Compositions and methods for modulating beta chain mediated immunity

Abstract

Compositions and methods for modulating beta chain mediated immunity are provided. Anti-V [beta] 17 antibodies or antigen-binding fragments thereof are described. Nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies to treat or prevent disease are also described.

Description

[0001] This application is a divisional application of the invention application with an application date of November 1, 2022, a Chinese national application number of 202280086558.9, and an invention name of “Compositions and methods for regulating β-chain-mediated immunity”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 274,430 filed on November 1, 2021, U.S. Provisional Patent Application No. 63 / 274,446 filed on November 1, 2021, and U.S. Provisional Patent Application No. 63 / 274,449 filed on November 1, 2021, the disclosures of which are incorporated herein by reference in their entirety.

[0004] Reference sequence listing submitted electronically

[0005] This application contains a sequence listing submitted electronically. The contents of the electronic sequence listing (065768-135WO1_SequenceListing.xml; size: 512,333 bytes; and creation date: October 31, 2022) are incorporated herein by reference in their entirety. Technical Field

[0006] In certain aspects, provided herein are antibodies that bind to Vβ17, as well as recombinant cells containing vectors and compositions containing antibodies. Also provided are methods of making and using the antibodies. Summary of the invention

[0007] In one aspect, the present disclosure provides an antibody that binds to Vβ17, the antibody comprising: a heavy chain variable region (VH), the VH comprising a VH complementarity determining region 1 (CDR1), a VH CDR2, and a VH CDR3, respectively having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of VH comprising the amino acid sequence of SEQ ID NO: 31; and a light chain variable region (VL), the VL comprising a VL CDR1, a VL CDR2, and a VL CDR3, respectively having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of VL comprising the amino acid sequence of SEQ ID NO: 32.

[0008] In another aspect, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 65; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 66.

[0009] In one embodiment, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, of a VH comprising the amino acid sequence of SEQ ID NO: 99; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL comprising the amino acid sequence of SEQ ID NO: 100.

[0010] In another embodiment, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 133; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 134.

[0011] In one aspect, the present disclosure provides an antibody that binds to Vβ17, the antibody comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 167; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 168.

[0012] On the other hand, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising VH CDR1, VH CDR2 and VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3 of VH comprising the amino acid sequence of SEQ ID NO: 201; and a VL comprising VL CDR1, VL CDR2 and VL CDR3 respectively having the amino acid sequences of VLCDR1, VL CDR2 and VL CDR3 of VL comprising the amino acid sequence of SEQ ID NO: 202.

[0013] In one embodiment, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, of a VH comprising the amino acid sequence of SEQ ID NO: 235; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL comprising the amino acid sequence of SEQ ID NO: 236.

[0014] In another embodiment, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 269; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 270.

[0015] In one aspect, the present disclosure provides an antibody that binds to Vβ17, the antibody comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 303; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 304.

[0016] On the other hand, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising VH CDR1, VH CDR2 and VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3 of VH comprising the amino acid sequence of SEQ ID NO: 337; and a VL comprising VL CDR1, VL CDR2 and VL CDR3 respectively having the amino acid sequences of VLCDR1, VL CDR2 and VL CDR3 of VL comprising the amino acid sequence of SEQ ID NO: 338.

[0017] In one embodiment, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 respectively having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 371; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 372.

[0018] In another embodiment, the present disclosure provides an antibody that binds to Vβ17, comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 405; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 406.

[0019] In one aspect, the present disclosure provides an antibody that binds to Vβ17, the antibody comprising: a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 439; and a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 440.

[0020] The present disclosure also provides an antibody, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Kabat numbering system.

[0021] The present disclosure also provides an antibody, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Chothia numbering system.

[0022] The present disclosure also provides an antibody, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the AbM numbering system.

[0023] The present disclosure also provides an antibody, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Contact numbering system.

[0024] The present disclosure also provides an antibody, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the IMGT numbering system.

[0025] The present disclosure also provides an antibody, wherein the antibody is a humanized antibody.

[0026] The present disclosure also provides an antibody, wherein the antibody is an IgG antibody. The present disclosure also provides an antibody, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0027] The present disclosure also provides an antibody, wherein the antibody comprises a kappa light chain. The present disclosure also provides an antibody, wherein the antibody comprises a lambda light chain.

[0028] The present disclosure also provides an antibody, wherein the antibody is a monoclonal antibody.

[0029] The present disclosure also provides an antibody, wherein the antibody binds to a Vβ17 antigen. The present disclosure also provides an antibody, wherein the antibody binds to a Vβ17 epitope.

[0030] The present disclosure also provides an antibody, wherein the antibody specifically binds to Vβ17.

[0031] The present disclosure also provides an antibody, wherein the antibody is multivalent. The present disclosure also provides an antibody, wherein the antibody is capable of binding to at least three antigens. The present disclosure also provides an antibody, wherein the antibody is capable of binding to at least four antigens. The present disclosure also provides an antibody, wherein the antibody is capable of binding to at least five antigens.

[0032] The present disclosure also provides an antibody, wherein the antibody is a multispecific antibody. The present disclosure also provides an antibody, wherein the antibody is a bispecific antibody. The present disclosure also provides an antibody, wherein the antibody is a trispecific antibody. The present disclosure also provides an antibody, wherein the antibody is a tetraspecific antibody.

[0033] In one aspect, the present disclosure provides a nucleic acid encoding an antibody disclosed herein.

[0034] In one aspect, the present disclosure provides a vector comprising a nucleic acid disclosed herein.

[0035] In one aspect, the present disclosure provides a host cell comprising a vector disclosed herein.

[0036] In one aspect, the present disclosure provides a kit comprising a vector disclosed herein and instructions for using the vector. In one aspect, the present disclosure provides a kit comprising an antibody disclosed herein and instructions for using the antibody.

[0037] In one aspect, the present disclosure provides a pharmaceutical composition comprising an antibody disclosed herein and a pharmaceutically acceptable carrier.

[0038] In one aspect, the present disclosure provides a method of producing a pharmaceutical composition disclosed herein, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0039] In one aspect, the present disclosure provides a method of activating a T cell expressing Vβ17, comprising contacting an antibody disclosed herein with a T cell expressing Vβ17.

[0040] The present disclosure also provides a method, wherein the contacting increases CD69, CD25 and / or granzyme B expression compared to T cells expressing Vβ17 that have not been contacted with an antibody disclosed herein.

[0041] In one aspect, the present disclosure provides a method for preparing an antibody that binds to more than one target molecule, the method comprising: a step for performing the function of obtaining a first binding domain that binds to Vβ17 present on T cells; a step for performing the function of obtaining a second binding domain that binds to a second target on the surface of a target cell; and a step for performing the function of providing an antibody that binds to Vβ17 present on T cells and a second target on the surface of a target cell.

[0042] The present disclosure also provides a method, wherein the step of performing the function of obtaining a second binding domain that binds to a second target on the surface of a target cell is repeated n times, and also includes n steps for performing the function of providing a first binding domain that binds to Vβ17 present on a T cell and n target molecules, wherein n is at least 2.

[0043] In one aspect, the present disclosure provides a method for preparing an antibody disclosed herein, the method comprising culturing a host cell disclosed herein under conditions that produce the antibody. In another aspect, the method further comprises isolating the antibody.

[0044] In one aspect, the present disclosure provides a method of directing a T cell expressing Vβ17 to a target cell, the method comprising contacting an antibody disclosed herein with the target cell, wherein a second target is present on the surface of the target cell, and wherein the contact directs the T cell to the target cell.

[0045] In one aspect, the present disclosure provides a method of inhibiting the growth or proliferation of a target cell, the method comprising contacting an antibody disclosed herein with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell expressing Vβ17, and wherein the contacting results in inhibiting the growth or proliferation of the target cell.

[0046] In one aspect, the present disclosure provides a method of eliminating a target cell in a subject, the method comprising contacting an antibody disclosed herein with a target cell having a second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell expressing Vβ17, and wherein the contacting results in elimination of the target cell.

[0047] In one aspect, the present disclosure provides a method of treating a disease in a subject, the method comprising administering to the subject an effective amount of an antibody disclosed herein, wherein the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. In another embodiment, the subject is a human. In one embodiment, the subject is a subject in need. BRIEF DESCRIPTION OF THE DRAWINGS

[0048] The foregoing summary and the following detailed description of specific embodiments of the present patent application can be better understood when read in conjunction with the accompanying drawings. However, it should be understood that the present patent application is not limited to the precise embodiments shown in the accompanying drawings.

[0049] Figure 1 Several monoclones specifically binding to Vβ17 identified by flow cytometry using different cell lines and primary cells are shown.

[0050] Figure 2 Twenty-six monoclones were shown to induce proliferation of Vβ17+ cells.

[0051] Figure 3 Shown are the differential proliferation kinetics observed for the 26 purified antibodies.

[0052] Figure 4 Shown are the differential CD71 upregulation kinetics observed for the 26 purified antibodies.

[0053] Figure 5 The ten best agonistic monoclonal clones that specifically bind to Vβ17 using the SKW3 cell line variants are shown.

[0054] Figure 6 It was shown that the 10 purified Vβ17 antibodies bound well to PBMCs.

[0055] Figure 7 Ten candidate monoclonals are shown that differ in isotype based on their heterozygous parents.

[0056] Figure 8 The internalization assay used to screen the 10 listed antibodies is shown. Monoclones from the 28B2 parent showed good internalization. Monoclones from 28C9 with agonistic properties showed poor internalization. Monoclones from parents 28D2 and 14H7 showed no internalization.

[0057] Figure 9A-9C The epitope binning matrix of 10 candidate antibodies using Octet RED966 is shown. Purified monoclonal antibodies from 3 different parents were classified into 3 different groups ( Fig. 9B ).

[0058] Figure 10A-10C It is shown that 10 candidate antibodies classified differently compared to a commercial antibody (TCR Vβ17-PE; Beckman coulter, cat. no. IM2048) as a positive control.

[0059] Fig.11It is shown that the monoclones from the same parent have the same VH sequence. The heavy chain sequences of the monoclones belonging to the three different hybrids are different from each other.

[0060] Fig.12 It is shown that monoclones from the same parent have identical VK sequences. The light chain sequences of monoclones belonging to the three different hybrids differ from each other.

[0061] Fig.13 Twelve new antibodies were shown with moderate agonistic properties and good PBMC binding.

[0062] Figure 14A-Figure 14C It is shown that monoclones from the hybrid parent 23A9 classified similarly to the positive control antibody TCRVβ17-PE.

[0063] Figure 15A-Figure 15C It is shown that single clones from the parent 23A9 and the positive control TCRVβ17-PE were classified as different from single clones from the other hybrid parents.

[0064] Fig.16 It was shown that most monoclonal clones did not compete with the positive control TCR Vβ17 for binding to cells expressing Vβ17. DETAILED DESCRIPTION

[0065] Various publications, articles, and patents are cited or described in the background and throughout the specification; each of these references is incorporated herein by reference in its entirety. The discussion of documents, acts, materials, devices, articles, etc. included in this specification is intended to provide a context for the present invention. Such discussion is not an admission that any or all of these matters form part of the prior art with respect to any invention disclosed or claimed.

[0066] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Otherwise, certain terms used herein have the meanings described in this specification.

[0067] It must be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0068] Unless otherwise indicated, any numerical value, such as a concentration or concentration range described herein, is understood to be modified by the term "about" in all cases. Therefore, numerical values ​​generally include ± 10% of the value. For example, a concentration of 1 mg / mL generally includes 0.9 mg / mL to 1.1 mg / mL. Similarly, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). Unless the context clearly indicates otherwise, as used herein, the numerical range used explicitly includes all possible subranges, all single values ​​within the range, including integers within such ranges and fractions within the range.

[0069] Unless otherwise indicated, the term "at least" preceding a series of elements is to be understood to refer to every element in the series.

[0070] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, numerous equivalents to the specific embodiments described herein. Such equivalents are intended to be encompassed by the present invention.

[0071] As used herein, the terms "comprises," "including," "having," or "containing," or any other variation thereof, should be understood to mean including the specified integer or group of integers, but not excluding any other integer or group of integers, and are intended to be non-exclusive or open-ended. For example, a composition, mixture, process, method, article, or apparatus that includes a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to these compositions, mixtures, processes, methods, articles, or apparatuses. In addition, unless expressly indicated to the contrary, "or" refers to an inclusive or rather than an exclusive or. For example, a condition A or B is satisfied by any of the following: A is true (or present) and B is false (or absent), A is false (or absent) and B is true (or present), and both A and B are true (or present).

[0072] As used herein, the connection term "and / or" between multiple listed elements is understood to include both single options and combined options. For example, where two elements are connected by "and / or", the first option refers to the application of the first element without the second element. The second option refers to the application of the second element without the first element. The third option refers to the application of the first element and the second element together. Any of these options is understood to fall within the meaning and therefore meets the requirements of the term "and / or" as used herein. The parallel applicability of more than one option is also understood to fall within the meaning and therefore meets the requirements of the term "and / or".

[0073] As used herein, the term "consisting of" used throughout the specification and claims means including any listed integer or group of integers, but additional integers or groups of integers cannot be added to the specified method, structure, or composition.

[0074] As used herein, the term "consisting essentially of" used throughout the specification and claims means including any recited integer or group of integers, and optionally including any recited integer or group of integers that does not materially change the basic or novel characteristics of the specified method, structure, or composition.

[0075] As used herein, "subject" refers to any animal, preferably a mammal, most preferably a human. As used herein, the term "mammal" encompasses any mammal. Examples of mammals include, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc. In a specific embodiment, the subject is a human.

[0076] It should also be understood that when referring to the dimensions or characteristics of the components of the embodiments provided herein, the terms "about", "approximately", "substantially" and similar terms used herein indicate that the dimensions / characteristics described are not strict boundaries or parameters, and minor variations that are functionally the same or similar are not excluded, as understood by those of ordinary skill in the art. At a minimum, such references including numerical parameters will include variations using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.) that will not change the least significant digits.

[0077] In the context of two or more nucleic acid or polypeptide sequences (e.g., Vβ17 antibodies and polynucleotides encoding them, Vβ17 polynucleotides encoding them), the terms "same" or "percent identity" refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection.

