Materials and methods for modulating T cell-mediated immunity

Abstract

To provide anti-T cell receptor gamma 9 (TRGV9) antibodies or antigen binding fragments thereof.SOLUTION: The present invention provides nucleic acids encoding anti-TRGV9 antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies for treating or preventing diseases, such as cancer. In some embodiments, the antibodies comprise a heavy chain variable region (VH) and a light chain variable region (VL).SELECTED DRAWING: None

Description

TECHNICAL FIELD

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Patent Application No. 62 / 844,959, filed on May 8, 2019, U.S. Patent Application No. 62 / 844,966, filed on May 8, 2019, U.S. Patent Application No. 62 / 844,970, filed on May 8, 2019, U.S. Patent Application No. 62 / 844,976, filed on May 8, 2019, and U.S. Patent Application No. 62 / 844,995, filed on May 8, 2019, each of which is hereby incorporated by reference in its entirety into the present specification.

[0002] (FIELD OF THE INVENTION) The present invention relates, inter alia, to anti-TRGV9 molecules comprising anti-TRGV9 antibodies, anti-TRGV9 / anti-cancer associated antigen bispecific antibodies, as well as nucleic acids encoding the antibodies and expression vectors, recombinant cells comprising the vectors, and compositions comprising the antibodies. Also provided are methods of making the antibodies, and methods of using the antibodies to kill cancer cells.

[0003] (REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY) This application contains a sequence listing submitted electronically via EFS-Web as an ASCII-formatted sequence listing with the file name "14620-021-228_SEQLIST", a creation date of May 4, 2020, and a size of 349,509 bytes. The sequence listing submitted via EFS-Web is part of the present specification and is hereby incorporated by reference in its entirety into the present specification. SUMMARY OF THE INVENTION MEANS FOR SOLVING THE PROBLEMS

[0004] ​​​​​​ In one embodiment, T cell receptor gamma variable 9 (TRG) Antibodies that bind to V9) are provided herein. In some embodiments, the antibody binds to the heavy chain The heavy chain variable region (VH) and the light chain variable region (light chain variable region) Includes the ble region (VL).

[0005] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH complementarity determining region having amino acid sequence number 1 on, CDR)1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and SEQ ID NO: 31 VH containing VH CDR3 having the amino acid sequence of (ii) the amino acid of SEQ ID NO: 4 VL CDR1 having the sequence, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL contains VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In the application form, the antibody contains VH having the amino acid sequence of SEQ ID NO: 34. Several applications In form, the antibody contains a VL having the amino acid sequence of SEQ ID NO: 8. Several embodiments So, the antibody has VH with the amino acid sequence of SEQ ID NO: 34 and the amino acid sequence of SEQ ID NO: 8 It includes a VL having a certain property. In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In this embodiment, the antibody is a humanized antibody. In a specific embodiment, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, IgG3, or IgG4 isoform. It is a type. In some embodiments, the antibody is a bispecific antibody. Specific embodiments In this embodiment, the antibody is polyvalent. In another embodiment, the antibody binds to at least three antigens. This is possible. In some embodiments, the antibody binds to at least five antigens. It is possible.

[0006] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 having amino acid sequence number 1, VH having amino acid sequence number 2 VH includes VH CDR3 having the amino acid sequence of CDR2 and SEQ ID NO: 32, (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, amino acid sequence of SEQ ID NO: 5 Includes VL CDR2 having the amino acid sequence of SEQ ID NO: 6 and VL CDR3 having the amino acid sequence of SEQ ID NO: 6 , including VL. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 35. It contains VH. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 8. It contains L. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 35. and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody is , specifically binds to TRGV9. In other embodiments, TRGV9 binds to the surface of γδ T cells. It is present on the surface. In some embodiments, the antibody is a humanized antibody. Specific embodiments In this embodiment, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, I The antibody is either IgG3 or IgG4 isotype. In some embodiments, the antibody is bispecific. It is a sex antibody. In certain embodiments, the antibody is polyvalent. In other embodiments, the antibody is It can bind to at least three antigens. In some embodiments, the antibody is small It can bind to at least five antigens.

[0007] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 having amino acid sequence number 1, VH having amino acid sequence number 2 VH includes VH CDR3 having the amino acid sequence of CDR2 and SEQ ID NO: 33, (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, amino acid sequence of SEQ ID NO: 5 Includes VL CDR2 having the amino acid sequence of SEQ ID NO: 6 and VL CDR3 having the amino acid sequence of SEQ ID NO: 6 , including VL. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 36. It contains VH. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 8. It contains L. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 36. and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody is , specifically binds to TRGV9. In other embodiments, TRGV9 binds to the surface of γδ T cells. It is present on the surface. In some embodiments, the antibody is a humanized antibody. Specific embodiments In this embodiment, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, I The antibody is either IgG3 or IgG4 isotype. In some embodiments, the antibody is bispecific. It is a sex antibody. In certain embodiments, the antibody is polyvalent. In other embodiments, the antibody is It can bind to at least three antigens. In some embodiments, the antibody is small It can bind to at least five antigens.

[0008] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 has the amino acid sequence of number 1, and V has the amino acid sequence of sequence number 76. VH includes H CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 3, (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 77, and the amino acid sequence of SEQ ID NO: 5 VL CDR2 has a column, and VL CDR3 has the amino acid sequence of SEQ ID NO: 6. It includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and is an anti The body has (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 60, and the amino acid sequence of SEQ ID NO: 61. VH CDR2 having an amino acid sequence, and VH CD having the amino acid sequence of SEQ ID NO 62. VH containing R3, and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 63, VL CDR2 having the amino acid sequence of sequence number 64, and having the amino acid sequence of sequence number 6 VL CDR3 is included, and VL is included. In some embodiments, the antibody is SEQ ID NO It contains VH having an amino acid sequence of 65. In some embodiments, the antibody is SEQ ID NO: 6 It contains a VL having an amino acid sequence of 6. In some embodiments, the antibody is SEQ ID NO: 65 It contains VH having the amino acid sequence of SEQ ID NO: 66 and VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody contains VH having the amino acid sequence of SEQ ID NO: 67. In several embodiments, the antibody contains a VL having the amino acid sequence of SEQ ID NO: 68. In that embodiment, the antibody is VH having the amino acid sequence of SEQ ID NO: 67 and SEQ ID NO: 68 It includes VL having the amino acid sequence of the following. In some embodiments, the antibody is used in TRGV9 It binds specifically. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is It is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, IgG3, or I It is the gG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is polyvalent. In other embodiments, the antibody is at least three It can bind to the antigen. In some embodiments, the antibody binds to at least five antigens. It can be combined with the original.

[0009] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 has amino acid sequence number 98, and has amino acid sequence number 99. VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 100 are included. H and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 101, SEQ ID NO: 102 VL CDR2 having the amino acid sequence of SEQ ID NO: 103, and V The antibody contains L CDR3 and VL. In some embodiments, the antibody is SEQ ID NO: 104 It contains VH having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody is SEQ ID NO: 105 It contains VL having the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody is SEQ ID NO: 104 It includes VH having the amino acid sequence of SEQ ID NO: 105 and VL having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is used. It is a nitrated antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, Antibodies are IgG1, IgG2, IgG3, or IgG4 isotypes. In the embodiment, the antibody is a bispecific antibody. In a specific embodiment, the antibody is polyvalent. In other embodiments, the antibody can bind to at least three antigens. In that embodiment, the antibody can bind to at least five antigens.

[0010] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 has amino acid sequence number 107, and has amino acid sequence number 108. Includes VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 109. , VH and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 110, SEQ ID NO: 1 VL CDR2 has an amino acid sequence of 11, and has the amino acid sequence of SEQ ID NO: 112. VL CDR3 is included, and VL is included. In some embodiments, the antibody is SEQ ID NO: 1 It contains VH having a 13-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 1 It contains a VL having a 14-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 1 It contains VH, which has a 13-amino acid sequence, and VL, which has the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is , a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments The antibody is either IgG1, IgG2, IgG3, or IgG4 isotype. In that embodiment, the antibody is a bispecific antibody. In a particular embodiment, the antibody is polyvalent. In other embodiments, the antibody can bind to at least three antigens. In some embodiments, the antibody can bind to at least five antigens.

[0011] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 has amino acid sequence number 117, and has amino acid sequence number 118. Includes VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 119. , VH and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 120, SEQ ID NO: 1 VL CDR2 has an amino acid sequence of 21, and has the amino acid sequence of SEQ ID NO: 122. VL CDR3 is included, and VL is included. In some embodiments, the antibody is SEQ ID NO: 1 It contains VH having a 23-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 1 It contains a VL having a 24-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 1 It contains VH having the amino acid sequence of 23 and VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is , a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments The antibody is either IgG1, IgG2, IgG3, or IgG4 isotype. In that embodiment, the antibody is a bispecific antibody. In a particular embodiment, the antibody is polyvalent. In other embodiments, the antibody can bind to at least three antigens. In some embodiments, the antibody can bind to at least five antigens.

[0012] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 has amino acid sequence number 127, and has amino acid sequence number 128. Includes VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 129. , VH and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 130, SEQ ID NO: 1 VL CDR2 has a 31-amino acid sequence, and has the amino acid sequence of SEQ ID NO: 132. VL CDR3 is included, and VL is included. In some embodiments, the antibody is SEQ ID NO: 1 It contains VH having a 33-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 1 It contains a VL having a 34-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 1 It contains VH, which has a 33-amino acid sequence, and VL, which has the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is , a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments The antibody is either IgG1, IgG2, IgG3, or IgG4 isotype. In that embodiment, the antibody is a bispecific antibody. In a particular embodiment, the antibody is polyvalent. In other embodiments, the antibody can bind to at least three antigens. In some embodiments, the antibody can bind to at least five antigens.

[0013] Furthermore, nucleic acids encoding antibodies that bind to TRGV9 are provided herein. Furthermore, the herein provides a nucleic acid encoding an antibody that binds to TRGV9. A processor is provided. Furthermore, an antibody that binds to TRGV9 is provided herein. A host cell is provided that contains a vector containing nucleic acids. Also provided herein are TR Includes a vector containing nucleic acid encoding an antibody that binds to GV9, and a package for that vector. Hmm, a kit will be provided.

[0014] Furthermore, the antibody that binds to TRGV9 provided herein and a pharmaceutically acceptable carrier A pharmaceutical composition containing is provided. A method for producing the pharmaceutical composition is also provided, and the method This includes obtaining a pharmaceutical composition by combining an antibody with a pharmaceutically acceptable carrier.

[0015] Furthermore, a method for activating γδ T cells expressing TRGV9 is provided, and the method is γδ This involves contacting T cells with an antibody that binds to TRGV9, as provided herein. In some embodiments, contact is made with control γδ T cells expressing TRGV9. In comparison, this results in increased expression of CD69, CD25, and / or granzyme B. A method is provided for inactivating γδ T cells expressing TRGV9, and the method is for γδ T This involves contacting cells with an antibody that binds to TRGV9, as provided herein. A method is provided to block the activation of γδ T cells expressing TRGV9, and the method is γδ This involves contacting T cells with an antibody that binds to TRGV9, as provided herein. Furthermore, a method is provided for regulating the activity of γδ T cells expressing TRGV9, and the method is γ This involves contacting δ T cells with an antibody that binds to TRGV9, as provided herein. .

[0016] In another embodiment, (a) a first binding domain that binds to TRGV9, and (b) TRGV9 A bispecific antibody comprising a second binding domain that binds to a second target, not the first, is described herein. Provided to. In a particular embodiment, the first binding domain of the bispecific antibody is TRGV It specifically binds to 9. In some embodiments, TRGV9 is on the surface of γδ T cells. It is present in [location]. In some embodiments, the antibody is a humanized antibody. In certain embodiments, In other embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, IgG 3. It is an IgG4 isotype.

[0017] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 1. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and SEQ ID NO: 3 VH containing VH CDR3 having an amino acid sequence, and (ii) the amino acid sequence of SEQ ID NO: 4 VL CDR1 having a column, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL includes VL CDR3 having the amino acid sequence of column number 6. Several implementations Morphologically, the first binding domain contains VH having the amino acid sequence of SEQ ID NO: 7. In several embodiments, the first binding domain has a VL having the amino acid sequence of SEQ ID NO: 8. Includes. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO: 7. It includes VH and VL having the amino acid sequence of SEQ ID NO: 8. In a particular embodiment, two The first binding domain of the heavily specific antibody specifically binds to TRGV9. Several implementations Morphologically, TRGV9 is present on the surface of γδ T cells. In some embodiments, The antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. Other embodiments Morphologically, antibodies are IgG1, IgG2, IgG3, or IgG4 isotypes.

[0018] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 1. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and SEQ ID NO: 31 VH containing VH CDR3 having the amino acid sequence of (ii) the amino acid of SEQ ID NO: 4 VL CDR1 having the sequence, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL contains VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In the application form, the first binding domain contains VH having the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO: 8. Contains L. In some embodiments, the first binding domain is the amino acid sequence of SEQ ID NO: 34. It comprises VH having a column and VL having the amino acid sequence of SEQ ID NO: 8. In certain embodiments The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In this case, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In this embodiment, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. be.

[0019] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 1. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and SEQ ID NO: 32 VH containing VH CDR3 having the amino acid sequence of (ii) the amino acid of SEQ ID NO: 4 VL CDR1 having the sequence, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL contains VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In the application form, the first binding domain contains VH having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO: 8. Contains L. In some embodiments, the first binding domain is the amino acid sequence of SEQ ID NO: 35. It comprises VH having a column and VL having the amino acid sequence of SEQ ID NO: 8. In certain embodiments The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In this case, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In this embodiment, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. be.

[0020] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 1. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and SEQ ID NO: 33 VH containing VH CDR3 having the amino acid sequence of (ii) the amino acid of SEQ ID NO: 4 VL CDR1 having the sequence, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL contains VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In the application form, the first binding domain contains VH having the amino acid sequence of SEQ ID NO: 36. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO: 8. Contains L. In some embodiments, the first binding domain is the amino acid sequence of SEQ ID NO: 36. It comprises VH having a column and VL having the amino acid sequence of SEQ ID NO: 8. In certain embodiments The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In this case, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In this embodiment, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. be.

[0021] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 1. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and SEQ ID NO: 3 VH containing VH CDR3 having the amino acid sequence of (ii) the amino acid of SEQ ID NO: 77 VL CDR1 having an acid sequence, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL includes VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, A bispecific antibody is provided herein, wherein the antibody (a) first binds to TRGV9 (b) A binding domain and a second binding domain that binds to a second target other than TRGV9. The first binding domain includes (i) VH CD having the amino acid sequence of SEQ ID NO: 60. R1, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and amino acid sequence of SEQ ID NO: 62 VH containing VH CDR3 having an acid sequence, and (ii) the amino acid sequence of SEQ ID NO: 63 VL CDR1 having, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and sequence VL includes VL CDR3 having amino acid sequence number 6. Several implementations In this state, the first binding domain contains VH having the amino acid sequence of SEQ ID NO: 65. In one embodiment, the first binding domain is a VL having the amino acid sequence of SEQ ID NO: 66. Includes. In some embodiments, the first binding domain is the amino acid sequence of SEQ ID NO: 65. It includes VH having and VL having the amino acid sequence of SEQ ID NO: 66. Several implementation forms In this state, the first binding domain contains VH having the amino acid sequence of SEQ ID NO: 67. In one embodiment, the first binding domain is a VL having the amino acid sequence of SEQ ID NO: 68. Includes. In some embodiments, the first binding domain, the amino acid sequence of SEQ ID NO: 67 VH has the amino acid sequence of SEQ ID NO: 68, and VL has the amino acid sequence of SEQ ID NO: 68. In certain embodiments, dual The first binding domain of the specific antibody specifically binds to TRGV9. Several implementations In this state, TRGV9 is present on the surface of γδ T cells. In some embodiments, anti The body is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. Other embodiments In this state, the antibody is either IgG1, IgG2, IgG3, or IgG4 isotype.

[0022] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of SEQ ID NO: 89 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 90, and SEQ ID NO: VH containing VH CDR3 having an amino acid sequence of 91, and (ii) the a of sequence number 92 VL CDR1 having an amino acid sequence, VL CDR having the amino acid sequence of SEQ ID NO: 93 2, and VL containing VL CDR3 having the amino acid sequence of SEQ ID NO: 94. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO: 95. Contains H. In some embodiments, the first binding domain is the amino acid of SEQ ID NO: 96 It includes a VL having a column. In some embodiments, the first binding domain is sequence number 95 It contains VH having the amino acid sequence of SEQ ID NO: 96 and VL having the amino acid sequence of SEQ ID NO: 96. In one embodiment, the first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In several embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is IgG It is an antibody. In other embodiments, the antibody is IgG1, IgG2, IgG3, or IgG4 It is an isotype.

[0023] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of SEQ ID NO: 98 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 99, and SEQ ID NO: VH containing VH CDR3 having a 100 amino acid sequence, and (ii) SEQ ID NO: 101 VL CDR1 has the amino acid sequence of SEQ ID NO: 102, VL VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 103. Includes. In some embodiments, the first binding domain is the amino acid sequence of SEQ ID NO: 104. It includes VH having the following: In some embodiments, the first binding domain is sequence number 105 It contains a VL having the amino acid sequence. In some embodiments, the first binding domain is VH having the amino acid sequence of SEQ ID NO: 104 and having the amino acid sequence of SEQ ID NO: 105 Includes VL. In certain embodiments, the first binding domain of the bispecific antibody is TRGV It specifically binds to 9. In some embodiments, TRGV9 is on the surface of γδ T cells. It is present in [location]. In some embodiments, the antibody is a humanized antibody. In certain embodiments, In other embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, IgG 3. It is an IgG4 isotype.

[0024] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of SEQ ID NO: 107 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and sequence VH containing VH CDR3 having amino acid sequence number 109, and (ii) SEQ ID NO: 1 VL CDR1 has a 10-amino acid sequence, and V has the amino acid sequence of SEQ ID NO: 111. VL CDR3 contains L CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 112. This includes the amino acids of SEQ ID NO: 113. In some embodiments, the first binding domain is the amino acid of SEQ ID NO: 113. It contains a VH having the sequence. In some embodiments, the first binding domain is sequence number 1 It contains a VL having a 14-amino acid sequence. In some embodiments, a first binding domain VH has the amino acid sequence of SEQ ID NO: 113 and has the amino acid sequence of SEQ ID NO: 114 It includes VL. In certain embodiments, the first binding domain of the bispecific antibody is TR It specifically binds to GV9. In some embodiments, TRGV9 binds to the surface of γδ T cells. It is present on the surface. In some embodiments, the antibody is a humanized antibody. Specific embodiments In this embodiment, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, I It is either the IgG3 or IgG4 isotype.

[0025] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 117 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and sequence VH containing VH CDR3 having amino acid sequence number 119, and (ii) SEQ ID NO: 1 VL CDR1 has a 20-amino acid sequence, and V has the amino acid sequence of SEQ ID NO: 121. VL CDR3 contains L CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 122. This includes the amino acids of SEQ ID NO: 123. In some embodiments, the first binding domain is the amino acid of SEQ ID NO: 123. It contains a VH having the sequence. In some embodiments, the first binding domain is sequence number 1 It contains a VL having a 24-amino acid sequence. In some embodiments, a first binding domain VH has the amino acid sequence of SEQ ID NO: 123 and SEQ ID NO: 124 It includes VL. In certain embodiments, the first binding domain of the bispecific antibody is TR It specifically binds to GV9. In some embodiments, TRGV9 binds to the surface of γδ T cells. It is present on the surface. In some embodiments, the antibody is a humanized antibody. Specific embodiments In this embodiment, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, I It is either the IgG3 or IgG4 isotype.

[0026] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of Sequence ID No. 127 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and sequence VH containing VH CDR3 having amino acid sequence number 129, and (ii) SEQ ID NO: 1 VL CDR1 has an amino acid sequence of 30, and V has an amino acid sequence of SEQ ID NO: 131. VL CDR3 contains L CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 132. This includes the amino acids of SEQ ID NO: 133. In some embodiments, the first binding domain is the amino acid of SEQ ID NO: 133. It contains a VH having the sequence. In some embodiments, the first binding domain is sequence number 1 It contains a VL having a 34-amino acid sequence. In some embodiments, a first binding domain VH has the amino acid sequence of SEQ ID NO: 133, and VH has the amino acid sequence of SEQ ID NO: 134 It includes VL. In certain embodiments, the first binding domain of the bispecific antibody is TR It specifically binds to GV9. In some embodiments, TRGV9 binds to the surface of γδ T cells. It is present on the surface. In some embodiments, the antibody is a humanized antibody. Specific embodiments In this embodiment, the antibody is an IgG antibody. In other embodiments, the antibody is IgG1, IgG2, I It is either the IgG3 or IgG4 isotype.

[0027] In another embodiment, (a) a first binding domain that binds to TRGV9, and (b) the surface of cancer cells. This specification describes a bispecific antibody that includes a second binding domain that binds to cancer antigens present on the surface. Provided in the book. In some embodiments, the antigen on the surface of cancer cells is a tumor-specific antigen. It is a tumor-associated antigen or a novel antigen. In certain embodiments, the first conjugated drug of a bispecific antibody The main component specifically binds to TRGV9. In some embodiments, TRGV9 is γ It is present on the surface of δ T cells. In some embodiments, a bispecific antibody is used on γδ T cells. When TRGV9 binds to the surface of cells and to antigens on the surface of cancer cells, the cancer cells die. In some embodiments, the first binding domain is humanized, or the second binding domain The in is either humanized or both the first and second binding domains are It is humanized. In some embodiments, the bispecific antibody is an IgG antibody. In some embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 isopropyl alcohol. It's that type.

[0028] In another embodiment, (a) a first binding domain that binds to TRGV9, and (b) CD123 A bispecific antibody comprising a second binding domain that binds to a specific target is provided herein. In this embodiment, the first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In one embodiment, CD123 is located on the surface of the cell. In a specific embodiment, TRGV 9 is present on the surface of γδ T cells, and CD123 is present on the surface of some cells. In this embodiment, the bispecific antibody is applied to TRGV9 on the surface of γδ T cells and on the surface of the cells. When it binds to CD123, cells that have CD123 on their surface die. In the embodiment, CD123 is on the surface of cancer cells. In a specific embodiment, TRGV9 CD123 is present on the surface of γδ T cells, while CD123 is present on the surface of cancer cells. In this embodiment, the bispecific antibody is applied to TRGV9 on the surface of γδ T cells and on the surface of the cells. When it binds to CD123, cancer cells are killed. In some embodiments, the first binding The main domain is humanized, or the second binding domain is humanized, or the first Both the first and second binding domains are humanized. Several implementations In this configuration, the bispecific antibody is an IgG antibody. In some embodiments, the antibody is Ig It is a G1, IgG2, IgG3, or IgG4 isotype.

[0029] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) comprising a first binding domain that binds to CD123 The second binding domain is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 9, VH CDR2 having the amino acid sequence of sequence number 10, and the amino acid sequence of sequence number 11 (ii) VH having VH CDR3, and V having the amino acid sequence of SEQ ID NO: 12 L CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 13, and SEQ ID NO: 14 VL includes VL CDR3 having the amino acid sequence. In some embodiments, The second binding domain contains VH having the amino acid sequence of SEQ ID NO: 15. In this embodiment, the second binding domain includes a VL having the amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain has the amino acid sequence of SEQ ID NO: 15. It comprises VH and VL having the amino acid sequence of SEQ ID NO: 16. In some embodiments, CD123 is located on the surface of the cell. In certain embodiments, TRGV9 is located on the γδ T cell. CD123 is present on the surface of the cell. In some embodiments, two The heavily specific antibody binds to TRGV9 on the surface of γδ T cells and CD123 on the surface of the cells. When combined, cells having CD123 on their surface die. In some embodiments, C D123 is present on the surface of cancer cells. In certain embodiments, TRGV9 is found on γδ T cells. CD123 is present on the surface of cancer cells. In some embodiments, two The heavily specific antibody binds to TRGV9 on the surface of γδ T cells and CD123 on the surface of the cells. When combined, cancer cells are killed. In some embodiments, the first binding domain is humanized. The second binding domain is either humanized or the first binding domain and Both the first and second binding domains are humanized. In some embodiments, the second specific The sex antibody is an IgG antibody. In some embodiments, the antibody is IgG1, IgG2, It is either an IgG3 or IgG4 isotype.

[0030] In some embodiments of the various bispecific antibodies provided herein, TRGV9 The first binding domain to bind is a V having an amino acid sequence, as provided herein. H CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and Includes VL CDR3. In some embodiments, a first coupling is coupled to TRGV9. The main component is a VH domain having an amino acid sequence, as provided herein. Includes DR1, VH CDR2, and VH CDR3. In some embodiments, TRG The first binding domain that binds to V9 has an amino acid sequence as provided herein. This includes VL CDR1, VL CDR2, and VL CDR3 of the VL domain. In some embodiments, the first binding domain that binds to TRGV9 is provided herein. VH CDR1, VH CDR2, and VH domains having amino acid sequences such as the above. VH CDR3 and VL C of the VL domain having the amino acid sequence provided herein Includes DR1, VL CDR2, and VL CDR3. In some embodiments, TR The first binding domain that binds to GV9 has an amino acid sequence as provided herein. It contains a VH domain. In some embodiments, a first binding that binds to TRGV9 The domain includes a VL domain having an amino acid sequence, as provided herein. In some embodiments, a first binding domain that binds to TRGV9 is provided herein. A VH domain having an amino acid sequence such as the one described herein, and the amino acid sequence provided herein Includes VL domains that have columns.

[0031] Furthermore, (a) a first binding domain that binds to TRGV9, as provided herein. (b) a dual feature including a second binding domain that binds to a second target other than TRGV9. A nucleic acid encoding an isoantibody is provided. Also provided herein is a nucleic acid that binds to TRGV9. A vector is provided that contains a nucleic acid encoding a bispecific antibody that matches. The vector contains nucleic acids encoding a bispecific antibody that binds to TRGV9, which is provided to the customer. A host cell is provided. Also, a bispecific binding to TRGV9 provided herein A kit is provided that includes a vector containing nucleic acid encoding a sex antibody, and a package for that vector. To be served.

[0032] In another embodiment, (a) a first binding domain that binds to TRGV9, and (b) TRGV It includes a second binding domain that binds to a second target other than 9, and a pharmaceutically acceptable carrier. A pharmaceutical composition containing is provided herein. A bispecific antibody provided herein This is also intended in the pharmaceutical composition. In a particular embodiment, the second binding domain is Combine with CD123.

[0033] In another aspect, this specification describes a method for directing γδ T cells expressing TRGV9 to cancer cells. The method provided herein involves contacting γδ T cells with the bispecific antibody provided herein. This includes bringing γδ T cells into contact with cancer cells. In some embodiments, contacting γδ T cells with cancer cells. To give direction.

[0034] In another embodiment, a method for inhibiting the growth or proliferation of cancer cells that express cancer antigens on their cell surface. The method provided herein involves contacting cancer cells with the bispecific antibody provided herein. This includes bringing cancer cells into contact with the pharmaceutical composition. In some embodiments, this includes bringing cancer cells into contact with the pharmaceutical composition. It inhibits cell growth or proliferation. In some embodiments, cancer cells are contacted with a bispecific antibody. During contact, TRGV9-expressing γδ T cells are present.

[0035] In another embodiment, a method for eliminating cancer cells in a subject is provided herein, and the method This includes administering an effective amount of a bispecific antibody, such as those provided herein, to the target. In some embodiments, the subject is the subject that requires the method. In this case, the subject is a human being.

[0036] In another embodiment, a method for activating γδ T cells expressing TRGV9 is provided herein. The method involves contacting γδ T cells with a bispecific antibody such as that provided herein. This includes doing so.

[0037] Isolated TRGV9 bispecific antibodies or their antigen-binding fragments are provided herein. The isolated TRGV9 bispecific antibody or its antigen-binding fragment is, a. The first heavy chain (HC1), b. The second heavy chain (HC2), c. The first light chain (LC1), d. Including the second light chain (LC2), HC1 is related to LC1, HC2 is related to LC2, and HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 3, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively, or iv. Each contains the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. Heavy chain complementarity determining region 1 (HCDR) 1) Including HCDR2 and HCDR3, LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. Light chain complementarity determining region 1 (LCDR) 1) LCDR2, and a compound comprising LCDR2 that forms a binding site for the first antigen, HC2 and LC2 form binding sites for the second antigen. In one embodiment, isolated The TRGV9 bispecific antibody or its antigen-binding fragment is SEQ ID NO: 7, SEQ ID NO: For an amino acid sequence selected from 34, SEQ ID NO: 35, or SEQ ID NO: 36, at least It contains HC1 which has 95% identical amino acid sequences, and LC1 is the amino acid sequence of SEQ ID NO: 8 It includes an amino acid sequence having at least 95% identity with the no-acid sequence. Another embodiment Therefore, the isolated TRGV9 bispecific antibody or its antigen-binding fragment is, 7. Includes an amino acid sequence selected from SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36. It contains HC1, and LC1 contains the amino acid sequence of SEQ ID NO: 8.

