherein the biological sample is added to the mixture at a dilution ratio of from about 1: 10 and 1:40.

53. The method of claim 39, wherein the method further comprises contacting the biological sample a goat anti -human secondary antibody capable of specifically binding IgGl antibodies and conjugated to a detectable label.

54. The method of claim 53, wherein the detectable label is Alexa Fluor 647.

55. The method of claim 39, wherein the antibody or antigen-binding fragment thereof or conjugate comprises a heavy chain polypeptide and a light chain polypeptide, wherein: the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence: QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 333; 15H3); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 339; 15K3).

56. A meso-scale discovery-based anti-drug antibody assay method, the method comprising: a) contacting an anti-CD7 chimeric antigen receptor (anti-CD7 CAR) polypeptide or antigen-binding fragment thereof bound to an electrode with the antibody or antigen-binding fragment thereof of any one of claims 1-24 or 36 and an anti-CD7 CAR polypeptide, or antigen-binding fragment thereof, labeled using an electrochemiluminescent label under conditions sufficient for the three polypeptides to form a complex; b) detecting formation of the complex by applying electricity to the electrode and detecting an electrochemiluminescent signal generated by the electrochemiluminescent label.

57. The method of claim 56, wherein the electrochemiluminescent label is a SULFO- TAG.

58. The method of claim 56 or claim 57, wherein the anti-CD7 CAR polypeptide or antigen-binding fragment thereof is bound to the electrode using a biotin-streptavidin bridge.

59. A method of detecting an anti-CD7 antibody or antigen-binding fragment thereof in a biological sample, the method comprising: a) contacting the biological sample with the antibody or antigen-binding fragment thereof of any one of claims 1-24 or 36 or the conjugate of any one of claims 29-31 under conditions sufficient for the antibody or antigen-binding fragment thereof or conjugate to bind to the anti-CD7 antibody, or antigen binding fragment thereof, in the biological sample, and(b) detecting the antibody bound to the anti-CD7 antibody or antigen-binding fragment thereof.

60. The method of claim 59, wherein the detecting is direct or indirect.

61. The method of claim 60, wherein detecting binding comprises fluorescence activated flow cytometry.

62. The method of any one of claims 59-61, wherein the biological sample is a tissue sample or a blood sample.

63. The method of claim 62, wherein the sample is from a subject that has been administered anti-CD7 CAR T cells.

64. The method of claim 63, wherein the subject is being treated for a neoplasia.

65. The method of claim 64, wherein the neoplasia is a leukemia or a lymphoma.

66. The method of claim 63, further comprising characterizing the persistence of CAR-T cells in the subject.

67. The method of claim 59, wherein contacting the biological sample with the antibody or antigen-binding fragment thereof or conjugate comprises preparing a mixture comprising the biological sample and from about 2 pg / ml to about 3 pg / ml of the antibody or antigen- binding fragment thereof or conjugate.

68. The method of claim 59, wherein contacting the biological sample with the antibody or antigen-binding fragment thereof or conjugate comprises preparing a mixture comprising the biological sample and the antibody or antigen-binding fragment thereof or conjugate, wherein the mixture comprises human serum.

69. The method of claim 68, wherein the biological sample is added to the mixture at a dilution ratio of from about 1: 10 and 1:40.

70. The method of claim 59, wherein the method further comprises contacting the biological sample a goat anti -human secondary antibody capable of specifically binding IgGl antibodies and conjugated to a detectable label.

71. The method of claim 70, wherein the detectable label is Alexa Fluor 647.

72. The method of claim 59, wherein the antibody or antigen-binding fragment thereof or conjugate comprises a heavy chain polypeptide and a light chain polypeptide, wherein: the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence: QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 333; 15H3); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 339; 15K3).

73. A method of selecting cells from a cell population, the method comprising:a) contacting a cell population expressing an anti-CD7 CAR polypeptide with the antibody or antigen-binding fragment thereof of any one of claims 1-24 or 36 or the conjugate of any one of claims 29-31 under conditions sufficient for the antibody or antigen- binding fragment thereof or conjugate to bind to the anti-CD7 CAR polypeptide, or antigen binding fragment thereof, in the cell population, b) selecting cells bound with the antibody or antigen-binding fragment thereof or conjugate.

74. The method of claim 73, wherein the cells bound with the antibody or antigen-binding fragment thereof or conjugate are selected by immunoaffinity-based separation.

75. The method of claim 73, wherein the cells bound with the antibody or antigen-binding fragment thereof or conjugate are selected by flow cytometry.

76. The method of any one of claims 73-75, wherein the cell population comprises T cells.

77. The method of any one of claims 73-75, wherein the cell population comprises T cells expressing the anti-CD7 CAR polypeptide have been engineered to knock out expression of one or more polypeptides selected from the group consisting of CD7, TRAC, CD62, PD-1, CD3 -epsilon, and CD3 -gamma.