[0078] For sequence comparison, usually one sequence is used as a reference sequence to which a test sequence is compared. When using a sequence comparison algorithm, the test sequence and the reference sequence are input into a computer, subsequence coordinates are specified (if necessary), and program parameters for the sequence algorithm are specified. Then, the sequence comparison algorithm calculates the sequence identity percentage for the test sequence relative to the reference sequence based on the specified program parameters.

[0079] Optimal alignment of sequences for comparison can be performed, for example, by the local homology algorithm of Smith & Waterman (Adv. Appl. Math. 2:482 (1981), by using the homology alignment algorithm of Needleman & Wunsch, J Mol. Biol., 48:443 (1970), by searching the similarity method of Pearson & Lipman (Proc. Nat'l. Acad. Sci. USA 85:2444 (1988)), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package (Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (see generally, Current Protocols in Molecular Biology, FM Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc. (1995 supplemented edition) (Ausubel)).

[0080] Examples of algorithms suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., (1990) J. Mol. Biol., 215: 403-410 and Altschul et al., (1997) Nucleic Acids Res. 25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. The algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence that match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased.

[0081] For nucleotide sequences, the cumulative score is calculated using the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is ​​used to calculate the cumulative score. Extension of the word hits in each direction is stopped when: the cumulative alignment score falls by the amount X from its maximum achieved value; the cumulative score goes to zero or lower due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) of 10, M=5, N=-4, and a comparison of both chains. For amino acid sequences, the BLASTP program uses as defaults a word length (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).

[0082] In addition to calculating the percentage of sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin and Altschul, Proc. Nat'l. Acad. Sci. USA 90: 5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability that a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.

[0083] Another indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid immunologically cross-reacts with the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, e.g., where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions.

[0084] As used herein, the term "polynucleotide", which is synonymously referred to as "nucleic acid molecule", "nucleotide" or "nucleic acid", refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. "Polynucleotide" includes, but is not limited to, single-stranded and double-stranded DNA, DNA that is a mixture of single-stranded and double-stranded regions, single-stranded and double-stranded RNA, and RNA that is a mixture of single-stranded and double-stranded regions, and hybrid molecules comprising DNA and RNA that may be single-stranded or more typically double-stranded or a mixture of single-stranded and double-stranded regions. In addition, "polynucleotide" refers to a triple-stranded region comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNA or RNA containing one or more modified bases, and DNA or RNA having a main chain modified for stability or other reasons. "Modified" bases include, for example, tritylated bases and rare bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, "polynucleotide" includes chemically, enzymatically, or metabolically modified forms of polynucleotides that commonly occur in nature, as well as chemical forms of DNA and RNA that are unique to viruses and cells."Polynucleotide" also includes relatively short nucleic acid chains, commonly referred to as oligonucleotides.

[0085] As used herein, the term "vector" is a replicon into which another nucleic acid segment may be operably inserted so as to bring about the replication or expression of that segment.

[0086] As used herein, the term "host cell" refers to a cell comprising a nucleic acid molecule as provided herein. A "host cell" can be any type of cell, for example, a primary cell, a cell in culture, or a cell from a cell line. In one embodiment, a "host cell" is a cell transfected with a nucleic acid molecule as provided herein. In another embodiment, a "host cell" is a progeny or potential progeny of such a transfected cell. The progeny of a cell may or may not be identical to the parent cell, for example, due to mutations or environmental influences that may occur in the progeny or due to the integration of the nucleic acid molecule into the host cell genome.

[0087] As used herein, the term "expression" refers to the biosynthesis of a gene product. The term encompasses the transcription of a gene into RNA. The term also encompasses the translation of RNA into one or more polypeptides, and also encompasses all naturally occurring post-transcriptional and post-translational modifications. The expressed antibody may be in the cytoplasm of a host cell, in an extracellular environment such as a growth medium for a cell culture, or anchored to a cell membrane.

[0088] As used herein, the terms "peptide", "polypeptide" or "protein" may refer to molecules composed of amino acids and may be recognized as proteins by those skilled in the art. Conventional single-letter or three-letter codes for amino acid residues are used herein. The terms "peptide", "polypeptide" and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may contain modified amino acids, and it may be interspersed with non-amino acids. The term also encompasses amino acid polymers that have been modified naturally or by intervention; natural or interventional modifications are, for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. The definition also includes, for example, polypeptides containing one or more amino acid analogs (including, for example, non-natural amino acids, etc.) and other modifications known in the art.

[0089] The peptide sequences described herein are written according to the usual convention, with the N-terminal region of the peptide on the left and the C-terminal region on the right. Although isomeric forms of amino acids are known, unless otherwise expressly indicated, it is the L form of the amino acid represented.

[0090] Antibody

[0091] Provided herein are Vβ17 antibodies or antigen-binding fragments thereof, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided are methods for preparing these antibodies, and methods for using these antibodies to treat diseases. The antibodies disclosed herein have one or more desired functional properties, including but not limited to high affinity binding to Vβ17 or high specificity for Vβ17. In certain embodiments, the antibodies disclosed herein have the ability to treat or prevent a disease or condition when administered to a subject alone or in combination with other therapies.

[0092] As used herein, the term "antibody" is used in a broad sense and includes immunoglobulins or antibody molecules, including human antibodies, humanized antibodies, composite antibodies and chimeric antibodies and monoclonal or polyclonal antibody fragments. Generally speaking, an antibody is a protein or peptide chain that exhibits binding specificity for a specific antigen. The structure of an antibody is well known. According to the amino acid sequence of the heavy chain constant domain, immunoglobulins can be designated as five major classes (i.e., IgA, IgD, IgE, IgG, and IgM). IgA and IgG are further subclassified into isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Therefore, the antibodies provided herein may be any of the five main species or corresponding subclasses. In a specific embodiment, the antibodies provided herein are IgG1, IgG2, IgG3, or IgG4. Based on the amino acid sequence of its constant domain, the antibody light chain of a vertebrate species can be designated as one of two completely different types, i.e., K and λ. Therefore, in certain embodiments, the antibodies provided herein may include a K light chain constant domain. In certain embodiments, the antibodies provided herein may also include a λ light chain constant domain. According to specific embodiments, the antibodies provided herein include a heavy chain constant region and / or a light chain constant region from a mouse antibody or a human antibody. In specific embodiments, the constant region is a human constant region.

[0093] In addition to the heavy and light chain constant domains, antibodies also contain an antigen binding region consisting of a light chain variable region (VL) and a heavy chain variable region (VH), wherein each variable region contains three domains (i.e., complementarity determining region 1 (CDR1), CDR2, and CDR3). "CDR" refers to one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) within the non-framework region of the immunoglobulin (Ig or antibody) VH β-sheet framework, or one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) within the non-framework region of the antibody VL β-sheet framework. Thus, CDRs are variable region sequences interspersed within framework region sequences. CDR regions are well known to those skilled in the art and have been defined, for example, by Kabat as the most hypervariable region within an antibody variable (V) domain (Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat, Adv. Prot. Chem. 32: 1-75 (1978)). Chothia also structurally defines CDR region sequences as those residues that are not part of the conserved β-sheet framework and are therefore able to adapt to different conformations (Chothia and Lesk, J. Mol. Biol., 196: 901-917 (1987)). Both terms are recognized in the art. CDR region sequences are also defined by AbM, Contact and IMGT. Exemplary CDR region sequences are shown herein, for example, in the table provided below. The positions of CDRs within canonical antibody variable regions have been determined by comparing many structures (Al-Lazikani et al., J. Mol. Biol., 273: 927-948 (1997); Morea et al., Methods 20: 267-279 (2000)). Because the number of residues within the hypervariable region varies among different antibodies, additional residues relative to the canonical position are usually numbered with a, b, c, etc. next to the residue number in the canonical variable region numbering scheme (Al-Lazikani et al., supra, 1997). Such nomenclature is also well known to those skilled in the art.

[0094] The light chain variable region CDR1 domain is interchangeably referred to herein as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is interchangeably referred to herein as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is interchangeably referred to herein as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is interchangeably referred to herein as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR3 or VH CDR3.

[0095] As used herein, the term "hypervariable region" (such as VH or VL) when used herein refers to a region in an antibody variable region that is hypervariable in sequence and / or forms structurally defined loops. Typically, an antibody comprises six hypervariable regions; three in VH (HCDR1, HCDR2, HCDR3) and three in VL (LCDR1, LCDR2, LCDR3). Many hypervariable region descriptions are in use and are included herein. The "Kabat" CDR is based on sequence variability and is the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Edition, Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). "Chothia" in contrast refers to the position of the structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol., 196:901-917 (1987)). When numbered using the Kabat numbering convention, the ends of the Chothia CDR-HCDR1 loop vary between H32 and H34, depending on the length of the loop (this is because the Kabat numbering scheme places the insertion at H35A and H35B; if both 35A and 35B are absent, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The "AbM" hypervariable regions represent a compromise between the Kabat CDR and Chothia structural loops and are used by Oxford Molecular's AbM antibody modeling software (see, e.g., Martin, Antibody Engineering, Vol. 2, Chapter 3, Springer Verlag). The "Contact" hypervariable regions are based on analysis of available complex crystal structures.

[0096] Recently, a universal numbering system has been developed and widely adopted, the ImMunoGeneTics (IMGT) Information (Lafranc et al., Dev. Comp. Immunol. 27(1):55-77 (2003)). IMGT is an integrated information system dedicated to the study of immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of humans and other vertebrates. In this article, CDRs are referenced both by amino acid sequence and by position within the light or heavy chain. Since the "position" of CDRs within the immunoglobulin variable domain structure is conserved between species and is present in structures called loops, CDRs and framework residues are easily identified by using a numbering system that aligns variable domain sequences based on structural features. This information can be used to transplant and replace CDR residues from an immunoglobulin from one species into an acceptor framework, usually from a human antibody. Honegger and Plückthun developed an additional numbering system (AHon), J. Mol. Biol., 309:657-670 (2001). The correspondence between numbering systems, including, for example, Kabat numbering and the IMGT unique numbering system, is well known to those skilled in the art (see, for example, Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra). The exemplary system shown herein combines Kabat and Chothia.

[0097] Exemplary IMGT Kabat AbM Chothia Contact <![CDATA[V H CDR1]]> 26-35 27-38 31-35 26-35 26-32 30-35 <![CDATA[V H CDR2]]> 50-65 56-65 50-65 50-58 53-55 47-58 <![CDATA[V H CDR3]]> 95-102 105-117 95-102 95-102 96-101 93-101 <![CDATA[V L CDR1]]> 24-34 27-38 24-34 24-34 26-32 30-36 <![CDATA[V L CDR2]]> 50-56 56-65 50-56 50-56 50-52 46-55 <![CDATA[V L CDR3]]> 89-97 105-117 89-97 89-97 91-96 89-96

[0098] Hypervariable regions may include "extended hypervariable regions" as follows: 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2), and 89-97 or 89-96 (LCDR3) in VL, and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102 or 95-102 (HCDR3) in VH. CDR sequences reflecting each of the above numbering schemes are provided herein, included in Tables 1 to 6.

[0099] The term "constant region" or "constant domain" refers to the carboxyl terminal portion of the light chain and the heavy chain, which is not directly involved in the binding of the antibody to the antigen, but exhibits various effector functions, such as interactions with Fc receptors. These terms refer to the portion of the immunoglobulin molecule that has a more conserved amino acid sequence relative to the rest of the immunoglobulin (the variable region containing the antigen binding site). The constant region may include the CH1, CH2 and CH3 regions of the heavy chain and the CL region of the light chain.

[0100] The term "framework" or "FR" residues are those variable region residues that flank the CDRs. FR residues are found, for example, in chimeric, humanized, human domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are those variable domain residues other than hypervariable region residues or CDR residues.

[0101] As used herein, the term "isolated antibody" refers to an antibody that is substantially free of other antibodies with different antigenic specificities (e.g., an isolated antibody that specifically binds to Vβ17 is substantially free of antibodies that do not bind to Vβ17). In addition, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0102] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a group of substantially homogeneous antibodies, i.e., the individual antibodies constituting the group are identical except for possible naturally occurring mutations that may be present in small amounts. The monoclonal antibodies provided herein can be prepared by hybridoma methods, phage display techniques, single lymphocyte gene cloning techniques, or by recombinant DNA methods. For example, a monoclonal antibody can be produced by a hybridoma comprising a B cell obtained from a transgenic non-human animal such as a transgenic mouse or rat, the transgenic non-human animal having a genome comprising a human heavy chain transgene and a light chain transgene.

[0103] As used herein, the term "antigen binding fragment" refers to an antibody fragment, such as, for example, a diabody, Fab, Fab', F(ab')2, an Fv fragment, a disulfide-stabilized Fv fragment (dsFv), (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide-stabilized diabody (dsdiabody), a single-chain antibody molecule (scFv), a single domain antibody (sdAb), a scFv dimer (a bivalent bivalent antibody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a camelized single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not contain a complete antibody structure. An antigen binding fragment is capable of binding to the same antigen as the antigen to which the parent antibody or parent antibody fragment binds. According to specific embodiments, the antigen binding fragment comprises a light chain variable region, a light chain constant region, and an Fd segment of the heavy chain. According to other specific embodiments, the antigen binding fragment comprises Fab and F(ab').

[0104] As used herein, the term "single-chain antibody" refers to a conventional single-chain antibody in the art, which comprises a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single-domain antibody" refers to a conventional single-domain antibody in the art, which comprises a heavy chain variable region and a heavy chain constant region or only a heavy chain variable region.

[0105] As used herein, the term "human antibody" refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human prepared using any technique known in the art. This definition of a human antibody includes complete or full-length antibodies, fragments thereof, and / or antibodies comprising at least one human heavy chain polypeptide and / or light chain polypeptide.

[0106] As used herein, the term "humanized antibody" refers to a non-human antibody that has been modified to increase sequence homology with a human antibody, such that the antigen-binding properties of the antibody are retained but its antigenicity in the human body is reduced.

