Bioengineered T cell-mediated immunization, materials, and other methods for modulating differentiation antigen group IV and / or VIII

Abstract

In certain aspects, provided herein are antibodies that bind to a CDS, as well as recombinant cells containing a vector, and compositions comprising the antibodies. Also provided herein are antibodies that bind to CD4, as well as recombinant cells containing a vector, and compositions comprising the antibodies. Also provided herein are multispecific antibodies that bind to CD4 and a CDS, as well as recombinant cells containing the vector, and compositions comprising the antibodies. Methods for producing antibodies are also provided.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 091,078, filed on 13 October 2020, the entire disclosure of which is incorporated herein by reference.

[0002] (Field of Invention) In certain embodiments, recombinant cells containing an antibody that binds to CD4, as well as a vector, and compositions comprising the antibody are provided herein. In certain embodiments, recombinant cells containing an antibody that binds to CD8, as well as a vector, and compositions comprising the antibody are also provided herein. In certain embodiments, recombinant cells containing a multispecific antibody that binds to CD4 and CD8, as well as a vector, and compositions comprising the antibody are also provided herein. Methods for producing and using antibodies are also provided.

[0003] (Reference to electronically submitted sequence listings) This application includes a sequence listing submitted electronically via EFS-Web as an ASCII-formatted sequence listing, named "14620-269-228_SL.txt", created on October 7, 2021, and having a size of 1,812,826 bytes. The sequence listing submitted via EFS-Web is part of this specification and is incorporated herein by reference in its entirety. [Overview of the Initiative] [Means for solving the problem]

[0004] In one embodiment, an antibody that binds to CD8 is provided herein. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 201, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 202. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 269, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 270.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 337, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 338. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 405, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 406.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 439, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 440. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 473, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 474. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 541, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 542.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 575, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 576. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 609, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 610. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 677, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 678.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 711, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 712. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 745, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 746. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 779, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 780. In one embodiment, the CD8 antibody comprises (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL, respectively, and The antibody comprises (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 847, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 848. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 881, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 882. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 949, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 950.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 983, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 984. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1017, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1018. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1051, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1052. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1085, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1086.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1119, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1120. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1153, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1154. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1187, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1188. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1221, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1222.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1255, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1256. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1289, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1290. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1323, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1324. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1357, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1358.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1391, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1392. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1425, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1426. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1459, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1460. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1493, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1494.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1561, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1562. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1595, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1596. In one embodiment, the CD8 antibody comprises (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. The CD8 antibody comprises (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VH VH CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VH VH CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VH VH CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1697, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1698. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1765, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1766.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1799, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1800. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1867, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1868. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1901, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1902.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1935, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1936. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1969, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1970. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In another embodiment, an antibody that binds to CD8 is provided herein. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 2071, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 2072. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 2139, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 2140. In one embodiment, the CD8 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 2173, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 2174.

[0005] In some embodiments, the amino acid sequences of the CD8 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Kabat numbering system. In some embodiments, the amino acid sequences of the CD8 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Chothia numbering system. In some embodiments, the amino acid sequences of the CD8 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the AbM numbering system. In some embodiments, the amino acid sequences of the CD8 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Contact numbering system. In some embodiments, the amino acid sequences of the CD8 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the IMGT numbering system.

[0006] In some embodiments, the antibody binds to the CD8 antigen. In some embodiments, the antibody binds to the CD8 epitope. In some embodiments, the antibody specifically binds to CD8. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD8 antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD8 epitope. In some embodiments, CD8 is present on the surface of T cells.

[0007] In some embodiments, the antibody binds to CD8α. In some embodiments, the antibody binds to the CD8α antigen. In some embodiments, the antibody binds to the CD8α epitope. In some embodiments, the antibody specifically binds to CD8α. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD8α antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD8α epitope. In some embodiments, CD8α is present on the surface of T cells.