[0038] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the amino acid of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 contain the sequence, and LC1 each contains LCDR1, LCDR2, containing the amino acid sequences of sequence number 4, sequence number 5, and sequence number 6, Furthermore, comprising LCDR3, which forms a binding site for the first antigen, HC2 and LC2 , forming a binding site for the second antigen. In one embodiment, isolated TRGV9 duplex The specific antibody or its antigen-binding fragment is less than the amino acid sequence of SEQ ID NO: 7. Both contain HC1, which has an amino acid sequence with 95% identity, and LC1 is the same as in SEQ ID NO: 8 It contains an amino acid sequence that has at least 95% identity with the amino acid sequence. Morphologically, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are sequence-based. HC1 contains the amino acid sequence of number 7, and LC1 contains the amino acid sequence of sequence number 8. .

[0039] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the amino acid of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. It contains HCDR1, HCDR2, and HCDR3, which include acid sequences, and LC1 is, LCDR1, LCDR2, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. , and also containing LCDR3, which forms a binding site for the first antigen, and HC2 and LC2 This forms a binding site for the second antigen. In one embodiment, isolated TRGV92 The hemispecific antibody or its antigen-binding fragment is less specific to the amino acid sequence of SEQ ID NO: 34. It contains HC1 which has at least 95% identical amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with the 8 amino acid sequences. In the embodiment, the isolated TRGV9 bispecific antibody or its antigen-binding fragment is HC1 contains the amino acid sequence of SEQ ID NO: 34, and LC1 contains the amino acid sequence of SEQ ID NO: 8 Includes.

[0040] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the amino acid of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. It contains HCDR1, HCDR2, and HCDR3, which include acid sequences, and LC1 is, LCDR1, LCDR2, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. , and also containing LCDR3, which forms a binding site for the first antigen, and HC2 and LC2 This forms a binding site for the second antigen. In one embodiment, isolated TRGV92 The hemispecific antibody or its antigen-binding fragment is less specific to the amino acid sequence of SEQ ID NO: 35. It contains HC1 which has at least 95% identical amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with the 8 amino acid sequences. In the embodiment, the isolated TRGV9 bispecific antibody or its antigen-binding fragment is HC1 contains the amino acid sequence of SEQ ID NO: 35, and LC1 contains the amino acid sequence of SEQ ID NO: 8 Includes.

[0041] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the amino acid of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. It contains HCDR1, HCDR2, and HCDR3, which include acid sequences, and LC1 is, LCDR1, LCDR2, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. , and also containing LCDR3, which forms a binding site for the first antigen, and HC2 and LC2 This forms a binding site for the second antigen. In one embodiment, isolated TRGV92 The hemispecific antibody or its antigen-binding fragment is less specific to the amino acid sequence of SEQ ID NO: 36. It contains HC1 which has at least 95% identical amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with the 8 amino acid sequences. In the embodiment, the isolated TRGV9 bispecific antibody or its antigen-binding fragment is HC1 contains the amino acid sequence of SEQ ID NO: 36, and LC1 contains the amino acid sequence of SEQ ID NO: 8 Includes.

[0042] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the amino acid of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. It contains HCDR1, HCDR2, and HCDR3, which include acid sequences, and LC1 is, LCDR1, LCDR containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6 2, and including LCDR3, a binding site for the first antigen is formed, and HC2 and LC 2 forms a binding site for the second antigen. In one embodiment, isolated TRGV9 The bispecific antibody or its antigen-binding fragment is related to the amino acid sequence of SEQ ID NO: 65 It contains HC1 which has at least 95% identity of amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 66. In another embodiment, an isolated TRGV9 bispecific antibody or its antigen-binding fragment is used. HC1 contains the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66 Contains an acid sequence. In one embodiment, isolated TRGV9 bispecific antibody or its antigen conjugate. The fragment has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. It contains HC1 which has an amino acid sequence, and LC1 has a small amount of amino acid sequence compared to the amino acid sequence of SEQ ID NO: 68. It contains an amino acid sequence that has at least 95% identity. In another embodiment, isolated T The RGV9 bispecific antibody or its antigen-binding fragment is the amino acid sequence of SEQ ID NO: 67. It contains HC1, and LC1 contains the amino acid sequence of SEQ ID NO: 68.

[0043] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the same as in SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3, each containing a mino acid sequence, are included, LCDR1, L containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6 Including CDR2 and LCDR3, it forms a binding site for the first antigen, and HC2 and LC2 forms a binding site for the second antigen. In one embodiment, isolated TR The GV9 bispecific antibody or its antigen-binding fragment has the amino acid sequence of SEQ ID NO: 65 In contrast, HC1 contains an amino acid sequence having at least 95% identity, and LC1 contains, An amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66 Includes. In another embodiment, an isolated TRGV9 bispecific antibody or its antigen-binding flag. The ment contains HC1 with the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66 It contains an amino acid sequence. In one embodiment, an isolated TRGV9 bispecific antibody or its anti The original binding fragment has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. HC1 contains an amino acid sequence having the amino acid sequence of SEQ ID NO: 68 and include an amino acid sequence having at least 95% identity. In another embodiment, isolated The TRGV9 bispecific antibody or its antigen-binding fragment is the amino acid of SEQ ID NO: 67. It contains HC1 which includes an acid sequence, and LC1 which contains the amino acid sequence of SEQ ID NO: 68.

[0044] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 is the same as sequence numbers 89, 90, and 91, respectively. HCDR1, HCDR2, and HCDR3, each containing a mino acid sequence, are included, Furthermore, LCDR1 containing the amino acid sequences of SEQ ID NOs. 92, 93, and 94, It includes LCDR2 and LCDR3, forming a binding site for the first antigen, and HC2 And LC2 forms a binding site for the second antigen. In one embodiment, isolated T The RGV9 bispecific antibody or its antigen-binding fragment is the amino acid sequence of SEQ ID NO: 95 It contains HC1 which has at least 95% identity with the amino acid sequence, and LC1 is an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 96 This includes an isolated TRGV9 bispecific antibody or its antigen-binding funnel. In another embodiment, an isolated TRGV9 bispecific antibody or its antigen-binding funnel is included. The component contains HC1 with the amino acid sequence of SEQ ID NO: 95, and LC1 contains SEQ ID NO: 96 It contains the amino acid sequence.

[0045] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 corresponds to sequence numbers 98, 99, and 100, respectively. LC1 contains HCDR1, HCDR2, and HCDR3, which have amino acid sequences, and Each contains the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. It comprises DR1, LCDR2, and LCDR3, forming a binding site for the first antigen. HC2 and LC2 form binding sites for the second antigen. In one embodiment, isolation The TRGV9 bispecific antibody or its antigen-binding fragment is the one specified in SEQ ID NO: 104. It contains HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence. LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 105. Includes an amino acid sequence. In another embodiment, an isolated TRGV9 bispecific antibody or the The antigen-binding fragment contains HC1, which has the amino acid sequence of SEQ ID NO: 104, and LC1 is It contains the amino acid sequence of SEQ ID NO: 105.

[0046] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 corresponds to SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 10 LC1 includes HCDR1, HCDR2, and HCDR3, each containing a 9-amino acid sequence, Each contains the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. Including LCDR1, LCDR2, and LCDR3, the binding site for the first antigen is formed Thus, HC2 and LC2 form binding sites for the second antigen. In one embodiment, The isolated TRGV9 bispecific antibody or its antigen-binding fragment is SEQ ID NO: 113 HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence of [the specified amino acid sequence] Including, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 114. It includes the amino acid sequence. In another embodiment, an isolated TRGV9 bispecific antibody or The antigen-binding fragment contains HC1 with the amino acid sequence of SEQ ID NO: 113, and LC 1 contains the amino acid sequence of SEQ ID NO: 114.

[0047] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 corresponds to SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 11 LC1 includes HCDR1, HCDR2, and HCDR3, each containing a 9-amino acid sequence, Each contains the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. Including LCDR1, LCDR2, and LCDR3, the binding site for the first antigen is formed Thus, HC2 and LC2 form binding sites for the second antigen. In one embodiment, The isolated TRGV9 bispecific antibody or its antigen-binding fragment is SEQ ID NO: 123 HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence of [the specified amino acid sequence] Including, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 124. It includes the amino acid sequence. In another embodiment, an isolated TRGV9 bispecific antibody or The antigen-binding fragment contains HC1 with the amino acid sequence of SEQ ID NO: 123, and LC 1 contains the amino acid sequence of SEQ ID NO: 124.

[0048] Furthermore, isolated TRGV9 bispecific antibodies or their antigen-binding fragments are specified herein. The TRGV9 bispecific antibody or its antigen-binding fragment provided and isolated is ( a) HC1, (b) HC2, (c) LC1, and (d) LC2, where HC1 is L Related to C1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC In relation to 2, HC1 corresponds to Sequence ID 127, Sequence ID 128, and Sequence ID 12, respectively. LC1 includes HCDR1, HCDR2, and HCDR3, each containing a 9-amino acid sequence, Each contains the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. Including LCDR1, LCDR2, and LCDR3, the binding site for the first antigen is formed Thus, HC2 and LC2 form binding sites for the second antigen. In one embodiment, The isolated TRGV9 bispecific antibody or its antigen-binding fragment is SEQ ID NO: 133 HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence of [the specified amino acid sequence] Including, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 134. It includes the amino acid sequence. In another embodiment, an isolated TRGV9 bispecific antibody or The antigen-binding fragment contains HC1 with the amino acid sequence of SEQ ID NO: 133, and LC 1 contains the amino acid sequence of SEQ ID NO: 134.

[0049] In another embodiment, the binding site for the first antigen is linked to TRGV9 on γδ T cells. To combine.

[0050] In another embodiment, the binding site for the second antigen is a cancer antigen present on the surface of cancer cells. Combine.

[0051] In another embodiment, a bispecific antibody is used to target TRGV9 present on the surface of γδ T cells. The binding of cancer antigens, which are present on the surface of cancer cells, leads to the death of cancer cells.

[0052] In another embodiment, the TRGV9 bispecific antibody comprises humanized HC1 and humanized LC1. nothing.

[0053] In another embodiment, the HC2 and LC2 of the TRGV9 antibody bind to CD123.

[0054] In another embodiment, the bispecific antibody or its antigen-binding fragment is IgG1, Ig It is a G2, IgG3, or IgG4 isotype.

[0055] In certain embodiments, the bispecific antibody or its antigen-binding fragment is IgG4 I It is a sotype.

[0056] In another embodiment, the TRGV9 bispecific antibody or its antigen-binding fragment is approximately 5 EC below 00 pM50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro to do so.

[0057] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 3 00 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro to do so.

[0058] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 1 60 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro to do so.

[0059] In one embodiment, the EC 50 is evaluated with a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0060] In another embodiment, the ratio of effector cells to target cells is from about 0.01:1 to about 5:1 .

[0061] In yet another embodiment, the ratio of effector cells to target cells is from about 0.1:1 to about 2:1 .

[0062] In a specific embodiment, the ratio of effector cells to target cells is about 1:1.

[0063] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is multivalent .

[0064] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is capable of binding to at least three antigens.

[0065] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is at least capable of binding to at least 5 antigens.

[0066] Also provided is an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof , wherein the isolated γδ T cell bispecific antibody or antigen-binding fragment thereof a. HC1, and b. HC2, and c. LC1, and d. LC2. HC1 is associated with LC1, and HC2 is associated with LC2, HC1 and LC1 form a binding site for a first antigen on γδ T cells, and HC2 and LC2 form a binding site for a second antigen.

[0067] Also provided herein is a bispecific antibody comprising a first means capable of specifically binding to a T cell receptor gamma chain, and a T cell recep a second means capable of specifically binding to a target molecule that is not a T cell receptor gamma chain The bispecific antibody is provided herein.

[0068] Also provided is a process for producing a molecule capable of specifically binding to two or more target molecules , wherein the molecule performs the function of obtaining an oligopeptide or polypeptide capable of binding to a T cell receptor gamma chain a step that performs the function of obtaining an oligopeptide or polypeptide capable of binding to a target , and a step that performs the function of providing a molecule capable of specifically binding to the T cell receptor gamma chain and the target molecule .

[0069] In one embodiment, the step that performs the function of obtaining an oligopeptide or polypeptide capable of binding to a target is repeated n times, and the T cell receptor gamma chain and n target molecules The process further includes n steps to perform the function of providing a molecule that can specifically bind to a target. n is at least 2.

[0070] Isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment This is provided herein, a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 3, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively, or iv. Each contains the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. Including HCDR1, HCDR2, and HCDR3, LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. The first component includes LCDR1, LCDR2, and LCDR3, which specifically bind to Vγ9. HC2 forms a binding site for the antigen, and, respectively, SEQ ID NO: 9, SEQ ID NO: 10, and It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence of SEQ ID NO: 11. LC2 contains the amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. It includes LCDR1, LCDR2, and LCDR3, and specifically binds to CD123. It forms a binding site for a second antigen. In one embodiment, isolated anti-TRGV9 / Anti-CD123 bispecific antibodies or antigen-binding fragments include SEQ ID NO: 7, SEQ ID NO: 34, at least 95% relative to the amino acid sequence selected from SEQ ID NO: 35 or SEQ ID NO: 36 HC1 comprising an amino acid sequence having the identity of, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8 column. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is configured as an amino acid sequence selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 HC1 comprising: and LC1 comprises the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is configured as comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15 HC2, and LC2 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 16 one sex. In another embodiment, the isolated anti-TRGV9 / anti-CD 123 bispecific antibody or antigen-binding fragment comprises the amino acid sequence of SEQ ID NO: 15 HC2, and LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0071] Also provided herein is an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof ment, comprising (a) HC1, (b) HC2, (c) LC1, (d ) LC2, wherein HC1 is associated with LC1, HC2 is associated with LC2, and HC1 is HCDR1 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively HCDR2, and HCDR3, and LC1 is, respectively, SEQ ID NO: 4, SEQ ID NO: 5, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 6 Then, HC2 forms a binding site for the first antigen that specifically binds to Vγ9, and each Therefore, HCDR1, H, containing the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11 Includes CDR2 and HCDR3, where LC2 is sequence number 12 and sequence number 13, respectively. , and LCDR1, LCDR2, and LCDR3 containing the amino acid sequence of SEQ ID NO: 14 It contains and forms a binding site for a second antigen that specifically binds to CD123. Morphologically, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-conjugated fragments. The nucleotide has at least 95% identity with the selected amino acid sequence of SEQ ID NO: 7. It contains HC1 which has an amino acid sequence, and LC1 which has less amino acid sequence than SEQ ID NO: 8 It contains an amino acid sequence with at least 95% identity. In another embodiment, isolated anti-T The RGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO: 7 HC1 contains an amino acid sequence, and LC1 contains the amino acid sequence of SEQ ID NO. Another implementation In this state, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment The amino acids have at least 95% identity with the amino acid sequence of SEQ ID NO: 15. The HC2 contains the sequence, and the LC2 contains at least 9 amino acids relative to the amino acid sequence of SEQ ID NO: 16. It contains an amino acid sequence with 5% identity. In another embodiment, isolated anti-TRGV9 / Anti-CD123 bispecific antibody or antigen-binding fragment, the amino acid sequence of SEQ ID NO: 15 The HC2 contains the column, and the LC2 contains the amino acid sequence of SEQ ID NO: 16.

[0072] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. , HCDR2 and HCDR3 are included, and LC1 is sequence number 4 and sequence number 5 respectively. , and LCDR1, LCDR2, and LCDR3 containing the amino acid sequence of SEQ ID NO: 6 Then, HC2 forms a binding site for the first antigen that specifically binds to Vγ9, Each of these HCDR1s contains the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11. HCDR2 and HCDR3 are included, and LC2 is sequence number 12 and sequence number 1, respectively. 3, and LCDR1, LCDR2, and LCDR3, which include the amino acid sequence of SEQ ID NO: 14. It contains and forms a binding site for a second antigen that specifically binds to CD123. In the application form, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding flag Ment has at least 95% identity with the selected amino acid sequence of SEQ ID NO: 34. It contains HC1 which has the amino acid sequence, and LC1 has the amino acid sequence of SEQ ID NO: 8 It contains an amino acid sequence having at least 95% identity. In another embodiment, isolated Anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: 34 HC1 contains the amino acid sequence of SEQ ID NO: 8, and LC1 contains the amino acid sequence of SEQ ID NO: 8. In the embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-conjugated fura The component has at least 95% identity with the amino acid sequence of SEQ ID NO: 15. It contains HC2 with a amino acid sequence, and LC2 is less than the amino acid sequence of SEQ ID NO: 16. Both contain amino acid sequences with 95% identity. In another embodiment, isolated anti-TR GV9 / anti-CD123 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO. 15. It contains HC2 with a no-acid sequence, and LC2 contains the amino acid sequence of SEQ ID NO. 16.

[0073] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. , HCDR2 and HCDR3 are included, and LC1 is sequence number 4 and sequence number 5 respectively. , and LCDR1, LCDR2, and LCDR3 containing the amino acid sequence of SEQ ID NO: 6 Then, HC2 forms a binding site for the first antigen that specifically binds to Vγ9, Each of these HCDR1s contains the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11. HCDR2 and HCDR3 are included, and LC2 is sequence number 12 and sequence number 1, respectively. 3, and LCDR1, LCDR2, and LCDR3, which include the amino acid sequence of SEQ ID NO: 14. It contains and forms a binding site for a second antigen that specifically binds to CD123. In the application form, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding flag Ment has at least 95% identity with the selected amino acid sequence of SEQ ID NO: 35. It contains HC1 which has the amino acid sequence, and LC1 has the amino acid sequence of SEQ ID NO: 8 It contains an amino acid sequence having at least 95% identity. In another embodiment, isolated Anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: 35 HC1 contains the amino acid sequence of SEQ ID NO: 8, and LC1 contains the amino acid sequence of SEQ ID NO: 8. In the embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-conjugated fura The component has at least 95% identity with the amino acid sequence of SEQ ID NO: 15. It contains HC2 with a amino acid sequence, and LC2 is less than the amino acid sequence of SEQ ID NO: 16. Both contain amino acid sequences with 95% identity. In another embodiment, isolated anti-TR GV9 / anti-CD123 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO. 15. It contains HC2 with a no-acid sequence, and LC2 contains the amino acid sequence of SEQ ID NO. 16.

[0074] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. , HCDR2 and HCDR3 are included, and LC1 is sequence number 4 and sequence number 5 respectively. , and LCDR1, LCDR2, and LCDR3 containing the amino acid sequence of SEQ ID NO: 6 Then, HC2 forms a binding site for the first antigen that specifically binds to Vγ9, Each of these HCDR1s contains the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11. HCDR2 and HCDR3 are included, and LC2 is sequence number 12 and sequence number 1, respectively. 3, and LCDR1, LCDR2, and LCDR3, which include the amino acid sequence of SEQ ID NO: 14. It contains and forms a binding site for a second antigen that specifically binds to CD123. In the application form, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding flag Ment has at least 95% identity with the selected amino acid sequence of SEQ ID NO: 36. It contains HC1 which has the amino acid sequence, and LC1 has the amino acid sequence of SEQ ID NO: 8 It contains an amino acid sequence having at least 95% identity. In another embodiment, isolated The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: 36 HC1 contains the amino acid sequence of SEQ ID NO: 8, and LC1 contains the amino acid sequence of SEQ ID NO: 8. In the embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-conjugated fura The component has at least 95% identity with the amino acid sequence of SEQ ID NO: 15. It contains HC2 with a amino acid sequence, and LC2 is less than the amino acid sequence of SEQ ID NO: 16. Both contain amino acid sequences with 95% identity. In another embodiment, isolated anti-TR GV9 / anti-CD123 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO. 15. It contains HC2 with a no-acid sequence, and LC2 contains the amino acid sequence of SEQ ID NO. 16.

[0075] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. , HCDR2 and HCDR3 are included, and LC1 is sequence number 77, sequence number LCDR1, LCDR2, and LCDR3 containing the amino acid sequences of 5 and SEQ ID NO: 6 It contains and forms a binding site for the first antigen that specifically binds to Vγ9, and HC2 is HCDR1 containing the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. , HCDR2 and HCDR3 are included, and LC2 is sequence number 12, sequence number 12, respectively. LCDR1, LCDR2, and LCDR containing the amino acid sequences of 13 and SEQ ID NO: 14 It contains 3, which forms a binding site for a second antigen that specifically binds to CD123. In the embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-conjugated fura The gument has at least 95% identity with the selected amino acid sequence of SEQ ID NO: 65. HC1 contains an amino acid sequence having the amino acid sequence of SEQ ID NO: 66 and include an amino acid sequence having at least 95% identity. In another embodiment, isolated The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: HC1 contains the amino acid sequence of 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66. In one embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragment is identical to the selected amino acid sequence of SEQ ID NO: 67 by at least 95%. HC1 contains a monogeneous amino acid sequence, and LC1 contains the amino acid sequence of SEQ ID NO: 68. It contains an amino acid sequence having at least 95% identity with respect to. In another embodiment, The detached anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is sequence HC1 contains the amino acid sequence of number 67, and LC1 contains the amino acid sequence of sequence number 68. Includes. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or anti The original binding fragment has at least 95% identity with the amino acid sequence of SEQ ID NO: 15. HC2 contains an amino acid sequence having the amino acid sequence of SEQ ID NO: 16 and include an amino acid sequence having at least 95% identity. In another embodiment, isolated The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: HC2 contains 15 amino acid sequences, and LC2 contains the amino acid sequence of SEQ ID NO: 16. .

[0076] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCD containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. R1, HCDR2, and HCDR3 are included, and LC1 is sequence number 63, sequence LCDR1, LCDR2, and LC, which include the amino acid sequences of number 64 and sequence number 65. Containing DR3, it forms a binding site for a first antigen that specifically binds to Vγ9, and HC 2 contains the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. Includes CDR1, HCDR2, and HCDR3, where LC2 is sequence number 12, LCDR1, LCDR2, and containing the amino acid sequences of SEQ ID NO: 13 and SEQ ID NO: 14. It contains LCDR3 and forms a binding site for a second antigen that specifically binds to CD123. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen is used. The binding fragment is at least 95% of the selected amino acid sequence of SEQ ID NO: 65. HC1 contains an amino acid sequence having the same identity as LC1, and LC1 contains the amino acid sequence of SEQ ID NO: 66 It includes an amino acid sequence having at least 95% identity with respect to the sequence. In another embodiment, The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is HC1 contains the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66 Includes a column. In one embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or The antigen-binding fragment has at least 9 amino acids relative to the selected amino acid sequence of SEQ ID NO: 67. It contains HC1 containing an amino acid sequence with 5% identity, and LC1 is the amino acid sequence of SEQ ID NO: 68. It includes an amino acid sequence having at least 95% identity with the no-acid sequence. Another embodiment Then, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment HC1 contains the amino acid sequence of SEQ ID NO: 67, and LC1 contains the amino acid sequence of SEQ ID NO: 68. Contains an acid sequence. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific anti The body or antigen-binding fragment is at least 95% of the amino acid sequence of SEQ ID NO: 15. HC2 contains an amino acid sequence having the same identity as LC2, and LC2 contains the amino acids of SEQ ID NO: 16 It includes an amino acid sequence having at least 95% identity with respect to the sequence. In another embodiment, The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is HC2 contains the amino acid sequence of SEQ ID NO: 15, and LC2 contains the amino acid sequence of SEQ ID NO: 16 Includes columns.

[0077] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDs containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. R1, HCDR2, and HCDR3 are included, and LC1 is sequence number 92, sequence LCDR1, LCDR2, and LC, which include the amino acid sequences of number 93 and sequence number 94. Containing DR3, it forms a binding site for a first antigen that specifically binds to Vγ9, and HC 2 contains the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. Includes CDR1, HCDR2, and HCDR3, where LC2 is sequence number 12, LCDR1, LCDR2, and containing the amino acid sequences of SEQ ID NO: 13 and SEQ ID NO: 14. It contains LCDR3 and forms a binding site for a second antigen that specifically binds to CD123. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen is used. The binding fragment is at least 95% of the selected amino acid sequence of SEQ ID NO: 95. HC1 contains an amino acid sequence having the same identity as LC1, and LC1 contains the amino acid sequence of SEQ ID NO: 96 It includes an amino acid sequence having at least 95% identity with respect to the sequence. In another embodiment, The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is HC1 contains the amino acid sequence of SEQ ID NO: 95, and LC1 contains the amino acid sequence of SEQ ID NO: 96 Includes a column. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or The antigen-binding fragment is at least 95% identical to the amino acid sequence of SEQ ID NO: 15. HC2 contains a monogeneous amino acid sequence, and LC2 contains the amino acid sequence of SEQ ID NO: 16 It contains an amino acid sequence having at least 95% identity with respect to. In another embodiment, The detached anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is sequence HC2 contains the amino acid sequence of number 15, and LC2 contains the amino acid sequence of sequence number 16. include.

[0078] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is Each contains the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. Includes DR1, HCDR2, and HCDR3, and LC1 is each sequence number 101. LCDR1, LCDR2, and the amino acid sequences of SEQ ID NO: 102 and SEQ ID NO: 103 It also contains LCDR3, forming a binding site for a first antigen that specifically binds to Vγ9. Furthermore, HC2 corresponds to the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. Includes HCDR1, HCDR2, and HCDR3, where LC2 is the sequence number LCDR1, LCDR2, containing the amino acid sequences of No. 12, SEQ ID NO: 13, and SEQ ID NO: 14 , and a binding site for a second antigen that specifically binds to CD123, comprising LCDR3. Forms a position. In one embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody Alternatively, the antigen-binding fragment is less than the selected amino acid sequence of SEQ ID NO: 104. Both contain HC1, which has an amino acid sequence with 95% identity, and LC1 is sequence number 10. It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of 5. In the embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-conjugated fura The component contains HC1 containing the amino acid sequence of SEQ ID NO: 104, and LC1 contains SEQ ID NO: 104 It contains the amino acid sequence 05. In another embodiment, isolated anti-TRGV9 / anti-CD123 The bispecific antibody or antigen-binding fragment is less than the amino acid sequence of SEQ ID NO: 15. It contains HC2 with at least 95% identical amino acid sequences, and LC2 is sequence number 1. It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of 6. In the embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-conjugated fura The component contains HC2 with the amino acid sequence of SEQ ID NO: 15, and LC2 contains SEQ ID NO: 16 It contains the amino acid sequence.

[0079] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is Each contains the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. HCDR1, HCDR2, and HCDR3 are included, and LC1 is each sequence number 11 LCDR1, LCDR2, containing the amino acid sequences of 0, SEQ ID NO: 111, and SEQ ID NO: 112 , and also comprising LCDR3, a binding site for a first antigen that specifically binds to Vγ9 The HC2 molecules are formed from the amino acids of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. HCDR1, HCDR2, and HCDR3 contain sequences, and LC2 each contains LCDR1, LCD containing the amino acid sequences of sequence number 12, sequence number 13, and sequence number 14 R2, and LCDR3, are included in the second antigen that specifically binds to CD123. Forms a mating site. In one embodiment, isolated anti-TRGV9 / anti-CD123 bispecificity The antibody or antigen-binding fragment is less than the selected amino acid sequence of SEQ ID NO: 113. It contains HC1 which has at least 95% identical amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with 114 amino acid sequences. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen binding is used. The fragment contains HC1, which contains the amino acid sequence of sequence number 113, and LC1, which contains the sequence number Contains amino acid sequence 114. In another embodiment, isolated anti-TRGV9 / anti-CD1 23. The bispecific antibody or antigen-binding fragment is relative to the amino acid sequence of SEQ ID NO: 15. It contains HC2 having at least 95% identical amino acid sequences, and LC2 is sequence number It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 16. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen binding is used. The fragment contains HC2 with the amino acid sequence of SEQ ID NO: 15, and LC2 is SEQ ID NO: It contains a sequence of 16 amino acids.

[0080] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is Each contains the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. Includes HCDR1, HCDR2, and HCDR3, where LC1 is each sequence number 12 LCDR1, LCDR2, containing the amino acid sequences of 0, SEQ ID NO: 121, and SEQ ID NO: 122 , and also comprising LCDR3, a binding site for a first antigen that specifically binds to Vγ9 The HC2 molecules are formed from the amino acids of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. HCDR1, HCDR2, and HCDR3 contain sequences, and LC2 each contains LCDR1, LCD containing the amino acid sequences of sequence number 12, sequence number 13, and sequence number 14 R2, and LCDR3, are included in the second antigen that specifically binds to CD123. Forms a mating site. In one embodiment, isolated anti-TRGV9 / anti-CD123 bispecificity The antibody or antigen-binding fragment is less than the selected amino acid sequence of SEQ ID NO: 123. It contains HC1 which has at least 95% identical amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with the 124 amino acid sequences. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen binding is used. The fragment contains HC1, which contains the amino acid sequence of sequence number 123, and LC1, which contains the sequence number Contains amino acid sequence 124. In another embodiment, isolated anti-TRGV9 / anti-CD1 23. The bispecific antibody or antigen-binding fragment is relative to the amino acid sequence of SEQ ID NO: 15. It contains HC2 having at least 95% identical amino acid sequences, and LC2 is sequence number It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 16. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen binding is used. The fragment contains HC2 with the amino acid sequence of SEQ ID NO: 15, and LC2 is SEQ ID NO: It contains a sequence of 16 amino acids.