[0107] As used herein, the term "chimeric antibody" refers to an antibody whose amino acid sequence of an immunoglobulin molecule is derived from two or more species. The variable regions of both the light and heavy chains often correspond to the variable regions of an antibody with desired specificity, affinity and capacity derived from one mammalian species (e.g., mouse, rat, rabbit, etc.), while the constant region corresponds to a sequence in an antibody derived from another mammalian species (e.g., human) to avoid eliciting an immune response in that species.

[0108] As used herein, the term "multi-specific antibody" refers to an antibody comprising multiple immunoglobulin variable domain sequences, wherein the first immunoglobulin variable domain sequence in the multiple immunoglobulin variable domain sequences has binding specificity to the first epitope, and the second immunoglobulin variable domain sequence in the multiple immunoglobulin variable domain sequences has binding specificity to the second epitope. In one embodiment, the first epitope and the second epitope do not overlap or do not overlap substantially. In one embodiment, the first epitope and the second epitope are on different antigens such as different proteins (or different subunits of multimeric proteins). In one embodiment, the multi-specific antibody comprises the third, fourth or fifth immunoglobulin variable domain. In one embodiment, the multi-specific antibody is a bispecific antibody molecule, a tri-specific antibody molecule or a tetra-specific antibody molecule.

[0109] As used herein, the term "bispecific antibody" refers to a multispecific antibody that binds no more than two epitopes or two antigens, such as two epitopes or antigens of different genetic targets (e.g., Vβ17, CD69 or CD25). Bispecific antibodies are characterized by having a first immunoglobulin variable domain sequence with binding specificity to a first epitope (e.g., an epitope on a Vβ17 antigen) and a second immunoglobulin variable domain sequence with binding specificity to a second epitope. In one embodiment, the first epitope and the second epitope are on different antigens, such as different proteins (or different subunits of a multimeric protein). In one embodiment, the bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence with binding specificity to a first epitope and a heavy chain variable domain sequence and a light chain variable domain sequence with binding specificity to a second epitope. In one embodiment, the bispecific antibody comprises a half antibody or a fragment thereof with binding specificity to a first epitope and a half antibody or a fragment thereof with binding specificity to a second epitope. In one embodiment, the bispecific antibody comprises a scFv or fragment thereof having binding specificity for a first epitope and a scFv or fragment thereof having binding specificity for a second epitope.

[0110] As used herein, the term "Vβ17" refers to a T cell receptor expressed in response to an immune response on cytotoxic T cells. CD8+T cells expressing Vβ17 are generally produced in response to a subject being exposed to influenza A virus. CD8+T cells expressing Vβ17 provide great recall in response to a subject being exposed to influenza. The term "Vβ17" includes any Vβ17 variants, isotypes, and species homologs that are naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNAs encoding the polypeptide. Unless otherwise indicated, preferably, Vβ17 is human Vβ17. Exemplary human Vβ17 amino acid sequences are provided by GenBank Accession No. AAB49730.1.

[0111] As used herein, an antibody that "specifically binds to Vβ17" refers to an antibody that specifically binds to Vβ17 at a concentration of 1×10 -7 M or smaller such as 1×10 -8 M or smaller, 5×10 -9 M or smaller, 1×10 -9 M or smaller, 5×10 -10 M or smaller, or 1×10 -10 An antibody that binds to Vβ17 (preferably human Vβ17) with a KD of M or less.

[0112] The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as a molar concentration (M). According to the present disclosure, the KD value of an antibody can be determined using methods in the art. For example, the KD of an antibody can be determined using surface plasmon resonance, such as by using a biosensor system (e.g., System), or by using bio-layer interferometry technology (such as Octet RED96 system). The smaller the value of antibody KD, the higher the affinity of the antibody for binding to the target antigen.

[0113] In one aspect, provided herein is an antibody that binds to Vβ17. In some embodiments, the antibody comprises a heavy chain variable region and a light chain variable region. In some embodiments, the Vβ17 antibody is not a single domain antibody or a nanobody. In some embodiments, the Vβ17 antibody is a humanized antibody.

[0114] In certain embodiments, provided herein is a Vβ17 antibody comprising the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and / or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VH region of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VL region of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VH CDR1, VH CDR2 and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VL CDR1, VL CDR2 and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VL CDR1, VL CDR2 and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a Vβ17 antibody comprising the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and the VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. Representative VH and VL amino acid sequences of the Vβ17 antibodies provided herein are provided in Tables 1 to 6, including VH CDR1, VH CDR2, VH CDR3, VLCDR1, VL CDR2, and VL CDR3 amino acid sequences.

[0115] In some embodiments, the antibody specifically binds to Vβ17. In other embodiments, Vβ17 is present on the surface of a T cell.

[0116] In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, the antibody is capable of binding at least five antigens.

[0117] In certain embodiments, a Vβ17 antibody is provided that is a complete antibody. In other embodiments, a Vβ17 antibody is provided that is an antigen-binding fragment of a Vβ17 antibody. In some embodiments, the antigen-binding fragment of a Vβ17 antibody is a functional fragment.

[0118] In some embodiments, the antigen binding fragment is a bivalent antibody. In some embodiments, the antigen binding fragment is Fab. In some embodiments, the antigen binding fragment is Fab'. In some embodiments, the antigen binding fragment is F(ab')2. In some embodiments, the antigen binding fragment is an Fv fragment. In some embodiments, the antigen binding fragment is a disulfide-stabilized Fv fragment (dsFv). In some embodiments, the antigen binding fragment is (dsFv)2. In some embodiments, the antigen binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen binding fragment is a disulfide-stabilized bivalent antibody (ds bivalent antibody). In some embodiments, the antigen binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen binding fragment is an scFv dimer (bivalent bivalent antibody). In some embodiments, the antigen binding fragment is a multispecific antibody formed by a portion of an antibody comprising one or more CDRs. In some embodiments, the antigen binding fragment is a camelized single domain antibody. In some embodiments, the antigen binding fragment is a nanobody. In some embodiments, the antigen binding fragment is a domain antibody. In some embodiments, the antigen binding fragment is a bivalent domain antibody. In some embodiments, the antigen binding fragment is an antibody fragment that binds to an antigen but does not contain a complete antibody structure.

[0119] In specific embodiments, the Vβ17 antibody comprises a VH region and a VL region. In some embodiments, the Vβ17 antibody is a single-chain antibody. In some embodiments, the Vβ17 antibody is a single-domain antibody. In some embodiments, the Vβ17 antibody is a nanobody. In certain embodiments, the Vβ17 antibody is a VHH antibody. In certain embodiments, the Vβ17 antibody is a llama antibody. In some embodiments, the Vβ17 antibody is not a single-chain antibody. In some embodiments, the Vβ17 antibody is not a single-domain antibody. In some embodiments, the Vβ17 antibody is not a nanobody. In certain embodiments, the Vβ17 antibody is not a VHH antibody. In certain embodiments, the Vβ17 antibody is not a llama antibody. In some embodiments, the Vβ17 antibody is a multispecific antibody. In other embodiments, Vβ17 is a bispecific antibody. In certain embodiments, the multispecific antibody comprises an antigen-binding fragment of the Vβ17 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen-binding fragment of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody is an agonist antibody. In certain embodiments, the Vβ17 antibody activates T cells. In other embodiments, the Vβ17 antibody is an antagonist antibody. In certain embodiments, the Vβ17 antibody inactivates T cells. In some embodiments, the Vβ17 antibody blocks the activation of T cells. In some embodiments, the Vβ17 antibody modulates the activity of T cells. In some embodiments, the Vβ17 antibody neither activates nor inactivates the activity of T cells. In specific embodiments, the T cells are human T cells.

[0120] In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences are according to the Kabat numbering system. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences are according to the Chothia numbering system. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences are according to the Exemplary numbering system. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences are according to the Contact numbering system. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences are according to the IMGT numbering system. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 sequences are according to the AbM numbering system. Exemplary groups of 6 CDRs (VH CDR1-3 and VL CDR1-3) of certain antibody embodiments are provided herein. Other CDR groups are contemplated and are within the scope of the antibody embodiments provided herein.

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128]

[0129] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 7, 8, and 9, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 10, 11, and 12, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 13, 14, and 15, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 16, 17, and 18, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 19, 20, and 21, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 22, 23, and 24, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 25, 26, and 27, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 28, 29, and 30, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 32.In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 31. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence of SEQ ID NO: 32. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 31 and a VL having an amino acid sequence of SEQ ID NO: 32. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 31. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 32. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:31, and a VL having an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:32.

[0130] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 35, 36, and 37, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 38, 39, and 40, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 41, 42, and 43, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 44, 45, and 46, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 47, 48, and 49, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 50, 51, and 52, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 53, 54, and 55, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VLCDR3 having an amino acid sequence of SEQ ID NOs: 56, 57, and 58, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 62, 63, and 64, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VHCDR2, and VH CDR3, respectively, of SEQ ID NO: 65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 66.In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 65. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence of SEQ ID NO: 66. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 65 and a VL having an amino acid sequence of SEQ ID NO: 66. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:65, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:66.

[0131] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 69, 70, and 71, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 72, 73, and 74, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 75, 76, and 77, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 78, 79, and 80, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 81, 82, and 83, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 84, 85, and 86, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 87, 88, and 89, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 90, 91, and 92, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 93, 94, and 95, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 96, 97, and 98, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 100.In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 99. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence of SEQ ID NO: 99 and a VL having an amino acid sequence of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 99. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 100. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:99, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:100.

[0132] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 103, 104, and 105, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 106, 107, and 108, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 109, 110, and 111, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 112, 113, and 114, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 115, 116, and 117, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 118, 119, and 120, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 121, 122, and 123, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 124, 125, and 126, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 127, 128, and 129, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 130, 131, and 132, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 133. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134.

[0133] In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 137, 138, and 139, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 140, 141, and 142, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 143, 144, and 145, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 146, 147, and 148, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 149, 150, and 151, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 152, 153, and 154, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 155, 156, and 157, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 158, 159, and 160, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 161, 162, and 163, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 164, 165, and 166, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 167. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 167 and a VL having the amino acid sequence of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 167. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 167, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 168.

[0134] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 171, 172, and 173, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 174, 175, and 176, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 177, 178, and 179, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 180, 181, and 182, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 183, 184, and 185, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 186, 187, and 188, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 189, 190, and 191, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 192, 193, and 194, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VHCDR3 having amino acid sequences of SEQ ID NOs: 195, 196, and 197, respectively; and (ii) a VL comprising a VL CDR1, a VLCDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 198, 199, and 200, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 201. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 201 and a VL having the amino acid sequence of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 201. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 202. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 201, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 202.

[0135] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 205, 206, and 207, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 208, 209, and 210, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 211, 212, and 213, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 214, 215, and 216, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 217, 218, and 219, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 220, 221, and 222, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 223, 224, and 225, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 226, 227, and 228, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 229, 230, and 231, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 232, 233, and 234, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 235; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 235. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 235 and a VL having the amino acid sequence of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 236. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 235, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 236.

[0136] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 239, 240, and 241, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 242, 243, and 244, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 245, 246, and 247, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 248, 249, and 250, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 251, 252, and 253, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 254, 255, and 256, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 257, 258, and 259, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 260, 261, and 262, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 263, 264, and 265, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 266, 267, and 268, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 269. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 269 and a VL having the amino acid sequence of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 269. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 270. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 269, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 270.

[0137] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 273, 274, and 275, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 276, 277, and 278, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 279, 280, and 281, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 282, 283, and 284, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 285, 286, and 287, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 288, 289, and 290, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 291, 292, and 293, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 294, 295, and 296, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 297, 298, and 299, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 300, 301, and 302, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 303; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 303. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 303 and a VL having the amino acid sequence of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 303. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 304. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 303, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 304.

[0138] In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 307, 308, and 309, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 310, 311, and 312, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 313, 314, and 315, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 316, 317, and 318, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 319, 320, and 321, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 322, 323, and 324, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 325, 326, and 327, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 328, 329, and 330, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 331, 332, and 333, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 334, 335, and 336, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 337. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 337 and a VL having the amino acid sequence of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 337. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 338. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 337, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 338.

[0139] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 341, 342, and 343, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 344, 345, and 346, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 347, 348, and 349, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 350, 351, and 352, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 353, 354, and 355, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 356, 357, and 358, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 359, 360, and 361, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 362, 363, and 364, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 365, 366, and 367, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 368, 369, and 370, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 371; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 371. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 371 and a VL having the amino acid sequence of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 371. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 372. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 371, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 372.

[0140] In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 375, 376, and 377, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 378, 379, and 380, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 381, 382, ​​and 383, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 384, 385, and 386, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 387, 388, and 389, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 390, 391, and 392, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 393, 394, and 395, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 396, 397, and 398, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 399, 400, and 401, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 402, 403, and 404, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 405; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 405. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 405 and a VL having the amino acid sequence of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 405. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 406. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 405, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 406.

[0141] In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 409, 410, and 411, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 412, 413, and 414, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of SEQ ID NOs: 415, 416, and 417, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of SEQ ID NOs: 418, 419, and 420, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 421, 422, and 423, respectively; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 424, 425, and 426, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of SEQ ID NOs: 427, 428, and 429, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of SEQ ID NOs: 430, 431, and 432, respectively. In one aspect, provided herein is an antibody that binds to Vβ17, comprising: (i) a VH comprising a VHCDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of SEQ ID NOs: 433, 434, and 435, respectively; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of SEQ ID NOs: 436, 437, and 438, respectively.In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 439; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 439. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VL having the amino acid sequence of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, the antibody comprising a VH having the amino acid sequence of SEQ ID NO: 439 and a VL having the amino acid sequence of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 439. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 440. In one aspect, provided herein is an antibody that binds to Vβ17, comprising a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 439, and a VL having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 440.

[0142] In another aspect, provided herein are antibodies that compete with any of the Vβ17 antibodies described herein for binding to Vβ17. In another aspect, provided herein are antibodies that bind to the same epitope as any of the Vβ17 antibodies described herein. In another aspect, provided herein are Vβ17 antibodies that bind to an epitope on Vβ17 that overlaps with an epitope on Vβ17 that is bound by the Vβ17 antibodies described herein.

[0143] In one aspect, antibodies are provided that compete with a Vβ17 reference antibody for binding to Vβ17. In another aspect, Vβ17 antibodies are provided that bind to the same Vβ17 epitope as the Vβ17 reference antibody. In another aspect, Vβ17 antibodies are provided that bind to an epitope on Vβ17 that overlaps with an epitope on Vβ17 bound by the Vβ17 reference antibody.