[0008] In some embodiments, the antibody binds to CD8β. In some embodiments, the antibody binds to the CD8β antigen. In some embodiments, the antibody binds to the CD8β epitope. In some embodiments, the antibody specifically binds to CD8β. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD8β antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD8β epitope. In some embodiments, CD8β is present on the surface of T cells.

[0009] In some embodiments, the antibody binds at the interface between CD8α and CD8β. In some embodiments, the antibody binds to the antigen at the interface between CD8α and CD8β. In some embodiments, the antibody binds to the epitope at the interface between CD8α and CD8β. In some embodiments, the antibody specifically binds at the interface between CD8α and CD8β. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the antigen at the interface between CD8α and CD8β. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the epitope at the interface between CD8α and CD8β. In some embodiments, the interface between CD8α and CD8β is located on the surface of the T cell.

[0010] In some embodiments, the CD8 antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the CD8 antibody is an IgG1 antibody. In some embodiments, the CD8 antibody is an IgG2 antibody. In some embodiments, the CD8 antibody is an IgG3 antibody. In some embodiments, the CD8 antibody is an IgG4 antibody. In some embodiments, the CD8 antibody contains a kappa light chain. In some embodiments, the CD8 antibody contains a lambda light chain. In some embodiments, the CD8 antibody is a monoclonal antibody. In some embodiments, the CD8 antibody is polyvalent. In some embodiments, the CD8 antibody can bind to at least three antigens. In some embodiments, the CD8 antibody can bind to at least four antigens. In some embodiments, the CD8 antibody can bind to at least five antigens. In some embodiments, the CD8 antibody is a multispecific antibody. In some embodiments, the CD8 antibody is a bispecific antibody. In some embodiments, the CD8 antibody is a triplicate antibody. In some embodiments, the CD8 antibody is a quadruplicate antibody.

[0011] In some embodiments, the multispecific CD8 antibody comprises (i) a first binding domain that binds to CD8, and (b) a second binding domain that binds to a second target; (ii) a first binding domain that binds to CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target; or (iii) a first binding domain that binds to CD8, a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD4. In some embodiments, the second target is a T cell receptor (TCR) complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain. In some embodiments, the second target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is CD4, and the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain. In some embodiments, the second target is CD4, and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is the TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain, and the third target is the T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1.In some embodiments, the second target is CD4, the third target is the TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain, and the fourth target is the T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1.

[0012] In one embodiment, multispecific CD8 antibodies are also provided herein, wherein the multispecific CD8 antibody comprises a first binding domain that binds to CD8, a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD4, the third target is a TCR complex, and the fourth target is a T cell co-stimulatory molecule. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the fourth target is CD28. In some embodiments, the fourth target is CTLA4. In some embodiments, the fourth target is ICOS. In some embodiments, the fourth target is 4-1BB. In some embodiments, the fourth target is GITR. In some embodiments, the fourth target is CD27. In some embodiments, the fourth target is OX40. In some embodiments, the fourth target is CD40L. In some embodiments, the fourth target is HVEM. In some embodiments, the fourth target is galectin-9. In some embodiments, the fourth target is TIM-1. In some embodiments, the fourth target is LFA1. In some embodiments, the fourth target is CD2. In some embodiments, the fourth target is PD1.

[0013] Multispecific CD8 antibodies are also provided herein, wherein the multispecific CD8 antibody comprises a first binding domain that binds to CD8, and a second binding domain that binds to CD4.

[0014] In certain embodiments, a multispecific antibody is provided comprising a first binding domain that binds to CD8 and a second binding domain that binds to CD4. In one particular embodiment, the first binding domain that binds to CD8 is the CD8 antibody provided herein. In another embodiment, the second binding domain that binds to CD4 is the CD4 antibody provided herein. In a particular embodiment, the first binding domain that binds to CD8 is the CD8 antibody provided herein, and the second binding domain that binds to CD4 is the CD4 antibody provided herein. In a particular embodiment, the multispecific antibody further binds to a third target provided herein. In another embodiment, the multispecific antibody further binds to a third target and a fourth target provided herein.