[0081] Also, isolated anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding flags. A ment is provided herein, comprising (a) HC1, (b) HC2, (c) LC1, and (d )Includes LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is Each contains the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. HCDR1, HCDR2, and HCDR3 are included, and LC1 is each sequence number 13. LCDR1, LCDR2, containing the amino acid sequences of 0, SEQ ID NO: 131, and SEQ ID NO: 132 , and also comprising LCDR3, a binding site for a first antigen that specifically binds to Vγ9 The HC2 molecules are formed from the amino acids of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. HCDR1, HCDR2, and HCDR3 contain sequences, and LC2 each contains LCDR1, LCD containing the amino acid sequences of sequence number 12, sequence number 13, and sequence number 14 R2, and LCDR3, are included in the second antigen that specifically binds to CD123. Forms a mating site. In one embodiment, isolated anti-TRGV9 / anti-CD123 bispecificity The antibody or antigen-binding fragment is less than the selected amino acid sequence of SEQ ID NO: 133. It contains HC1 which has at least 95% identical amino acid sequences, and LC1 is sequence number It contains an amino acid sequence that has at least 95% identity with 134 amino acid sequences. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen binding is used. The fragment contains HC1, which contains the amino acid sequence of sequence number 133, and LC1, which contains the sequence number Contains amino acid sequence 134. In another embodiment, isolated anti-TRGV9 / anti-CD1 23. The bispecific antibody or antigen-binding fragment is relative to the amino acid sequence of SEQ ID NO: 15. It contains HC2 having at least 95% identical amino acid sequences, and LC2 is sequence number It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 16. In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen binding is used. The fragment contains HC2 with the amino acid sequence of SEQ ID NO: 15, and LC2 is SEQ ID NO: It contains a sequence of 16 amino acids.

[0082] In another embodiment, TRGV9 is located on the surface of γδ T cells.

[0083] In another embodiment, CD123 is present on the surface of tumor cells or CD34+ stem cells.

[0084] In another embodiment, bispecific antibodies against TRGV9 present on the surface of γδ T cells The binding of CD123 to the body and to the surface of cancer cells leads to the strong death of cancer cells.

[0085] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti The original binding fragments include humanized HC1 and humanized LC1.

[0086] In another embodiment, isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigenic antibody The composite fragment contains humanized HC2 and humanized LC2.

[0087] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti The proto-binding fragment is an IgG1, IgG2, IgG3, or IgG4 isotype. In certain embodiments, the bispecific antibody is an IgG4 isotype.

[0088] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti The original binding fragment has an EC of less than approximately 500 pM. 50 In vitro, cancer cells γδ It induces T cell-dependent cell-mediated cytotoxicity.

[0089] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti The original binding fragment has an EC of less than approximately 300 pM. 50 In vitro, cancer cells γδ It induces T cell-dependent cell-mediated cytotoxicity.

[0090] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti The original binding fragment has an EC of less than approximately 160 pM. 50 In vitro, cancer cells γδ It induces T cell-dependent cell-mediated cytotoxicity.

[0091] In one embodiment, EC 50 This refers to γδ T effector cells and Kasumi3 AML It is evaluated using a mixture of target cells.

[0092] In another embodiment, the effector cell to target cell ratio is approximately 0.01:1 to approximately 5:1. be.

[0093] In yet another embodiment, the effector cell to target cell ratio is approximately 0.1:1 to approximately 2:1 That is the case.

[0094] In certain embodiments, the ratio of effector cells to target cells is approximately 1:1.

[0095] Furthermore, the isolated anti-TRGV9 / anti-CD123 bispecific antibody provided herein or A method for producing the antigen-binding fragment is provided herein, and the method is bispecific. Under conditions that produce antibodies or their antigen-binding fragments, anti-TRGV9 / anti-CD123 To culture cells containing a bispecific antibody or nucleic acid encoding its antigen-binding fragment. This includes recovering a bispecific antibody or its antigen-binding fragment.

[0096] In another embodiment, an isolated TRGV9 bispecific antibody or its antigen epitope-conjugated filament The component provided herein is an isolated TRGV9 bispecific antibody or its antigen epithelium. The tope-binding fragment has a binding site for the first antigen and a binding site for the second antigen. The binding site for the first antigen is located at the TRGV9 epitope on γδ T cells. The binding site for the second antigen is located on the epitope of the second antigen on the surface of the target cell. It binds to the TRGV9 epitope on γδ T cells and to the second antigen epitope on target cells. Tope binding leads to the death of target cells.

[0097] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 3, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively, or iv. Each contains the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. Including HCDR1, HCDR2, and HCDR3, LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. LCDR1, LCDR2, and LCDR2 form a binding site for the first antigen. Thus, HC2 and LC2 form binding sites for the second antigen epitope. In the application form, the TRGV9 bispecific antibody or antigen-binding fragment is sequence number 7, sequence number 7. For amino acid sequences selected from sequence number 34, sequence number 35, or sequence number 36, less Both contain HC1, which has an amino acid sequence with 95% identity, and LC1 is the same as in SEQ ID NO: 8 It contains an amino acid sequence that has at least 95% identity with the amino acid sequence. In terms of form, the TRGV9 bispecific antibody or antigen-binding fragment is sequence number 7, sequence number Contains HC1 with an amino acid sequence selected from No. 34, SEQ ID NO: 35, or SEQ ID NO: 36. Furthermore, LC1 contains the amino acid sequence of SEQ ID NO: 8.

[0098] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In connection therewith, HC2 is related to LC2, and HC1 is related to Sequence ID 1, Sequence ID 2, and respectively. It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence of SEQ ID NO: 3, L C1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. DR1, LCDR2, and LCDR2 together form a binding site for the first antigen. HC2 and LC2 form binding sites for the second antigen epitope. Another implementation In this state, the TRGV9 bispecific antibody or antigen-binding fragment is the amino acid of SEQ ID NO: 7 It contains HC1 which has an amino acid sequence having at least 95% identity with the sequence, and LC 1 is an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. Includes a column. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is HC1 contains the amino acid sequence of SEQ ID NO: 7, and LC1 contains the amino acid sequence of SEQ ID NO: 8 include.

[0099] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In connection therewith, HC2 is related to LC2, and HC1 is related to Sequence ID 1, Sequence ID 2, and respectively. It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence of SEQ ID NO: 31. LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. CDR1, LCDR2, and LCDR2 together form a binding site for the first antigen. Furthermore, HC2 and LC2 form binding sites for the second antigen epitope. Another implementation Morphologically, the TRGV9 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO: 34. It contains HC1 having an amino acid sequence that has at least 95% identity with the no-acid sequence, LC1 is an amino acid that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. Contains an acid sequence. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment. HC1 contains the amino acid sequence of SEQ ID NO: 34, and LC1 contains the amino acid sequence of SEQ ID NO: 8 Includes arrays.

[0100] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In connection therewith, HC2 is related to LC2, and HC1 is related to Sequence ID 1, Sequence ID 2, and respectively. It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence of SEQ ID NO: 32. LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. CDR1, LCDR2, and LCDR2 together form a binding site for the first antigen. Furthermore, HC2 and LC2 form binding sites for the second antigen epitope. Another implementation Morphologically, the TRGV9 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO: 35. It contains HC1 having an amino acid sequence that has at least 95% identity with the no-acid sequence, LC1 is an amino acid that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. Contains an acid sequence. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment. HC1 contains the amino acid sequence of SEQ ID NO: 35, and LC1 contains the amino acid sequence of SEQ ID NO: 8 Includes arrays.

[0101] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In connection therewith, HC2 is related to LC2, and HC1 is related to Sequence ID 1, Sequence ID 2, and respectively. It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence of SEQ ID NO: 33. LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. CDR1, LCDR2, and LCDR2 together form a binding site for the first antigen. Furthermore, HC2 and LC2 form binding sites for the second antigen epitope. Another implementation Morphologically, the TRGV9 bispecific antibody or antigen-binding fragment is the amine of SEQ ID NO: 36. It contains HC1 having an amino acid sequence that has at least 95% identity with the no-acid sequence, LC1 is an amino acid that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. Contains an acid sequence. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment. HC1 contains the amino acid sequence of SEQ ID NO: 36, and LC1 contains the amino acid sequence of SEQ ID NO: 8 Includes arrays.

[0102] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC1 is related to Sequence ID 1, Sequence ID 76, and It contains HCDR1, HCDR2, and HCDR3, which include the amino acid sequence of SEQ ID NO: 3. LC1 contains the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. LCDR1, LCDR2, and LCDR2 form a binding site for the first antigen. Thus, HC2 and LC2 form binding sites for the second antigen epitope. In the application form, the TRGV9 bispecific antibody or antigen-binding fragment is the A of SEQ ID NO: 65 It contains HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence. LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 66. Contains a mino acid sequence. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment The nucleotide contains HC1 containing the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66 Contains a mino acid sequence. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment The amino acid has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. It contains HC1 containing an acid sequence, and LC1 has at least the amino acid sequence of SEQ ID NO: 68 It contains amino acid sequences with 95% identity. In another embodiment, TRGV9 bispecificity. The antibody or antigen-binding fragment contains HC1 with the amino acid sequence of SEQ ID NO: 67, L C1 contains the amino acid sequence of SEQ ID NO: 68.

[0103] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC1 is related to sequence numbers 60 and 61, respectively. and HCDR1, HCDR2, and HCDR3 containing the amino acid sequence of SEQ ID NO: 62 LC1 is the amino acid sequence of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively. LCDR1, LCDR2, and an LCDR2 comprising a binding site for the first antigen Forming a binding site, HC2 and LC2 form a binding site for the second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is SEQ ID NO. 6 HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence of 5 LC1 contains at least 95% identity with the amino acid sequence of SEQ ID NO: 66. It includes an amino acid sequence. In another embodiment, a TRGV9 bispecific antibody or antigen-binding antibody Ragment contains HC1 containing the amino acid sequence of SEQ ID NO: 65, and LC1 contains SEQ ID NO: 6 It contains a sequence of 6 amino acids. In another embodiment, a TRGV9 bispecific antibody or antigen-binding antibody Ragment has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. It contains HC1 which includes the amino acid sequence, and LC1 is less than the amino acid sequence of SEQ ID NO: 68. It contains amino acid sequences with at least 95% identity. In another embodiment, TRGV9 duplex The specific antibody or antigen-binding fragment contains HC1 with the amino acid sequence of SEQ ID NO: 67. Furthermore, LC1 contains the amino acid sequence of SEQ ID NO: 68.

[0104] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC1 is related to sequence numbers 89 and 90, respectively. and HCDR1, HCDR2, and HCDR3 containing the amino acid sequence of SEQ ID NO: 91 LC1 is the amino acid combination of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively. LCDR1, LCDR2, and LCDR2, including the column, binding to the first antigen. HC2 and LC2 form binding sites for a second antigenic epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is SEQ ID NO: HC containing an amino acid sequence that has at least 95% identity with 95 amino acid sequences Including 1, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 96 It contains an amino acid sequence. In another embodiment, it is a TRGV9 bispecific antibody or antigen-binding agent. The fragment contains HC1, which has the amino acid sequence of SEQ ID NO: 95, and LC1, which has the amino acid sequence of SEQ ID NO: 95. It contains a sequence of 96 amino acids.

[0105] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC1 is related to sequence numbers 98 and 99, respectively. and HCDR1, HCDR2, and HCDR3 containing the amino acid sequence of SEQ ID NO: 100 Including LC1, the following are the sequences 101, 102, and 103, respectively. LCDR1 and LCDR2 containing the mino acid sequence, and LCDR2 containing the first antigen HC2 and LC2 form binding sites for the second antigen epitope. Forms. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is An amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104 It contains HC1, and LC1 contains at least 95 amino acids relative to the amino acid sequence of SEQ ID NO: 105. It contains an amino acid sequence having % identity. In another embodiment, a TRGV9 bispecific antibody Alternatively, the antigen-binding fragment contains HC1 containing the amino acid sequence of SEQ ID NO: 104, and LC 1 contains the amino acid sequence of SEQ ID NO: 105.

[0106] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC2 is related to LC2, and HC1 is related to sequence number 107 and sequence number 10, respectively. HCDR1, HCDR2, and HCDR 8, which include the amino acid sequence of SEQ ID NO: 109 Including 3, LC1 includes sequence numbers 110, 111, and 112, respectively. LCDR1, LCDR2, and the first antigen, which include the amino acid sequence of LCDR2. HC2 and LC2 form binding sites for the second antigen epitope. Forms a position. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment is used. This refers to an amino acid that has at least 95% identity with the amino acid sequence of SEQ ID NO: 113. The HC1 contains the sequence, and the LC1 has at least the amino acid sequence of SEQ ID NO: 114 It contains amino acid sequences with 95% identity. In another embodiment, TRGV9 bispecificity. The antibody or antigen-binding fragment contains HC1 having the amino acid sequence of SEQ ID NO: 113. LC1 contains the amino acid sequence of SEQ ID NO: 114.

[0107] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC2 is related to LC2, and HC1 is related to sequence number 117 and sequence number 11, respectively. HCDR1, HCDR2, and HCDR 8, which include the amino acid sequence of SEQ ID NO: 119 Including 3, LC1 is sequence number 120, sequence number 121, and sequence number 122, respectively. LCDR1, LCDR2, and the first antigen, which include the amino acid sequence of LCDR2. HC2 and LC2 form binding sites for the second antigen epitope. Forms a position. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment is used. This refers to an amino acid that has at least 95% identity with the amino acid sequence of SEQ ID NO: 123. The HC1 contains the sequence, and the LC1 has at least the amino acid sequence of SEQ ID NO: 124 It contains amino acid sequences with 95% identity. In another embodiment, TRGV9 bispecificity. The antibody or antigen-binding fragment contains HC1 having the amino acid sequence of SEQ ID NO: 123. LC1 contains the amino acid sequence of SEQ ID NO: 124.

[0108] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is (a)HC (b)HC2, (c)LC1, and (d)LC2, wherein HC1 is related to LC1. In relation to HC2, HC1 is related to sequence number 127 and sequence number 127, respectively. HCDR1, HCDR2, and HCDR 8, which include the amino acid sequence of SEQ ID NO: 129 Including 3, LC1 includes sequence numbers 130, 131, and 132, respectively. LCDR1, LCDR2, and the first antigen, which include the amino acid sequence of LCDR2. HC2 and LC2 form binding sites for the second antigen epitope. Forms a position. In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment is used. This refers to an amino acid that has at least 95% identity with the amino acid sequence of SEQ ID NO: 133. The HC1 contains the sequence, and the LC1 has at least the amino acid sequence of SEQ ID NO: 134 It contains amino acid sequences with 95% identity. In another embodiment, TRGV9 bispecificity. The antibody or antigen-binding fragment contains HC1 having the amino acid sequence of SEQ ID NO: 133. LC1 contains the amino acid sequence of SEQ ID NO: 134.

[0109] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is humanized H Includes C1 and humanized LC.

[0110] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is CD12 It binds to three epitopes.

[0111] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is SEQ ID NO: HC containing an amino acid sequence that has at least 95% identity with 15 amino acid sequences 2, and LC2 has at least 95% identity to the amino acid sequence of SEQ ID NO: 16 comprises the amino acid sequence having the identity described above.

[0112] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises SEQ ID NO HC2 comprising the amino acid sequence of 15, and LC2 comprises the amino acid sequence of SEQ ID NO: 16 .

[0113] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is of the Ig G1, IgG2, and IgG3, or IgG4 isotype. In certain embodiments , the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isoty pe.

[0114] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 5 00 pM 50 to induce γδ T cell-dependent cytotoxicity of cancer cells in vitro .

[0115] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 3 00 pM 50 to induce γδ T cell-dependent cytotoxicity of cancer cells in vitro .

[0116] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 1 60 pM 50 to induce γδ T cell-dependent cytotoxicity of cancer cells in vitro .

[0117] In one embodiment, the EC 50 is determined using γδ T effector cells and Kasumi3 AML It is evaluated using a mixture of target cells.

[0118] In another embodiment, the effector cell to target cell ratio is approximately 0.01:1 to approximately 5:1. In another embodiment, the effector cell to target cell ratio is approximately 0.1:1 to approximately 2:1. In certain embodiments, the ratio of effector cells to target cells is approximately 1:1.

[0119] Furthermore, isolated γδ T cell bispecific antibodies or their antigen-binding fragments are provided. The isolated γδ T cell bispecific antibody or its antigen-binding fragment is the first antibody It includes a binding site for the primary epitope and a binding site for the second antigen epitope, The binding site for antigen epitope 1 binds to the first antigen on the γδ T cell, and the second The binding site for the antigen epitope binds to the epitope of a second antigen on the surface of the target cell. and binding of the first antigen epitope on γδ T cells and the second antigen epitope on target cells The binding of the substance leads to the death of target cells.

[0120] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment is, a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 3, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively, or iv. Each contains the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. Including HCDR1, HCDR2, and HCDR3, LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. LCDR1, LCDR2, and LCDR2 form a binding site for the first antigen. Thus, HC2 and LC2 form binding sites for the second antigen. In one embodiment, The isolated nucleic acid is selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36. HC1 containing an amino acid sequence that has at least 95% identity with the amino acid sequence It encodes a TRGV9 bispecific antibody, and LC1 is compared to the amino acid sequence of SEQ ID NO: 8. and containing an amino acid sequence having at least 95% identity. In another embodiment, isolated nucleic acid The amino acid is selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36. The TRGV9 bispecific antibody containing HC1 with an acid sequence is encoded, and LC1 is sequence number 8. It contains the amino acid sequence.

[0121] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCDR2, containing the amino acid sequences of sequence number 1, sequence number 2, and sequence number 3, and HCDR3, LC1 is sequence number 4, sequence number 5, and sequence number 4, respectively. LCDR1, LCDR2, and a first anti- HC2 and LC2 form binding sites for the first antigen and then form binding sites for the second antigen. In one embodiment, the isolated nucleic acid is at least 95% relative to the amino acid sequence of SEQ ID NO: 7. Encodes a TRGV9 bispecific antibody containing HC1 with an amino acid sequence having % identity. Furthermore, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. It contains an amino acid sequence. In another embodiment, the isolated nucleic acid contains the amino acid sequence of SEQ ID NO: 7. The TRGV9 bispecific antibody containing C1 encodes LC1, and LC1 is the amino acid sequence of SEQ ID NO: 8. Includes.

[0122] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCDR2, containing the amino acid sequences of sequence number 1, sequence number 2, and sequence number 31. , and HCDR3, LC1 is sequence number 4, sequence number 5, and sequence number, respectively. LCDR1, LCDR2, and LCDR2, which contain the amino acid sequence of No. 6, HC2 and LC2 form binding sites for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO: 34. A TRGV9 bispecific antibody containing HC1 with an amino acid sequence having 95% identity was used. Furthermore, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. It contains the amino acid sequence of SEQ ID NO: 34. In another embodiment, the isolated nucleic acid contains the amino acid sequence of SEQ ID NO: 34. It encodes a TRGV9 bispecific antibody containing HC1, and LC1 is the amino acid of SEQ ID NO: 8. Contains acid sequences.

[0123] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCDR2, containing the amino acid sequences of sequence number 1, sequence number 2, and sequence number 32. , and HCDR3, LC1 is sequence number 4, sequence number 5, and sequence number, respectively. LCDR1, LCDR2, and LCDR2, which contain the amino acid sequence of No. 6, HC2 and LC2 form binding sites for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO: 35. A TRGV9 bispecific antibody containing HC1 with an amino acid sequence having 95% identity was used. Furthermore, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. It contains the amino acid sequence of SEQ ID NO: 35. In another embodiment, the isolated nucleic acid contains the amino acid sequence of SEQ ID NO: 35. It encodes a TRGV9 bispecific antibody containing HC1, and LC1 is the amino acid of SEQ ID NO: 8. Contains acid sequences.

[0124] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCDR2, containing the amino acid sequences of sequence number 1, sequence number 2, and sequence number 33. , and HCDR3, LC1 is sequence number 4, sequence number 5, and sequence number, respectively. LCDR1, LCDR2, and LCDR2, which contain the amino acid sequence of No. 6, HC2 and LC2 form binding sites for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO: 36. A TRGV9 bispecific antibody containing HC1 with an amino acid sequence having 95% identity was used. Furthermore, LC1 has at least 95% identity with the amino acid sequence of SEQ ID NO: 8. It contains the amino acid sequence of SEQ ID NO: 36. In another embodiment, the isolated nucleic acid contains the amino acid sequence of SEQ ID NO: 36. It encodes a TRGV9 bispecific antibody containing HC1, and LC1 is the amino acid of SEQ ID NO: 8. Contains acid sequences.

[0125] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCDR2 containing the amino acid sequences of sequence number 1, sequence number 76, and sequence number 3. , and HCDR3, LC1 is sequence number 77, sequence number 5, and sequence number LCDR1, LCDR2, and LCDR2, which contain amino acid sequence number 6, HC2 and LC2 form binding sites for the second antigen. To form. In one embodiment, the isolated nucleic acid is at least the amino acid sequence of SEQ ID NO: 65 A TRGV9 bispecific antibody containing HC1, which has an amino acid sequence with 95% identity, The coded LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 66. It contains the amino acid sequence of SEQ ID NO: 65. In another embodiment, the isolated nucleic acid contains the amino acid sequence of SEQ ID NO: 65. The column encodes a TRGV9 bispecific antibody containing HC1, and LC1 is sequence number 66. It contains an amino acid sequence. In one embodiment, the isolated nucleic acid has an amino acid sequence of SEQ ID NO: 67 TRGV9 dual features containing HC1, which has at least 95% identity with the amino acid sequence. Encoding an isogammagenic antibody, LC1 is at least 95% of the amino acid sequence of SEQ ID NO: 68. It contains an amino acid sequence having the same identity as SEQ ID NO: 67. In another embodiment, the isolated nucleic acid is the same as SEQ ID NO: 67. The TRGV9 bispecific antibody containing HC1, which contains the amino acid sequence, encodes LC1, which contains the sequence It contains amino acid sequence number 68.

[0126] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCD containing the amino acid sequences of sequence number 60, sequence number 61, and sequence number 62 R2 and HCDR3 are included, and LC1 is sequence number 63, sequence number 64, and LCDR1, LCDR2, and LCDR2 containing the amino acid sequence of SEQ ID NO: 6 , forming a binding site for the first antigen, HC2 and LC2 bind to the second antigen. It forms a site. In one embodiment, the isolated nucleic acid is slightly different from the amino acid sequence of SEQ ID NO: 65. TRGV9 bispecificity containing HC1, which has at least 95% identical amino acid sequences. The antibody is encoded, and LC1 is at least 95% identical to the amino acid sequence of SEQ ID NO: 66. It contains a monogenetic amino acid sequence. In another embodiment, the isolated nucleic acid is the amino acid sequence of SEQ ID NO. 65. The TRGV9 bispecific antibody containing HC1 with an acid sequence is encoded, and LC1 is sequence number It contains a sequence of 66 amino acids. In one embodiment, the isolated nucleic acid is the amino acid sequence of SEQ ID NO: 67. TRGV9 containing HC1, which has at least 95% identity with the amino acid sequence of the same amino acid sequence as the above. Encoding a bispecific antibody, LC1 has at least the amino acid sequence of SEQ ID NO: 68 It contains an amino acid sequence with 95% identity. In another embodiment, the isolated nucleic acid is the sequence number. The TRGV9 bispecific antibody containing HC1 with a 67-amino acid sequence is encoded, and LC1 is It contains the amino acid sequence of SEQ ID NO: 68.

[0127] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HCD containing the amino acid sequences of sequence number 89, SEQ ID NO: 90, and SEQ ID NO: 91 R2 and HCDR3 are included, and LC1 is sequence number 92, sequence number 93, and LCDR1, LCDR2, and LCDR2 containing the amino acid sequence of sequence number 94 Then, HC2 and LC2 form a binding site for the first antigen, and then bind to the second antigen. It forms a mating site. In one embodiment, the isolated nucleic acid is relative to the amino acid sequence of SEQ ID NO: 95 TRGV9 bispecificity containing HC1 with amino acid sequences having at least 95% identity Encoding a sex antibody, LC1 is at least 95% of the amino acid sequence of SEQ ID NO: 96 It contains an amino acid sequence that is identical. In another embodiment, the isolated nucleic acid is the amino acid sequence of SEQ ID NO: 95 The TRGV9 bispecific antibody containing HC1, which contains the minoic acid sequence, encodes LC1, which is the sequence number. Contains amino acid sequence number 96.

[0128] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1, HC, containing the amino acid sequences of sequence number 98, sequence number 99, and sequence number 100 DR2 and HCDR3 are included, and LC1 is sequence number 101 and sequence number 10, respectively. 2, and LCDR1, LCDR2, and LCDR containing the amino acid sequence of SEQ ID NO: 103 Including 2, it forms a binding site for the first antigen, and HC2 and LC2 bind to the second antigen. It forms a binding site for the opposite. In one embodiment, the isolated nucleic acid is the amino acid sequence of SEQ ID NO: 104 TRGV containing HC1 with an amino acid sequence having at least 95% identity with respect to the column 9. Encoding a bispecific antibody, LC1 has less amino acid sequence than SEQ ID NO: 105. Both contain amino acid sequences with 95% identity. In another embodiment, the isolated nucleic acid is sequence Encodes a TRGV9 bispecific antibody containing HC1 with amino acid sequence number 104, L C1 contains the amino acid sequence of SEQ ID NO: 105.

[0129] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1 containing the amino acid sequences of sequence number 107, sequence number 108, and sequence number 109, HCDR2 and HCDR3 are included, and LC1 is sequence number 110, sequence number 110, respectively. LCDR1, LCDR2, and LC, which include the amino acid sequences of 111 and SEQ ID NO: 112. Including DR2, it forms a binding site for the first antigen, and HC2 and LC2 are the second antigen It forms a binding site to the source. In one embodiment, the isolated nucleic acid is the amino acid of SEQ ID NO: 113. TR containing HC1, which has an amino acid sequence with at least 95% identity to the acid sequence. The GV9 bispecific antibody encodes LC1, which has a small amino acid sequence relative to the sequence of SEQ ID NO: 114. It contains an amino acid sequence with at least 95% identity. In another embodiment, the isolated nucleic acid is This encodes a TRGV9 bispecific antibody containing HC1, which contains the amino acid sequence of SEQ ID NO: 113. LC1 contains the amino acid sequence of SEQ ID NO: 114.

[0130] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1 containing the amino acid sequences of sequence number 117, sequence number 118, and sequence number 119, HCDR2 and HCDR3 are included, and LC1 is sequence number 120, sequence number 120, respectively. LCDR1, LCDR2, and LC, which include the amino acid sequences of 121 and SEQ ID NO: 122. Including DR2, it forms a binding site for the first antigen, and HC2 and LC2 are the second antigen It forms a binding site to the source. In one embodiment, the isolated nucleic acid is the amino acid of SEQ ID NO: 123. TR containing HC1, which has an amino acid sequence with at least 95% identity to the acid sequence. The GV9 bispecific antibody encodes LC1, which has a small amino acid sequence relative to SEQ ID NO: 124. It contains an amino acid sequence with at least 95% identity. In another embodiment, the isolated nucleic acid is This encodes a TRGV9 bispecific antibody containing HC1 with the amino acid sequence of SEQ ID NO: 123. LC1 contains the amino acid sequence of SEQ ID NO: 124.

[0131] In another embodiment, the encoding of a TRGV9 bispecific antibody or its antigen-binding fragment is provided. Isolated nucleic acids are provided herein, along with isolated TRGV9 bispecific antibodies or their antigen-conjugates. The fragment consists of (a) HC1, (b) HC2, (c) LC1, and (d) LC2. Including, HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to each other. HCDR1 containing the amino acid sequences of sequence number 127, sequence number 128, and sequence number 129, HCDR2 and HCDR3 are included, and LC1 is sequence number 130, sequence number 130, respectively. LCDR1, LCDR2, and LC, which include the amino acid sequences of 131 and SEQ ID NO: 132. Including DR2, it forms a binding site for the first antigen, and HC2 and LC2 are the second antigen It forms a binding site to the source. In one embodiment, the isolated nucleic acid is the amino acid of SEQ ID NO: 133. TR containing HC1, which has an amino acid sequence with at least 95% identity to the acid sequence. The GV9 bispecific antibody encodes LC1, which has a small amino acid sequence relative to SEQ ID NO: 134. It contains an amino acid sequence with at least 95% identity. In another embodiment, the isolated nucleic acid is This encodes a TRGV9 bispecific antibody containing HC1, which contains the amino acid sequence of SEQ ID NO: 133. LC1 contains the amino acid sequence of SEQ ID NO: 134.

[0132] In another embodiment, the isolated nucleic acid is a first antigen that binds to TRGV9 on γδ T cells. This encodes a TRGV9 bispecific antibody that includes the binding site.

[0133] In another embodiment, the isolated nucleic acid is a second antibody that binds to cancer antigens present on the surface of cancer cells. This encodes a TRGV9 bispecific antibody that includes a binding site to the source.

[0134] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody against γδ T cells. The binding of bispecific antibodies to TRGV9 present on the surface, and the presence of on the surface of cancer cells The binding of cancer antigens to these cells leads to the death of cancer cells.

[0135] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and HC1 and L C1 has been humanized.

[0136] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and HC2 and L C2 is coupled to CD123.

[0137] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragment is IgG1, IgG2, IgG3, or IgG4. It is a sotype.