78. A method of depleting anti-CD7 CAR T cells in a subject, the method comprising administering to the subject a composition comprising the conjugate of claim 32 or claim 33, wherein the subject has been administered the anti-CD7 CAR T cells.

79. A kit suitable for use in any of the above methods, wherein the kit comprises the antibody or antigen-binding fragment thereof, the polynucleotide, the vector, the cell, or the conjugate of any of the above claims.

80. An antibody or an antigen-binding fragment thereof that specifically binds to an anti- cluster of differentiation 7 (CD7) antibody, or an antigen-binding fragment thereof, wherein the binding polypeptide comprises a heavy chain polypeptide and a light chain polypeptide, wherein:a) the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence: QSLEESGGDLVKSGASLTLTCTASGFSFSSSYWICWVRQAPGKGLEWIACIHGGSSGNTAYA SWAKGRFTISKTSSTTVTLQMTSLTAADTATYFCARSDYTGGNYFNLWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KP KDTLM I S RTP EVTC VWDVSHED PEVKFNWYVDGVEVHNAKTKPRE EQ YNS TYRWS VLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO: 331; 2H3); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:DVVMTQTPSSVEAAVGGTVTIKCQASQRINSWLAWYQQKPGQPPKLLIYYASNLESGVPSRF KGSGSGTEYTLTISDLECDDAATYYCQSAYGSTNADIFVFGGGTEVWKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 337; 2K1); b) the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:QEQLVESGGGLVQPEGSLTLTCTASGFSFSSSYYMCWVRQAPGKGLEWIGCIAIGSGSAYYA NWAKGRFTITRSTSLNTVTLQLNSLTAADTATYFCARDDYAGGGYFNLWGQGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFP PKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL TVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK (SEQ ID NO: 332; 5H1); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:ALVMTQTPSSASEPVGGTVTIKCQAGESISSRLAWYQQKPGQPPKLLIYAASYLASGVPSRF KGSESGTEYTLTISDLECDDAATYYCQSVSASGSGDTRAFGGGTEVWKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 338; 5K3); c) the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:QEQLKESGGGLVLPGGSLKLSCKASGFDFSSYGMNWVRQAPGKGLEWIGYIDPVHGTTYYAN WVNGRFTISSHNVQKKLYLQLNSLTAADTATYFCARDDI YGYAGYAYATAFNLWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS VFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR WSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQV SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC SVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 333; 15H3); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:AQVLTQTPASVSAAVGGTVTIKCQASQSISGNLAWYQQKPGQPPKLLIYSASTLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQYGYTYNSGDIAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 339; 15K3); d) the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence: QSLEESGGDLVKPGASLTLTCTASGFDFSSSYYMCWVRQAPGKGPEWIACIWGGSSGTTYYA NWAKGRFTISRTSSTTVTLQMTSLTAADTATYFCARDDYAGGGYINLRGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KP KDTLM I S RTP EVTC VWDVSHED PEVKFNWYVDGVEVHNAKTKPRE EQ YNS TYRWS VLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO: 334; 20H1); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:ALVMTQTPSSVSAAVGGTVTINCQASQNIYSNLGWYQQKPGQPPKLLIYAASYLSSGVPSRF KGSGSGTDFTLTISDLECADAATYYCQSAADSSSGDFFYAFGGGTEWVKRTVAAPSVFIFP PSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 340; 20K3); e) the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:QSLEESGGDLVKPGASLTLTCTASGFSFSSSYSICWVRQAPGKGLEWIACIYAGSSGSTYYA SWAKGRFTI SKTSSTTVTLQMTSLTAADTATYFCARI EYYS YGDVGYGYNYGMDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRWSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF SCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 335; 39H2); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:AQVLTQTPASVEAAVGGTITVNCQASQSIGTDLAWYQQKPGQRPKLLIYAASNLASGVPSRF KGSGSGTQFTLTISDLECADAATYYCQCTYYDSSYGNAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 341; 39K2); or f) the heavy chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence: QSLEESGGDLVKPGASLTLTCTASGFSFSSGYDMCWVRQAPGKGLEWIACRHGGSSGSTHYA TWAKGRFTISRTSSTTVTLQMTSLTAADTATYFCARDDSAAGGYFNLWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP KP KDTLM I S RTP EVTC VWDVSHED PEVKFNWYVDGVEVHNAKTKPRE EQ YNS TYRWS VLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA LHNHYTQKSLSLSPGK (SEQ ID NO: 336; 45H2); and the light chain polypeptide comprises an amino acid sequence with at least about 90% identity to the following sequence:AIEMTQTPFSVSAAVGGTVTINCQASENIYSNLGWYQQKPGQPPKLLIYAASYLASGVPSRF KGSGSGTEYTLTISGVQCADAATYYCQSATYSSGTDRAFGGGTEWVKRTVAAPSVFIFPPS DEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSK ADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 342; 45K2).

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