[0015] Also provided herein are multispecific CD8 antibodies comprising a first binding domain that binds CD8, a second binding domain that binds a second target, and a third binding domain that binds a third target. In some embodiments, the second target is a TCR complex and the third target is a T cell costimulatory molecule. In some embodiments, the second target is CD3. In some embodiments, the second target is CD3ε. In some embodiments, the second target is CD3γ. In some embodiments, the second target is CD3δ. In some embodiments, the second target is CD3ζ. In some embodiments, the second target is a TCRα chain. In some embodiments, the second target is a TCRβ chain. In some embodiments, the second target is a TCRγ chain. In some embodiments, the second target is a TCRδ chain. In some embodiments, the third target is CD28. In some embodiments, the third target is CTLA4. In some embodiments, the third target is ICOS. In some embodiments, the third target is 4-1BB. In some embodiments, the third target is GITR. In some embodiments, the third target is CD27. In some embodiments, the third target is OX40. In some embodiments, the third target is CD40L. In some embodiments, the third target is HVEM. In some embodiments, the third target is galectin-9. In some embodiments, the third target is TIM-1. In some embodiments, the third target is LFA1. In some embodiments, the third target is CD2. In some embodiments, the third target is PD1.

[0016] In another aspect, provided herein is a nucleic acid encoding a CD8 antibody provided herein. Also provided is a vector comprising a nucleic acid encoding a CD8 antibody provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a CD8 antibody provided herein. Also provided is a kit comprising a vector comprising a nucleic acid encoding a CD8 antibody provided herein, and a package therefor.

[0017] In another embodiment, a kit is provided that includes a CD8 antibody provided herein and a package therefor.

[0018] In another embodiment, a pharmaceutical composition is provided comprising a CD8 antibody provided herein and a pharmaceutically acceptable carrier.

[0019] In another embodiment, a method is provided for producing a pharmaceutical composition comprising a CD8 antibody provided herein, the method comprising combining the CD8 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0020] In another embodiment, a method is provided for activating CD8-expressing T cells, the method comprising contacting the T cells with a CD8 antibody provided herein. In one embodiment, the contact results in increased expression of CD69, CD25, and / or granzyme B compared to CD8-expressing control T cells.

[0021] In another embodiment, a method is provided for enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD8-expressing cells, comprising: providing a sample containing CD8-expressing cells; contacting the sample with a CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD8-expressing cells bound to the CD8 antibody. In another embodiment, a method is provided for enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD8-expressing cells, comprising: contacting CD8-expressing cells with a CD8 antibody provided herein; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD8-expressing cells bound to the CD8 antibody. In some embodiments, the CD8-expressing cells are T cells. In some embodiments, the CD8-expressing cells are CD8+ cytotoxic T lymphocytes (CTLs). In some embodiments, the CD8-expressing cells are provided as a sample containing a population of cells. In some embodiments, the cells are lymphocytes. In some embodiments, the cells are T cells. In some embodiments, the sample is a blood sample. In some embodiments, the sample is a tissue sample. In some embodiments, the CD8 antibody is a multispecific CD8 antibody provided herein.