[0138] In certain embodiments, the bispecific antibody or its antigen-binding fragment is IgG4 I It is a sotype.

[0139] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragments have an EC of less than approximately 500 pM. 50 In vitro It induces γδ T cell-dependent cytotoxicity in cancer cells.

[0140] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragments have an EC of less than approximately 300 pM. 50 In vitro It induces γδ T cell-dependent cytotoxicity in cancer cells.

[0141] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragments have an EC of less than approximately 160 pM. 50 In vitro It induces γδ T cell-dependent cytotoxicity in cancer cells.

[0142] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and EC 50 teeth, Evaluation is performed using a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0143] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and an effector The cell-to-target cell ratio is approximately 0.01:1 to approximately 5:1. In one embodiment, the effector - The cell-to-target cell ratio is approximately 0.1:1 to approximately 2:1. In yet another embodiment, F The ratio of factor cells to target cells is approximately 1:1.

[0144] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragments are polyvalent.

[0145] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragment can bind to at least three antigens.

[0146] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody The body or its antigen-binding fragment can bind to at least five antigens.

[0147] Furthermore, a vector containing the isolated nucleic acid provided herein is also provided.

[0148] Furthermore, host cells containing the vectors provided herein are also provided.

[0149] Furthermore, a kit is provided which includes the vectors and packaging for them. To be served.

[0150] A pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 dual-type Heterogender antibodies or their antigen-binding fragments, a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 3, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively, or iv. Each contains the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. Including HCDR1, HCDR2, and HCDR3, LC1 contains the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. LCDR1, LCDR2, and LCDR2 form a binding site for the first antigen. The isolated TRG consists of HC2 and LC2, which form a binding site for the second antigen. V9 bispecific antibody or its antigen-binding fragment, (B) A pharmaceutically acceptable carrier, comprising: In one embodiment, the pharmaceutical composition is: 7. For an amino acid sequence selected from SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 HC1 containing an amino acid sequence having at least 95% identity, and the amino acid sequence of SEQ ID NO: 8 LC1 includes an amino acid sequence having at least 95% identity with the acid sequence, Contains bispecific antibodies. In another embodiment, the pharmaceutical composition contains SEQ ID NO: 7, SEQ ID NO: 34, HC1 containing an amino acid sequence selected from SEQ ID NO: 35 or SEQ ID NO: 36, and SEQ ID NO: It contains a bispecific antibody containing LC1, which has an 8-amino acid sequence.

[0151] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 is the amino acid of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. It contains HCDR1, HCDR2, and HCDR3, which have acid sequences, and LC1 is, LCDR1, LCDR2, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. , and also containing LCDR2, which forms a binding site for the first antigen, and HC2 and LC2 However, an isolated TRGV9 bispecific antibody or that forms a binding site for the second antigen. The antigen-binding fragment comprises (B) a pharmaceutically acceptable carrier. In one embodiment, The pharmaceutical composition has at least 95% identity with the amino acid sequence of SEQ ID NO: 7. HC1 containing the amino acid sequence and at least 95% of the amino acid sequence of SEQ ID NO: 8 A bispecific antibody comprising LC1 containing a monogenetic amino acid sequence. Another embodiment The pharmaceutical composition contains HC1 with the amino acid sequence of SEQ ID NO: 7 and the amino acid sequence of SEQ ID NO: 8. It contains a bispecific antibody containing LC1 containing the sequence.

[0152] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to the amicin of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. It contains HCDR1, HCDR2, and HCDR3, which have no acid sequences, and LC1 is, LCDR1, LCDR, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. 2, and including LCDR2, a binding site for the first antigen is formed, and HC2 and LC 2 is an isolated TRGV9 bispecific antibody that forms a binding site for the second antigen. (B) comprises the antigen-binding fragment and a pharmaceutically acceptable carrier. In one embodiment, The pharmaceutical composition has at least 95% identity with the amino acid sequence of SEQ ID NO: 34. HC1 containing the amino acid sequence and at least 95% of the amino acid sequence of SEQ ID NO: 8 A bispecific antibody comprising LC1 containing an amino acid sequence having the same identity. In terms of form, the pharmaceutical composition contains HC1 containing the amino acid sequence of SEQ ID NO: 34 and the amino acid sequence of SEQ ID NO: 8. It contains a bispecific antibody that includes LC1 containing a mino acid sequence.

[0153] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to the EMI of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. It contains HCDR1, HCDR2, and HCDR3, which have no acid sequences, and LC1 is, LCDR1, LCDR, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. 2, and including LCDR2, a binding site for the first antigen is formed, and HC2 and LC 2 is an isolated TRGV9 bispecific antibody that forms a binding site for the second antigen. (B) comprises the antigen-binding fragment and a pharmaceutically acceptable carrier. In one embodiment, The pharmaceutical composition has at least 95% identity with the amino acid sequence of SEQ ID NO: 35. HC1 containing the amino acid sequence and at least 95% of the amino acid sequence of SEQ ID NO: 8 A bispecific antibody comprising LC1 containing an amino acid sequence having the same identity. In terms of form, the pharmaceutical composition contains HC1 containing the amino acid sequence of SEQ ID NO: 35 and the amino acid sequence of SEQ ID NO: 8. It contains a bispecific antibody that includes LC1 containing a mino acid sequence.

[0154] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to the amicin of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. It contains HCDR1, HCDR2, and HCDR3, which have no acid sequences, and LC1 is, LCDR1, LCDR, containing the amino acid sequences of SEQ ID NOs. 4, 5, and 6. 2, and including LCDR2, a binding site for the first antigen is formed, and HC2 and LC 2 is an isolated TRGV9 bispecific antibody that forms a binding site for the second antigen. (B) comprises the antigen-binding fragment and a pharmaceutically acceptable carrier. In one embodiment, The pharmaceutical composition has at least 95% identity with the amino acid sequence of SEQ ID NO: 36. HC1 containing the amino acid sequence and at least 95% of the amino acid sequence of SEQ ID NO: 8 A bispecific antibody comprising LC1 containing an amino acid sequence having the same identity. In terms of form, the pharmaceutical composition comprises HC1 containing the amino acid sequence of SEQ ID NO: 36 and the amino acid sequence of SEQ ID NO: 8. It contains a bispecific antibody that includes LC1 containing a mino acid sequence.

[0155] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to the IAM of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. It contains HCDR1, HCDR2, and HCDR3, which have no acid sequences, and LC1 is, LCDR1, LCD, containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6 R2 and LCDR2 are included to form a binding site for the first antigen, and HC2 and L Isolated TRGV9 bispecific antibody, where C2 forms the binding site for the second antigen. Or comprising the antigen-binding fragment and (B) a pharmaceutically acceptable carrier. One embodiment Therefore, the pharmaceutical composition has at least 95% identity with respect to the amino acid sequence of SEQ ID NO: 65. HC1 containing the amino acid sequence and at least 9 of the amino acid sequence of SEQ ID NO: 66 It contains a bispecific antibody containing LC1, which has an amino acid sequence with 5% identity. In this embodiment, the pharmaceutical composition comprises HC1 containing the amino acid sequence of SEQ ID NO: 65 and SEQ ID NO: 6 The present invention includes a bispecific antibody comprising LC1 containing an amino acid sequence of 6. In one embodiment, the present invention is a pharmaceutical The composition has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. HC1 containing an acid sequence is at least 95% identical to the amino acid sequence of SEQ ID NO. 68. The present invention comprises a bispecific antibody comprising LC1 containing an amino acid sequence having a property. The pharmaceutical composition contains HC1 containing the amino acid sequence of SEQ ID NO: 67 and amino acid sequence of SEQ ID NO: 68. It contains a bispecific antibody that includes LC1 containing an acid sequence.

[0156] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to sequence numbers 60, 61, and 62, respectively. It contains HCDR1, HCDR2, and HCDR3, which have amino acid sequences, and LC1 is LCDR1 containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, Including LCDR2 and LCDR2, it forms a binding site for the first antigen, and HC2 And LC2 forms a binding site for the second antigen, isolated TRGV9 bispecific (B) A sex antibody or its antigen-binding fragment, and (B) a pharmaceutically acceptable carrier. In the application form, the pharmaceutical composition contains at least 95% of the amino acid sequence of SEQ ID NO: 65. HC1 contains a monogenetic amino acid sequence, and less than the amino acid sequence of SEQ ID NO: 66. The product contains a bispecific antibody that includes LC1, which has an amino acid sequence with 95% identity. In another embodiment, the pharmaceutical composition comprises HC1 containing the amino acid sequence of SEQ ID NO: 65, and sequence The present embodiment includes a bispecific antibody containing LC1 containing amino acid sequence number 66. The pharmaceutical composition has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. HC1 containing the amino acid sequence and at least 95% of the amino acid sequence of SEQ ID NO: 68 A bispecific antibody comprising LC1 containing an amino acid sequence having the same identity. In form, the pharmaceutical composition comprises HC1 containing the amino acid sequence of SEQ ID NO: 67 and SEQ ID NO: 68 It contains a bispecific antibody that includes LC1 containing an amino acid sequence.

[0157] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to sequence numbers 89, 90, and 91, respectively. It contains HCDR1, HCDR2, and HCDR3, which have amino acid sequences, and LC1 is These include the amino acid sequences of SEQ ID NOs. 92, 93, and 94, respectively, in LCDR1 , LCDR2, and an HC comprising LCDR2 to form a binding site for the first antigen, Isolated TRGV9 bivalent, where 2 and LC2 form the binding site for the second antigen. (B) A pharmaceutically acceptable carrier comprises an isoantibody or its antigen-binding fragment. In this embodiment, the pharmaceutical composition contains at least 95% of the amino acid sequence of SEQ ID NO: 95 HC1 containing an identical amino acid sequence and less than the amino acid sequence of SEQ ID NO: 96 A bispecific antibody containing LC1, which has an amino acid sequence with at least 95% identity. In another embodiment, the pharmaceutical composition comprises HC1 containing the amino acid sequence of SEQ ID NO: 95, and The present invention contains a bispecific antibody that includes LC1 containing the amino acid sequence of column number 96.

[0158] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to sequence numbers 98, 99, and 100, respectively. It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence, and LC1 is Each contains the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103. CDR1, LCDR2, and LCDR2 together form a binding site for the first antigen. In isolated TRGV, HC2 and LC2 form binding sites for the second antigen. 9. A bispecific antibody or its antigen-binding fragment and (B) a pharmaceutically acceptable carrier Includes. In one embodiment, the pharmaceutical composition includes at least the amino acid sequence of SEQ ID NO: 104 HC1, which contains an amino acid sequence with 95% identity, and the amino acid sequence of SEQ ID NO: 105 A dual feature comprising LC1 containing an amino acid sequence having at least 95% identity with respect to It contains heterozygous antibodies. In another embodiment, the pharmaceutical composition contains the amino acid sequence of SEQ ID NO: 104. This contains a bispecific antibody comprising HC1 and LC1 containing the amino acid sequence of SEQ ID NO: 105. nothing.

[0159] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 1, respectively. It contains HCDR1, HCDR2, and HCDR3, which have the amino acid sequence 09, and LC1 is These contain the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. LCDR1, LCDR2, and LCDR2, including the binding site for the first antigen Isolated TRs are formed, in which HC2 and LC2 form binding sites for the second antigen. (B) a pharmaceutically acceptable carrier comprising a GV9 bispecific antibody or its antigen-binding fragment, and (B) a pharmaceutically acceptable carrier. This includes. In one embodiment, the pharmaceutical composition has less than the amino acid sequence of SEQ ID NO: 113 HC1 containing an amino acid sequence with at least 95% identity, and the amino acids of SEQ ID NO: 114 The two include LC1, which contains an amino acid sequence having at least 95% identity with the sequence, Contains a despecific antibody. In another embodiment, the pharmaceutical composition contains the amino acid sequence of SEQ ID NO: 113 A bispecific antibody comprising HC1 containing the amino acid sequence of SEQ ID NO: 114 and LC1 containing the amino acid sequence of SEQ ID NO: 114. Includes.

[0160] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 1 It contains HCDR1, HCDR2, and HCDR3, which have 19 amino acid sequences, and LC1 is These contain the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. LCDR1, LCDR2, and LCDR2, including the binding site for the first antigen Isolated TRs are formed, in which HC2 and LC2 form binding sites for the second antigen. (B) a pharmaceutically acceptable carrier comprising a GV9 bispecific antibody or its antigen-binding fragment, and (B) a pharmaceutically acceptable carrier. This includes. In one embodiment, the pharmaceutical composition has less than the amino acid sequence of SEQ ID NO: 123 HC1, which contains an amino acid sequence with at least 95% identity, and the amino acids of SEQ ID NO: 124 The two include LC1, which contains an amino acid sequence having at least 95% identity with the sequence, Contains a hemispecific antibody. In another embodiment, the pharmaceutical composition contains the amino acid sequence of SEQ ID NO: 123 A bispecific antibody containing HC1 containing the amino acid sequence of SEQ ID NO: 124 Includes.

[0161] Furthermore, a pharmaceutical composition is provided herein, and the pharmaceutical composition comprises (A) isolated TRGV9 A bispecific antibody or its antigen-binding fragment, comprising (a) HC1 and (b) HC2 (c) LC1 and (d) LC2 are included, where HC1 is related to LC1 and HC2 is L In relation to C2, HC1 corresponds to SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 1 It contains HCDR1, HCDR2, and HCDR3, which have 29 amino acid sequences, and LC1 is These contain the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. LCDR1, LCDR2, and LCDR2, including the binding site for the first antigen Isolated TRs are formed, in which HC2 and LC2 form binding sites for the second antigen. (B) a pharmaceutically acceptable carrier comprising a GV9 bispecific antibody or its antigen-binding fragment, and (B) a pharmaceutically acceptable carrier. This includes. In one embodiment, the pharmaceutical composition has less than the amino acid sequence of SEQ ID NO: 133 HC1 containing an amino acid sequence with at least 95% identity, and the amino acids of SEQ ID NO: 134 The two include LC1, which contains an amino acid sequence having at least 95% identity with the sequence, Contains a hemispecific antibody. In another embodiment, the pharmaceutical composition contains the amino acid sequence of SEQ ID NO: 133 A bispecific antibody comprising HC1 containing the amino acid sequence of SEQ ID NO: 134 and LC1 containing the amino acid sequence of SEQ ID NO: 134. Includes.

[0162] In another embodiment, the pharmaceutical composition is a first antigen that binds to TRGV9 on γδ T cells. It contains a bispecific antibody that includes a binding site for [the target of the antibody].

[0163] In another embodiment, the pharmaceutical composition comprises a bispecific antibody and a binding site for a second antigen. The nucleotide binds to cancer antigens present on the surface of cancer cells.

[0164] In another embodiment, the pharmaceutical composition comprises a bispecific antibody present on the surface of γδ T cells. The binding of bispecific antibodies to TRGV9 present, and cancer antigens present on the surface of cancer cells. This binding leads to the death of cancer cells.

[0165] In another embodiment, the pharmaceutical composition comprises bispecific antibodies, wherein HC1 and LC1 are human It has been transformed.

[0166] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein HC2 and LC2 are CD Combine with 123.

[0167] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, and the bispecific antibody or its anti- The proto-binding fragment is an IgG1, IgG2, IgG3, or IgG4 isotype. ru.

[0168] Furthermore, a method is provided for directing Vγ9-expressing γδ T cells to cancer cells, and the method involves Vγ9 The process involves contacting expressed γδ T cells with the pharmaceutical composition provided herein, and Vγ9 cells Contacting current γδ T cells with a pharmaceutical composition allows Vγ9-expressing γδ T cells to be used with cancer cells. To direct towards.

[0169] Furthermore, a method is provided for inhibiting the growth or proliferation of cancer cells that express cancer antigens on their cell surface. The method comprises contacting cancer cells with a pharmaceutical composition provided herein, and the cancer cells Contact with the pharmaceutical composition inhibits the growth or proliferation of cancer cells.

[0170] In one embodiment, cancer cells are subjected to an anti-TRGV9 bispecific antibody or its antigen-binding fragment. While in contact with the T cells, Vγ9-expressing γδ T cells are present.

[0171] Furthermore, methods for providing cancer treatment to those who require it are provided, and these methods are a. Identifying individuals who require cancer treatment, b. Administering the pharmaceutical compositions provided herein to subjects in need thereof, Includes, Administering a pharmaceutical composition to a subject in need of it treats cancer in that subject.

[0172] Furthermore, a method for activating Vγ9-expressing γδ T cells is provided, and the method involves Vγ9-expressing γδ The method involves contacting T cells with the pharmaceutical composition provided herein, and expressing Vγ9 γδ Contacting T cells with a pharmaceutical composition results in a difference compared to control Vγ9-expressing γδ T cells in CD This results in increased expression of 69, CD25, and / or granzyme B.

[0173] Furthermore, a method for producing the pharmaceutical composition provided herein is provided, and the method is dual specific Sex antibodies or their antigen-binding fragments are combined with a pharmaceutically acceptable carrier to form pharmaceuticals. This includes obtaining a composition. [Brief explanation of the drawing]

[0174] The above summary, as well as the following detailed description of specific embodiments of this application, are accompanied by the attached drawings and It will be better understood when read together. However, this application is shown in the drawings. It should be understood that this is not limited to the embodiment itself. [Figure 1] A schematic diagram is shown demonstrating the binding of an anti-TRGV9 / antitumor-associated antigen (TAA) bispecific antibody to recruit γδ T cells to cancer cells and induce cancer cell death. [Figure 2] This graph demonstrates that zoledronic acid selectively increases Vγ9Vδ2 T cells from whole peripheral blood mononuclear cells (PBMCs). [Figure 3A] This shows the phenotypic characterization of Vγ9+γδ T cells. A schematic diagram of the gate used to illustrate γδ T cell differentiation is shown (left). Representative FACS dot plots show the differentiation profiles of Vδ9+γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (right). The number of quadrants reflects the frequency (mean ± SEM) of each population between fresh Vγ9+γδ T cells and activated Vγ9+γδ T cells. The data shown are the mean (± SEM) of 5 donors (n=5) from a single experiment. [Figure 3B] This shows the phenotypic characterization of Vγ9+ γδ T cells. The number of representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+ γδ T cells positive for each activation marker, from either fresh PBMCs (top panel) or PBMCs cultured for 14 days in zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) of 7 donors (n=7) for CD62L, CD69, and CD44 expression data from two independent experiments. n represents 5 donors for NKG2D expression data and 2 donors each for CD45RO and CD71 expression data from a single experiment. [Figure 3C]This shows the phenotypic characterization of Vγ9+γδ T cells. The dot plots show the number of cells beyond the gate, indicating the frequency (mean ± SEM) of Vδ9+γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top panel) or PBMCs cultured for 14 days in zoledronic acid + IL-2 + IL-15 (bottom panel). The data presented herein are the mean (± SEM) from two independent experiments, with 5 donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression, and 7 donors (n=7) for 2B4 and TIM3 surface expression data. [Figure 3D] This shows the phenotypic characterization of Vγ9+ γδ T cells. Representative FACS dot plots demonstrate the frequency (mean ± SEM) of intracellular granzyme B (left column) and perforin (right column) Vδ9+ γδ T cells from fresh PBMCs (top panel) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) of granzyme B and perforin data from 4 (n=4) and 7 (n=7) donors, respectively, from two independent experiments. [Figure 3E] This shows the phenotypic characteristics of Vγ9+ γδ T cells. The bar graphs show the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant at days 0 and 14 of PBMC culture with zoledronic acid + IL-2 + IL-15. The data presented are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 4] The histogram shows that VG1 (an anti-TRGV9 / anti-CD123 bispecific antibody) recruits Vγ9+ T cells, as demonstrated by conjugate formation between γδ T cells and Kasumi-3 cells. [Figure 5A] The graphs demonstrate VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecificity-mediated γδ T cell cytotoxicity against Kasumi-3 cells at different effector-to-target cell ratios (1:1 for Figure 5A). [Figure 5B]The graphs demonstrate VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecificity-mediated γδ T cell cytotoxicity against Kasumi-3 cells at different effector-to-target cell ratios (5:1 for 5B). [Figure 5C] The graphs demonstrate VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecificity-mediated γδ T cell cytotoxicity against Kasumi-3 cells at different effector-to-target cell ratios (10:1 for Figure 5C). [Figure 6A] The graph shows the expression of CD69 (Figure 6A) on Vγ9+γδ T cells, non-Vγ9+γδ T cells, and Pan-T cells (non-γδ T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or without bispecific antibodies. [Figure 6B] The graph (Figure 6B) demonstrates the expression of CD25 on Vγ9+γδ T cells, non-Vγ9+γδ T cells, and Pan-T cells (non-γδ T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or without bispecific antibodies. [Figure 6C] The graph shows the expression of granzyme B (Figure 6C) on Vγ9+γδ T cells, non-Vγ9+γδ T cells, and Pan-T cells (non-γδ T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or without bispecific antibodies. [Figure 7] This study demonstrates selective cell binding of anti-TAA1 (TAA mIgG2a, TAA1B1) to transfected Jurkat cells. The binding EC50 was ~1~2 nM. TAA1B1 endogenously expresses an unrelated protein (TAA1-NULL), but did not show any significant binding to ALL cell lines that do not express TAA1. [Figure 8] This study demonstrates the selective protein binding of anti-TAA1 proteins (TAA1 mIgG2a, TAA1B1) to recombinant TAA1 protein (TAA1W16). TAA1B1 did not show significant binding to an unrelated protein (TAA1-NULL-W16). [Figure 9]This shows the phenotype of Vg9+ cells used in a TAA1×Vγ9 bispecific (TAA1B50) cytotoxicity test from healthy donors. [Figure 10] This report demonstrates that the anti-TRGV9 / anti-TAA1 bispecific antibody mediates γδ T cell cytotoxicity against TAA1-expressing Jurkat cells in vitro. The cytotoxicity values ​​expressed here are calculated by subtracting the baseline cytotoxicity values ​​observed in the absence of the bispecific antibody. EC50 values ​​were calculated as described in the method. Representative data presented herein are from a single experiment. [Figure 11] This study demonstrates bispecific antibody-mediated cytotoxicity. Using enlarged and enriched Vγ9Vδ2 T cells from various donors, cytotoxicity was induced in Jurkat cell lines in the presence of Vγ9×TAA1 at the indicated concentrations (E:T ratio 1:1). The assay was performed for 16 hours. The percentage of target cells killed under various conditions is shown in the figure. [Figure 12] The anti-TRGV9 / anti-TAA2 bispecific antibody (TAA2V9B106(B3)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 13] The anti-TRGV9 / anti-TAA2 bispecific antibody (HC1:VG9B420-LH-scFv;HC2:TAA2-Fab(TAA2V9B71.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 14]The anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P18_D08-Fab RF, TAA2-scFv(TAA2V9B100.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 15] The anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P18_C12-Fab RF, TAA2-scFv(TAA2V9B101.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 16] The anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P19_C03-Fab RF, TAA2-scFv(TAA2V9B103.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Modes for carrying out the invention]

[0175] In the background technology and throughout this specification, various publications, articles, and patents are cited or The full contents of each of these references are incorporated herein by reference. The discussion of documents, operations, materials, devices, articles, etc. included in the details is within the context of the present invention. This is to give an answer. Such considerations are based on the fact that any or all of these things are disclosed or This allows it to constitute part of the prior art to any of the claimed inventions. isn't it.

[0176] Unless otherwise specified, all technical and scientific terms used herein are defined in accordance with the present invention. It has the same meaning as generally understood by those skilled in the art to which it belongs. Otherwise, Certain terms used herein have the meanings set forth herein.

[0177] When used herein and in the appended claims, the singular forms "a", "an", and " It is important to note that "the" can refer to multiple objects unless it is particularly clear from the context. There is.

[0178] Unless otherwise specified, all numerical values, such as concentrations or concentration ranges, described herein are subject to change. In all cases, it should be understood as being modified by the term "approximately". Therefore, the values ​​typically include ±10% of the stated value. For example, A concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Similarly, 1% to 10 The concentration range of %(w / v) includes 0.9%(w / v) to 11%(w / v). When used, the use of a numerical range is limited unless the context explicitly indicates otherwise. All possible subranges, including integers and fractions of values, and all individual numbers within that range. Explicitly include.

[0179] Unless otherwise stated, the term “at least” preceding a set of elements means all of the set. It should be understood that this refers to the elements of the subject. Those skilled in the art will know that using only ordinary experimental procedures... By doing so, one can recognize many equivalents to the specific embodiments described herein, or This can be confirmed. Such equivalents are intended to be included by the present invention. It will be done.

[0180] When used in this specification, the terms "comprises" and "comprising" are used interchangeably. "includes", "include", "has", "having )", "contains", or "contains", or any of these Other variations of this intention are intended to include the integers or groups of integers mentioned, but these It does not exclude any other integers or groups of integers, and is non-exclusive or non-restrictive. The intention will be understood. For example, a composition, mixture, process, which includes a series of elements. Methods, articles, or apparatus are not necessarily limited to those elements only, but expressly... Any composition, mixture, process, method, article, or apparatus not listed herein, or which is not included in this list, is included in this list. It may include other elements that have not been present. Furthermore, unless explicitly stated otherwise, "or" " or " refers to an inclusive "or" and not an exclusive "or". For example Condition A or B is such that A is true (or exists) and B is false (or does not exist). In the case where A is false (or does not exist) and B is true (or exists), and If both A and B are true (or exist), then the condition is satisfied by either one of them.

[0181] As used herein, the connecting term "and / or" between multiple enumerated elements means It is understood to encompass both individual and combined options. For example, two When the elements are connected by "and / or", the first option is the second option without the second element. This indicates that element 1 is applicable. The second option is that element 2 is applicable without element 1. This refers to applicability. The third option is that the first and second elements are applicable together. This refers to the act of doing so. One of these options is included in the meaning, and therefore, this When used in a specification, it is understood that the requirements of the term "and / or" are met. Options The simultaneous applicability of two or more of these is also included in the meaning, and therefore the term "and / or" It is understood that the requirements are met.

[0182] When used herein, the term "consists of" or "consist" Variations such as "of)" or "consisting of" are used in the specification and claims. When used across the entire range, it includes any enumerated integer or set of integers, but additional This indicates that integers or groups of integers will not be added to the specified method, structure, or composition.

[0183] When used herein, the term "consists essentially of" or This means "to essentially become of" or "to essentially become of" Variations such as "isting essentially of" are used throughout the specification and claims. When used, it includes any enumerated integer or group of integers, and optionally specifies a method and structure. , or any enumerated integer or that does not substantially alter the basic or novel properties of the composition This demonstrates that integer groups are also included. See MPEP §2111.03.

[0184] As used herein, “subject” means any animal, e.g., mammal, e.g., human. This means. When used in this specification, the term "mammal" encompasses all mammals. Examples of mammals include, but are not limited to, cows, horses, sheep, Pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc., or for example Humans are one example.

[0185] The terms "about" and "approximately" as used herein when referring to the dimensions or characteristics of a component, The terms “generally,” “substantially,” and similar terms are understood by those skilled in the art to be the dimensions described. Features are not strict boundaries or parameters, but rather functionally the same or similar, from It should also be understood that this does not exclude slight differences. At the minimum value, Such references, including numerical parameters, are based on mathematics accepted in the relevant field. Using objective and industrial principles (e.g., rounding, measurement, or other systematic errors, manufacturing tolerances, etc.) When used, it will include variant forms in which the minimum number of significant figures remains unchanged.

[0186] The terms "identical" or "identical" percentage refer to two or three or more nucleic acids or polypeptides. Petid sequences (for example, anti-TRGV9 / anti-cancer-related antigen bispecific antibodies and encoding them) The polynucleotides, anti-TRGV9 / anti-CD123 bispecific antibodies and the encoding of them The polynucleotide, TRGV9 polypeptide, and the TRGV9 that encodes it / Polynucleotides, CD123 polypeptides and the CD123 polynucleotides encoding them In relation to nucleotides, use one of the following sequence comparison algorithms or aim When measured by visual inspection, comparison and alignment are performed to maximize agreement. An amino acid residue or nucleotide that is the same as, or the same in a specific percentage of, the same as, This refers to two or more sequences or subsequences having [a specific characteristic].

[0187] For sequence comparison, typically one sequence is used as the reference sequence against which the test sequence is compared. It works. When using a sequence comparison algorithm, the test and reference sequences are entered into the computer. The program is then forced, and if necessary, sub-sequence coordinates are specified, and the array algorithm program is... The parameters are specified. Then the array comparison algorithm uses the specified program parameters. Based on the data, the sequence identity percentage of the test sequence to the reference sequence is calculated.

[0188] The optimal alignment of sequences for comparison is, for example, Smith & Waterman. The local homology algorithm of Adv.Appl.Math.2:482(1981), Ne The phase of edleman & Wunsch, J.Mol.Biol.48:443 (1970) Same-sex alignment algorithm, Pearson & Lipman, Proc. Nat' Similarity search method for l.Acad.Sci.USA85:2444(1988), these Computerized implementation of argolism (Wisconsin Genetics So ftware Package,Genetics Computer Group,5 75 Science Dr., Madison, WI: GAP, BESTFIT , FASTA, and TFASTA), or visual inspection (generally, Current Pro tocols in Molecular Biology,FMAusubel et al., eds., Current Protocols, a joint ve nature between Greene Publishing Associates es, Inc. and John Wiley & Sons, Inc., (1995 Su This can be done by (see Ausubel).