[0144] In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 31; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to a VL having an amino acid sequence of SEQ ID NO: 32. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 33. NO:65; and (ii) VL, which comprises VLCDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO:66. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 99; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to a VL having an amino acid sequence of SEQ ID NO: 100. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 101. NO: 133; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, which VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 134.In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 167; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to a VL having an amino acid sequence of SEQ ID NO: 168. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 169. NO: 201; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 202. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 235; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 236.In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 269; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to a VL having an amino acid sequence of SEQ ID NO: 270. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 271. NO: 303; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 304. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 337; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 338. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 371; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 372.In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: 405; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, which VL CDRs belong to a VL having an amino acid sequence of SEQ ID NO: 406. In one embodiment, the Vβ17 reference antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, which VH CDRs belong to a VH having an amino acid sequence of SEQ ID NO: NO: 439; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2 and VL CDR3, respectively, which VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 440.

[0145] In some embodiments, the multispecific antibodies provided herein are diabodies, crossbodies, or multispecific antibodies obtained via controlled Fab arm exchange, such as those described herein.

[0146] In some embodiments, the multispecific antibodies include IgG-like molecules with complementary CH3 domains that promote heterodimerization; recombinant IgG-like dual-targeting molecules, wherein each side of the molecule contains a portion of the Fab fragment or Fab fragment of at least two different antibodies; IgG fusion molecules, in which the full-length IgG antibody is fused with an additional Fab fragment or a portion of the Fab fragment; Fc fusion molecules, in which a single-chain Fv molecule or a stable diabody is fused to a heavy chain constant domain, an Fc region or a portion thereof; Fab fusion molecules, in which different Fab fragments are fused together; heavy chain antibodies (e.g., domain antibodies, nanobodies) based on ScFv and diabodies, in which different single-chain Fv molecules or different diabodies or different heavy chain antibodies (e.g., domain antibodies, nanobodies) are fused to each other or to another protein or carrier molecule.

[0147] In some embodiments, IgG-like molecules with complementary CH3 domain molecules include Triomab / Ouadroma (Trion Pharma / Fresenius Biotech), Knobs-into-Holes antibodies (Genentech), CrossMAbs (Roche) and electrostatically-matched (Amgen), LUZ-Y (Genentech), Strand Exchange Engineered Domain body (SEEDbody) (EMD Serono), Biclonic (Merus) and DuoBody (GenmabA / S).

[0148] In some embodiments, recombinant IgG-like dual-targeting molecules include dual-targeting (DT)-Ig (GSK / Domantis), two-in-one antibodies (Genentech), cross-linked Mabs (Karmanos Cancer Center), mAb2 (F-Star) and CovX body (CovX / Pfizer).

[0149] In some embodiments, IgG fusion molecules include dual variable domain (DVD)-Ig (Abbott), IgG-like bispecific antibodies (ImClone / Eli Lilly), Ts2Ab (MedImmune / AZ) and BsAb (Zymogenetics), HERCULES (Biogen Idec), and TvAb (Roche).

[0150] In some embodiments, Fc fusion molecules may include ScFv / Fc fusion (Academic Institution), SCORPION (Emergent BioSolutions / Trubion, Zymogenetics / BMS), dual affinity retargeting technology (Fc-DART) (MacroGenics), and bi-(ScFv)2-Fab (National Research Center for Antibody Medicine--China).

[0151] In some embodiments, Fab fusion bispecific antibodies include F(ab)2 (Medarex / AMGEN), Dual-Action or Bis-Fab (Genentech), Dock-and-Lock (DNL) (ImmunoMedics), bivalent bispecific antibodies (Biotecnol) and Fab-Fv (UCB-Celltech). ScFv-based, bivalent antibody-based domain antibodies include but are not limited to bispecific T cell engagers (BiTE) (Micromet), tandem bivalent antibodies (Tandab) (Affimed), dual affinity retargeting technology (DART) (MacroGenics), single-chain bivalent antibodies (Academic), TCR-like antibodies (AIT, ReceptorLogics), human serum albumin ScFv fusions (Merrimack) and COMBODY (Epigen Biotech), dual-targeted nanobodies (Ablynx), dual-targeted heavy chain domain antibodies only.

[0152] The full-length bispecific antibodies provided herein can be generated, for example, using Fab arm exchange (or half-molecule exchange) between two monospecific bivalent antibodies by the following manner: a substitution is introduced at the heavy chain CH3 interface in each half molecule to promote the formation of heterodimers of two antibody half molecules with different specificities in an in vitro cell-free environment or using co-expression. The Fab arm exchange reaction is the result of a disulfide bond isomerization reaction and a CH3 domain dissociation-association. The heavy chain disulfide bonds in the hinge region of the parent monospecific antibody are reduced. The resulting free cysteine ​​of one of the parent monospecific antibodies forms an inter-heavy chain disulfide bond with a cysteine ​​residue of a second parent monospecific antibody molecule, while the CH3 domain of the parent antibody is released and re-formed by dissociation-association. The CH3 domain of the Fab arm can be engineered to promote heterodimerization rather than homodimerization. The resulting product is a bispecific antibody with two Fab arms or half molecules, each of which binds to a different epitope, for example, an epitope on a first anti-target and an epitope on a second target. Other methods of making multispecific antibodies are known and contemplated.

[0153] As used herein, "homodimerization" refers to the interaction of two heavy chains having the same CH3 amino acid sequence. As used herein, "homodimer" refers to an antibody having two heavy chains having the same CH3 amino acid sequence.

[0154] As used herein, "heterodimerization" refers to the interaction of two heavy chains with different CH3 amino acid sequences. As used herein, "heterodimer" refers to an antibody with two heavy chains containing different CH3 amino acid sequences.

[0155] The "knob-in-hole" strategy (see, e.g., PCT Publication WO2006 / 028936) can be used to generate full-length bispecific antibodies. In short, selected amino acids that form the interface of the CH3 domains in human IgG can be mutated at positions that affect the interaction of the CH3 domains, thereby promoting heterodimer formation. Amino acids with small side chains (knobs) are introduced into the heavy chain of an antibody that specifically binds a first antigen, and amino acids with large side chains (knobs) are introduced into the heavy chain of an antibody that specifically binds a second antigen. Upon co-expression of the two antibodies, heterodimers are formed due to the preferential interaction of the heavy chain with the "hole" with the heavy chain with the "knob". Exemplary CH3 substitution pairs that form a knob-in-hole structure (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain) are: T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S, and T366W / T366S_L368A_Y407V.

[0156] Other strategies may also be used, such as using electrostatic interactions to promote heavy chain heterodimerization by replacing positively charged residues on one CH3 surface and negatively charged residues on a second CH3 surface, such as U.S. Patent Publication No. US2010 / 0015133, U.S. Patent Publication No. US2009 / 0182127, U.S. Patent Publication No. US2010 / 028637; or U.S. Patent Publication No. US2011 / 0123532. In other strategies, heterodimerization can be promoted by the following substitutions (represented as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): L351Y_F405AY407V / T394W, T366I_K392M_T394W / F405A_Y407V, T366L_K392M_T394W / F405A_Y407V, L351Y_Y407A / T366A_K409F, L351Y_Y407A / T366V K409F Y407A / T366A_K409F or T350V_L351Y_F405AY407V / T350V_T366L_K392L_T394W, such as US Patent Publication No. US2012 / 0149876 or US Patent Publication No. US2013 / 0195849.

[0157] In addition to the above methods, the bispecific antibodies provided herein can also be generated in an in vitro cell-free environment by the following means: introducing asymmetric mutations in the CH3 region of two monospecific homodimeric antibodies, and forming bispecific heterodimeric antibodies from two parental monospecific homodimeric antibodies under reducing conditions, thereby publishing antibodies according to international patents. In the method, the first monospecific bivalent antibody and the second monospecific bivalent antibody are engineered to have certain substitutions at the CH3 domain that promote the stability of the heterodimer; these antibodies are incubated together under reducing conditions sufficient to isomerize the disulfide bonds of the cysteine ​​in the hinge region; thereby generating bispecific antibodies by exchanging Fab arms. The incubation conditions can optionally be restored to non-reducing conditions. Exemplary reducing agents that can be used are 2-mercaptoethylamine (2-MEA), dithiothreitol (DTT), dithioerythritol (DTE), glutathione, tris (2-carboxyethyl) phosphine (TCEP), L-cysteine ​​and β-mercaptoethanol, preferably a reducing agent selected from the group consisting of 2-mercaptoethylamine, dithiothreitol and tris (2-carboxyethyl) phosphine. For example, the following conditions can be used: in the presence of at least 25mM 2-MEA or in the presence of at least 0.5mM dithiothreitol, at a pH of 5 to 8, for example, at a pH of 7.0 or at a pH of 7.4, at a temperature of at least 20°C, incubated for at least 90 minutes.

[0158] In some embodiments, the Vβ17 antibody comprises a single-chain antibody. In some embodiments, the Vβ17 antibody comprises a single domain antibody. In certain embodiments, the Vβ17 antibody comprises a nanobody. In certain embodiments, the Vβ17 antibody comprises a VHH antibody. In certain embodiments, the Vβ17 antibody comprises a llama antibody. In some embodiments, the Vβ17 antibody does not include a single-chain antibody. In some embodiments, the Vβ17 antibody does not include a single domain antibody. In certain embodiments, the Vβ17 antibody does not include a nanobody. In certain embodiments, the Vβ17 antibody does not include a VHH antibody. In certain embodiments, the Vβ17 antibody does not include a llama antibody.

[0159] According to another specific aspect, provided herein is a Vβ17 antibody or an antigen-binding fragment thereof that induces antibody-dependent cell-mediated cytotoxicity (ADCC). The antibody or antigen-binding fragment thereof can, for example, induce ADCC in vitro.

[0160] In certain embodiments, a TRGV9 antibody has an EC of less than about 160 pM in vitro when evaluated at a 1:1 effector cell to target cell ratio. 50 Induces T-cell-dependent cytotoxicity of secondary cells.

[0161] In some embodiments, Vβ17 is present on the surface of a T cell. In some embodiments, Vβ17 is present on the surface of a T cell, and the second target antigen is on the surface of a second cell. In some embodiments, when the multispecific antibody binds to Vβ17 on the surface of a T cell and the second target antigen on the surface of a second cell, the second cell is killed.

[0162] In some embodiments, the multispecific antibody has an EC of less than about 500 pM in vitro. 50 Induces T cell-dependent cytotoxicity of a second cell. In some embodiments, the multispecific antibody has an EC of less than about 300 pM in vitro. 50 Induces T cell-dependent cytotoxicity of a second cell. In some embodiments, the multispecific antibody has an EC of less than about 160 pM in vitro. 50 Inducing γδT cell-dependent cytotoxicity of a second cell. In some embodiments, a mixture of γδT effector cells and target cells expressing a second target antigen is used to assess EC 50 In some embodiments, the ratio of effector cells to target cells is about 0.01:1 to about 5:1. In some embodiments, the ratio of effector cells to target cells is about 0.1:1 to about 2:1. In some embodiments, the ratio of effector cells to target cells is about 1:1.

[0163] In certain embodiments, EC 50 Less than about 1000pM, less than about 900pM, less than about 800pM, less than about 700pM, less than about 600pM, less than about 500pM, less than about 400pM, less than about 300pM, less than about 200pM, less than about 190pM, less than about 180pM, less than about 170pM, less than about 160pM, less than about 150pM, less than about 140pM, less than about 130pM, less than about 120pM, less than about 110pM, less than about 100pM, less than about 90βM, less than about 80pM, less than about 70pM, less than about 60pM, less than about 50pM, less than about 40pM, less than about 30pM, less than about 20pM or less than about 10pM.

[0164] In certain embodiments, the ratio of effector cells to target cells can be, for example, 0.01:1, 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1. In certain embodiments, the concentration of the multispecific antibody is about 0.000005 ng / mL, about 0.00005 ng / mL, about 0.0005 ng / mL, about 0.005 ng / mL, about 0.005 ng / mL, about 0.01 ng / mL, about 0.02 ng / mL, about 0.03 ng / mL, about 0.04 ng / mL, about 0.05 ng / mL, about 0.06 ng / mL, about 0.07 ng / mL, about 0.08 ng / mL, about 0.09 ng / mL, about 0.1 ng / mL, about 0.5 ng / mL, about 1.0 ng / mL, about 10 ng / mL, about 20 ng / mL, about 30 ng / mL, about 40 ng / mL, about 50 ng / mL, about 60 ng / 1 nL, about 70 ng / mL, about 80 ng / mL, about 90 ng / mL, about 100 ng / mL, or about 1000 ng / mL.

[0165] On the other hand, provided herein is an antibody that competes with any of the Vβ17 antibodies described herein for binding to Vβ17. On the other hand, provided herein is an antibody that binds to the same epitope as any of the Vβ17 antibodies described herein. On the other hand, a Vβ17 antibody is provided that binds to an epitope on Vβ17 that overlaps with an epitope on Vβ17 bound by the Vβ17 antibodies described herein. In some embodiments, the Vβ17 antibody comprises VH CDR1, VH CDR2, and VH CDR3 of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises VL CDR1, VLCDR2, and VL CDR3 of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises VH CDR1, VHCDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises VH of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VL of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VH and VL of the Vβ17 antibody provided herein. In some embodiments, the Vβ17 antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the Vβ17 antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the Vβ17 antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2 and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VLCDR1, VL CDR2 and VL CDR3 amino acid sequences of the Vβ17 antibody are according to the IMGT numbering system. In certain embodiments, the Vβ17 antibody is a multispecific antibody. In some embodiments, the Vβ17 antibody is a bispecific antibody.