[0022] In another embodiment, antibodies that bind to CD4 are provided herein. In one embodiment, the CD4 antibody comprises (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2207, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2208. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2241, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2242, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2275, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2276, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2309, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2310, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2343, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2344, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2377, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2378, respectively, and comprising VL having VL CDR1, VL CDR2, and VL CDR3. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2411, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2412, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2445, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2446, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2479, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2480, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2513, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2514, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2547, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2548, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2581, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2582, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2615, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2616, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2649, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2650, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2683, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2684, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2717, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2718, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2751, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2752, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2785, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2786, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2819, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2820, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2853, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2854, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2887, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2888, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2921, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2922, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2955, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2956, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 2989, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 2990, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3023, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3024. In one embodiment, (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3057, and (ii) sequence. An antibody that binds to CD4 is provided, comprising VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of sequence number 3058, respectively. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of sequence number 3091, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of sequence number 3092, respectively. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3125, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3126, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3159, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3160, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3193, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3194, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3227, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3228, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3261, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3262, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3295, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3296, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3329, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3330, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3363, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3364, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3397, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3398, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3431, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3432, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3465, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3466, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3499, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3500, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3533, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3534, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3567, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3568, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3601, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3602, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3635, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3636, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3669, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3670, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3703, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3704, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3737, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3738, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3771, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3772, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3805, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3806, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3839, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3840, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3873, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3874, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3907, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3908, and (ii) VL having VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, (i) VH of SEQ ID NO: 3941. (i) an antibody that binds to CD4 is provided, comprising VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of CDR1, VH CDR2, and VH CDR3, respectively, and VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3942. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 3975, and VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 3976. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4009, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4010, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4043, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4044, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4077, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4078, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4111, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4112, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4145, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4146, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4179, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4180, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4213, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4214, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4247, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4248, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4281, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4282, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4315, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4316, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4349, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4350, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4383, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4384, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4417, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4418, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4451, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4452, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4485, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4486, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4519, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4520, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4553, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4554, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4587, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4588, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4621, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4622, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4655, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4656, respectively, and comprising VL CDR1, VL CDR2, and VL CDR3. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4689, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4690, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4723, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4724, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4757, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4758, andIn one embodiment, (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4791, and (ii) the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4792. An antibody that binds to CD4 is provided, comprising VL, which includes VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4825, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4826. In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4859, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4860, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4893, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4894, and In one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4927, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4928, andIn one embodiment, an antibody that binds to CD4 is provided, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4961, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4962, and

[0023] In some embodiments, the amino acid sequences of the CD4 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Kabat numbering system. In some embodiments, the amino acid sequences of the CD4 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Chothia numbering system. In some embodiments, the amino acid sequences of the CD4 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the AbM numbering system. In some embodiments, the amino acid sequences of the CD4 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Contact numbering system. In some embodiments, the amino acid sequences of the CD4 antibodies VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the IMGT numbering system.

[0024] In some embodiments, the antibody binds to the CD4 antigen. In some embodiments, the antibody binds to the CD4 epitope. In some embodiments, the antibody specifically binds to CD4. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD4 antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the CD4 epitope. In some embodiments, CD4 is present on the surface of T cells.

[0025] In some embodiments, the CD4 antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the CD4 antibody is an IgG1 antibody. In some embodiments, the CD4 antibody is an IgG2 antibody. In some embodiments, the CD4 antibody is an IgG3 antibody. In some embodiments, the CD4 antibody is an IgG4 antibody. In some embodiments, the CD4 antibody contains a kappa light chain. In some embodiments, the CD4 antibody contains a lambda light chain. In some embodiments, the CD4 antibody is a monoclonal antibody. In some embodiments, the CD4 antibody is polyvalent. In some embodiments, the CD4 antibody can bind to at least four antigens. In some embodiments, the CD4 antibody can bind to at least five antigens. In some embodiments, the CD4 antibody is a multispecific antibody. In some embodiments, the CD4 antibody is a bispecific antibody. In some embodiments, the CD4 antibody is a triplicate antibody. In some embodiments, the CD4 antibody is a quadruplicate antibody.

[0026] In some embodiments, the multispecific CD4 antibody comprises (i) a first binding domain that binds to CD4, and (b) a second binding domain that binds to a second target; (ii) a first binding domain that binds to CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target; or (iii) a first binding domain that binds to CD4, a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD8. In some embodiments, the second target is CD8, and the second binding domain binds to CD8α. In some embodiments, the second target is CD8, and the second binding domain binds at the interface between CD8α and CD8β. In some embodiments, the second target is a T cell receptor (TCR) complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain. In some embodiments, the second target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is CD8, and the third target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain. In some embodiments, the second target is CD8, and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1. In some embodiments, the second target is a TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain, and the third target is a T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1.In some embodiments, the second target is CD8, the third target is the TCR complex, CD3, CD3ε, CD3γ, CD3δ, CD3ζ, TCRα chain, TCRβ chain, TCRγ chain, or TCRδ chain, and the fourth target is the T cell costimulatory molecule, CD28, CTLA4, ICOS, 4-1BB, GITR, CD27, OX40, CD40L, HVEM, galectin-9, TIM-1, LFA1, CD2, or PD1.