[0189] An example of a suitable algorithm for determining the percentage of sequence identity and sequence similarity is A ltschul et al. (1990) J.Mol.Biol.215:403-4 10, and Altschul et al. (1997) Nucleic Acids BLAST and BLAST as described in Res.25:3389-3402 respectively This is the 2.0 algorithm. The software used for BLAST analysis is provided by the National Center for Biotechnology, Information and Technology. It is publicly available through the National Center for Biotechnology Information. Yes, this algorithm first sorts words of the same length and ara in the database array. When incremented, it matches, or satisfies a threshold score T of several positive values. By identifying short words of length W in either of the query sequences, a high score can be achieved. This includes identifying sequence pairs (HSPs). T is the adjacent word score threshold (Altschu). (L et al., above) are referred to as these initial adjacent word hits that contain It serves as a seed to initiate a search for finding HSPs longer than this. As long as the cumulative alignment score can be increased, word hits along each sequence Extend the toe in both directions.

[0190] Regarding nucleotide sequences, parameter M (reward for matching residue pairs) Uses Core (always > 0) and N (penalty score for mismatched residues, always < 0). Then calculate the cumulative score. For amino acid sequences, use a scoring matrix. Then calculate the cumulative score. The cumulative alignment score is lowered by X from its maximum score. When this occurs, the accumulation of alignment of one or more negative scoring residues results in When the cumulative score becomes zero or less, or when the end of any sequence is reached, each direction Stop the extension of word hits in BLAST algorithm. BLAST algorithm parameters W, T, And X determines the sensitivity and speed of the alignment. BLASTN program (Nucre Regarding the Otchido array, by default, the word length (W) is 11, the expected value is 10, and M=5. Use N=-4 and compare both chains. For amino acid sequences, see BLASTP The program defaults to word length (W) 3, expected value (E) 10, and BLOSU Use the M62 scoring matrix (Henikoff & Henikoff, P (See roc.Natl.Acad.Sci.USA 89:10915(1989)) .

[0191] In addition to calculating sequence identity percentage, the BLAST algorithm uses two sequences Statistical analysis of similarities between columns is also performed (e.g., Karlin & Altschul, Proc. See Nat'l.Acad.Sci.USA 90:5873-5787 (1993). ). One measure of similarity provided by the BLAST algorithm is the minimum sum probability ( P(N)) is a combination of two nucleotides or amino acid sequences, where the matching occurs by chance. It provides an index of the probability of [something happening]. For example, nucleic acids provide an index of the minimum probability of [something happening] in a comparison between a test nucleic acid and a reference nucleic acid. If the count probability is less than approximately 0.1, less than approximately 0.01, or less than approximately 0.001, the reference array It is considered similar to [this].

[0192] Further indicators that two nucleic acid sequences or polypeptides are substantially identical are described below. As shown, the polypeptide encoded by the first nucleic acid is coded by the second nucleic acid. It is immunologically reactive with the polypeptide being treated. Therefore, the polypeptide The peptide is typically substantially identical to the second polypeptide, for example, two peptides. The sequences differ only by conservative substitutions. Another indicator that two nucleic acid sequences are substantially identical is: This refers to the hybridization of two molecules under stringent conditions.

[0193] As used herein, the term "polynucleotide" is synonymous with "nucleic acid molecule." Also called "nucleotide" or "nucleic acid," it refers to unmodified RNA or DNA or modified RNA. Any polyribonucleotide or polydeoxyribonucleonucleotide, which may be NA or DNA. It refers to creotides. However, the term "polynucleotide" is not limited to these. , single-stranded and double-stranded DNA, DNA which is a mixture of single-stranded and double-stranded regions, single-stranded and Double-stranded RNA, and RNA which is a mixture of single-stranded and double-stranded regions, single-stranded or more It contains DNA and RNA that may be double-stranded or a mixture of single-stranded and double-stranded regions. Hybrid molecules are one example. In addition, "polynucleotides" are RNA or D This refers to a triple-stranded region containing both NA or RNA and DNA. The term polynucleotide includes... DNA or RNA containing one or more modified bases, and stability or other properties This also includes DNA or RNA having a main chain modified by a base. A "modified" base is, for example, This includes tritylated bases and abnormal bases, such as inosine. Various modifications are made to DNA and R It can be done in NA. Therefore, "polynucleotides" are typically found in nature. Chemically, enzymatically, or metabolically modified forms of polynucleotides, as well as viruses and It encompasses the chemical forms that have the characteristics of DNA and RNA in cells. "Polynucleotide" It also includes relatively short nucleic acid chains (often called oligonucleotides).

[0194] As used herein, the term "vector" refers to a functionally distinct nucleic acid segment. Replicons that can replicate or express a segment by being inserted And so it is.

[0195] As used herein, the term “host cell” refers to the nucleic acid molecules provided herein. This refers to cells containing [the specified element]. "Host cells" are, for example, primary cells, cultured cells, or cells derived from a cell line. It may be any type of cell. In one embodiment, the "host cell" is the present These are cells transfected with nucleic acid molecules provided in the details. In another embodiment, " "Chief cells" are the offspring or potential offspring of such transfected cells. The offspring of the cell may undergo mutations or environmental influences that may occur in subsequent generations, or host cell gene mutations. The incorporation of nucleic acid molecules into the cell may result in the cell being identical to or different from the parent cell.

[0196] As used herein, the term “expression” refers to the biosynthesis of a gene product. This includes the transcription of genes into RNA. Furthermore, such terms may refer to one or two RNA molecules. This also includes translation into the polypeptides mentioned above, as well as all naturally occurring post-transcriptional and post-translational modifications. It is included. The bispecific antibodies expressed are found in the cytoplasm of host cells, in cell culture growth media, etc. It may be present in the extracellular environment or may be fixed to the cell membrane.

[0197] As used herein, the terms "peptide," "polypeptide," or "protein" are used. This can refer to a molecule composed of amino acids, which is recognized as a protein by those skilled in the art. This can be recognized. In this specification, conventional one-letter or three-letter codes for amino acid residues are used. The terms "peptide," "polypeptide," and "protein" refer to amino acids of any length. The polymer can be used interchangeably in this specification to refer to the polymer. They may be linear or branched, and may contain modified amino acids, with non-amino acids being the main component. It may be dismissed. This term is also modified by nature or by intervention. It includes amino acid polymers. For example, disulfide bond formation, glycosylation, lipidation, Acetylation, phosphorylation, or any other operation or modification, for example, with the labeled component An oxyglyceride. Also, the definition includes, for example, one or more analogs of amino acids (for example) Polypeptides containing non-natural amino acids, etc., and in the field of the said technology Other known modifiers are included.

[0198] The peptide sequences described herein are described in accordance with common practice, and the N-terminal region of the peptide is shown. The region is on the left, and the C-terminal region is on the right. The isomer forms of amino acids are known, but separately Unless explicitly stated otherwise, the L-form of amino acids is shown.

[0199] antibody Anti-TRGV9 antibody or its antigen-binding fragment, nucleic acid encoding the antibody and expression vector This specification provides for recombinant cells containing a ter, a vector, and a composition containing an antibody. Also, anti-TRGV9 bispecific antibodies or their antigen-binding fragments, and antibodies encoding Nucleic acids and expression vectors, recombinant cells containing vectors, and a set comprising bispecific antibodies Products are provided herein. Also, anti-TRGV9 / anti-CD123 bispecific antibodies or Antigen-binding fragments, nucleic acids encoding bispecific antibodies, and expression vectors, vectors Recombinant cells containing and a composition comprising a bispecific antibody are provided herein. Methods for creating bodies and methods for using antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein have high affinity binding to TRGV9 and / or CD123 High affinity binding to, high specificity for TRGV9 and / or high specificity for CD123 Its specificity, and its ability to treat cancer when administered alone or in combination with other anticancer therapies. Having one or more desirable functional characteristics, including but not limited to the ability to prevent. do.

[0200] As used herein, the term “antibody” is used in a broad sense, and does not include immunoglobulin or mo Antibodies including human, humanized, complex, and chimeric antibodies that are noclonal or polyclonal. It includes body molecules and antibody fragments. Generally speaking, an antibody is defined as a molecule that binds to a specific antigen. It is a protein or peptide chain that exhibits specificity. The structure of an antibody is publicly known. Immunoglobulin Phosphorus is classified into five main classes (i.e., IgA) depending on the amino acid sequence of the heavy chain constant domain. IgA and IgG can be assigned to IgD, IgE, IgG, and IgM. These are isotypes IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4 They are further subdivided. Therefore, the antibodies provided herein are divided into five main classes. Or it may be one of the corresponding lower classes. In a particular embodiment, this The antibody provided in this specification is IgG1. In some embodiments, provided herein The antibody used is IgG2. In some embodiments, the antibody provided herein is , IgG3. In some embodiments, the antibody provided herein is IgG4 Yes. Antibody light chains of vertebrate species have two distinct amino acid sequences based on the amino acid sequence of their constant domain. It can be assigned to one of two different types, namely κ and λ. The antibodies provided herein may contain kappa or lambda light chain constant domains. According to certain embodiments, the antibodies provided herein are derived from rat or human antibodies. It includes the heavy chain and / or light chain constant regions.

[0201] In addition to heavy and light constant domains, antibodies consist of an antigen comprising a light chain variable region and a heavy chain variable region. It contains binding regions, each of which has three domains (i.e., complementarity-determining regions 1-3) Contains CDR1, CDR2, and CDR3). "CDR" stands for immunoglobulin (I g or antibody) VH β-sheet framework: three hypervariables within the non-framework region One of the regions (HCDR1, HCDR2, or HCDR3), or antibody VL β - One of the three hypervariable regions within the non-framework region of the sheet framework (L This refers to CDR1, LCDR2, or LCDR3. Therefore, CDR is a frame. It is a variable region array scattered within the work region array. The CDR region is well known to those skilled in the art. For example, Kabat can be used to define the majority of the hypervariable regions within the antibody variable (V) domain. (Kabat et al., J. Biol. Chem. 252:66) 09-6616(1977), Kabat,Adv.Prot.Chem.32:1-7 5(1978)). The CDR region sequence is also part of the conserved β-sheet framework. It is structurally defined by Chothia as a residue that is not [a different type of residue], and therefore, it is different. It is possible to adapt to the stereoconformation. Chothia and Lesk, J. Mol Biol. 196:901-917 (1987). Both terms are used in the relevant technical field. It is well recognized. The CDR region sequence also includes AbM, Contact, and IM. Defined by GT. Exemplary CDR region sequences are shown herein, for example, in the sequence listing. , and as illustrated in the table provided in the following examples, the position of the CDR within the standard antibody variable region. The position is determined by the non-nuclear structure of numerous structures (Al-Lazikani et al ., J. Mol. Biol. 273:927-948 (1997), Morea et al. al., Methods 20:267-279 (2000). Residues within the hypervariable region Since the number varies in different antibodies, additional residues at standard positions are conventionally considered standard. A variable region numbering scheme (Al-Lazikani et al., above (199) 7)) The residue number is followed by a, b, c, etc. Such nomenclature is used in our industry. This is common knowledge among those involved.

[0202] In this specification, the light chain variable region CDR1 domain is referred to as LCDR1 or VL CDR1. It is interchangeably referred to as the CDR2 domain of the light chain variable region. In this specification, the CDR2 domain is referred to as LCDR2 Alternatively, it is referred to interchangeably with VL CDR2. The light chain variable region CDR3 domain is described herein. In this context, it is interchangeably referred to as LCDR3 or VL CDR3. Heavy chain variable region CDR1 domain In this specification, the term "in" is interchangeably referred to as HCDR1 or VH CDR1. The variable region CDR2 domain is, in this specification, compatible with HCDR2 or VH CDR2. It is called the heavy chain variable region CDR1 domain. In this specification, the heavy chain variable region CDR1 domain is referred to as HCDR3 or VH It is called CDR3 for compatibility.

[0203] As used herein, the terms VH or VL, etc., “super variable region” means super variable region in the arrangement. This refers to the region of the antibody variable region that is variable and / or forms a structurally defined loop. Generally, antibodies have six hypervariable regions, VH(HCDR1, HCDR2, HCD). Includes three R3s and three VLs (LCDR1, LCDR2, LCDR3). Numerous The depiction of the hypervariable region is used and is included herein. The "Kabat" CDR is It is based on sequence variability and is the most commonly used (e.g., Kabat et al.) al.,Sequences of Proteins of Immunologic al Interest,5th Ed.Public Health Service ,National Institutes of Health,Bethesda, See MD. (1991). "Chothia" instead refers to the structure loop. It indicates a location (for example, Chothia and Lesk, J.Mol.Biol.19) See 6:901-917 (1987). Using Kabat numbering conventions The end of the Chothia CDR-HCDR1 loop when numbered is the loop length It changes from H32 to H34 accordingly (this is because the Kabat numbering scheme is H This is to place the insertions in 35A and H35B, and if neither 35A nor 35B exists, If the loop ends at 32 and only 35A exists, the loop ends at 33, and 35A and 3 If both 5B exist, the loop ends at 34). The "AbM" hypervariable region is Kab At the Oxford Mole Museum, it represents a compromise between CDR and Chothia structural loops. Used by cular AbM antibody modeling software (e.g., Mart in,in Antibody Engineering,Vol.2,Chapter 3. See Springer Verlag. "Contact" Super Variable Territory The region is based on the analysis of available composite crystal structures.

[0204] In recent years, universal numbering systems have been developed and widely adopted (ImMunoGe neTics(IMGT) Information System(Registered Trademark)(Laf ranc et al.,Dev.Comp.Immunol.27(1):55-77 (2003))). IMGT is immunoglobulin (IG), T cell receptor The body (T cell receptor, TR), as well as the major histocompatibility complex (MAJ) of humans and other vertebrates. or histocompatibility complex (MHC) is a specialized integrated information system. In this regard, CDR is defined in terms of both the amino acid sequence and the position in the light chain or heavy chain. This means that the "location" of the CDR within the structure of the immunoglobulin variable region domain is maintained between species. Because it exists in a structure called a loop, the variable domain sequence is arranged according to its structural characteristics. By using a numbering system that is consistent with this, CDRs and framework residues are compatible. It is easily identified. This information typically identifies CDR residues from one species of immunoglobulin. It can be used to transplant and replace acceptor frameworks from human antibodies. Further numbering systems (AHon) are being developed by Honegger and Pluckth. Developed by un, J.Mol.Biol.309:657-670(2001) For example, numbering including Kabat numbering and IMGT-specific numbering systems. The correspondence between systems is well known to those skilled in the art (for example, Kabat, Chothia, etc.). and Lesk, above, Martin, above, Lefranc et al., above (See reference). The exemplary systems shown herein are Kabat and Choth It combines ia elements.

[0205] [Table 1]

[0206] The hypervariable region may include the following "extended hypervariable region": 24-36 within the VL These are 24-34 (LCDR1), 46-56 or 50-56 (LCDR2), and 89-9 7 or 89-96 (LCDR3), and 26-35 or 26-35A (HCD) within VH. R1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102, Or 95-102 (HCDR3). Each of the above numbering schemes included in the sequence listing A CDR sequence reflecting this is provided herein.

[0207] The term "constant region" or "constant domain" does not directly involve the binding of antibodies to an antigen. However, the light and heavy chains exhibit various effector functions, such as interactions with Fc receptors. This refers to the xy terminal portion. This term is used in immunoglobulins, which are variable regions containing antigen-binding sites. A portion of the immunoglobulin molecule that has a more conserved amino acid sequence compared to other parts of the molecule. This refers to the steady-state region, which consists of the CH1, CH2, and CH3 regions of the heavy chain, and the CL region of the light chain. It may contain.

[0208] The term "framework" or "FR" refers to a variable region residue adjacent to the CDR. FR residues are used in, for example, chimeric antibodies, human antibodies, human domain antibodies, diabolic antibodies, and linear antibodies. It is present in the body and in bispecific antibodies. FR residues are those other than hypervariable region residues or CDR residues. These are the variable domain residues.

[0209] As used herein, the term "isolated antibody" means other antibodies having different antigen specificities. This refers to antibodies that substantially do not contain (for example, an isolated antibody that specifically binds to TRGV9 is V The isolated antibody that substantially does not contain antibodies that do not bind to γ9 and specifically binds to CD123 is: (Substantially contains no antibodies that do not bind to CD123). Furthermore, the isolated antibodies are similar to other cellular materials and Substantially free of bacteria and / or chemical substances.

[0210] As used herein, the term "monoclonal antibody" refers to a substantially homogeneous group of antibodies. This refers to antibodies obtained from, that is, individual antibodies that make up a population may exist in trace amounts. They are identical except for naturally occurring mutations. The monoclonal antibodies provided herein are hybrid Doma method, phage display technology, single lymphocyte gene cloning technology, or recombinant It can be produced by DNA methods. For example, monoclonal antibodies are trans- B cells obtained from transgenic non-human animals, such as transgenic mice or rats. It can be produced by a hybridoma containing human heavy chain transgenes and light chain transgenes. It has a genome.

[0211] As used herein, the term “antigen-binding fragment” means, for example, a diabody. Fab, Fab', F(ab')2, Fv fragment, disulfide-stabilized Fv flag Ment(dsFv), (dsFv)2, bispecific dsFv(dsFv-dsFv'), Disulfide-stabilized diabody (ds diabody), single-chain antibody molecule (scFv), single One-domain antibody (sdAb) scFv dimer (bivalent diabody), one or more Multispecific antibodies formed from a portion of an antibody containing CDR, camelized single-domain antibodies, Nanobody, domain antibody, bivalent domain antibody, or antibody structure that binds to an antigen but is complete This refers to antibody fragments, including any other antibody fragments that are not included. Antigen-binding fragments The antibody can bind to the same antigen to which the parent antibody or parent antibody fragment binds. According to a specific embodiment, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and a heavy region. The chain contains an Fd fragment. According to other specific embodiments, the antigen-binding fragment is F Includes ab and F(ab').

[0212] As used herein, the term "single-chain antibody" refers to a short chain of approximately 15 to 20 amino acids. Conventional practices in this field include heavy chain variable regions and light chain variable regions connected by plutides. This refers to a single-chain antibody. As used herein, the term "single-domain antibody" refers to a heavy-chain variable-domain antibody. Conventional single units in this field that include the heavy chain constant region or include only the heavy chain variable region This refers to a single-domain antibody.

[0213] As used herein, the term "human antibody" means an antibody produced by a human, or Human-produced antibodies, manufactured using any known technique in the art. This refers to antibodies that have the corresponding amino acid sequence. This definition of human antibodies is for intact or intact antibodies. or a full-length antibody, its fragments, and / or at least one human heavy chain and / or Alternatively, it may include antibodies containing light chain polypeptides.

[0214] As used herein, the term "humanized antibody" means an antibody whose antigen-binding properties are preserved. However, the antigenicity of the antigen in the human body is reduced by modifying the sequence homology to that of human antibodies. This refers to non-human antibodies that have been increased against it.

[0215] As used herein, the term "chimeric antibody" refers to the amino acid sequence of an immunoglobulin molecule. This refers to antibodies derived from two or more species. The variable regions of both the light and heavy chains are often In this case, a single species of mammal (e.g., mouse) possessing the desired specificity, affinity, and capabilities. The variable region corresponds to the antibody derived from (such as rats, rabbits, etc.), while the constant region corresponds to that species. To avoid inducing an immune response in [the body], [the body] uses a substance derived from another species of mammal (e.g., human). This corresponds to the sequence of the antibody.

[0216] As used herein, the term "multispecific antibody" refers to a multispecific antibody that is variable in composition for multiple immunoglobulins. This refers to an antibody containing an in sequence, where the first of several immunoglobulin variable domain sequences is the second It has binding specificity to one epitope, and the second of several immunoglobulin variable domains The in sequence has binding specificity to a second epitope. In one embodiment, the first and The second epitope does not overlap or does not substantially overlap. In one embodiment, Epitope 1 and Epitope 2 are different antigens, e.g., different proteins (or different polymers) (on a protein subunit). In one embodiment, the multispecific antibody is third, 4. Containing a variable immunoglobulin domain, or a fifth immunoglobulin domain. In some embodiments, a multispecific antibody. These are bispecific antibody molecules, triplicate antibody branches, or quadruplicate antibody molecules.

[0217] As used herein, the term "bispecific antibody" means an antibody with two or fewer epitopes or two This refers to multispecific antibodies that bind to the following antigens. A bispecific antibody is a primary epitope (e.g., For example, the first immunoglobulin having binding specificity to the epitope on the TRGV9 antigen. The variable domain sequence, and a second epitope (e.g., tumor-associated antigen (e.g., CD12) 3. A second immunoglobulin variable domain with binding specificity to the epitope on the antigen. Characterized by an array. In one embodiment, the first and second epitopes are different Antigens, for example, on different proteins (or subunits of different multimeric proteins) In one embodiment, the bispecific antibody has binding specificity to the first epitope. The heavy chain variable domain sequence and the light chain variable domain sequence, and their binding to the second epitope. Includes a heavy chain variable domain sequence and a light chain variable domain sequence having specificity. One embodiment So, a bispecific antibody is a semi-antibody that has binding specificity to a first epitope or the same A fragment and a semi-antibody or fragment having binding specificity to a second epitope. Includes a nucleotide. In one embodiment, the bispecific antibody has binding characteristics to the first epitope. The binding specificity of an isomerized scFv or its fragment to a second epitope Includes an scFv or a fragment thereof. In one embodiment, the first epitope is The first epitope is located at TRGV9, and the second epitope is located at CD123. In one embodiment, the first The first epitope is located at TRGV9, and the second epitope is PD-1, PD-L1, C TLA-4, EGFR, HER-2, CD19, CD20, CD3, and / or other cancer-related It is located as an immunosuppressant or surface antigen.

[0218] As used herein, the term “half-antibody” refers to one antibody associated with one immunoglobulin light chain. Refers to one immunoglobulin heavy chain. An example half-antibody is shown in SEQ ID NO: 17. If present, the half-antibody can encapsulate that fragment, for example, a single fragment from a camelid family. It is easy to understand that it can also have an antigen-binding domain consisting of a variable domain. It is likely.

[0219] As used herein, the term "TRGV9" refers to γ ​​when expressed on the surface of a cell. This refers to polypeptides capable of forming δ T cell receptors. TRGV9-expressing γδ T The cells are the first T cells to develop in the human fetus and are the major gamma cells in healthy adult peripheral blood cells. δ is a T cell subset. The term "TRGV9" refers to cells (including T cells). It is either expressed naturally, or in the gene or cDNA that codes for its polypeptide. Any TRGV9 variant, isof which can be expressed on transfected cells. Includes foam and species homologues. Unless otherwise specified, TRGV9 is, in certain embodiments This is human TRGV9. The amino acid sequence of human TRGV9 is available on GenBank Accession. Provided by number NG_001336.2.

[0220] The term "CD123" refers to an intercellular cytokine that is important in the immune system. CD12 refers to a molecule found on cells that helps transmit the leukin-3 signal. 3 can also be called the "interleukin-3 receptor." The receptor is a type I cytokine receptor. It belongs to the symptom family and is paired with a common beta subunit (beta c or CD131). It is a heterodimer that has a unique alpha chain. The CD123 receptor is a pluripotent precursor. It can be found on cells, induces tyrosine phosphorylation within cells, and promotes proliferation and differentiation within hematopoietic cell lines. CD123 can promote acute myeloid leukemia. It can be expressed in the AML subtype. Unless otherwise specified, the term "CD123" refers to a detailed understanding of the disease. Genes that are naturally expressed by cells (including T cells) or that encode their polypeptides. Any CD12 that can be expressed on cells transfected with a gene or cDNA The three variants, isoforms, and species homologs are included, and in certain embodiments, "CD12 "3" is human CD123. The amino acid sequence of human CD123 is available on GenBank. Provided by instruction number AY789109.1.

[0221] When used in this specification, the antibody that "specifically binds to TRGV9" means TRGV9, For example, in human TRGV9, 1 × 10 -7 Less than or equal to M, for example, 1 × 10 -8 M or less, 5×1 0 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1 × 10 -10 M or less This refers to an antibody that binds at the KD ratio. The term "KD" refers to the ratio of Kd to Ka (i.e., Kd / Ka). This refers to the dissociation constant, which is obtained from the ratio and expressed as molar concentration (M). The KD value of the antibody is disclosed in this disclosure. This can be determined using methods in the relevant art, taking into consideration the K of the antibody. D is achieved by using surface plasmon resonance, for example, Biacore (registered trademark). By using a biosensor system of the ) system, or Octet R By using biolayer interferometry techniques such as the ED96 system, That is what can be sought.

[0222] When used in this specification, the antigen-binding domain that "specifically binds to tumor-associated antigens" or Antigen-binding fragments are fragments that bind to tumor-associated antigens in a 1 × 10⁻¹⁶ manner. -7 Less than or equal to M, for example, 1 × 10 - 8 M or less, 5×10 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1× 10 -10 This refers to an antigen-binding domain or antigen-binding fragment that binds with KD values ​​of M or less.

[0223] The term "KD" is derived from the ratio of Kd to Ka (i.e., Kd / Ka), and represents the molar concentration (M This refers to the dissociation constant expressed as ). The KD value of an antibody is used in the art in consideration of this disclosure. This can be determined using methods such as antigen-binding domains or antigen-binding flags. The KD of a ment is achieved by using surface plasmon resonance, for example, Biacore By using the (registered trademark) system's biosensor system, or by using Oc Using biolayer interferometry techniques such as the tet RED96 system It can be obtained by doing so.

[0224] When used herein, the antibody that "specifically binds to CD123" means CD123, For example, in human CD123, 1 × 10 -7 Less than or equal to M, for example, 1 × 10 -8 M or less, 5×1 0 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1 × 10 -10 M or less This refers to an antibody that binds at the KD ratio. The term "KD" refers to the ratio of Kd to Ka (i.e., Kd / Ka). This refers to the dissociation constant, which is obtained from the ratio and expressed as molar concentration (M). The KD value of the antibody is disclosed in this disclosure. This can be determined using methods in the relevant art, taking into consideration the K of the antibody. D is achieved by using surface plasmon resonance, for example, Biacore (registered trademark). By using a biosensor system of the ) system, or Octet R By using biolayer interferometry techniques such as the ED96 system, That is what can be sought.

[0225] The lower the KD value of an antibody, the higher its affinity for binding to the target antigen.

[0226] In one embodiment, an antibody that binds to TRGV9 is provided herein. Several embodiments The antibody then includes a heavy chain variable region and a light chain variable region. In some embodiments, TRG V9 antibodies are not single-domain antibodies or nanobodies. In some embodiments, TR GV1 antibody is a humanized antibody.

[0227] In certain embodiments, one of the VH regions of the antibodies described herein, V L area, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL C Anti-TRGV9 antibodies comprising DR2 and / or VL CDR3 are provided herein. In some embodiments, the VH region of any one of the antibodies described herein is included. Anti-TRGV9 antibodies are provided herein. In some embodiments, as described herein This specification provides an anti-TRGV9 antibody containing any one of the VL regions of the antibodies being provided. In some embodiments, one of the antibodies described herein is used. Anti-TRG comprising a region and one VL region of any of the antibodies described herein. V9 antibodies are provided herein. In some embodiments, the antibodies described herein Antibody containing any one of VH CDR1, VH CDR2, and VH CDR3 A TRGV9 antibody is provided herein. In some embodiments, as described herein One of the antibodies VL CDR1, VL CDR2, and VL CDR3 Anti-TRGV9 antibodies containing the above are provided herein. In some embodiments, as described herein One of the antibodies listed is VH CDR1, VH CDR2, or VH CD R3 and one of the antibodies described herein, VL CDR1, VL CD Anti-TRGV9 antibodies comprising R2 and VL CDR3 are provided herein. The TRGV9 antibodies provided in this book are VH CDR1, VH CDR2, VH CDR3, V Representative VH sequences including L CDR1, VL CDR2, and VL CDR3 amino acid sequences. The VL amino acid sequences are provided in the sequence listing and in Tables 1-31.

[0228] In certain embodiments, one of the VH regions of the antibodies described herein, V L area, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL C Includes a binding domain that binds to TRGV9 having DR2 and / or VL CDR3, Anti-TRGV9 bispecific antibodies are provided herein. In some embodiments, this specification A binding agent that binds to TRGV9 having one of the VH regions among the antibodies described in the book. A bispecific anti-TRGV9 antibody containing a domain is provided herein. Several implementations Morphologically, TRGV having one of the VL regions of the antibodies described herein. A bispecific anti-TRGV9 antibody containing a binding domain that binds to 9 is provided herein. In some embodiments, the VH region of any one of the antibodies described herein TRGV9 having the VL region of any one of the antibodies described herein A bispecific anti-TRGV9 antibody containing a binding domain is provided herein. In some embodiments, any one of the described antibodies VH CDR1, VH Anti-T RGV9 bispecific antibodies are provided herein. In some embodiments, One of the antibodies listed is VL CDR1, VL CDR2, and VL C Anti-TRGV9 bispecific antibody containing a TRGV9 cell binding domain with DR3 This is provided herein. In some embodiments, among the antibodies described herein, Any one of VH CDR1, VH CDR2, and VH CDR3, as specified herein One of the antibodies listed, VL CDR1, VL CDR2, and VL CDR3 This specification describes an anti-TRGV9 bispecific antibody containing a binding domain that binds to TRGV9. Provided for publication.