[0166] In another aspect, an antibody that competes with a Vβ17 reference antibody for binding to Vβ17 is provided. In another aspect, a Vβ17 antibody that binds to the same Vβ17 epitope as the Vβ17 reference antibody is provided. In another aspect, a Vβ17 antibody is provided that binds to an epitope on Vβ17 that overlaps with an epitope on Vβ17 bound by the Vβ17 reference antibody. In some embodiments, the Vβ17 reference antibody comprises the VH CDR1, VH CDR2, and VH CDR3 of the Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VL CDR1, VL CDR2, and VL CDR3 of the Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH CDR1, VH CDR2, VH CDR3, VLCDR1, VL CDR2, and VL CDR3 of the Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH of the Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VL of the Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH and VL of the Vβ17 reference antibody provided herein. In some embodiments, the Vβ17 reference antibody comprises the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VLCDR3 of the Vβ17 reference antibody provided herein. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the Vβ17 reference antibody are according to the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VLCDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the Vβ17 reference antibody are according to the IMGT numbering system. In certain embodiments, the antibody is a multispecific antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the Vβ17 reference antibody is a multispecific antibody.In some embodiments, the Vβ17 reference antibody is a bispecific antibody.

[0167] In some embodiments described herein, the immune effector properties of antibodies provided herein can be enhanced or silenced via Fc modification by techniques known to those skilled in the art. For example, Fc effector functions such as C1q binding, complement dependent cytotoxicity (CDC), antibody dependent cell-mediated cytotoxicity (ADCC), antibody dependent cell-mediated phagocytosis (ADCP), downregulation of cell surface receptors (e.g., B cell receptor; BCR), etc., can be provided and / or controlled by modifying residues in Fc that contribute to these activities.

[0168] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a cell-mediated reaction in which nonspecific cytotoxic cells expressing Fc receptors (FcRs), such as natural killer (NK) cells, neutrophils, and macrophages, recognize bound antibody on a target cell and subsequently cause lysis of the target cell.

[0169] The ability of antibodies to induce ADCC can be enhanced by engineering their oligosaccharide components. Most of the glycans in human IgG1 or IgG3 are N-glycosylated at Asn297 in the form of well-known bibranched G0, G0F, G1, G1F, G2 or G2F. Antibodies produced by unengineered CHO cells typically have a glycan fucose content of about at least 85%. Removing core fucose from bibranched complex-type oligosaccharides attached to the Fc region enhances the ADCC of antibodies via improved FcγRIIIa binding without changing antigen binding or CDC activity. Such antibodies can be achieved using different methods reported for the successful expression of relatively highly defucosylated antibodies with bibranched complex-type Fc oligosaccharides, such as controlling the culture osmotic pressure (Konno et al., Cytotechnology 64:249-65, 2012), using the variant CHO cell line Lec13 as a host cell line (Shields et al., J Biol Chem 277:26733-26740, 2002), using the variant CHO cell line EB66 as a host cell line (Olivier et al., MAbs; 2(4), 2010; Epub ahead of print; PMID: 20562582), using the rat hybridoma cell line YB2 / 0 as a host cell line (Shinkawa et al., J Biol Chem 277:26733-26740, 2002), using the variant CHO cell line EB66 as a host cell line (Olivier et al., MAbs; 2(4), 2010; Epub ahead of print; PMID: 20562582), using the rat hybridoma cell line YB2 / 0 as a host cell line (Shinkawa et al., J Biol Chem 278:3466-3473, 2003), introduction of small interfering RNA specific for the α-1,6-fucosyltransferase (FUT8) gene (Mori et al., Biotechnol Bioeng 88:901-908, 2004), or co-expression of β-1,4-N-acetylglucosaminyltransferase III and Golgi α-mannosidase II or the potent α-mannosidase I inhibitor, kifnosine (Ferrara et al., J Biol Chem 281:5032-5036, 2006, Ferrara et al., Biotechnol Bioeng 93:851-861, 2006; Xhou et al., Biotechnol Bioeng 99:652-65, 2008).

[0170] In some embodiments described herein, ADCC initiated by antibodies provided herein can also be enhanced by certain substitutions in antibody Fc. Exemplary substitutions are, for example, substitutions at amino acid positions 256, 290, 298, 312, 356, 330, 333, 334, 360, 378 or 430 (residues are numbered according to the EU index), as described in U.S. Patent No. 6,737,056.

[0171] In some embodiments, the Vβ17 antibodies provided herein are chimeric. In some embodiments, the Vβ17 antibodies provided herein are human. In some embodiments, the Vβ17 antibodies provided herein are humanized. In certain embodiments, the Vβ17 antibodies provided herein are isolated Vβ17 antibodies. In some embodiments, the Vβ17 antigen-binding fragments provided herein are chimeric. In some embodiments, the Vβ17 antigen-binding fragments provided herein are human. In some embodiments, the Vβ17 antigen-binding fragments provided herein are humanized. In certain embodiments, the Vβ17 antigen-binding fragments provided herein are isolated Vβ17 antigen-binding fragments. In some embodiments, the Vβ17 antibodies provided herein are IgG antibodies. In some embodiments, the IgG antibodies are IgG1 antibodies. In some embodiments, the IgG antibodies are IgG2 antibodies. In some embodiments, the IgG antibodies are IgG3 antibodies. In some embodiments, the IgG antibodies are IgG4 antibodies. In some embodiments, the Vβ17 antibodies provided herein are multivalent. In some embodiments, the Vβ17 antibodies are capable of binding to at least three antigens. In some embodiments, the Vβ17 antibody is capable of binding at least four antigens. In some embodiments, the Vβ17 antibody is capable of binding at least five antigens.

[0172] Also provided are nucleic acids encoding antibodies provided herein. In another general aspect, vectors are provided, the vectors comprising isolated nucleic acids encoding antibodies provided herein. In another general aspect, vectors are provided, the vectors comprising isolated nucleic acids encoding antibodies provided herein. Also provided are vectors, the vectors comprising nucleic acids encoding antibodies provided herein. Also provided are host cells comprising vectors, the vectors comprising nucleic acids encoding antibodies provided herein. Also provided are kits, the kits comprising vectors comprising nucleic acids encoding antibodies provided herein and packaging for the vectors. In another general aspect, isolated nucleic acids are provided herein, the nucleic acids encoding monoclonal antibodies or antigen-binding fragments thereof provided herein. In certain embodiments, the antibody is a Vβ17 antibody.

[0173] Those skilled in the art will appreciate that the coding sequence of a protein can be altered (e.g., substituted, deleted, inserted, etc.) without changing the amino acid sequence of the protein. Thus, those skilled in the art will appreciate that the nucleic acid sequences encoding the antibodies provided herein can be altered without changing the amino acid sequence of these proteins.

[0174] According to the present disclosure, any vector known to those skilled in the art, such as plasmid, cosmid, phage vector or viral vector, can be used. In some embodiments, the vector is a recombinant expression vector, such as a plasmid. The vector may include any element of the conventional function of establishing an expression vector, such as a promoter, a ribosome binding element, a terminator, an enhancer, a selection marker and an origin of replication. The promoter may be a constitutive, inducible or repressible promoter. A variety of expression vectors capable of delivering nucleic acids to cells are known in the art and can be used herein to produce antibodies or their antigen-binding fragments in cells. Conventional cloning techniques or artificial gene synthesis can be used to generate recombinant expression vectors according to certain embodiments. According to the present disclosure, such techniques are well known to those skilled in the art.

[0175] Also provided is a host cell comprising a nucleic acid encoding an antibody provided herein. Also provided is a host cell comprising a nucleic acid encoding an isolated Fab provided herein. In view of the disclosure, any host cell known to those skilled in the art can be used for recombinant expression of an antibody or its Fab provided herein. In some embodiments, the host cell is an Escherichia coli TG1 or BL21 cell (for expressing, for example, scFv or Fab antibodies), CHO-DG44 or CHO-K1 cell or HEK293 cell (for expressing, for example, full-length IgG antibodies). According to a specific embodiment, the recombinant expression vector is transformed into a host cell by conventional methods such as chemical transfection, heat shock or electroporation, wherein the recombinant expression vector is stably integrated into the host cell genome so that the recombinant nucleic acid is effectively expressed.

[0176] Also provided is a method for preparing an antibody as disclosed herein. The method includes culturing a cell comprising a nucleic acid encoding an antibody under conditions that produce the antibody, and recovering the antibody from the cell or cell culture (e.g., from the supernatant). The expressed antibody can be harvested from the cell and purified according to conventional techniques known in the art and as described herein.

[0177] Pharmaceutical composition

[0178] In another general aspect, a pharmaceutical composition is provided herein, comprising a Vβ17 antibody provided herein and a pharmaceutically acceptable carrier. In certain embodiments, the antibody is isolated. A method for producing the pharmaceutical composition is also provided, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0179] In another general aspect, a pharmaceutical composition is provided, comprising a Vβ17 multispecific antibody provided herein and a pharmaceutically acceptable carrier. In certain embodiments, the multispecific antibody is isolated. A method for producing the pharmaceutical composition is also provided, comprising combining the multispecific antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. Any antibody provided herein is contemplated in the pharmaceutical composition.

[0180] As used herein, the term "pharmaceutical composition" means a product comprising an antibody provided herein and a pharmaceutically acceptable carrier. The antibodies provided herein and compositions comprising the same can also be used to manufacture medicaments for therapeutic applications.

[0181] As used herein, the term "carrier" refers to any excipient, diluent, filler, salt, buffer, stabilizer, solubilizer, oil, lipid, lipid-containing vesicle, microsphere, liposome encapsulation or other materials known in the art for use in pharmaceutical preparations. It should be understood that the characteristics of the carrier, excipient or diluent will depend on the route of administration of the specific application. As used herein, the term "pharmaceutically acceptable carrier" refers to a non-toxic material that does not interfere with the effect of the composition provided herein or the biological activity of the composition provided herein. In view of the present disclosure, according to a specific embodiment, any pharmaceutically acceptable carrier suitable for antibody drug compositions can be used herein.

[0182] The preparation of pharmaceutically active ingredients and pharmaceutically acceptable carriers is known in the art, for example, "Remington: The Science and Practice of Pharmacy" (e.g., 21st edition (2005) and any subsequent editions). Non-limiting examples of additional ingredients include: buffers, diluents, solvents, tonicity regulators, preservatives, stabilizers and chelating agents. One or more pharmaceutically acceptable carriers can be used to formulate the pharmaceutical compositions provided herein.

[0183] In one embodiment, the pharmaceutical composition is a liquid formulation. A preferred example of a liquid formulation is an aqueous formulation, i.e., a formulation comprising water. The liquid formulation may comprise a solution, a suspension, an emulsion, a microemulsion, a gel, and the like. Aqueous formulations typically comprise at least 50% w / w of water, or at least 60% w / w, 70% w / w, 75% w / w, 80% w / w, 85% w / w, 90% w / w, or at least 95% w / w of water.

[0184] In one embodiment, the pharmaceutical composition can be formulated as an injection that can be injected, for example, via an injection device (eg, a syringe or an infusion pump). The injection can be delivered, for example, subcutaneously, intramuscularly, intraperitoneally, intravitreally, or intravenously.

[0185] In another embodiment, the pharmaceutical composition is a solid preparation, such as a freeze-dried or spray-dried composition, which can be used as is, or a solvent and / or diluent can be added by a physician or patient before use. Solid dosage forms can include tablets, such as compressed and / or coated tablets, and capsules (e.g., hard gelatin capsules or soft gelatin capsules). The pharmaceutical composition can also be in the form of a sachet, dragee, powder, granule, lozenge or powder, for example, for reconstitution.

[0186] Dosage forms may be immediate release, in which case they may contain a water soluble or water dispersible carrier, or they may be delayed release, sustained release or modified release, in which case they may contain a water insoluble polymer that modulates the dissolution rate of the dosage form in the gastrointestinal tract or subcutaneously.

[0187] In other embodiments, the pharmaceutical composition may be delivered intranasally, intrabuccally, or sublingually.

[0188] The pH in the aqueous formulation may be between pH 3 and pH 1v. In one embodiment, the pH of the formulation is from about 7.0 to about 9.5. In another embodiment, the pH of the formulation is from about 3.0 to about 7.0.

[0189] In another embodiment, the pharmaceutical composition comprises a buffer. The non-limiting example of a buffer includes: arginine, aspartic acid, bicine, citrate, sodium dihydrogen phosphate, fumaric acid, glycine, glycine, histidine, lysine, maleic acid, malic acid, sodium acetate, sodium carbonate, sodium dihydrogen phosphate, sodium phosphate, succinate, tartaric acid, triazine and tris (hydroxymethyl) aminomethane and mixtures thereof. The buffer may exist alone or in aggregates with a concentration of about 0.01 mg / mL to about 50 mg / mL, such as about 0.1 mg / mL to about 20 mg / mL. The pharmaceutical composition comprising each of these specific buffers constitutes an alternative embodiment.

[0190] In another embodiment, the pharmaceutical composition comprises an antiseptic. The non-limiting example of antiseptic comprises: benzethonium chloride, benzoic acid, benzyl alcohol, bromononitropropylene glycol, butyl 4-hydroxybenzoate, chlorobutanol, chlorocresol, chlorhexidine, chlorphenesin ether, o-cresol, meta-cresol, p-cresol, ethyl 4-hydroxybenzoate, imidourea, methyl 4-hydroxybenzoate, phenol, 2-phenoxyethanol, 2-phenylethanol, propyl 4-hydroxybenzoate, sodium dehydroacetate, thimerosal and their mixture. Antiseptic can exist alone or in aggregate with about 0.01mg / mL to about 50mg / mL, for example, about 0.1mg / mL to about 20mg / mL concentration exists. The pharmaceutical composition comprising each antiseptic in these specific antiseptics constitutes an alternative embodiment.

[0191] In another embodiment, the pharmaceutical composition comprises an isotonic agent. Non-limiting examples of this embodiment include salts (such as sodium chloride), amino acids (such as glycine, histidine, arginine, lysine, isoleucine, aspartic acid, tryptophan and threonine), sugar alcohols (such as glycerol, 1,2-propylene glycol, propylene glycol), 1,3-propylene glycol and 1,3-butylene glycol), polyethylene glycol (e.g., PEG400) and mixtures thereof. Another example of an isotonic agent includes sugar. Non-limiting examples of sugars may include monosaccharides, disaccharides or polysaccharides, or water-soluble glucans, including, for example, fructose, glucose, mannose, sorbose, xylose, maltose, lactose, sucrose, trehalose, dextran, amylopectin, dextrin, cyclodextrin, α And β-HPCD, soluble starch, hydroxyethyl starch or sodium carboxymethyl cellulose.Another example of isotonic agent is sugar alcohol, wherein the term "sugar alcohol" is defined as a C (4-8) hydrocarbon with at least one -OH group.The non-limiting example of sugar alcohol includes mannitol, sorbitol, inositol, galactitol, hexasol, xylitol and arabitol.Isotonic agent can exist alone or in aggregate with a concentration of about 0.01 mg / mL to about 50 mg / mL, such as about 0.1 mg / mL to about 20 mg / mL.The pharmaceutical composition comprising each isotonic agent in these specific isotonic agents constitutes an alternative embodiment.