[0229] In certain embodiments, the anti-TRGV9 antibody is a bispecific antibody. In this state, the anti-TRGV9 bispecific antibody is the VH of the anti-CD123 antibody provided herein. area, VL area, VH CDR1, VH CDR2, VH CDR3, VL CDR1, A second coupling that binds to CD123 having VL CDR2 and / or VL CDR3. The domain further includes. In some embodiments, the anti-TRGV9 bispecific antibody is described in this specification. The second binding involves the anti-CD123 antibody provided in the book having a VH region that binds to CD123. The domain further includes. In some embodiments, the anti-TRGV9 bispecific antibody is described in this specification. The second binding involves the anti-CD123 antibody provided in the book having a VL region that binds to CD123. The domain further includes. In some embodiments, the anti-TRGV9 bispecific antibody is described in this specification. The VH region of the anti-CD123 antibody provided in this book and the anti-CD123 antibody provided herein It further includes a second binding domain that binds to CD123 having the VL region. In this embodiment, the anti-TRGV9 bispecific antibody is an anti-CD123 antibody provided herein. CD123, which has VH CDR1, VH CDR2, and VH CDR3 in its body, binds to this CD123. It further includes a second binding domain. In some embodiments, it is anti-TRGV9 bispecific. The antibodies provided herein are VL CDR1, VL CDR2, and anti-CD123 antibodies. It further includes a second binding domain that binds to CD123 having VL CDR3. In several embodiments, the anti-TRGV9 bispecific antibody is an anti-CD12 antibody provided herein. The three antibodies VH CDR1, VH CDR2, and VH CDR3 are provided herein. It contains the anti-CD123 antibodies VL CDR1, VL CDR2, and VL CDR3. It further includes a second binding domain that binds to CD123.

[0230] In certain embodiments, an intact antibody, an anti-TRGV9 antibody, is provided. In this formulation, an anti-TRGV9 antibody is provided, and the antigen-binding fragment of the anti-TRGV9 antibody is Provided. In some embodiments, the antigen-binding fragment of the anti-TRGV9 antibody is provided. It is an active fragment. In some embodiments, the antigen-binding fragment is a diabetic fragment. It is. In some embodiments, the antigen-binding fragment is Fab. In one embodiment, the antigen-binding fragment is Fab'. In some embodiments, The antigen-binding fragment is F(ab')2. In some embodiments, antigen binding The fragment is an Fv fragment. In some embodiments, the antigen-binding fragment The term is 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-ds Fv'). In some embodiments, the antigen-binding fragment is disulfide-stable. It is a chemical diabody (DS diabody). In some embodiments, the antigen-binding flag A ment is a single-chain antibody molecule (scFv). How many? In that embodiment, the antigen-binding fragment is a single-domain antibody. dy, sdAb). In some embodiments, the antigen-binding fragment is scFv2 It is a mer (divalent diabody). In some embodiments, the antigen-binding fragment is It is a multispecific antibody formed from a portion of an antibody containing 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 this state, the antigen-binding fragment is a domain antibody. In some embodiments, the antigen The binding fragment is a bivalent domain antibody. In some embodiments, the antigen-binding fragment A ligment is an antibody fragment that binds to an antigen but does not contain a complete antibody structure.

[0231] In certain embodiments, the anti-TRGV9 antibody includes a VH region and a VL region. In some embodiments, the anti-TRGV9 antibody is not a single-chain antibody. In some embodiments, the anti-T RGV9 antibodies are not single-domain antibodies. In some embodiments, they are anti-TRGV9 antibodies. The body is not a nanobody. In certain embodiments, the anti-TRGV9 antibody is a VHH antibody. No. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody. Several embodiments In this configuration, the anti-TRGV9 bispecific antibody does not contain a single-chain antibody. In some embodiments, The anti-TRGV9 bispecific antibody does not contain a single-domain antibody. In certain embodiments, The anti-TRGV9 bispecific antibody does not contain nanobodies. In certain embodiments, anti-TRG The V9 bispecific antibody does not contain the VHH antibody. In certain embodiments, the anti-TRGV9 bispecific antibody is used. The specific antibody does not include llama antibody. In some embodiments, the anti-TRGV9 antibody is multi It is a bispecific antibody. In other embodiments, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, the multispecific antibody is the antigen of the anti-TRGV9 antibody provided herein. It includes a binding fragment. In other embodiments, bispecific antibodies are provided herein. It contains an antigen-binding fragment of an anti-TRGV9 antibody. In some embodiments, anti-TRGV Antibody 9 is an agonist antibody. In certain embodiments, the anti-TRGV9 antibody is γδ T It activates cells. In other embodiments, the anti-TRGV9 antibody is an antagonist antibody. In certain embodiments, anti-TRGV9 antibodies inactivate γδ T cells. In some embodiments, the anti-TRGV9 antibody blocks the activation of γδ T cells. Several implementations Morphologically, anti-TRGV9 antibodies regulate the activity of γδ T cells. In some embodiments, The anti-TRGV9 antibody neither activates nor inactivates γδ T cell activity. i. In certain embodiments, the γδ T cells are human γδ T cells. This includes a bispecific antibody, which contains the TRGV9 antibody provided herein in knob-in-hole form. A is provided. In some embodiments, the anti-TRGV9 antibody provided herein is two It may be included in the heavy-specific antibody. In some embodiments, the anti-TR provided herein GV9 bispecific antibodies may be included in multispecific antibodies. In certain embodiments, The bispecific antibody provided in this document binds to the first TRGV9 epitope. The first binding domain contains the provided anti-TRGV9 antibody, and the second TRGV9 epitope It comprises a second binding domain containing an anti-TRGV9 antibody provided herein that binds to it, The first TRGV9 epitope and the second TRGV9 epitope are not the same. In embodiments, the TRGV9 antibody or its antigen-binding fragment provided herein is It specifically binds to TRGV9. In certain embodiments, TRGV9 is provided herein. Antibodies or their antigen-binding fragments do not bind to the Vδ2 epitope.

[0232] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence The amino acids numbered 34 are VH CDR1, VH CDR2, and VH CDR3, respectively. VH, including VH CDR1, VH CDR2, and VH CDR3 having acid sequences, (ii) VL CDR1, VL CDR2, and VL CDR of Sequence ID 8, respectively Includes VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences 3. , including VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, antibody (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 VH CDR2 having a column, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31 (ii) VH and VL CDR1 having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5 VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and VL The present invention includes CDR3 and VL. In another embodiment, an antibody that binds to TRGV9 is described herein. The provided antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 196, sequence VH CDR2 having amino acid sequence number 197, and amino acid sequence of sequence number 198 VH containing VH CDR3 having (ii) the amino acid sequence of SEQ ID NO: 199 VL CDR1, VL CDR2 having the amino acid sequence of sequence number 200, and sequence number VL includes VL CDR3 having the amino acid sequence of No. 201. In another embodiment, An antibody that binds to TRGV9 is provided herein, and the antibody is (i) the amine of SEQ ID NO: 202 VH CDR1 has an amino acid sequence, and VH CDR has the amino acid sequence of SEQ ID NO 203. 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 204, comprising VH and (ii ) VL CDR1 having the amino acid sequence of SEQ ID NO: 205, and the amino acid sequence of SEQ ID NO: 206 VL CDR2 having a column, and VL CDR3 having the amino acid sequence of SEQ ID NO: 207 In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 208, SEQ ID NO: 20 VH CDR2 has the amino acid sequence of 9, and has the amino acid sequence of SEQ ID NO: 210 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 211 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 212, and SEQ ID NO: 213 VL includes VL CDR3 having the amino acid sequence. In another embodiment, TRGV An antibody that binds to 9 is provided herein, and the antibody is (i) the amino acid sequence of SEQ ID NO: 214 VH CDR1 having the amino acid sequence of SEQ ID NO: 215, and VH CDR2 having the amino acid sequence of SEQ ID NO: 215, VH containing VH CDR3 having the amino acid sequence of SEQ ID NO: 216, and (ii) sequence number VL CDR1 has the amino acid sequence of sequence number 217, and has the amino acid sequence of sequence number 218. This includes VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 219. Includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 214, and the amino acid sequence of SEQ ID NO: 702 VH CDR2 having an anoic acid sequence, and VH C having the amino acid sequence of SEQ ID NO 703. VH containing DR3 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 217 VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and amino acid sequence of SEQ ID NO: 219 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, wherein the antibody has (i) the amino acid sequence of SEQ ID NO: 220 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 221, and SEQ ID NO: VH containing VH CDR3 having a 222 amino acid sequence, and (ii) SEQ ID NO: 223 VL CDR1 has the amino acid sequence of SEQ ID NO: 224. VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 225. Includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 226, amino acid sequence of SEQ ID NO: 227 VH CDR2 having the amino acid sequence of SEQ ID NO: 228, and VH CDR3 having the amino acid sequence of SEQ ID NO: 228 (ii) VH and VL CDR1 having the amino acid sequence of sequence number 229, sequence number VL CDR2 having the amino acid sequence of number 230, and the amino acid sequence of sequence number 231 The antibody contains VL CDR3, and VL. In some embodiments, the antibody has sequence number It contains VH having amino acid sequence number 34. In some embodiments, the antibody is SEQ ID NO. It contains VL having an amino acid sequence of 8. The antibody has V having the amino acid sequence of SEQ ID NO: 34. It comprises H and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody This is an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 34. Includes a column, includes VH. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 8 In contrast, it contains VLs that have at least 95% identical amino acid sequences. In this embodiment, the antibody has at least 95% identity with respect to the amino acid sequence of SEQ ID NO: 34. VH includes an amino acid sequence having at least 9 amino acids relative to the amino acid sequence of SEQ ID NO: 8. It contains VL, which has an amino acid sequence with 5% identity.

[0233] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence The amino acids numbered 35 are VH CDR1, VH CDR2, and VH CDR3, respectively. VH, including VH CDR1, VH CDR2, and VH CDR3 having acid sequences, (ii) VL CDR1, VL CDR2, and VL CDR of Sequence ID 8, respectively Includes VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences 3. , including VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, antibody (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 VH CDR2 having a column, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32 (ii) VH and VL CDR1 having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5 VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and VL The present invention includes CDR3 and VL. In another embodiment, an antibody that binds to TRGV9 is described herein. The provided antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 232, sequence VH CDR2 having amino acid sequence number 233, and amino acid sequence of SEQ ID NO: 234 VH containing VH CDR3 having (ii) the amino acid sequence of SEQ ID NO: 235 VL CDR1, VL CDR2 having the amino acid sequence of sequence number 236, and sequence number VL includes VL CDR3 having amino acid sequence 237. In another embodiment, An antibody that binds to TRGV9 is provided herein, and the antibody is (i) the amine of SEQ ID NO: 238 VH CDR1 has an amino acid sequence, and VH CDR has the amino acid sequence of SEQ ID NO 239. 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 240, comprising VH and (ii ) VL CDR1 having the amino acid sequence of SEQ ID NO: 241, and the amino acid sequence of SEQ ID NO: 242 VL CDR2 having a column, and VL CDR3 having the amino acid sequence of SEQ ID NO: 243 In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 244, SEQ ID NO: 24 VH CDR2 has the amino acid sequence of 5, and has the amino acid sequence of SEQ ID NO: 246 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 247 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 248, and SEQ ID NO: 249 VL includes VL CDR3 having the amino acid sequence. In another embodiment, TRGV An antibody that binds to 9 is provided herein, and the antibody is (i) the amino acid sequence of SEQ ID NO: 250 VH CDR1 having the amino acid sequence of SEQ ID NO: 251, and VH CDR2 having the amino acid sequence of SEQ ID NO: 251, VH containing VH CDR3 having the amino acid sequence of sequence number 252, and (ii) sequence number VL CDR1 has the amino acid sequence of sequence number 253, and has the amino acid sequence of sequence number 254. This includes VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 255. Includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 250, and the amino acid sequence of SEQ ID NO: 704 VH CDR2 having an anoic acid sequence, and VH C having the amino acid sequence of SEQ ID NO 705 VH containing DR3 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 253 VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and amino acid sequence of SEQ ID NO: 255 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, and the antibody has (i) the amino acid sequence of SEQ ID NO: 256 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 257, and SEQ ID NO: VH containing VH CDR3 having a 258-amino acid sequence, and (ii) SEQ ID NO: 259 VL CDR1 has the amino acid sequence of SEQ ID NO: 260, VL VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 261. Includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 262, amino acid sequence of SEQ ID NO: 263 VH CDR2 having the amino acid sequence of SEQ ID NO: 264, and VH CDR3 having the amino acid sequence of SEQ ID NO: 264 (ii) VH and VL CDR1 having the amino acid sequence of sequence number 265, sequence number VL CDR2 having the amino acid sequence of number 266, and the amino acid sequence of sequence number 267 The antibody contains VL CDR3, and VL. In some embodiments, the antibody has sequence number It contains VH having the amino acid sequence of number 35. In some embodiments, the antibody is SEQ ID NO. It contains a VL having an 8-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 35 It contains VH having the amino acid sequence of SEQ ID NO: 8 and VL having the amino acid sequence of SEQ ID NO: 8. In several embodiments, the antibody has at least 95% of the amino acid sequence of SEQ ID NO: 35 It contains VH, which has an identical amino acid sequence. In some embodiments, the antibody is distributed Includes an amino acid sequence that has at least 95% identity with the amino acid sequence of column number 8. , including VL. In some embodiments, the antibody is compared to the amino acid sequence of SEQ ID NO: 35 VH and the amino acids of SEQ ID NO: 8, which contain amino acid sequences with at least 95% identity. It includes a VL containing an amino acid sequence having at least 95% identity with the sequence.

[0234] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence The amino acids of numbers 36, VH CDR1, VH CDR2, and VH CDR3, respectively. VH, including VH CDR1, VH CDR2, and VH CDR3 having acid sequences, (ii) VL CDR1, VL CDR2, and VL CDR of Sequence ID 8, respectively Includes VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences 3. , including VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, antibody (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 VH CDR2 having a column, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33 (ii) VH and VL CDR1 having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5 VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and VL The present invention includes CDR3 and VL. In another embodiment, an antibody that binds to TRGV9 is described herein. The provided antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 268, sequence VH CDR2 having amino acid sequence number 269, and amino acid sequence of SEQ ID NO: 270 VH containing VH CDR3 having (ii) the amino acid sequence of SEQ ID NO: 271 VL CDR1, VL CDR2 having the amino acid sequence of sequence number 272, and sequence number VL includes VL CDR3 having amino acid sequence 273. In another embodiment, An antibody that binds to TRGV9 is provided herein, and the antibody is (i) the amine of SEQ ID NO: 274 VH CDR1 has an amino acid sequence, and VH CDR has the amino acid sequence of SEQ ID NO 275. 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 276, comprising VH and (ii ) VL CDR1 having the amino acid sequence of SEQ ID NO: 277, and the amino acid sequence of SEQ ID NO: 278 VL CDR2 having a column, and VL CDR3 having the amino acid sequence of SEQ ID NO: 279 In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 280, SEQ ID NO: 28 VH CDR2 having amino acid sequence 1, and having amino acid sequence of SEQ ID NO: 282 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 283 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 284, and SEQ ID NO: 285 VL includes VL CDR3 having the amino acid sequence. In another embodiment, TRGV An antibody that binds to 9 is provided herein, and the antibody is (i) the amino acid sequence of SEQ ID NO: 286 VH CDR1 having the amino acid sequence of SEQ ID NO: 287, and VH containing VH CDR3 having the amino acid sequence of SEQ ID NO: 288, and (ii) sequence number VL CDR1 has the amino acid sequence of number 289, and has the amino acid sequence of sequence number 290. This includes VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 291. Includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 286, and the amino acid sequence of SEQ ID NO: 706 VH CDR2 having an anoic acid sequence, and VH C having the amino acid sequence of SEQ ID NO 707. VH containing DR3 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 289 VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and amino acid sequence of SEQ ID NO: 291 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, wherein the antibody has (i) the amino acid sequence of SEQ ID NO: 292 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 293, and SEQ ID NO: VH containing VH CDR3 having a 294 amino acid sequence, and (ii) SEQ ID NO: 295 VL CDR1 has the amino acid sequence of SEQ ID NO: 296. VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 297. Includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 298, and the amino acid sequence of SEQ ID NO: 299 VH CDR2 having the amino acid sequence of SEQ ID NO: 300, and VH CDR3 having the amino acid sequence of SEQ ID NO: 300. (ii) VH and VL CDR1 having the amino acid sequence of sequence number 301, sequence number VL CDR2 having the amino acid sequence of number 302, and the amino acid sequence of sequence number 303 The antibody contains VL CDR3, and VL. In some embodiments, the antibody has sequence number It contains VH having amino acid sequence number 36. In some embodiments, the antibody is SEQ ID NO. It contains a VL having an 8-amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 36 It contains VH having the amino acid sequence of SEQ ID NO: 8 and VL having the amino acid sequence of SEQ ID NO: 8. In several embodiments, the antibody has at least 95% of the amino acid sequence of SEQ ID NO: 36 It contains VH, which has an identical amino acid sequence. In some embodiments, the antibody is distributed Includes an amino acid sequence that has at least 95% identity with the amino acid sequence of column number 8. , including VL. In some embodiments, the antibody is compared to the amino acid sequence of SEQ ID NO: 36 VH and the amino acids of SEQ ID NO: 8, which contain amino acid sequences with at least 95% identity. It includes a VL containing an amino acid sequence having at least 95% identity with the sequence.

[0235] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence The amino acids of numbers 65, VH CDR1, VH CDR2, and VH CDR3, respectively. VH, including VH CDR1, VH CDR2, and VH CDR3 having acid sequences, (ii) VL CDR1, VL CDR2, and VL CD of Sequence ID No. 66, respectively. VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequence R3. It includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and is an anti The bodies are (i) VH CDR1, VH CDR2, and VH CDR1 of sequence number 67, respectively. VH CDR1, VH CDR2, and VH CDR3 have the amino acid sequence of CDR3. (ii) VH and VL CDR1 and VL CDR2 of sequence number 68, respectively. , and VL CDR1, VL CDR2, and VL CDR3, which have the amino acid sequence of VL CDR3. The present specification includes L CDR3 and VL. In another embodiment, the present specification includes an antibody that binds to TRGV9. Provided in the book, the antibody is (i) VH CDR1 having the amino acid sequence of Sequence ID No. 1, sequence VH CDR2 has the amino acid sequence of number 76, and has the amino acid sequence of SEQ ID NO: 3. (ii) VH containing VH CDR3, and VL having the amino acid sequence of SEQ ID NO: 77 VL CDR2 having the amino acid sequence of CDR1, SEQ ID NO: 5, and amino acid sequence of SEQ ID NO: 6 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, and the antibody has (i) the amino acid sequence of SEQ ID NO: 60. H CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and SEQ ID NO: 62 VH containing VH CDR3 having the amino acid sequence of (ii) the amino acid of SEQ ID NO: 63 VL CDR1 has an acid sequence, VL CDR2 has the amino acid sequence of SEQ ID NO: 64, and VL, which includes VL CDR3 having the amino acid sequence of SEQ ID NO: 6. Another embodiment Therefore, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) SEQ ID NO: 304 VH CDR1 has the amino acid sequence of SEQ ID NO: 305, VH VH includes VH CDR3 having the amino acid sequence of CDR2 and SEQ ID NO: 306, (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 307, and the amino acid sequence of SEQ ID NO: 308 VL CDR2 having an anoacid sequence, and VL C having the amino acid sequence of SEQ ID NO 309 The present invention includes DR3 and VL. In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody provided is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 310, sequence number VH CDR2 having the amino acid sequence of sequence number 311, and the amino acid sequence of sequence number 312 (ii) VH having VH CDR3 and having the amino acid sequence of SEQ ID NO: 313 VL CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 314, and SEQ ID NO: VL includes VL CDR3 having a 315 amino acid sequence. In another embodiment, T An antibody that binds to RGV9 is provided herein, and the antibody is (i) amino acid of SEQ ID NO: 316 VH CDR1 has an acid sequence, and VH CDR2 has the amino acid sequence of SEQ ID NO: 317. VH and (ii) VH CDR3 having the amino acid sequence of SEQ ID NO: 318 VL CDR1 having the amino acid sequence of SEQ ID NO: 319, amino acid sequence of SEQ ID NO: 320 VL CDR2 having the amino acid sequence of SEQ ID NO: 321, and VL CDR3 having the amino acid sequence of SEQ ID NO: 321 Includes, and includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, The antibodies are (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 322, SEQ ID NO: 323 VH CDR2 having the amino acid sequence of SEQ ID NO: 324, and V (ii) VH containing H CDR3 and VL C having the amino acid sequence of SEQ ID NO: 325 VL CDR2 having the amino acid sequence of DR1, SEQ ID NO: 326, and SEQ ID NO: 327 VL includes VL CDR3 having an amino acid sequence. In another embodiment, TRGV9 An antibody that binds to (i) the amino acid sequence of SEQ ID NO: 322 is provided herein, and the antibody VH CDR1 has the amino acid sequence of SEQ ID NO: 708, and VH CDR2 has the amino acid sequence of SEQ ID NO: 708, and VH containing VH CDR3 having the amino acid sequence of sequence number 709, and (ii) Sequence ID VL CDR1 has an amino acid sequence of 325, and has an amino acid sequence of SEQ ID NO: 326. VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 327 are included. Includes L. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 328, and amino acid sequence of SEQ ID NO: 329 VH CDR2 has an acid sequence, and VH CD has the amino acid sequence of SEQ ID NO: 330. VH containing R3, and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 331, VL CDR2 having the amino acid sequence of SEQ ID NO: 332, and the amino acid sequence of SEQ ID NO: 333 VL includes VL CDR3 having a sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, and the antibody has (i) the amino acid sequence of SEQ ID NO: 334. H CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 335, and SEQ ID NO: 3 VH containing VH CDR3 having a 36-amino acid sequence, and (ii) SEQ ID NO: 337 VL CDR1 has an amino acid sequence, and VL C has an amino acid sequence of SEQ ID NO: 338. VL contains DR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 339. In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) VH CDR1 having the amino acid sequence of sequence number 340, the amino acid sequence of sequence number 341 It contains VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 342. (ii) VH and VL CDR1 having the amino acid sequence of SEQ ID NO: 343, SEQ ID NO: VL CDR2 has an amino acid sequence of 344, and has an amino acid sequence of SEQ ID NO: 345 VL includes VL CDR3. In another embodiment, an antibody that binds to TRGV9 is Provided herein, the antibody is (i) VH CD having the amino acid sequence of SEQ ID NO: 346 R1, VH CDR2 having the amino acid sequence of SEQ ID NO: 347, and A VH containing VH CDR3 with a amino acid sequence, and (ii) the amino acid of SEQ ID NO: 349 VL CDR1 having the sequence, VL CDR2 having the amino acid sequence of SEQ ID NO: 350, VL and VL CDR3 having the amino acid sequence of SEQ ID NO: 351. In one embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody is (i) SEQ ID NO: 3 VH CDR1 has a 52-amino acid sequence, and V has the amino acid sequence of SEQ ID NO: 353. VH CDR3, which contains H CDR2 and the amino acid sequence of SEQ ID NO: 354, (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 355, SEQ ID NO: 356 VL CDR2 having an amino acid sequence, and VL having the amino acid sequence of SEQ ID NO: 357 The antibody comprising CDR3 and VL is described herein. In another embodiment, the antibody that binds to TRGV9 is described herein. The antibody provided is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 358, VH CDR2 having the amino acid sequence of sequence number 359, and the amino acid sequence of sequence number 360 VH containing VH CDR3 having a column, and (ii) having the amino acid sequence of SEQ ID NO: 361 VL CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and sequence VL includes VL CDR3 having amino acid sequence number 363. In another embodiment, An antibody that binds to TRGV9 is provided herein, and the antibody is (i) the antibody of SEQ ID NO: 358 VH CDR1 has a amino acid sequence, and VH CD has the amino acid sequence of SEQ ID NO: 710. VH and (i i) VL CDR1 having the amino acid sequence of SEQ ID NO: 361, amino acids of SEQ ID NO: 362 VL CDR2 having the sequence, and VL CDR having the amino acid sequence of SEQ ID NO: 363 In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 364, SEQ ID NO: 3 VH CDR2 has a 65-amino acid sequence, and has the amino acid sequence of SEQ ID NO: 366. (ii) VH containing VH CDR3 and VL having the amino acid sequence of SEQ ID NO: 367 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 368, and SEQ ID NO: 36 VL includes VL CDR3 having a 9-amino acid sequence. In another embodiment, TRG An antibody that binds to V9 is provided herein, and the antibody is (i) an amino acid compound of SEQ ID NO: 370 VH CDR1 having a column, VH CDR2 having the amino acid sequence of SEQ ID NO: 371, and VH and (ii) sequence containing VH CDR3 having the amino acid sequence of sequence number 372 VL CDR1 has amino acid sequence number 373, and has amino acid sequence number 374. Includes VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 375. , including VL. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 65. It contains VH. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 66 It contains VL. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 65. It includes H and VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, it is an anti The body contains VH having the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody It contains VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody is VH having the amino acid sequence of SEQ ID NO: 67, and V having the amino acid sequence of SEQ ID NO: 68 It includes L. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 71. The chain is included. In some embodiments, the antibody is a light chain having the amino acid sequence of SEQ ID NO: 72. Includes. In some embodiments, the antibody has a heavy chain having the amino acid sequence of SEQ ID NO: 71 and , comprising a light chain having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody is , containing the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody is SEQ ID NO: 74 It contains a heavy chain having the amino acid sequence of SEQ ID NO: 75 It contains a light chain having an amino acid sequence. In some embodiments, the antibody is the A of SEQ ID NO: 74 It contains a heavy chain having an amino acid sequence and a light chain having the amino acid sequence of SEQ ID NO: 75. In one embodiment, the antibody contains the amino acid sequence of SEQ ID NO: 73. In some embodiments, The antibody has at least 95% identity with the amino acid sequence of SEQ ID NO: 65. Contains VH, which contains the amino acid sequence. In some embodiments, the antibody contains the amino acid sequence of SEQ ID NO: 66. It contains a VL, which includes an amino acid sequence having at least 95% identity with the no-acid sequence. In some embodiments, the antibody is at least 95% relative to the amino acid sequence of SEQ ID NO: 65. VH and the amino acid sequence of SEQ ID NO: 66, which contain amino acid sequences with % identity. Includes VL containing an amino acid sequence having at least 95% identity. Several implementations Morphologically, the antibody has at least 95% identity with the amino acid sequence of SEQ ID NO: 67. The antibody contains VH, which includes the amino acid sequence. In some embodiments, the antibody is SEQ ID NO: 68 VL contains an amino acid sequence that has at least 95% identity with the amino acid sequence of the original. Includes. In some embodiments, the antibody is less than or equal to the amino acid sequence of SEQ ID NO: 67 VH and the amino acid sequence of sequence number 68 have 95% identical amino acid sequences. In contrast, it includes VL, which contains an amino acid sequence having at least 95% identity. In this embodiment, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO: 71. It contains a heavy chain containing an amino acid sequence having a property. In some embodiments, the antibody is a sequence number It includes an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 72, Light The chain is included. In some embodiments, the antibody is less than the amino acid sequence of SEQ ID NO: 71 A heavy chain containing an amino acid sequence with at least 95% identity, and the amino acid sequence of SEQ ID NO: 72 It includes a light chain containing an amino acid sequence having at least 95% identity with respect to the column. In some embodiments, the antibody contains the amino acid sequence of SEQ ID NO: 70. Therefore, the antibody has at least 95% identity with the amino acid sequence of SEQ ID NO: 74. It contains a heavy chain containing an amino acid sequence. In some embodiments, the antibody is the A of SEQ ID NO: 75 A light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence. In some embodiments, the antibody is at least 9 amino acids relative to the amino acid sequence of SEQ ID NO: 74. A heavy chain containing an amino acid sequence with 5% identity, and the amino acid sequence of SEQ ID NO: 75 It includes a light chain containing an amino acid sequence having at least 95% identity. In the application form, the antibody contains the amino acid sequence of SEQ ID NO: 73.