[0192] In another embodiment, the pharmaceutical composition comprises a chelating agent. Non-limiting examples of chelating agents include salts of citric acid, aspartic acid, ethylenediaminetetraacetic acid (EDTA), and mixtures thereof. The chelating agent may be present alone or in aggregates at a concentration of about 0.01 mg / mL to about 50 mg / mL, such as about 0.1 mg / mL to about 20 mg / mL. Pharmaceutical compositions comprising each of these specific chelating agents constitute alternative embodiments.

[0193] In another embodiment, the pharmaceutical composition comprises a stabilizer. Non-limiting examples of stabilizers include one or more aggregation inhibitors, one or more oxidation inhibitors, one or more surfactants, and / or one or more protease inhibitors.

[0194] In another embodiment, the pharmaceutical composition comprises a stabilizer, wherein the stabilizer is carboxyl / hydroxycellulose and its derivatives (such as HPC, HPC-SL, HPC-L and HPMC), cyclodextrin, 2-methylthioethanol, polyethylene glycol (such as PEG3350), polyvinyl alcohol (PVA), polyvinyl pyrrolidone, salts (such as sodium chloride), sulfur-containing substances (such as monothioglycerol) or thioglycolic acid. The stabilizer may be present alone or in aggregates at a concentration of about 0.01 mg / mL to about 50 mg / mL, for example, about 0.1 mg / mL to about 20 mg / mL. Pharmaceutical compositions comprising each of these specific stabilizers constitute alternative embodiments.

[0195] In other embodiments, the pharmaceutical composition comprises one or more surfactants, preferably a surfactant, at least one surfactant or two different surfactants. The term "surfactant" refers to any molecule or ion consisting of a water-soluble portion (hydrophilic) and a fat-soluble and part (lipophilic). For example, the surfactant can be selected from the group consisting of anionic surfactants, cationic surfactants, nonionic surfactants and / or zwitterionic surfactants. Surfactants can exist alone or in aggregates with a concentration of about 0.1 mg / mL to about 20 mg / mL. The pharmaceutical composition comprising each surfactant in these specific surfactants constitutes an alternative embodiment.

[0196] In another embodiment, the pharmaceutical composition comprises one or more protease inhibitors, such as, for example, EDTA and / or benzamidine hydrochloride (HCl). The protease inhibitors may be present alone or in aggregates at a concentration of about 0.1 mg / mL to about 20 mg / mL. Pharmaceutical compositions comprising each of these specific protease inhibitors constitute alternative embodiments.

[0197] In another general aspect, provided herein is a method for producing a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof provided herein, the method comprising combining the antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain a pharmaceutical composition.

[0198] How to use

[0199] The functional activity of the antibodies provided herein can be characterized by methods known in the art and as described herein. Methods for characterizing antibodies and antigen-binding fragments thereof include, but are not limited to, affinity and specificity assays, including Biacore, ELISA, and OctetRed analysis; binding assays for detecting binding of antibodies to target cells by FACS; binding assays for detecting binding of antibodies to target antigens on cells. According to specific embodiments, methods for characterizing antibodies and antigen-binding fragments thereof include those described below. In certain embodiments, the antibody is a Vβ17 antibody.

[0200] Also provided is a method of activating a T cell expressing Vβ17, the method comprising contacting the T cell with a Vβ17 antibody provided herein. In some embodiments, the contacting results in increased expression of CD69, CD25 and / or granzyme B compared to a control T cell expressing Vβ17.

[0201] In another general aspect, a method of inactivating a T cell expressing Vβ17 is provided, the method comprising contacting the T cell with an antibody that binds to Vβ17 provided herein. In another general aspect, a method of blocking the activation of a T cell expressing Vβ17 is provided, the method comprising contacting the T cell with an antibody that binds to Vβ17 provided herein. In another general aspect, a method of modulating the activation of a T cell expressing Vβ17 is provided, the method comprising contacting the T cell with an antibody that binds to Vβ17 provided herein.

[0202] Also provided herein is a method for treating a disease or disorder in a subject, the method comprising administering to the subject a Vβ17 antibody provided herein. Also provided herein is a method for treating a disease or disorder in a subject, the method comprising administering to the subject a Vβ17 antigen-binding fragment provided herein. Also provided herein is a method for treating a disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the Vβ17 antibody provided herein. Also provided herein is a method for treating a disease or disorder in a subject, the method comprising administering to the subject a pharmaceutical composition comprising the Vβ17 antigen-binding fragment provided herein.

[0203] Also provided herein are Vβ17 antibodies for use in treating a disease, wherein Vβ17 antibodies are provided herein. In some embodiments, the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. In some embodiments, the subject is a human. In some embodiments, the subject is a subject in need.

[0204] Also provided herein is the use of a Vβ17 antibody in the manufacture of a medicament for treating a disease, wherein a Vβ17 antibody is provided herein. In some embodiments, the disease is caused in whole or in part by a target cell having a second target present on the surface of the target cell. In some embodiments, the subject is a human. In some embodiments, the subject is a subject in need.

[0205] In some embodiments, the subject is a subject in need thereof. In some embodiments, the subject is a human. In specific embodiments, an effective amount is administered to the subject.

[0206] As used herein, the term "effective amount" refers to the amount of an active ingredient or component that elicits a desired biological or pharmacological response in a subject.

[0207] According to specific embodiments, an effective amount refers to a therapeutic amount sufficient to achieve one, two, three, four or more of the following effects: (i) reduce or ameliorate the severity of the disease, disorder or condition being treated or symptoms associated therewith; (ii) reduce the duration of the disease, disorder or condition being treated or symptoms associated therewith; (iii) prevent the development of the disease, disorder or condition being treated or symptoms associated therewith; (iv) cause regression of the disease, disorder or condition being treated or symptoms associated therewith; (v) prevent the development or onset of the disease, disorder or condition being treated or symptoms associated therewith; (vi) ) prevent recurrence of the disease, disorder or condition to be treated, or symptoms associated therewith; (vii) reduce hospitalization of a subject suffering from the disease, disorder or condition to be treated, or symptoms associated therewith; (viii) reduce the length of hospital stay of a subject suffering from the disease, disorder or condition to be treated, or symptoms associated therewith; (ix) improve survival of a subject suffering from the disease, disorder or condition to be treated, or symptoms associated therewith; (xi) inhibit or reduce the disease, disorder or condition to be treated, or symptoms associated therewith, in a subject; and / or (xii) enhance or improve the prophylactic or therapeutic effect of another therapy.

[0208] The effective amount or dosage may vary according to various factors, such as the disease, disorder or condition being treated, the mode of administration, the target site, the physiological state of the subject (including, for example, age, weight, health), whether the subject is human or animal, other drugs being administered, and whether the treatment is prophylactic or therapeutic. The therapeutic dose is optimally titrated to optimize safety and efficacy.

[0209] According to certain embodiments, the compositions described herein are formulated to be suitable for the intended route of administration to a subject. For example, the compositions described herein can be formulated to be suitable for intravenous, subcutaneous or intramuscular injection administration.

[0210] As used herein, the terms "treat," "treating," and "treatment" are all intended to refer to an improvement or reversal of at least one measurable physical parameter associated with cancer that is not necessarily identifiable in a subject, but is capable of being identified in a subject. The terms "treat" and "treatment" may also refer to causing regression, preventing development, or at least delaying the development of a disease, disorder, or condition. In a specific embodiment, "treat" and "treatment" refer to alleviating, preventing development or onset, or shortening the duration of one or more symptoms associated with a disease, disorder, or condition, such as a tumor or, more preferably, cancer. In a specific embodiment, "treat" and "treatment" refer to preventing the recurrence of a disease, disorder, or condition. In a specific embodiment, "treat" and "treatment" refer to improved survival of a subject suffering from a disease, disorder, or condition. In a specific embodiment, "treat" and "treatment" refer to the elimination of a disease, disorder, or condition in a subject.

[0211] In some embodiments, the Vβ17 antibodies provided herein are used in combination with complementary therapies.

[0212] As used herein, in the context of two or more therapies being applied to a subject, the term "combination" refers to the use of more than one therapy. The use of the term "combination" does not limit the order in which the therapy is applied to a subject. For example, the first therapy (e.g., compositions as described herein) can be applied to a subject before the second therapy (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks or 12 weeks ago), at the same time, or afterwards (e.g., 5 minutes, 1 5 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 16 hours, 24 hours, 48 ​​hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks or 12 weeks later) is applied.

[0213] The Vβ17 antibodies provided herein can also be used as reagents for detecting cells expressing Vβ17. Therefore, in another method, a method for detecting cells expressing Vβ17 is provided, the method comprising contacting the cells with the Vβ17 antibodies provided herein. In certain embodiments, the detection is performed by ELISA. In some embodiments, the detection is performed by FACS analysis. A kit comprising the Vβ17 antibodies provided herein and instructions for use is also provided.

[0214] Enrichment and detection methods

[0215] In one aspect, the Vβ17 antibodies provided herein are used as reagents for detecting cells expressing Vβ17. Therefore, in other methods, a method for detecting cells expressing Vβ17 is provided, the method comprising contacting the cells with the Vβ17 antibodies provided herein. In certain embodiments, the detection is performed by ELISA. In some embodiments, the detection is performed by FACS analysis. A kit comprising the Vβ17 antibodies provided herein and instructions for use is also provided.

[0216] Enrichment, separation, isolation, purification, sorting, selection, capture or detection or any combination thereof can be accomplished using known techniques such as beads, microfluidics, solid supports, columns, etc. For example, when combined with the Vβ17 antibodies provided herein, Vβ17 cells can be isolated or visualized using known methods.

[0217] The Vβ17 antibodies or multispecific Vβ17 antibodies provided herein can be used for selective enrichment, separation, isolation, purification, sorting, selection, capture or detection of cells expressing Vβ17. The Vβ17 antibodies or multispecific Vβ17 antibodies provided herein can be used in a bispecific form, for example, containing a first antigen binding domain that specifically binds to Vβ17 and a second antigen binding domain that specifically binds to a second target. In other embodiments, the multispecific Vβ17 antibodies provided herein can be used in the form of further incorporating a third antigen binding domain, which specifically binds to a third antigen (e.g., at a trispecific antibody). In other embodiments, the multispecific Vβ17 antibodies provided herein can be used in the form of further incorporating a fourth antigen binding domain, which specifically binds to a fourth antigen. (For example, as a tetraspecific antibody).

[0218] In one aspect, provided herein is a method for enriching cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and enriching for cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for separating cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and separating cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for isolating cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and isolating cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for purifying cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and purifying cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for sorting cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and sorting cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for selecting cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and selecting cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for capturing cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and capturing cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for detecting cells expressing Vβ17, the method comprising: providing a sample comprising cells expressing Vβ17; contacting the sample with a Vβ17 antibody provided herein; and detecting cells expressing Vβ17 that bind to the Vβ17 antibody.

[0219] In one aspect, provided herein is a method for enriching cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and enriching cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for separating cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and separating cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for isolating cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and isolating cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for purifying cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and purifying cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for sorting cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and sorting cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for selecting cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 body provided herein; and selecting cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for capturing cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and capturing cells expressing Vβ17 that bind to the Vβ17 antibody. In one aspect, provided herein is a method for detecting cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 body provided herein; and detecting cells expressing Vβ17 that bind to the Vβ17 antibody.

[0220] In one aspect, provided herein is a method for enriching cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and enriching cells expressing Vβ17 based on the binding of cells expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for separating cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and separating cells expressing Vβ17 based on the binding of cells expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for isolating cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and isolating cells expressing Vβ17 based on the binding of cells expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for purifying cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and purifying cells expressing Vβ17 based on the binding of cells expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for sorting cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 antibody provided herein; and sorting cells expressing Vβ17 based on the binding of cells expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for selecting cells expressing Vβ17, the method comprising: contacting cells expressing Vβ17 with a Vβ17 body provided herein; and selecting cells expressing Vβ17 based on the binding of cells expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for capturing a cell expressing Vβ17, the method comprising: contacting a cell expressing Vβ17 with a Vβ17 antibody provided herein; and capturing a cell expressing Vβ17 based on the binding of the cell expressing Vβ17 to the Vβ17 antibody. In one aspect, provided herein is a method for detecting a cell expressing Vβ17, the method comprising: contacting a cell expressing Vβ17 with a Vβ17 body provided herein; and detecting a cell expressing Vβ17 based on the binding of the cell expressing Vβ17 to the Vβ17 antibody.

[0221] In certain embodiments of the method, the cell expressing Vβ17 is a T cell. In some embodiments of the method, the cell expressing Vβ17 is in a cell population. In some embodiments of the method, the cell expressing Vβ17 is in a lymphocyte population. In some embodiments of the method, the cell expressing Vβ17 is in a T cell population. In some embodiments of the method, the cell expressing Vβ17 is provided as a cell population. In some embodiments of the method, the cell expressing Vβ17 is provided as a lymphocyte population. In some embodiments of the method, the cell expressing Vβ17 is provided as a T cell population. In some embodiments of the method, the cell expressing Vβ17 is provided as a sample comprising a cell population. In some embodiments of the method, the cell expressing Vβ17 is provided as a sample comprising a lymphocyte population. In some embodiments of the method, the cell expressing Vβ17 is provided as a sample comprising a T cell population. In some embodiments of the method, the sample is a blood sample. In some embodiments of the method, the sample is a tissue sample. In some embodiments of the method, the sample is a tissue culture sample.