[0236] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence Number 104, each containing VH CDR1, VH CDR2, and VH CDR3 VH and VH CDR3, which include VH CDR1, VH CDR2, and VH CDR3 having an acid sequence. (ii) VL CDR1, VL CDR2, and VL CDR1 of Sequence ID No. 105, respectively. VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequence of CDR3. In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody has (i) the amino acid sequence of SEQ ID NO: 98, VH CDR1, SEQ ID NO: 99 VH CDR2 having an amino acid sequence, and VH having the amino acid sequence of SEQ ID NO: 100 (ii) VH containing CDR3 and VL CD having the amino acid sequence of SEQ ID NO: 101 VL CDR2 having the amino acid sequence of R1, SEQ ID NO: 102, and A VL includes VL CDR3 having a mino acid sequence. In another embodiment, TRGV9 A binding antibody is provided herein, and the antibody (i) has the amino acid sequence of SEQ ID NO: 412 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 413, and sequence VH containing VH CDR3 having amino acid sequence number 414, and (ii) SEQ ID NO: 4 VL CDR1 has a 15-amino acid sequence, and V has the amino acid sequence of SEQ ID NO: 416. VL CDR3 contains L CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 417. This includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is ( i) VH CDR1 having the amino acid sequence of SEQ ID NO: 418, amino acid sequence of SEQ ID NO: 419 VH CDR2 having the sequence, and VH CDR having the amino acid sequence of SEQ ID NO: 420 (ii) VH containing 3, and VL CDR1 having the amino acid sequence of SEQ ID NO: 421, VL CDR2 having the amino acid sequence of sequence number 422, and the amino acid sequence of sequence number 423 VL includes VL CDR3 which has columns. In another embodiment, it is coupled to TRGV9. An antibody is provided herein, and the antibody is (i) a VH having the amino acid sequence of SEQ ID NO: 424. VH CDR2 having the amino acid sequence of CDR1, SEQ ID NO: 425, and SEQ ID NO: 42 VH containing VH CDR3 having an amino acid sequence of 6, and (ii) the a of sequence number 427 VL CDR1 has a amino acid sequence, and VL CD has the amino acid sequence of SEQ ID NO: 428. VL includes VL CDR3 having the amino acid sequence of R2 and SEQ ID NO: 429. In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence VH CDR1 has amino acid sequence number 430, and has amino acid sequence number 431. Includes VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 432. , VH and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 433, SEQ ID NO: 4 VL CDR2 has a 34-amino acid sequence, and also has the amino acid sequence of SEQ ID NO: 435. In another embodiment, an antibody that binds to TRGV9 is included. Provided in the specification, the antibody is (i) a VH CDR having the amino acid sequence of SEQ ID NO: 430. 1. VH CDR2 having the amino acid sequence of SEQ ID NO: 714, and the amino acid sequence of SEQ ID NO: 715 VH containing VH CDR3 having an anoacid sequence, and (ii) the amino acid sequence of SEQ ID NO 433 VL CDR1 having a column, VL CDR2 having the amino acid sequence of SEQ ID NO: 434, and VL contains VL CDR3 having the amino acid sequence of SEQ ID NO: 435. In this specification, an antibody that binds to TRGV9 is provided, and the antibody is (i) SEQ ID NO: 43 VH CDR1 has an amino acid sequence of 6, and VH has an amino acid sequence of SEQ ID NO: 437. VH and VH CDR3, which has the amino acid sequence of CDR2 and SEQ ID NO: 438 (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 439, and SEQ ID NO: 440 VL CDR2 having a amino acid sequence, and VL having the amino acid sequence of SEQ ID NO: 441 The present invention includes CDR3 and VL. In another embodiment, an antibody that binds to TRGV9 is described herein. The provided antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 442, sequence VH CDR2 having amino acid sequence number 443, and amino acid sequence of SEQ ID NO: 444 VH containing VH CDR3 having (ii) the amino acid sequence of SEQ ID NO: 445 VL CDR1, VL CDR2 having the amino acid sequence of sequence number 446, and sequence number VL includes VL CDR3 having amino acid sequence 447. Several implementations Morphologically, the antibody contains VH having the amino acid sequence of SEQ ID NO: 104. Several implementations Morphologically, the antibody contains a VL having the amino acid sequence of SEQ ID NO: 105. Several implementations Morphologically, the antibody has VH with the amino acid sequence of SEQ ID NO: 104 and A with the amino acid sequence of SEQ ID NO: 105 It includes a VL having a mino acid sequence. In some embodiments, the antibody is SEQ ID NO: 106 It contains an amino acid sequence. In some embodiments, the antibody contains the amino acid sequence of SEQ ID NO: 104. It contains VH, which has an amino acid sequence with at least 95% identity to it. In this embodiment, the antibody has at least 95% of the same amino acid sequence as SEQ ID NO: 105. The VL contains a monogenetic amino acid sequence. In some embodiments, the antibody contains a sequence It contains an amino acid sequence that has at least 95% identity with amino acid sequence number 104. VH has at least 95% identity with the amino acid sequence of SEQ ID NO: 105. The antibody contains an amino acid sequence, VL, and in some embodiments, the antibody is SEQ ID NO: 106 It contains the amino acid sequence.

[0237] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence Number 113, each containing VH CDR1, VH CDR2, and VH CDR3 VH and VH CDR3, which include VH CDR1, VH CDR2, and VH CDR3 having an acid sequence. (ii) VL CDR1, VL CDR2, and VL CDR1 of sequence number 114, respectively. VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequence of CDR3. In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 107, SEQ ID NO: 10 VH CDR2 has an amino acid sequence of 8, and has an amino acid sequence of SEQ ID NO: 109 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 110 VL CDR2 having the amino acid sequence of CDR1, SEQ ID NO: 111, and SEQ ID NO: 112 VL includes VL CDR3 having the amino acid sequence. In another embodiment, TRGV An antibody that binds to 9 is provided herein, and the antibody is (i) the amino acid sequence of SEQ ID NO: 448 VH CDR1 having the amino acid sequence of SEQ ID NO: 449, and VH containing VH CDR3 having the amino acid sequence of SEQ ID NO: 450, and (ii) sequence number VL CDR1 has the amino acid sequence of sequence number 451, and has the amino acid sequence of sequence number 452. VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 453 are included. Includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 454, and the amino acid sequence of SEQ ID NO: 455 VH CDR2 having an anoic acid sequence, and VH C having the amino acid sequence of SEQ ID NO 456. VH containing DR3 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 457 VL CDR2 having the amino acid sequence of SEQ ID NO: 458, and amino acid sequence of SEQ ID NO: 459 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, and the antibody has (i) the amino acid sequence of SEQ ID NO: 460 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 461, and SEQ ID NO: VH containing VH CDR3 having a 462 amino acid sequence, and (ii) SEQ ID NO: 463 VL CDR1 has the amino acid sequence of [sequence number], and VL has the amino acid sequence of SEQ ID NO: 464. VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 465. Includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 466, amino acid sequence of SEQ ID NO: 467 VH CDR2 having the amino acid sequence of SEQ ID NO: 468, and VH CDR3 having the amino acid sequence of SEQ ID NO: 468 (ii) VH and VL CDR1 having the amino acid sequence of sequence number 469, sequence number VL CDR2 having the amino acid sequence of number 470, and the amino acid sequence of sequence number 471 VL includes VL CDR3 having VL. In another embodiment, an antibody that binds to TRGV9 Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 466, VH C VH CDR2 having the amino acid sequence of DR1, SEQ ID NO: 716, and SEQ ID NO: 717 VH containing VH CDR3 having an amino acid sequence, and (ii) amino acid of SEQ ID NO: 469 VL CDR1 has an acid sequence, and VL CDR2 has the amino acid sequence of SEQ ID NO: 470. VL includes VL CDR3 having the amino acid sequence of SEQ ID NO: 471. In one embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody is (i) SEQ ID NO: VH CDR1 has a 472-amino acid sequence, and has the amino acid sequence of SEQ ID NO: 473. VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 474 are included. H and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 475, SEQ ID NO: 476 VL CDR2 having the amino acid sequence of SEQ ID NO: 477, and V The present specification includes L CDR3 and VL. In another embodiment, the present specification includes an antibody that binds to TRGV9. Provided in the book, the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 478, VH CDR2 having the amino acid sequence of SEQ ID NO: 479, and the amino acid sequence of SEQ ID NO: 480 VH containing VH CDR3 having the sequence, and (ii) the amino acid sequence of SEQ ID NO: 481 VL CDR1 has the amino acid sequence of SEQ ID NO: 482, and VL includes VL CDR3 having the amino acid sequence of column number 483. In the embodiment, the antibody contains VH having the amino acid sequence of SEQ ID NO: 113. In the embodiment, the antibody contains a VL having the amino acid sequence of SEQ ID NO: 114. In this embodiment, the antibody has VH having the amino acid sequence of SEQ ID NO: 113 and SEQ ID NO: 114 It includes VL having the amino acid sequence of SEQ ID NO: 11. In some embodiments, the antibody is SEQ ID NO: 11 It contains a heavy chain having an amino acid sequence of 5. In some embodiments, the antibody is SEQ ID NO: 11 It contains a light chain having a sequence of 6 amino acids. In some embodiments, the antibody is SEQ ID NO: 11 It comprises a heavy chain having the amino acid sequence of 5 and a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody has at least the amino acid sequence of SEQ ID NO: 113 It contains VH, which has an amino acid sequence with 95% identity. In some embodiments, it contains anti The body has at least 95% identity with the amino acid sequence of SEQ ID NO: 114. The antibody contains an acid sequence, and contains VL. In some embodiments, the antibody is the amino acid sequence of SEQ ID NO: 113 VH and sequence number containing an amino acid sequence having at least 95% identity with the acid sequence. It includes an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 114. Includes VL. In some embodiments, the antibody is compared to the amino acid sequence of SEQ ID NO: 115 It contains a heavy chain that has at least 95% identity of amino acid sequences. In the application form, the antibody exhibits at least 95% identity with the amino acid sequence of SEQ ID NO: 116. It includes a light chain containing an amino acid sequence having the following characteristics. In some embodiments, the antibody is an SEQ ID NO. It includes an amino acid sequence that has at least 95% identity with 115 amino acid sequences. The heavy chain and an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 116. It contains a light chain that includes an acid sequence.

[0238] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence Numbers 123, respectively, are VH CDR1, VH CDR2, and VH CDR3. VH and VH CDR3, which include VH CDR1, VH CDR2, and VH CDR3 having an acid sequence. (ii) VL CDR1, VL CDR2, and VL CDR1 of sequence number 124, respectively. VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequence of CDR3. In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 117, SEQ ID NO: 11 VH CDR2 has an amino acid sequence of 8, and has an amino acid sequence of SEQ ID NO: 119 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 120 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and SEQ ID NO: 122 VL includes VL CDR3 having the amino acid sequence. In another embodiment, TRGV An antibody that binds to 9 is provided herein, and the antibody is (i) the amino acid sequence of SEQ ID NO: 484 VH CDR1 having, VH CDR2 having the amino acid sequence of SEQ ID NO: 485, and VH containing VH CDR3 having the amino acid sequence of sequence number 486, and (ii) sequence number VL CDR1 has the amino acid sequence of sequence number 487, and has the amino acid sequence of sequence number 488. This includes VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 489. Includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 490, and the amino acid sequence of SEQ ID NO: 491 VH CDR2 having an anoic acid sequence, and VH C having the amino acid sequence of SEQ ID NO 492. VH containing DR3 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 493 VL CDR2 having the amino acid sequence of SEQ ID NO: 494, and amino acid sequence of SEQ ID NO: 495 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, and the antibody has (i) the amino acid sequence of SEQ ID NO: 496 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 497, and SEQ ID NO: VH containing VH CDR3 having a 498-amino acid sequence, and (ii) SEQ ID NO: 499 VL CDR1 has the amino acid sequence of SEQ ID NO: 500, VL VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 501. Includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 502, amino acid sequence of SEQ ID NO: 503 VH CDR2 having the amino acid sequence of SEQ ID NO: 504, and VH CDR3 having the amino acid sequence of SEQ ID NO: 504 (ii) VH and VL CDR1 having the amino acid sequence of sequence number 505, sequence number VL CDR2 having the amino acid sequence of number 506, and the amino acid sequence of sequence number 507 VL includes VL CDR3 having VL. In another embodiment, an antibody that binds to TRGV9 Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 502, VH C VH CDR2 having the amino acid sequence of DR1, SEQ ID NO: 718, and SEQ ID NO: 719 VH containing VH CDR3 having an amino acid sequence, and (ii) the amino acid of SEQ ID NO: 505 VL CDR1 has an acid sequence, and VL CDR2 has the amino acid sequence of SEQ ID NO: 506. VL includes VL CDR3 having the amino acid sequence of SEQ ID NO: 507. In one embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody is (i) SEQ ID NO: VH CDR1 has a 508-amino acid sequence, and has the amino acid sequence of SEQ ID NO: 509. VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 510 are included. H and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 511, SEQ ID NO: 512 VL CDR2 having the amino acid sequence of SEQ ID NO: 513, and V The present specification includes L CDR3 and VL. In another embodiment, the present specification includes an antibody that binds to TRGV9. Provided in the book, the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 514, VH CDR2 having the amino acid sequence of SEQ ID NO: 515, and the amino acid sequence of SEQ ID NO: 516 VH containing VH CDR3 having the sequence, and (ii) the amino acid sequence of SEQ ID NO: 517 VL CDR1 has the amino acid sequence of SEQ ID NO: 518, and VL CDR2 has the amino acid sequence of SEQ ID NO: 518, and VL includes VL CDR3 having the amino acid sequence of column number 519. In the embodiment, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 123. In the embodiment, the antibody contains a VL having the amino acid sequence of SEQ ID NO: 124. In this embodiment, the antibody has VH having the amino acid sequence of SEQ ID NO: 123 and SEQ ID NO: 124 It includes VL having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody is SEQ ID NO: 12 It contains a heavy chain having an amino acid sequence of 5. In some embodiments, the antibody is SEQ ID NO: 12 It contains a light chain having a sequence of 6 amino acids. In some embodiments, the antibody is SEQ ID NO: 12 It comprises a heavy chain having the amino acid sequence of 5 and a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody has at least the amino acid sequence of SEQ ID NO: 123 It contains VH, which has an amino acid sequence with 95% identity. In some embodiments, it contains anti The body has at least 95% identity with the amino acid sequence of SEQ ID NO: 124. The antibody contains an acid sequence, and contains VL. In some embodiments, the antibody is the amino acid sequence of SEQ ID NO: 123. VH and sequence number containing an amino acid sequence having at least 95% identity with the acid sequence. It includes an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 124. Includes VL. In some embodiments, the antibody is compared to the amino acid sequence of SEQ ID NO: 125. It contains a heavy chain that has at least 95% identity of amino acid sequences. In the application form, the antibody exhibits at least 95% identity to the amino acid sequence of SEQ ID NO: 126. It includes a light chain containing an amino acid sequence having the following characteristics. In some embodiments, the antibody is an SEQ ID NO. It includes an amino acid sequence that has at least 95% identity with 125 amino acid sequences, The heavy chain and an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 126. It contains a light chain that includes an acid sequence.

[0239] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody (i) sequence Number 133, each containing VH CDR1, VH CDR2, and VH CDR3 VH and VH CDR3, which include VH CDR1, VH CDR2, and VH CDR3 having an acid sequence. (ii) VL CDR1, VL CDR2, and VL CDR1 of sequence number 134, respectively. VL CDR1, VL CDR2, and VL CDR3 have the amino acid sequence of CDR3. In another embodiment, an antibody that binds to TRGV9 is provided herein. The antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 127, SEQ ID NO: 12 VH CDR2 has an amino acid sequence of 8, and has an amino acid sequence of SEQ ID NO: 129 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 130 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and SEQ ID NO: 132 VL includes VL CDR3 having the amino acid sequence. In another embodiment, TRGV An antibody that binds to 9 is provided herein, and the antibody is (i) the amino acid sequence of SEQ ID NO: 520 VH CDR1 having the amino acid sequence of SEQ ID NO: 521, and VH CDR2 having the amino acid sequence of SEQ ID NO: 521, VH containing VH CDR3 having the amino acid sequence of sequence number 522, and (ii) sequence number VL CDR1 has the amino acid sequence of sequence number 523, and has the amino acid sequence of sequence number 524. VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 525 are included. Includes VL. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 526, and the amino acid sequence of SEQ ID NO: 527 VH CDR2 having an anoic acid sequence, and VH C having the amino acid sequence of SEQ ID NO 528. VH containing DR3 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 529 VL CDR2 having the amino acid sequence of SEQ ID NO: 530, and amino acid sequence of SEQ ID NO: 531 VL includes VL CDR3 having an acid sequence. In another embodiment, it is bound to TRGV9. An antibody is provided herein, and the antibody has (i) the amino acid sequence of SEQ ID NO: 532 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 533, and SEQ ID NO: VH containing VH CDR3 having an amino acid sequence of 534, and (ii) SEQ ID NO: 535 VL CDR1 has the amino acid sequence of SEQ ID NO: 536. VL includes CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 537. Includes. In another embodiment, an antibody that binds to TRGV9 is provided herein, and the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 538, amino acid sequence of SEQ ID NO: 539 VH CDR2 having the amino acid sequence of SEQ ID NO: 540, and VH CDR3 having the amino acid sequence of SEQ ID NO: 540. (ii) VH and VL CDR1 having the amino acid sequence of sequence number 541, sequence number VL CDR2 having the amino acid sequence of number 542, and the amino acid sequence of sequence number 543 VL includes VL CDR3 having VL. In another embodiment, an antibody that binds to TRGV9 Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 538, VH C VH CDR2 having the amino acid sequence of DR1, SEQ ID NO: 720, and SEQ ID NO: 721 VH containing VH CDR3 having an amino acid sequence, and (ii) amino acid of SEQ ID NO: 541 VL CDR1 has an acid sequence, and VL CDR2 has the amino acid sequence of SEQ ID NO: 542. VL includes VL CDR3 having the amino acid sequence of SEQ ID NO: 543. In one embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody is (i) SEQ ID NO: VH CDR1 has an amino acid sequence of 544, and has an amino acid sequence of SEQ ID NO: 545. VH CDR2 and VH CDR3 having the amino acid sequence of SEQ ID NO: 546 are included. H and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 547, SEQ ID NO: 548 VL CDR2 having the amino acid sequence of SEQ ID NO: 549, and V The present specification includes L CDR3 and VL. In another embodiment, the present specification includes an antibody that binds to TRGV9. Provided in the book, the antibody is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 550, VH CDR2 having the amino acid sequence of SEQ ID NO: 551, and the amino acid sequence of SEQ ID NO: 552 VH containing VH CDR3 having the sequence, and (ii) the amino acid sequence of SEQ ID NO: 553 VL CDR1 has the amino acid sequence of SEQ ID NO: 554, and VL CDR2 has the amino acid sequence of SEQ ID NO: 554, and VL includes VL CDR3 having the amino acid sequence of column number 555. In the embodiment, the antibody contains VH having the amino acid sequence of SEQ ID NO: 133. In the embodiment, the antibody contains a VL having the amino acid sequence of SEQ ID NO: 134. In this embodiment, the antibody is VH having the amino acid sequence of SEQ ID NO: 133 and SEQ ID NO: 134 It includes VL having the amino acid sequence of SEQ ID NO: 13. In some embodiments, the antibody is SEQ ID NO: 13 It contains a heavy chain having an amino acid sequence of 5. In some embodiments, the antibody is SEQ ID NO: 13 It contains a light chain having a sequence of 6 amino acids. In some embodiments, the antibody is SEQ ID NO: 13 It comprises a heavy chain having the amino acid sequence of 5 and a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody has at least the amino acid sequence of SEQ ID NO: 133 It contains VH, which has an amino acid sequence with 95% identity. In some embodiments, it contains anti The body has at least 95% identity with the amino acid sequence of SEQ ID NO: 134. The antibody contains an acid sequence, and contains VL. In some embodiments, the antibody is the amino acid sequence of SEQ ID NO: 133. VH and sequence number containing an amino acid sequence having at least 95% identity with the acid sequence. It contains an amino acid sequence that has at least 95% identity with the amino acid sequence of No. 134. Includes VL. In some embodiments, the antibody is compared to the amino acid sequence of SEQ ID NO: 135 It contains a heavy chain that has at least 95% identity of amino acid sequences. In the application form, the antibody exhibits at least 95% identity to the amino acid sequence of SEQ ID NO: 136. It includes a light chain containing an amino acid sequence having the following characteristics. In some embodiments, the antibody is an SEQ ID NO. It includes an amino acid sequence that has at least 95% identity with 135 amino acid sequences. The heavy chain and an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 136. It contains a light chain that includes an acid sequence.

[0240] In some embodiments, the anti-TRGV9 antibody is not a single-chain antibody. In this state, the anti-TRGV9 antibody is not a single-domain antibody. In some embodiments, the anti- TRGV9 antibodies are not nanobodies. In certain embodiments, anti-TRGV9 antibodies are V It is not an HH antibody. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody.

[0241] In some embodiments, the anti-TRGV9 antibodies provided herein are, respectively, sequence VH CDR1, VH CDR having amino acid sequences numbered 730, 731, and 732 2, and does not include VH CDR3. In some embodiments, the anti- The TRGV9 antibodies have the amino acid sequences of SEQ ID NOs. 733, 734, and 735, respectively. It does not include VH CDR1, VH CDR2, and VH CDR3. Some implementations In terms of form, the anti-TRGV9 antibodies provided herein are, respectively, SEQ ID NOs. 736 and 736. VH CDR1, VH CDR2, and VH C have amino acid sequences 7 and 738, respectively. It does not contain DR3. In some embodiments, the anti-TRGV9 antibody provided herein is These are VH CDRs having the amino acid sequences of SEQ ID NOs. 739, 740, and 741, respectively. 1. Does not include VH CDR2 and VH CDR3. In some embodiments, this specification does not include The anti-TRGV9 antibodies provided in this book are, respectively, SEQ ID NOs. 742, 743, and 744. VH CDR1, VH CDR2, and VH CDR3, which have amino acid sequences, are not included. In some embodiments, the anti-TRGV9 antibodies provided herein are, respectively, sequence VH CDR1, VH CDR having amino acid sequences 745, 746, and 747 2, and does not include VH CDR3. In some embodiments, the anti- The TRGV9 antibodies have the amino acid sequences of SEQ ID NOs. 748, 749, and 750, respectively. It does not include VH CDR1, VH CDR2, and VH CDR3. Some implementations In terms of form, the anti-TRGV9 antibody provided herein has the amino acid sequence of SEQ ID NO: 751 It does not contain the VH domain. In some embodiments, the anti-TR provided herein The GV9 antibody does not contain the VH domain with the amino acid sequence of SEQ ID NO: 752. In that embodiment, the anti-TRGV9 antibody provided herein is the amino acid of SEQ ID NO: 753 It does not contain a VH domain having an acid sequence. In some embodiments provided herein The anti-TRGV9 antibody does not contain the VH domain with the amino acid sequence of SEQ ID NO: 754. In some embodiments, the anti-TRGV9 antibody provided herein is SEQ ID NO: 755 It does not contain a VH domain having the amino acid sequence. In some embodiments, as specified herein The provided anti-TRGV9 antibody has a VH domain with the amino acid sequence of SEQ ID NO: 756. Not included. In some embodiments, the anti-TRGV9 antibodies provided herein are sequence numbers It does not contain the VH domain having amino acid sequence 757.

[0242] In another embodiment, V has the amino acid sequence APNxGzYTbDF (SEQ ID NO: 758). An anti-TRGV9 antibody containing a VH domain including H CDR3 is provided herein. Then x is Y or M, z is M or D, and b is I or L. In another form... The anti-TRGV9 antibody contains a VH domain that includes the amino acid sequence of SEQ ID NO: 758. Provided in the details. In another embodiment, the amino acid sequence of GxTFzz (SEQ ID NO: 761) is An anti-TRGV9 antibody comprising a VH domain including VH CDR1 is provided herein. Here, x is F, D, or G, and z is S or N. In another embodiment, the sequence number An anti-TRGV9 antibody comprising a VH domain containing amino acid sequence 761 is provided herein. In another embodiment, VL having the amino acid sequence RxSQSz (SEQ ID NO: 762) An anti-TRGV9 antibody containing a VL domain including CDR1 is provided herein, and here, x is A or S, and Z is V or L. In another embodiment, amino acid of SEQ ID NO: 761 An anti-TRGV9 antibody comprising a VL domain containing an acid sequence is provided herein.

[0243] In another embodiment, an antibody that binds to TRGV9 is provided herein, wherein the antibody is (i) VH (ii) VH and VL CDs, including CDR1, VH CDR2, and VH CDR3. VL includes R1, VL CDR2, and VL CDR3. Several embodiments VH CDR1 contains a first polar amino acid. In some embodiments, VH CDR1 contains the last polar uncharged amino acid. In some embodiments, VH CDR 1 contains at least one tyrosine. In some embodiments, VH CDR1 is It contains at least 20% hydrophobic amino acids. In some embodiments, VH CDR1 is , comprising at least two hydrophobic amino acids. In some embodiments, VH CDR1 is , containing at least about 40% hydrophobic amino acids. In some embodiments, VH CDR 1 contains, VH CDR1 is the first polar amino acid, the last polar uncharged amino acid, less at least one tyrosine, at least 20% hydrophobic amino acids, at least two hydrophobic amino acids It contains amino acids and at least about 40% hydrophobic amino acids. Structure of VH CDR1 shown above. Any combination of two or more of the features is also intended. Several embodiments In VH CDR2, residue 13 contains a polar amino acid. In some embodiments, V H CDR2 contains hydrophobicity at amino acid position 15. In some embodiments, VH C DR2 has phenylalanine (F) or leucine (L) at position 15. ) contains. In some embodiments, VH CDR2 contains a polar amino acid at position 14. In some embodiments, VH CDR2 has lysine (K) or serine at position 14. (Contains serine, S). In some embodiments, VH CDR2 has hydrophobic amine at position 2. It contains an acid. In some embodiments, VH CDR2 contains a hydrophobic amino acid at the 3-position. In some embodiments, VH CDR2 contains the second-to-last amino acid of polarity. In some embodiments, VH CDR2 has a polar amino acid at residue 13 and a hydrophobic amino acid at position 15. Sexual amino acids, phenylalanine (F) or leucine (L) at position 15, polar amino acid at position 14 Acid, lysine (K) or serine (S) at position 14, hydrophobic amino acid at position 2 or 3, and polar It contains the second-to-last amino acid. Two of the structural features of VH CDR2 described above or Any combination of three or more is also considered. In some embodiments, VH CDR3 is , does not contain a polar charged amino acid at position 3. In some embodiments, VH CDR3 is 7 It contains a hydrophobic or polarly charged amino acid at the position. In some embodiments, VH CDR3 is The 6-position contains a polar uncharged or hydrophobic amino acid. In some embodiments, VH CDR3 It does not contain a polar charged amino acid at position 3, but has a hydrophobic or polar charged amino acid at position 7, and at position 6 Contains polar uncharged or hydrophobic amino acids. Two of the structural characteristics of VH CDR3 described above. Alternatively, any combination of three or more may be considered. In some embodiments, VL CDR 1 contains a polar amino acid at position 4. In some embodiments, VL CDR1 is polar. It contains a first amino acid which is an electrode. In some embodiments, VL CDR1 has a electrode at position 2. It contains a non-charged or hydrophobic amino acid. In some embodiments, VL CDR1 is at position 3. It contains serine. In some embodiments, VL CDR1 contains a polar amino acid at position 5. Hmm. In some embodiments, VL CDR1 contains a hydrophobic amino acid at position 6. How many? In that embodiment, VL CDR1 is a polar amino acid at position 4, with a polar charge, the first amino acid ano acids, polar uncharged or hydrophobic amino acids at position 2, serine at position 3, polar amino acids at position 5, and Contains a hydrophobic amino acid at position 6. Two or three of the structural features of VL CDR1 described above. Any combination of the above is also considered. In some embodiments, VL CDR2 is 7 It contains a polar amino acid at the 6 position. In some embodiments, VL CDR2 has a polar charge at the 6 position. or contains hydrophobic amino acids. In some embodiments, VL CDR2 has a polar charge at the 3-position. Contains electro-amino acids. In some embodiments, VL CDR2 has polar uncharged amino acids at the 4-position. It contains an acid. In some embodiments, VL CDR2 contains a hydrophobic amino acid at the 2-position. In some embodiments, VL CDR2 has a polar amino acid at position 7, a polar charge at position 6, or It is a hydrophobic amino acid, a polar charged amino acid at position 3, a polar uncharged amino acid at position 4, and a hydrophobic amino acid at position 2. Contains aqueous amino acids. Two or more of the structural features of VL CDR2 described above. Intended combinations are also considered. In some embodiments, the VL CDR3 has a hydrophobic end. It contains amino acids. In some embodiments, VL CDR3 contains terminal tyrosine. In some embodiments, VL CDR3 contains a polar uncharged amino acid at position 5. In some embodiments, VL CDR3 contains a polar amino acid at position 2. VL CDR3 contains a polar uncharged or hydrophobic amino acid at position 1. Several implementations In this state, VL CDR3 contains a hydrophobic amino acid at the 3-position. In some embodiments, V L CDR3 contains a hydrophilic or polar uncharged amino acid at the 6-position. In some embodiments, VL CDR3 does not contain a polar or hydrophobic amino acid at position 7. In some embodiments, VL CDR3 is a hydrophobic terminal amino acid, terminal tyrosine, and polar uncharged amino acid at position 5. , polar amino acid at position 2, polar uncharged or hydrophobic amino acid at position 1, hydrophobic amino acid at position 3, It contains a hydrophilic or polar uncharged amino acid at position 6, and does not contain a polar or hydrophobic amino acid at position 7. Any combination of two or more of the above structural features of VL CDR3 may also be considered. As shown in the figure, in certain embodiments, residue numbering follows exemplary numbering.

[0244] In some embodiments, the anti-TRGV9 antibody is a multispecific antibody. Other embodiments Therefore, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, it is a multispecific antibody. The body contains antigen-binding fragments of the anti-TRGV9 antibody provided herein. In this embodiment, the multispecific antibody binds to a first TRGV9 epitope. It includes a domain and a second domain that binds to a second TRGV9 epitope, and the first T The RGV9 epitope and the second TRGV9 epitope are different. In certain embodiments, multiple Heavily specific antibodies further include a third binding domain that binds to targets other than TRGV9.

[0245] In another embodiment, (a) a first binding domain that binds to TRGV9, and (b) TRGV9 A bispecific antibody comprising a second binding domain that binds to a second target, not the first, is described herein. It will be provided to.

[0246] In some embodiments, the bispecific antibody includes a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain includes a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain includes a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain connects the heavy chain variable region and the light chain variable region. The second binding domain includes a heavy chain variable region and a light chain variable region. Several implementations In this context, the TRGV9 antibody is not a single-domain antibody or a nanobody.

[0247] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the respective VH C of sequence number 7. VH CDR1 having the amino acid sequences of DR1, VH CDR2, and VH CDR3, VH and (ii) Sequence ID 8, including VH CDR2 and VH CDR3, respectively VL CDR1, VL CDR2, and VL CDR3 have amino acid sequences. VL includes CDR1, VL CDR2, and VL CDR3. In another embodiment, A bispecific antibody is provided herein, wherein the antibody has a first binding to (a) TRGV9 (b) A domain and a second binding domain that binds to a second target other than TRGV9. The first binding domain is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and having the amino acid sequence of SEQ ID NO: 3 (ii) VH containing VH CDR3, and VL having the amino acid sequence of SEQ ID NO: 4. VL CDR2 having the amino acid sequence of CDR1, SEQ ID NO: 5, and amino acid sequence of SEQ ID NO: 6 VL comprises VL CDR3 having an acid sequence. In another embodiment, a bispecific antibody is The antibodies provided herein have (a) a first binding domain that binds to TRGV9, and (b ) comprising a second binding domain that binds to a second target other than TRGV9, and the first binding domain The main components are (i) VH CDR1 with the amino acid sequence of SEQ ID NO: 160, and SEQ ID NO: 16 VH CDR2 having amino acid sequence 1, and having amino acid sequence of SEQ ID NO: 162 VH containing VH CDR3 and (ii) VL having the amino acid sequence of SEQ ID NO: 163 CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 164, and SEQ ID NO: 165 VL includes VL CDR3 having the amino acid sequence. In another embodiment, bispecific Sex antibodies are provided herein, and the antibody has (a) a first binding domain that binds to TRGV9. (b) a second binding domain that binds to a second target other than TRGV9, and the first The binding domain is (i) VH CDR1 having the amino acid sequence of sequence number 166, sequence VH CDR2 having amino acid sequence number 167, and amino acid sequence of SEQ ID NO: 168 VH containing VH CDR3 having (ii) the amino acid sequence of SEQ ID NO: 169 VL CDR1, VL CDR2 having the amino acid sequence of sequence number 170, and sequence number VL includes VL CDR3 having amino acid sequence 171. In another embodiment, A bispecific antibody is provided herein, wherein the antibody has a first binding to (a) TRGV9 (b) A domain and a second binding domain that binds to a second target other than TRGV9. The first binding domain is (i) a VH CDR having the amino acid sequence of SEQ ID NO: 172. 1. VH CDR2 having the amino acid sequence of SEQ ID NO: 173, and the amino acid sequence of SEQ ID NO: 174 VH containing VH CDR3 having an anoacid sequence, and (ii) the amino acid sequence of SEQ ID NO 175 VL CDR1 having a column, VL CDR2 having the amino acid sequence of SEQ ID NO: 176, and VL contains VL CDR3 having the amino acid sequence of SEQ ID NO: 177. In this specification, a bispecific antibody is provided, wherein the antibody (a) binds to TRGV9. (b) A binding domain that binds to a second target that is not TRGV9. The first binding domain contains (i) VH having the amino acid sequence of SEQ ID NO: 178. VH CDR2 having the amino acid sequence of CDR1, SEQ ID NO: 179, and SEQ ID NO: 18 VH containing VH CDR3 having amino acid sequence 0, and (ii) the a of sequence number 181 VL CDR1 has a amino acid sequence, and VL CD has the amino acid sequence of SEQ ID NO: 182. VL includes VL CDR3 having the amino acid sequence of R2 and SEQ ID NO: 183. In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first binding domain includes (i) the amino acid sequence of SEQ ID NO: 178 VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 700, and sequence VH containing VH CDR3 having amino acid sequence number 701, and (ii) SEQ ID NO: 1 VL CDR1 has an amino acid sequence of 81, and V has an amino acid sequence of SEQ ID NO: 182. VL CDR3 contains L CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 183. This includes (a)TRG (b) The first binding domain binds to V9, and (b) the second target binds to a target other than TRGV9. The first binding domain includes a second binding domain, and the first binding domain is (i) the amino acid of SEQ ID NO: 184 VH CDR1 having the sequence, VH CDR2 having the amino acid sequence of SEQ ID NO: 185, VH and (ii) a combination of VH CDR3 having the amino acid sequence of SEQ ID NO: 186 VL CDR1 having the amino acid sequence of sequence number 187, the amino acid sequence of sequence number 188 It contains VL CDR2 and VL CDR3 having the amino acid sequence of SEQ ID NO: 189. This includes VL. In another embodiment, a bispecific antibody is provided herein, and the antibody is (a (b) a first binding domain that binds to TRGV9, and (b) a second target that is not TRGV9. The first binding domain includes a second binding domain, the first binding domain being (i) Sequence ID 190 VH CDR1 has an amino acid sequence, and VH C has an amino acid sequence of SEQ ID NO: 191. VH and (VH CDR3 having the amino acid sequence of DR2 and SEQ ID NO: 192) ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 193, and amino acid sequence of SEQ ID NO: 194 VL CDR2 has an acid sequence, and VL CD has the amino acid sequence of SEQ ID NO: 195. Includes R3 and VL. In some embodiments, the first binding domain is sequence number It contains VH having an amino acid sequence of 7. In some embodiments, the first binding domain is , containing VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first bond The domain has VH with the amino acid sequence of SEQ ID NO: 7 and SEQ ID NO: 8 It includes the VL. In some embodiments, the first binding domain is the A of Sequence ID No. 23. It contains a heavy chain having a mino acid sequence. In some embodiments, the first binding domain is sequence It contains a light chain having amino acid sequence number 24. In some embodiments, the first binding domain The yin has a heavy chain having the amino acid sequence of SEQ ID NO: 23 and an amino acid sequence of SEQ ID NO: 24 It includes a light chain. In some embodiments, the first binding domain is the A of Sequence ID No. 17 It contains a amino acid sequence. In some embodiments, the first binding domain is the a of sequence number 69. It contains a heavy chain having a mino acid sequence. In some embodiments, the first binding domain is sequence It contains a light chain having amino acid sequence number 24. In some embodiments, the first binding domain The yin has a heavy chain with the amino acid sequence of SEQ ID NO: 69 and an amino acid sequence of SEQ ID NO: 24. It includes a light chain. In some embodiments, the first binding domain is the amine of Sequence ID No. 7. It contains a VH that includes an amino acid sequence having at least 95% identity with the no-acid sequence. In some embodiments, the first binding domain is slightly different to the amino acid sequence of SEQ ID NO: 8. Includes a VL containing an amino acid sequence having at least 95% identity. Several embodiments Therefore, the first binding domain is at least 95% identical to the amino acid sequence of SEQ ID NO: 7. VH, which contains a monogeneous amino acid sequence, and at least the amino acid sequence of SEQ ID NO: 8 It also includes VL, which contains an amino acid sequence having 95% identity. In some embodiments, The first binding domain is at least 95% identical to the amino acid sequence of SEQ ID NO: 23. It contains a heavy chain containing an amino acid sequence having properties. In some embodiments, the first binding domain The amino acid has at least 95% identity with the amino acid sequence of SEQ ID NO: 24. It contains an acid sequence and a light chain. In some embodiments, the first binding domain is sequence number A heavy amino acid sequence containing an amino acid sequence that has at least 95% identity with 23 amino acid sequences. The chain and amino acids having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. The sequence includes a light chain. In some embodiments, the first binding domain is the sequence number. It contains a sequence of 17 amino acids. In some embodiments, the first binding domain is sequence number A heavy amino acid sequence containing an amino acid sequence that has at least 95% identity with 69 amino acid sequences. The chain is included. In some embodiments, the first binding domain is the amino acid sequence of SEQ ID NO: 24. It contains a light chain that has at least 95% identity with respect to the column. In that embodiment, the first binding domain is less than the amino acid sequence of SEQ ID NO: 69 The heavy chain and the amino acid sequence of SEQ ID NO: 24 both contain amino acid sequences with 95% identity. It includes a light chain containing an amino acid sequence having at least 95% identity with respect to the given amino acid sequence.

[0248] In another embodiment, a bispecific antibody is provided herein, wherein the antibody is (a) bound to TRGV9. (b) The first binding domain and the second binding domain which binds to a second target that is not TRGV9 The first combining domain includes (i) the VH of sequence number 34. VH CDR1 has the amino acid sequences of CDR1, VH CDR2, and VH CDR3. VH, including VH CDR2 and VH CDR3, and (ii) Sequence ID 8, each Therefore, VL has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3. VL includes CDR1, VL CDR2, and VL CDR3. In another embodiment, A bispecific antibody is provided herein, wherein the antibody (a) has a first specificity that binds to TRGV9. (b) The binding domain and a second binding domain that binds to a second target other than TRGV9 The first binding domain includes (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1. VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and the amino acid sequence of SEQ ID NO: 31 VH containing VH CDR3 having (ii) V having the amino acid sequence of SEQ ID NO: 4 L CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and A VL comprises VL CDR3 having a mino acid sequence. In another embodiment, bispecific anti The body provided herein is an antibody having (a) a first binding domain that binds to TRGV9, (b) comprising a second binding domain that binds to a second target other than TRGV9, and the first binding The combined domain is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 196, SEQ ID NO: VH CDR2 has an amino acid sequence of 197, and has an amino acid sequence of SEQ ID NO: 198 (ii) VH containing VH CDR3, and V having the amino acid sequence of SEQ ID NO: 199 L CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and SEQ ID NO: 2 VL includes VL CDR3 having the amino acid sequence 01. In another embodiment, dual A specific antibody is provided herein, and the antibody (a) binds to TRGV9 as a first binding domain (b) comprising a second binding domain that binds to a second target other than TRGV9, The first binding domain is (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 202, VH CDR2 having the amino acid sequence of SEQ ID NO: 203, and the amino acid sequence of SEQ ID NO: 204 VH containing VH CDR3 having the sequence, and (ii) the amino acid sequence of SEQ ID NO: 205 VL CDR1 has the amino acid sequence of SEQ ID NO: 206, and VL CDR2 has the amino acid sequence of SEQ ID NO: 206, and VL includes VL CDR3 having the amino acid sequence of column number 207. In another embodiment, A bispecific antibody is provided herein, wherein the antibody (a) first binds to TRGV9 (b) A binding domain and a second binding domain that binds to a second target other than TRGV9. The first binding domain is (i) VH C having the amino acid sequence of SEQ ID NO: 208. VH CDR2 having the amino acid sequence of DR1, SEQ ID NO: 209, and SEQ ID NO: 210 VH containing VH CDR3 having an amino acid sequence, and (ii) the amino acid of SEQ ID NO: 211 VL CDR1 has an acid sequence, and VL CDR2 has the amino acid sequence of SEQ ID NO: 212. VL includes VL CDR3 having the amino acid sequence of SEQ ID NO: 213. In this embodiment, a bispecif...

Claims

1. A pharmaceutical composition comprising a bispecific antibody for the treatment of blood cancer, The aforementioned bispecific antibody is (a) A first binding domain that binds to TRGV9, (b) comprising a second binding domain that binds to a second target other than TRGV9, The first binding domain is (A) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6, (B) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6, (C) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6, (D) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6, (E) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 77, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6, (F) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 60, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and VH CDR3 having the amino acid sequence of SEQ ID NO: 62, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 63, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6, (G) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 89, VH CDR2 having the amino acid sequence of SEQ ID NO: 90, and VH CDR3 having the amino acid sequence of SEQ ID NO: 91, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 92, VL CDR2 having the amino acid sequence of SEQ ID NO: 93, and VL CDR3 having the amino acid sequence of SEQ ID NO: 94, (H) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 98, VH CDR2 having the amino acid sequence of SEQ ID NO: 99, and VH CDR3 having the amino acid sequence of SEQ ID NO: 100, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and VL CDR3 having the amino acid sequence of SEQ ID NO: 103, (I) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 107, VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and VH CDR3 having the amino acid sequence of SEQ ID NO: 109, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and VL CDR3 having the amino acid sequence of SEQ ID NO: 112, (J) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 117, VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and VH CDR3 having the amino acid sequence of SEQ ID NO: 119, (ii) VL including VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and VL CDR3 having the amino acid sequence of SEQ ID NO: 122, or (K) (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 127, VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and VH CDR3 having the amino acid sequence of SEQ ID NO: 129, (ii) A VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and VL CDR3 having the amino acid sequence of SEQ ID NO: 132, The second target is a cancer antigen present on the surface of cancer cells. Pharmaceutical composition.

2. (A) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 34, and / or VL having the amino acid sequence of SEQ ID NO: 8, (B) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 35 and / or VL having the amino acid sequence of SEQ ID NO: 8, (C) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 36, and / or VL having the amino acid sequence of SEQ ID NO:

8. (D) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 7 and / or VL having the amino acid sequence of SEQ ID NO:

8. (E) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 65 and / or VL having the amino acid sequence of SEQ ID NO: 66 (F) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 67 and / or VL having the amino acid sequence of SEQ ID NO:

68. (G) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 95 and / or VL having the amino acid sequence of SEQ ID NO: 96 (H) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 104 and / or VL having the amino acid sequence of SEQ ID NO:

105. (I) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 113 and / or VL having the amino acid sequence of SEQ ID NO: 114, (J) The first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 123 and / or VL having the amino acid sequence of SEQ ID NO: 124, or (K) The pharmaceutical composition according to claim 1, wherein the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 133 and / or VL having the amino acid sequence of SEQ ID NO:

134.

3. The pharmaceutical composition according to claim 1 or 2, wherein the antigen on the surface of the cancer cells is a tumor-specific antigen, a tumor-associated antigen, or a novel antigen.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the second target is CD123.

5. The second binding domain described above is (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 9, VH CDR2 having the amino acid sequence of SEQ ID NO: 10, and VH CDR3 having the amino acid sequence of SEQ ID NO: 11, (ii) The pharmaceutical composition according to claim 4, comprising VL having the amino acid sequence of SEQ ID NO: 12, VL having the amino acid sequence of SEQ ID NO: 13, and VL having the amino acid sequence of SEQ ID NO:

14.

6. The pharmaceutical composition according to claim 5, wherein the second binding domain comprises VH having the amino acid sequence of SEQ ID NO: 15 and / or VL having the amino acid sequence of SEQ ID NO:

16.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the TRGV9 is present on the surface of γδ T cells.

8. The pharmaceutical composition according to any one of claims 1 to 6, wherein the TRGV9 is present on the surface of γδ T cells, and the second target is a cancer antigen expressed on the surface of cancer cells.

9. The pharmaceutical composition according to claim 8, wherein when the bispecific antibody binds to the TRGV9 on the surface of the γδ T cells and to the antigen on the surface of the cancer cells, the cancer cells are killed.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the first binding domain is humanized, the second binding domain is humanized, or both the first and second binding domains are humanized.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the bispecific antibody is an IgG antibody.

12. The pharmaceutical composition according to claim 11, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

13. A pharmaceutical composition for treating hematological cancers comprising an isolated TRGV9 bispecific antibody or its antigen-binding fragment, wherein the isolated TRGV9 bispecific antibody or its antigen-binding fragment is a. The first heavy chain (HC1), b. The second heavy chain (HC2), c. The first light chain (LC1), d. Including a second light chain (LC2), (A) HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 33, respectively, or iv. Each comprises heavy chain complementarity determination regions 1 (HCDR1), HCDR2, and HCDR3, respectively, which include the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO:

3. LC1 includes light chain complementarity determining regions 1 (LCDR1), LCDR2, and LCDR3, respectively, which contain the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, and forms a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, (B) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. LC1 contains LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, forming a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, (C) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, forming a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, (D) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. LC1 contains LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, forming a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, (E) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, (F) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, (G) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen, or (H)HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, forming a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen. The binding site for the first antigen binds to TRGV9 on γδ T cells, A pharmaceutical composition wherein the binding site for a second antigen binds to a cancer antigen present on the surface of a cancer cell.

14. (A) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 65, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 67, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 95, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104, and LC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 113, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 123, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 13, wherein (H)HC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO:

134.

15. (A) HC1 contains the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains the amino acid sequence of SEQ ID NO: 67, and LC1 contains the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains the amino acid sequence of SEQ ID NO: 95, and LC1 contains the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains the amino acid sequence of SEQ ID NO: 104, and LC1 contains the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains the amino acid sequence of SEQ ID NO: 113, and LC1 contains the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains the amino acid sequence of SEQ ID NO: 123, and LC1 contains the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 14, wherein (H)HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

16. The pharmaceutical composition according to any one of claims 13 to 15, wherein the binding of the bispecific antibody to TRGV9 present on the surface of the γδ T cells and the binding of the bispecific antibody to the cancer antigen present on the surface of the cancer cells result in the death of the cancer cells.

17. The pharmaceutical composition according to any one of claims 13 to 16, wherein HC1 and LC1 are humanized.

18. The pharmaceutical composition according to any one of claims 13 to 17, wherein HC2 and LC2 are bonded to CD123.

19. The pharmaceutical composition according to any one of claims 13 to 18, wherein the bispecific antibody or its antigen-binding fragment is an IgG1, IgG2, IgG3, or IgG4 isotype.

20. The pharmaceutical composition according to any one of claims 13 to 19, wherein the bispecific antibody or its antigen-binding fragment is an IgG4 isotype.

21. The bispecific antibody or its antigen-binding fragment has an EC of less than 500 pM. ５０ This induces γδ T cell-dependent cytotoxicity in cancer cells in vitro. The bispecific antibody or its antigen-binding fragment has an EC of less than 300 pM. ５０ This induces γδ T cell-dependent cytotoxicity in cancer cells in vitro, or The bispecific antibody or its antigen-binding fragment has an EC of less than 160 pM. ５０ This induces γδ T cell-dependent cytotoxicity in cancer cells in vitro. A pharmaceutical composition according to any one of claims 13 to 20.

22. The EC ５０ The pharmaceutical composition according to claim 21, which is evaluated with a mixture of γδ T effector cells and Kasumi3 AML target cells.

23. The ratio of effector cells to target cells is 0.01:1 to 5:

1. The ratio of effector cells to target cells is 0.1:1 to 2:1, or The ratio of effector cells to target cells is 1:

1. The pharmaceutical composition according to claim 22.

24. The bispecific antibody or its antigen-binding fragment is polyvalent. The bispecific antibody or its antigen-binding fragment can bind to at least three antigens, or The pharmaceutical composition according to any one of claims 13 to 23, wherein the bispecific antibody or its antigen-binding fragment can bind to at least five antigens.

25. A pharmaceutical composition for treating hematological cancers comprising an isolated γδ T cell bispecific antibody or its antigen-binding fragment, wherein the isolated γδ T cell bispecific antibody or its antigen-binding fragment is a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, (A) HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 33, respectively, or iv. Each comprises HCDR1, HCDR2, and HCDR3, which contain the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen on the γδ T cell. (B) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen on the γδ T cell. (C) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen on the γδ T cell, (D) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for the first antigen on the γδ T cell. (E) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for the first antigen on the γδ T cell, (F) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for the first antigen on γδ T cells, (G) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for the first antigen on γδ T cells, or (H)HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, forming a binding site for the first antigen on γδ T cells. HC2 and LC2 form binding sites for the second antigen. A pharmaceutical composition wherein the second antigen is a cancer antigen present on the surface of cancer cells.

26. A pharmaceutical composition for treating hematological cancers comprising an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment, wherein the isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment is a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, (A) HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 33, respectively, or iv. Each comprises HCDR1, HCDR2, and HCDR3, which contain the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, (B) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, (C) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, (D) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, (E) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, (F) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, (G) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen that specifically binds to Vγ9, or (H)HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, forming a binding site for a first antigen that specifically binds to Vγ9. A pharmaceutical composition in which HC2 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, and LC2 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, to form a binding site for a second antigen that specifically binds to CD123.

27. (A) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 65, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 67, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 95, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104, and LC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 113, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 123, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 26, wherein (H)HC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO:

134.

28. (A) HC1 contains the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains the amino acid sequence of SEQ ID NO: 67, and LC1 contains the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains the amino acid sequence of SEQ ID NO: 95, and LC1 contains the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains the amino acid sequence of SEQ ID NO: 104, and LC1 contains the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains the amino acid sequence of SEQ ID NO: 113, and LC1 contains the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains the amino acid sequence of SEQ ID NO: 123, and LC1 contains the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 27, wherein (H)HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

29. The pharmaceutical composition according to any one of claims 26 to 28, wherein HC2 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 15, and LC2 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO:

16.

30. The pharmaceutical composition according to claim 29, wherein HC2 comprises the amino acid sequence of SEQ ID NO: 15, and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

31. The pharmaceutical composition according to any one of claims 26 to 30, wherein the TRGV9 is located on the surface of γδ T cells.

32. The pharmaceutical composition according to any one of claims 28 to 31, wherein the CD123 is located on the surface of tumor cells or CD34+ stem cells.

33. The pharmaceutical composition according to any one of claims 26 to 32, wherein the binding of the bispecific antibody to TRGV9 present on the surface of γδ T cells and the binding of the bispecific antibody to CD123 on the surface of cancer cells results in the death of cancer cells.

34. The pharmaceutical composition according to any one of claims 26 to 33, wherein HC1 and LC1 are humanized.

35. The pharmaceutical composition according to any one of claims 26 to 34, wherein HC2 and LC2 are humanized.

36. The pharmaceutical composition according to any one of claims 26 to 35, wherein the bispecific antibody or its antigen-binding fragment is an IgG1, IgG2, IgG3, or IgG4 isotype.

37. The pharmaceutical composition according to any one of claims 26 to 36, wherein the bispecific antibody or its antigen-binding fragment is an IgG4 isotype.

38. The bispecific antibody or its antigen-binding fragment has an EC of less than 500 pM. ５０ This induces γδ T cell-dependent cytotoxicity in cancer cells in vitro. The bispecific antibody or its antigen-binding fragment has an EC of less than 300 pM. ５０ This induces γδ T cell-dependent cytotoxicity in cancer cells in vitro, or The bispecific antibody or its antigen-binding fragment has an EC of less than 160 pM. ５０ A pharmaceutical composition according to any one of claims 26 to 37, which induces γδ T cell-dependent cytotoxicity in cancer cells in vitro.

39. The EC ５０ The pharmaceutical composition according to claim 38, which is evaluated with a mixture of γδ T effector cells and Kasumi3 AML target cells.

40. The ratio of effector cells to target cells is 0.01:1 to 5:

1. The ratio of effector cells to target cells is 0.1:1 to 2:1, or The pharmaceutical composition according to claim 39, wherein the ratio of effector cells to target cells is 1:

1.

41. A pharmaceutical composition for treating hematological cancers comprising an isolated TRGV9 bispecific antibody or its antigen-binding fragment, wherein the isolated TRGV9 bispecific antibody or its antigen-binding fragment is a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, (A) HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 33, respectively, or iv. Each comprises HCDR1, HCDR2, and HCDR3, which contain the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen. (B) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen. (C) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen. (D) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for the first antigen. (E) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for the first antigen. (F) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for the first antigen. (G) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for the first antigen, or (H)HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, forming a binding site for the first antigen. HC2 and LC2 form binding sites for the second antigen epitope. The binding site for the first antigen binds to TRGV9 on γδ T cells, A pharmaceutical composition wherein the binding site for a second antigen binds to a cancer antigen present on the surface of a cancer cell.

42. (A) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 65, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 67, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 95, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104, and LC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 113, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 123, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 41, wherein (H)HC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO:

134.

43. (A) HC1 contains the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains the amino acid sequence of SEQ ID NO: 67, and LC1 contains the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains the amino acid sequence of SEQ ID NO: 95, and LC1 contains the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains the amino acid sequence of SEQ ID NO: 104, and LC1 contains the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains the amino acid sequence of SEQ ID NO: 113, and LC1 contains the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains the amino acid sequence of SEQ ID NO: 123, and LC1 contains the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 42, wherein (H)HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

44. The pharmaceutical composition according to any one of claims 41 to 43, wherein HC1 and LC1 are humanized.

45. The pharmaceutical composition according to any one of claims 41 to 44, wherein HC2 and LC2 are bound to the CD123 epitope.

46. The pharmaceutical composition according to claim 45, wherein HC2 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 15, and LC2 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO:

16.

47. The pharmaceutical composition according to claim 46, wherein HC2 comprises the amino acid sequence of SEQ ID NO: 15, and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

48. The pharmaceutical composition according to any one of claims 42 to 47, wherein the bispecific antibody or its antigen-binding fragment is an IgG1, IgG2, IgG3, or IgG4 isotype.

49. The pharmaceutical composition according to any one of claims 42 to 46, wherein the bispecific antibody or its antigen-binding fragment is an IgG4 isotype.

50. The bispecific antibody or antigen-binding fragment thereof induces γδ T cell-dependent cytotoxicity of cancer cells in vitro at an EC less than 500 pM ５０ , The bispecific antibody or its antigen-binding fragment has an EC of less than 300 pM. ５０ This induces γδ T cell-dependent cytotoxicity in cancer cells in vitro, or The bispecific antibody or its antigen-binding fragment has an EC of less than 160 pM. ５０ A pharmaceutical composition according to any one of claims 42 to 49, which induces γδ T cell-dependent cytotoxicity in cancer cells in vitro.

51. The EC ５０ The pharmaceutical composition according to claim 50, which is evaluated with a mixture of γδ T effector cells and Kasumi3 AML target cells.

52. The ratio of effector cells to target cells is 0.01:1 to 5:

1. The ratio of effector cells to target cells is 0.1:1 to 2:1, or The pharmaceutical composition according to claim 51, wherein the ratio of effector cells to target cells is 1:

1.

53. An isolated TRGV9 bispecific antibody or its antigen-binding fragment, a. HC1 and, b. HC2 and, c. LC1 and, d. Including LC2, (A) HC1 is i. Sequence ID 1, Sequence ID 2, and Sequence ID 31, respectively ii. Sequence ID 1, Sequence ID 2, and Sequence ID 32, respectively iii. Sequence ID 1, Sequence ID 2, and Sequence ID 33, respectively, or iv. Each comprises HCDR1, HCDR2, and HCDR3, which contain the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen. (B) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen. (C) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen. (D) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for the first antigen. (E) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for the first antigen. (F) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. LC1 includes LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for the first antigen. (G) HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for the first antigen, or (H)HC1 comprises HCDR1, HCDR2, and HCDR3, each containing the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. LC1 comprises LCDR1, LCDR2, and LCDR3, each containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, forming a binding site for the first antigen. HC2 and LC2 form binding sites for the second antigen. The binding site for the first antigen binds to TRGV9 on γδ T cells, The binding site for the second antigen is an isolated TRGV9 bispecific antibody or its antigen-binding fragment, which binds to a cancer antigen present on the surface of cancer cells. A pharmaceutical composition for treating blood cancer, comprising a pharmaceutically acceptable carrier.

54. (A) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 65, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 67, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 95, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104, and LC1 contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 113, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 123, and LC1 contains an amino acid sequence that has at least 95% identity with the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 53, wherein (H)HC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO:

134.

55. (A) HC1 contains the amino acid sequence of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and LC1 contains the amino acid sequence of SEQ ID NO: 8, (B) HC1 contains the amino acid sequence of SEQ ID NO: 65, and LC1 contains the amino acid sequence of SEQ ID NO: 66, (C) HC1 contains the amino acid sequence of SEQ ID NO: 67, and LC1 contains the amino acid sequence of SEQ ID NO: 68, (D) HC1 contains the amino acid sequence of SEQ ID NO: 95, and LC1 contains the amino acid sequence of SEQ ID NO: 96, (E) HC1 contains the amino acid sequence of SEQ ID NO: 104, and LC1 contains the amino acid sequence of SEQ ID NO: 105, (F) HC1 contains the amino acid sequence of SEQ ID NO: 113, and LC1 contains the amino acid sequence of SEQ ID NO: 114, (G) HC1 contains the amino acid sequence of SEQ ID NO: 123, and LC1 contains the amino acid sequence of SEQ ID NO: 124, or The pharmaceutical composition according to claim 54, wherein (H)HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

56. The pharmaceutical composition according to any one of claims 53 to 55, wherein the binding of the bispecific antibody to TRGV9 present on the surface of the γδ T cells and the binding of the bispecific antibody to the cancer antigen present on the surface of the cancer cells result in the death of the cancer cells.

57. The pharmaceutical composition according to any one of claims 53 to 56, wherein HC1 and LC1 are humanized.

58. The pharmaceutical composition according to any one of claims 53 to 57, wherein HC2 and LC2 are bonded to CD123.

59. The pharmaceutical composition according to any one of claims 53 to 58, wherein the bispecific antibody or its antigen-binding fragment is an IgG1, IgG2, IgG3, or IgG4 isotype.

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