[0222] In some embodiments of the method, the Vβ17 antibody is a multispecific Vβ17 antibody provided herein. In some embodiments of the method, the Vβ17 antibody is a bispecific Vβ17 antibody provided herein. In some embodiments of the method, the Vβ17 antibody is a trispecific Vβ17 antibody provided herein. In some embodiments of the method, the Vβ17 antibody is a tetraspecific Vβ17 antibody provided herein. In certain embodiments, the Vβ17 antibody specifically binds to Vβ17. In one embodiment, the multispecific Vβ17 antibody comprises: (a) a first binding domain that binds to Vβ17, and (b) a second binding domain that binds to a second target (e.g., a target that is not Vβ17). In one embodiment, the multispecific Vβ17 antibody comprises: (a) a first binding domain that binds to Vβ17, and (b) a second binding domain that binds to a second target (e.g., a target that is not Vβ17), and (c) a third binding domain that binds to a third target (e.g., a target that is not Vβ17). In one embodiment, a multispecific Vβ17 antibody comprises: (a) a first binding domain that binds Vβ17, and (b) a second binding domain that binds a second target (e.g., a target that is not Vβ17), (c) a third binding domain that binds a third target (e.g., a target that is not Vβ17), and (d) a fourth binding domain that binds a fourth target (e.g., a target that is not Vβ17). In one embodiment, a multispecific Vβ17 antibody comprises: (a) a first binding domain that specifically binds Vβ17, and (b) a second binding domain that specifically binds a second target (e.g., a target that is not Vβ17). In one embodiment, a multispecific Vβ17 antibody comprises: (a) a first binding domain that specifically binds Vβ17, and (b) a second binding domain that specifically binds a second target (e.g., a target that is not Vβ17), and (c) a third binding domain that specifically binds a third target (e.g., a target that is not Vβ17). In one embodiment, the multispecific Vβ17 antibody comprises: (a) a first binding domain that specifically binds to Vβ17, and (b) a second binding domain that specifically binds to a second target (e.g., a target that is not Vβ17), (c) a third binding domain that specifically binds to a third target (e.g., a target that is not Vβ17), and (d) a fourth binding domain that specifically binds to a fourth target (e.g., a target that is not Vβ17).

[0223] In specific embodiments of the methods provided herein, the methods use multi-marker detection. In some embodiments, multi-marker detection uses a multi-specific Vβ17 antibody provided herein. In some embodiments, multi-marker detection uses a bi-specific Vβ17 antibody provided herein. In some embodiments, multi-marker detection uses a tri-specific Vβ17 antibody provided herein. In some embodiments, multi-marker detection uses a tetra-specific Vβ17 antibody provided herein.

[0224] In certain embodiments of the methods provided herein, these methods are included as steps in a T cell manufacturing process. In certain embodiments, the cell is a CAR-T cell. In certain embodiments of the methods provided herein, these methods are included as steps in a T cell modification process.

[0225] In certain embodiments of the methods provided herein, the methods are included as a step in a method of diagnosis. In certain embodiments of the methods provided herein, the methods are included as a step in a method of quantifying T cells expressing Vβ17.

[0226] In certain embodiments of the methods provided herein, the method further comprises amplifying enriched, separated, isolated, purified, sorted, selected, captured or detected cells expressing Vβ17. In certain embodiments, the amplification is performed in vitro. In certain embodiments, the amplification is performed in vivo. In certain embodiments of the methods provided herein, the method further comprises culturing enriched, separated, isolated, purified, sorted, selected, captured or detected cells expressing Vβ17. In certain embodiments, the culturing is performed in vitro. In certain embodiments, the culturing is performed in vivo. In certain embodiments of the methods provided herein, the method further comprises quantitatively enriched, separated, isolated, purified, sorted, selected, captured or detected cells expressing Vβ17.

[0227] Implementation

[0228] The present invention provides the following non-limiting embodiments.

[0229] In one set of embodiments, there is provided:

[0230] A1. An antibody that binds to Vβ17, the antibody comprising:

[0231] (1) (i) a VH comprising VHCDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VHCDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL comprising VL CDR1, VL CDR2 and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VLCDR3, respectively, wherein these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 32;

[0232] (2) (i) a VH comprising VHCDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VHCDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 65; and (ii) a VL comprising VL CDR1, VL CDR2 and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VLCDR3, respectively, wherein these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 66;

[0233] (3) (i) a VH comprising VHCDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VHCDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 99; and (ii) a VL comprising VL CDR1, VL CDR2 and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VLCDR3, respectively, wherein these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 100;

[0234] (4) (i) a VH comprising VHCDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VHCDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising VL CDR1, VL CDR2 and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VLCDR3, respectively, wherein these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 134;

[0235] (5) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 167; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 168;

[0236] (6) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 202;

[0237] (7) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 235; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 236;

[0238] (8) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 269; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 270;

[0239] (9) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 303; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 304;

[0240] (10) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 337; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 338;

[0241] (11) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 371; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 372;

[0242] (12) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 405; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 406; or

[0243] (13) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 439; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 440.

[0244] A2. The antibody of embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Kabat numbering system.

[0245] A3. The antibody of embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Chothia numbering system.

[0246] A4. The antibody of embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the AbM numbering system.

[0247] A5. The antibody of embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Contact numbering system.

[0248] A6. The antibody of embodiment A1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the IMGT numbering system.

[0249] A7. The antibody according to any one of embodiments A1 to A6, wherein the antibody is a humanized antibody.

[0250] A8. The antibody according to any one of embodiments A1 to A7, wherein the antibody is an IgG antibody.

[0251] A9. The antibody according to embodiment A8, wherein the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.

[0252] A10. The antibody of any one of embodiments A1 to A9, wherein the antibody comprises a kappa light chain.

[0253] A11. The antibody of any one of embodiments A1 to A9, wherein the antibody comprises a lambda light chain.

[0254] A12. The antibody according to any one of embodiments A1 to A11, wherein the antibody is a monoclonal antibody.

[0255] A13. The antibody of any one of embodiments A1 to A12, wherein the antibody binds to the Vβ17 antigen.

[0256] A14. The antibody of any one of embodiments A1 to A12, wherein the antibody binds to the Vβ17 epitope.

[0257] A15. The antibody according to any one of embodiments A1 to A14, wherein the antibody specifically binds to Vβ17.

[0258] A16. The antibody according to any one of embodiments A1 to A15, wherein the VHCDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2 and VLCDR3 form a binding site for an antigen of the Vβ17.

[0259] A17. The antibody according to any one of embodiments A1 to A15, wherein the VHCDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2 and VLCDR3 form a binding site for an epitope of the Vβ17.

[0260] A18. The antibody according to any one of embodiments A1 to A17, wherein the Vβ17 is present on the surface of a T cell.

[0261] A19. The antibody of any one of embodiments A1 to A18, wherein said antibody is multivalent.

[0262] A20. The antibody of embodiment A19, wherein the antibody is capable of binding at least three antigens.

[0263] A21. The antibody of embodiment A19, wherein the antibody is capable of binding at least four antigens.

[0264] A22. The antibody of embodiment A19, wherein the antibody is capable of binding at least five antigens.

[0265] A23. The antibody of any one of embodiments A1 to A22, wherein the antibody is a multispecific antibody.

[0266] A24. The antibody of embodiment A23, wherein the antibody is a bispecific antibody.

[0267] A25. The antibody of embodiment A23, wherein the antibody is a trispecific antibody.

[0268] A26. The antibody of embodiment A23, wherein the antibody is a tetraspecific antibody.

[0269] A27. A nucleic acid encoding the antibody according to any one of embodiments A1 to A26.

[0270] A28. A vector comprising the nucleic acid according to embodiment A27.

[0271] A29. A host cell comprising the vector according to embodiment A28.

[0272] A30. A kit comprising the vector according to embodiment A28 and packaging for the vector.

[0273] A31. A kit comprising the antibody according to any one of embodiments A1 to A26 and packaging for the antibody.

[0274] A32. A method for directing a T cell expressing Vβ17 to a target cell, the method comprising contacting the Vβ17 antibody according to any one of embodiments A1 to A26 with the target cell, wherein the second target is present on the surface of the target cell, and wherein the contact directs the T cell to the target cell.

[0275] A33. A method for inhibiting the growth or proliferation of a target cell, the method comprising contacting the Vβ17 antibody according to any one of embodiments A1 to A26 with the target cell having the second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell expressing the Vβ17, and wherein the contacting results in inhibiting the growth or proliferation of the target cell.

[0276] A34. A method of eliminating a target cell in a subject, the method comprising contacting the Vβ17 antibody according to any one of embodiments A1 to A26 with the target cell having the second target present on the surface of the target cell, wherein the contacting is in the presence of a T cell expressing the Vβ17, and wherein the contacting results in the elimination of the target cell.

[0277] In one set of embodiments, there is provided:

[0278] B1. A pharmaceutical composition comprising an antibody that binds to Vβ17 and a pharmaceutically acceptable carrier.

[0279] B2. A pharmaceutical composition according to embodiment B1, wherein the antibody that binds to Vβ17

[0280] Include:

[0281] (1) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 32;

[0282] (2) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 65; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 66;

[0283] (3) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 99; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 100;

[0284] (4) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 134;

[0285] (5) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 167; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 168;

[0286] (6) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 202;

[0287] (7) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 235; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 236;

[0288] (8) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 269; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 270;

[0289] (9) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 303; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 304;

[0290] (10) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 337; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 338;

[0291] (11) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 371; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 372;

[0292] (12) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 405; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 406; or

[0293] (13) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 439; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 440.

[0294] B3. A pharmaceutical composition according to embodiment B2, wherein the VH CDR1, VHCDR2, VH CDR3, VLCDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Kabat numbering system.

[0295] B4. A pharmaceutical composition according to embodiment B2, wherein the VH CDR1, VHCDR2, VH CDR3, VLCDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Chothia numbering system.

[0296] B5. A pharmaceutical composition according to embodiment B2, wherein the VH CDR1, VHCDR2, VH CDR3, VLCDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the AbM numbering system.

[0297] B6. A pharmaceutical composition according to embodiment B2, wherein the VH CDR1, VHCDR2, VH CDR3, VLCDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Contact numbering system.

[0298] B7. A pharmaceutical composition according to embodiment B2, wherein the VH CDR1, VHCDR2, VH CDR3, VLCDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the IMGT numbering system.

[0299] B8. A pharmaceutical composition according to any one of embodiments B1 to B7, wherein the antibody is a humanized antibody.

[0300] B9. A pharmaceutical composition according to any one of embodiments B1 to B8, wherein the antibody is an IgG antibody.

[0301] B10. A pharmaceutical composition according to embodiment B9, wherein the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.

[0302] B11. A pharmaceutical composition according to any one of embodiments B1 to B10, wherein the antibody comprises a K light chain.

[0303] B12. The pharmaceutical composition of any one of embodiments B1 to B11, wherein the antibody comprises a lambda light chain.

[0304] B13. The pharmaceutical composition according to any one of embodiments B1 to B12, wherein the antibody is a monoclonal antibody.

[0305] B14. The pharmaceutical composition according to any one of embodiments B1 to B13, wherein the antibody binds to the Vβ17 antigen.

[0306] B15. The pharmaceutical composition according to any one of embodiments B1 to B13, wherein the antibody binds to the Vβ17 epitope.

[0307] B16. A pharmaceutical composition according to any one of embodiments B1 to B15, wherein the antibody specifically binds to Vβ17.

[0308] B17. The pharmaceutical composition according to any one of embodiments B1 to B16, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VLCDR3 form a binding site for an antigen of Vβ17.

[0309] B18. A pharmaceutical composition according to any one of embodiments B1 to B16, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VLCDR3 form a binding site for an epitope of Vβ17.

[0310] B19. A pharmaceutical composition according to any one of embodiments B1 to B18, wherein the Vβ17 is present on the surface of T cells.

[0311] B20. A pharmaceutical composition according to any one of embodiments B1 to B19, wherein the antibody is multivalent.

[0312] B21. A pharmaceutical composition according to embodiment B20, wherein the antibody is capable of binding to at least three antigens.

[0313] B22. A pharmaceutical composition according to embodiment B20, wherein the antibody is capable of binding to at least four antigens.

[0314] B23. A pharmaceutical composition according to embodiment B20, wherein the antibody is capable of binding to at least five antigens.

[0315] B24. A pharmaceutical composition according to any one of embodiments B1 to B23, wherein the antibody is a multispecific antibody.

[0316] B25. A pharmaceutical composition according to embodiment B24, wherein the antibody is a bispecific antibody.

[0317] B26. A pharmaceutical composition according to embodiment B24, wherein the antibody is a trispecific antibody.

[0318] B27. A pharmaceutical composition according to embodiment B24, wherein the antibody is a tetraspecific antibody.

[0319] B28. A method for producing a pharmaceutical composition according to any one of embodiments B1 to B27, the method comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0320] In one set of embodiments, there is provided:

[0321] C1. A method of treating a disease in a subject, the method comprising administering to the subject an effective amount of an antibody that binds Vβ17, wherein the disease is caused in whole or in part by a target cell having the second target present on the surface of the target cell.

[0322] C2. The method according to embodiment C1, wherein the antibody that binds to Vβ17 comprises:

[0323] (1) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 32;

[0324] (2) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 65; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 66;

[0325] (3) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 99; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 100;

[0326] (4) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 134;

[0327] (5) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 167; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 168;

[0328] (6) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 202;

[0329] (7) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 235; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 236;

[0330] (8) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 269; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 270;

[0331] (9) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 303; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 304;

[0332] (10) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, wherein the VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 337; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, wherein the VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 338;

[0333] (11) (i) a VH comprising VHCDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 371; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 372;

[0334] (12) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 405; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 406; or

[0335] (13) (i) a VH comprising VHCDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 439; and (ii) a VL comprising VL CDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, and these VL CDRs belong to the VL having the amino acid sequence of SEQ ID NO: 440.

[0336] C3. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Kabat numbering system.

[0337] C4. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Chothia numbering system.

[0338] C5. The method of embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the AbM numbering system.

[0339] C6. A method according to embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Contact numbering system.

[0340] C7. A method according to embodiment C2, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the IMGT numbering system.

[0341] C8. The method of any one of embodiments C1 to C7, wherein the antibody is a humanized antibody.

[0342] C9. The method of any one of embodiments C1 to C8, wherein the antibody is an IgG antibody.

[0343] C10. A method according to embodiment C9, wherein the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.

[0344] C11. A method according to any one of embodiments C1 to C10, wherein the antibody comprises a K light chain.

[0345] C12. A method according to any one of embodiments C1 to C10, wherein the antibody comprises a λ light chain.

[0346] C13. The method of any one of embodiments C1 to C12, wherein the antibody is a monoclonal antibody.

[0347] C14. The method of any one of embodiments C1 to C13, wherein the antibody binds to the Vβ17 antigen.

[0348] C15. The method of any one of embodiments C1 to C13, wherein the antibody binds to the Vβ17 epitope.

[0349] C16. A method according to any one of embodiments C1 to C15, wherein the antibody specifically binds to Vβ17.

[0350] C17. A method according to any one of embodiments C1 to C16, wherein the VHCDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2 and VLCDR3 form a binding site for an antigen of the Vβ17.

[0351] C18. A method according to any one of embodiments C1 to C16, wherein the VHCDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2 and VLCDR3 form a binding site for an epitope of the Vβ17.

[0352] C19. A method according to any one of embodiments C1 to C18, wherein the Vβ17 is present on the surface of a T cell.

[0353] C20. The method of any one of embodiments C1 to C19, wherein the antibody is multivalent.

[0354] C21. A method according to embodiment C20, wherein the antibody is capable of binding at least three antigens.

[0355] C22. A method according to embodiment C20, wherein the antibody is capable of binding at least four antigens.

[0356] C23. A method according to embodiment C20, wherein the antibody is capable of binding at least five antigens.

[0357] C24. The method of any one of embodiments C1 to C23, wherein the antibody is a multispecific antibody.

[0358] C25. A method according to embodiment C24, wherein the antibody is a bispecific antibody.

[0359] C26. A method according to embodiment C24, wherein the antibody is a trispecific antibody.

[0360] C27. A method according to embodiment C24, wherein the antibody is a tetraspecific antibody.

[0361] C28. A method according to any one of embodiments C1 to C27, wherein the subject is a human.

[0362] C29. A method according to any one of embodiments C1 to C27, wherein the subject is a subject in need thereof.

[0363] C30. A method of activating a T cell expressing Vβ17, the method comprising contacting the T cell with the antibody according to any one of embodiments C1 to C29.

[0364] C31. A method according to embodiment C30, wherein the contacting results in increased expression of CD69, CD25 and / or granzyme B compared to control T cells expressing Vβ17.

[0365] C32. A method for preparing an antibody that binds to more than one target molecule, the method comprising: a step for performing the function of obtaining a first binding domain that binds to Vβ17 present on T cells; a step for performing the function of obtaining a second binding domain that binds to a second target on the surface of a target cell; and a step for performing the function of providing an antibody that binds to Vβ17 present on T cells and a second target on the surface of a target cell.

[0366] C33. A method according to embodiment C32, wherein the step for performing the function of obtaining a second binding domain that binds to a second target on the surface of a target cell is repeated n times, and further includes n steps for performing the function of providing a first binding domain that binds to Vβ17 present on T cells and n target molecules, wherein n is at least 2.

[0367] Exemplary antibodies that bind to Vβ17 are provided in the Examples herein.

[0368] Exemplary binding agents that bind to Vβ17 are provided herein, for example in the Examples and Tables 1 to 6.

[0369] Specific embodiments of the present invention are described herein. After reading the foregoing description, variations of the disclosed embodiments may become apparent to those skilled in the art, and it is expected that such variations may be appropriately adopted by those skilled in the art. Therefore, the present invention is intended to be practiced in a manner different from that specifically described herein, and the present invention includes all modifications and equivalents of the subject matter recorded in the appended claims where applicable law permits. In addition, unless otherwise specified herein or otherwise clearly contradictory to the context, any combination of the above elements in all possible variations thereof is encompassed in the present invention. A number of embodiments of the present invention have been described. However, it should be understood that various modifications may be made without departing from the spirit and scope of the present invention. Therefore, the description in the embodiment section is intended to illustrate rather than limit the scope of the present invention described in the claims.

[0370] Example

[0371] Example 1: Antibodies that bind to Vβ17

[0372] 1.1: Identification of Vβ17 monoclonal

[0373] A cell-based approach was used to identify Vβ17-specific monoclones.

[0374] Mice were tolerized with NS0-WT cells during the neonatal period and then boosted three times per week with the NS0 cell line expressing TCRVα10.2*Vβ17.2.

[0375] High titers were evaluated by examining specificity for Vβ17.2 using three variants of the SKW3 cell line [SKW3-1 (Vα10*Vβ17), SKW3-2 (Vα12*Vβ17), SKW3-3 (Vα10*Vβ7 / 9)].

[0376] like Figure 1 As shown, several monoclonal antibodies binding to Vβ17 were identified by flow cytometry using different cell lines and primary cells. Anti-TCR Vβ17-PE Ab, Beckman-Colter, Cat: IM2048 was used as a positive control. Goat anti-mouse IgG PE, Southern Biotech, Cat: 1030-09, E2518-RJ69Y was used as a negative control.

[0377] Example 2: Evaluation of Vβ17 Antibody Properties

[0378] 2.1: Proliferation and activation

[0379] To test the proliferation of Vβ17+ cells, 96-well ELISA plates were coated with 10ug / ml of Vβ17 antibody or control antibody (B17B21) and incubated for 24 hours. PBMCs were thawed and labeled with cell tracer purple to track proliferation. 0.5MPBMC cells / well / 200ul of 10% RPMI medium (without IL-2) were cultured in a CO2 incubator for 24 hours. Cells were transferred from 96 wells to 48-well culture plates containing 200μl of 10% RPMI medium (without IL-2). The proliferation and activation status of CTV dilutions were examined using markers CD25, CD69, and CD71.

[0380] like Figure 2 As shown, single clones from 7 parents showed good agonistic properties. 26 single clones with good agonistic properties were selected for purification.

[0381] Differential proliferation kinetics were observed for 26 purified antibodies. Figure 3 As shown, single clones from parents 28B2, 28C9 and 28D2 showed good proliferation and were used for further assays.

[0382] Differential CD71 upregulation was observed for 26 purified antibodies. Figure 4 As shown, monoclones from parental 28B2, 28C9 and 28D2 showed good CD71 upregulation and were used for further assays.

[0383] 2.2: Vβ17 binding

[0384] The 10 best agonistic mAbs binding to Vβ17 were evaluated using variants of the SKW3 cell line. Figure 5 As shown, 10 purified antibodies belonging to 3 different parents bind well to SKW3-1 and SKW3-2 cell lines, but not to SKW3-3 cells that do not express Vβ17. Purified antibodies from the 14H7 parent did not bind well to the SKW3-2 cell line and were included as a negative control.

[0385] The binding of 10 selected purified monoclonal clones to PBMCs was evaluated. Figure 6 As shown, 10 purified antibodies belonging to 3 different parentages bound well to T cells on PBMCs.

[0386] like Figure 7 As shown, these 10 candidate monoclonals differ in isotype based on their heterozygous parents. Purified monoclonal antibodies from 3 different parents have different isotypes: 28D2 has IgG1, 28B2 has IgG2a, and 28C9 has IgG2b.

[0387] 2.3: VB17 antibody internalization

[0388] Internalization assay was used to screen 10 candidate antibodies. MMAF and antibody were added to 5000 cells / well / 50μl, 50nM concentration per well, Ab control, MMAF control and 3-fold dilution until point 7. MMAF antibody was incubated with cells for 20 minutes and the assay was repeated. The plate was incubated at 37°C for 96 hours and Cell Titre Glo was added to the plate. Luminescence was read in TECANSPARK and viability was calculated using the formula MMAF+Ab / MMAF X 100%. Data were plotted in GraphPad Prism.

[0389] like Figure 8 As shown, monoclones from the 28B2 parent showed good internalization. Monoclones from the parent 28C9, which had very good agonist properties, showed poor internalization. Monoclones from the parents 28D2 and 14H7 showed no internalization.

[0390] Example 3: Epitope binning of Vβ17 monoclonal

[0391] Epitope classification helps to separate the final monoclonals into individual epitope recognition groups and antibodies that recognize epitopes that are different from those of commercial antibodies. The distinction in epitope recognition is supported by the diversity of V gene sequences.

[0392] like Figure 9A-9C As shown, the epitope classification matrix of 10 candidate antibodies using OctetRED96 shows 3 separate specificities. Antibody 1 was loaded onto an anti-mouse IgG Fc capture (AMC) sensor, then allowed to bind to the antigen (TCRVα10.2*Vβ17 huFc), and then they were run on the antibody 2 panel. Purified monoclonal antibodies from 3 different parents were classified into 3 different groups.

[0393] In addition, 10 candidate antibodies were classified differently compared to a commercial positive control antibody as assessed using Octet RED96. Figure 10A-10C As shown, the positive control antibody TCRVb17 PE (Beckman-colter, catalog number: IM2048) was classified differently from the 10 candidate antibodies.

[0394] like Fig.11 As shown, monoclonal clones from the same parent have the same VH sequence. The heavy chain sequences of monoclonal clones belonging to the three different hybrids are different from each other.

[0395] like Fig.12 As shown, monoclonal clones from the same parent have identical VK sequences. The light chain sequences of monoclonal clones belonging to the three different hybrids are different from each other.

[0396] Example 4: Further characterization of other VB17 antibodies

[0397] like Fig.13 As shown, 12 additional antibodies were tested for proliferation and activation curves. These 12 additional antibodies had moderate agonistic properties and good PBMC binding and were used for epitope sorting and cell-based competition assays.

[0398] like Figure 14A-Figure 14C As shown in , monoclonal clones from one hybrid parent 23A9 were classified similarly to the positive control antibody (TCRVb17-PE).

[0399] like Figure 15A-Figure 15C As shown, monoclonals from 23A9 and commercial antibodies were classified as similar to each other but different from monoclonals from other hybrid parents.

[0400] Example 5: Cell-based competition assay for Vβ17 antibodies

[0401] Cells were treated with live / dead dye for 15 minutes at 4°C and then plated in 96-well plates. Cells were treated with different concentrations of humanized Vb17 antibody (B17B633.001) and incubated for 40 minutes at 4°C. Cells were washed and incubated with 20ug / ml purified mouse Vb17 antibody for 40 minutes at 4°C. Cells were stained with secondary antibodies, washed and read on Novocyte. Fig.16 As shown in , most monoclonals did not compete with the commercial antibodies for binding to cells expressing Vβ17.

[0402]

[0403] It will be appreciated by those skilled in the art that modifications may be made to the above embodiments without departing from the broad inventive concept of the present invention. Therefore, it should be understood that the present invention is not limited to the specific embodiments disclosed, but is intended to cover modifications within the spirit and scope of the present invention as defined in this specification.

Claims

1. An antibody that binds to Vβ17, the antibody comprising: (1) (i) a heavy chain variable region (VH), comprising a VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3, respectively, having the amino acid sequences of VHCDR1, VHCDR2, and VHCDR3 of VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a light chain variable region (VL), comprising VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 of VL having the amino acid sequence of SEQ ID NO: 32; (2) (i) a VH comprising a VH CDR1, a VH CDR2 and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 65; and (ii) a VL comprising a VLCDR1, a VL CDR2 and a VL CDR3 having the amino acid sequences of VL having the amino acid sequence of SEQ ID NO: 66; (3) (i) a VH comprising a VH CDR1, a VH CDR2 and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 99; and (ii) a VL comprising a VLCDR1, a VL CDR2 and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 100; (4) (i) a VH comprising a VH CDR1, a VH CDR2 and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising a VLCDR1, a VL CDR2 and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 134; (5) (i) a VH comprising a VH CDR1, a VH CDR2 and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 167; and (ii) a VL comprising a VLCDR1, a VL CDR2 and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 168; (6) (i) a VH comprising a VH CDR1, a VH CDR2 and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL comprising a VLCDR1, a VL CDR2 and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 202; (7) (i) a VH comprising a VH CDR1, a VH CDR2 and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 235; and (ii) a VL comprising a VLCDR1, a VL CDR2 and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 236; (8) (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 269; and (ii) a VL comprising a VLCDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 270; (9) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 303; and (ii) a VL comprising VLCDR1, VL CDR2 and VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 304; (10) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 337; and (ii) a VL comprising VLCDR1, VL CDR2 and VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 338; (11) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3 of a VH comprising the amino acid sequence of SEQ ID NO: 371; and (ii) a VL comprising VLCDR1, VL CDR2 and VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3 of a VL comprising the amino acid sequence of SEQ ID NO: 372; (12) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 405; and (ii) a VL comprising VLCDR1, VL CDR2 and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 406; or (13) (i) a VH comprising VH CDR1, VH CDR2 and VH CDR3 respectively having the amino acid sequences of VH CDR1, VH CDR2 and VH CDR3 of VH comprising the amino acid sequence of SEQ ID NO: 439; and (ii) a VL comprising VLCDR1, VL CDR2 and VL CDR3 respectively having the amino acid sequences of VL CDR1, VL CDR2 and VL CDR3 of VL comprising the amino acid sequence of SEQ ID NO:

440.

2. The antibody of claim 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the Kabat numbering system.

3. The antibody of claim 1, wherein the VH CDR1, VH CDR2, VH CDR3, VLCDR1, VLCDR2 and VLCDR3 amino acid sequences are according to the Chothia numbering system.

4. The antibody of claim 1, wherein the VH CDR1, VH CDR2, VH CDR3, VLCDR1, VLCDR2 and VLCDR3 amino acid sequences are according to the AbM numbering system.

5. The antibody of claim 1, wherein the VH CDR1, VH CDR2, VH CDR3, VLCDR1, VLCDR2 and VLCDR3 amino acid sequences are according to the Contact numbering system.

6. The antibody of claim 1, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences are according to the IMGT numbering system.

7. The antibody according to any one of claims 1 to 6, wherein the antibody is a humanized antibody.

8. The antibody according to any one of claims 1 to 7, wherein the antibody is an IgG antibody.

9. The antibody according to claim 8, wherein the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.

10. The antibody of any one of claims 1 to 9, wherein the antibody comprises a kappa light chain.

Images