[0027] In one embodiment, a multispecific CD4 antibody is also provided herein, comprising a first binding domain that binds to CD4, a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target. In some embodiments, the second target is CD8, the third target is the TCR complex, and the fourth target is a T cell costimulatory molecule. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is the TCRα chain. In some embodiments, the third target is the TCRβ chain. In some embodiments, the third target is the TCRγ chain. In some embodiments, the third target is the TCRδ chain. In some embodiments, the fourth target is CD28. In some embodiments, the fourth target is CTLA4. In some embodiments, the fourth target is ICOS. In some embodiments, the fourth target is 4-1BB. In some embodiments, the fourth target is GITR. In some embodiments, the fourth target is CD27. In some embodiments, the fourth target is OX40. In some embodiments, the fourth target is CD40L. In some embodiments, the fourth target is HVEM. In some embodiments, the fourth target is galectin-9. In some embodiments, the fourth target is TIM-1. In some embodiments, the fourth target is LFA1. In some embodiments, the fourth target is CD2. In some embodiments, the fourth target is PD1.

[0028] Multiple specificity CD4 antibodies are also provided herein, which include a first binding domain that binds to CD4 and a second binding domain that binds to CD8.

[0029] Also provided herein are multispecific CD4 antibodies comprising a first binding domain that binds to CD4, a second binding domain that binds to a second target, and a third binding domain that binds to a third target. In some embodiments, the second target is a TCR complex, and the third target is a T cell costimulatory molecule. In some embodiments, the second target is CD3. In some embodiments, the second target is CD3ε. In some embodiments, the second target is CD3γ. In some embodiments, the second target is CD3δ. In some embodiments, the second target is CD3ζ. In some embodiments, the second target is the TCRα chain. In some embodiments, the second target is the TCRβ chain. In some embodiments, the second target is the TCRγ chain. In some embodiments, the second target is the TCRδ chain. In some embodiments, the third target is CD28. In some embodiments, the third target is CTLA4. In some embodiments, the third target is ICOS. In some embodiments, the third target is 4-1BB. In some embodiments, the third target is GITR. In some embodiments, the third target is CD27. In some embodiments, the third target is OX40. In some embodiments, the third target is CD40L. In some embodiments, the third target is HVEM. In some embodiments, the third target is galectin-9. In some embodiments, the third target is TIM-1. In some embodiments, the third target is LFA1. In some embodiments, the third target is CD2. In some embodiments, the third target is PD1.

[0030] In another embodiment, nucleic acids encoding the CD4 antibody provided herein are provided. Also provided are vectors comprising nucleic acids encoding the CD4 antibody provided herein. Also provided are host cells comprising vectors comprising nucleic acids encoding the CD4 antibody provided herein. Also provided are kits comprising vectors comprising nucleic acids encoding the CD4 antibody provided herein and packaging therefor.

[0031] In another embodiment, a kit is provided that includes a CD4 antibody provided herein and a package therefor.

[0032] In another embodiment, a pharmaceutical composition is provided comprising a CD4 antibody provided herein and a pharmaceutically acceptable carrier.

[0033] In another embodiment, a method is provided for producing a pharmaceutical composition comprising a CD4 antibody provided herein, the method comprising combining the CD4 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0034] In another embodiment, a method is provided for activating CD4-expressing T cells, the method comprising contacting the T cells with a CD4 antibody provided herein. In one embodiment, the contact results in increased expression of CD69, CD25, and / or granzyme B compared to CD4-expressing control T cells.

[0035] In another embodiment, a method is provided for concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells, comprising: providing a sample containing CD4-expressing cells; contacting the sample with a CD4 antibody provided herein; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells bound to the CD4 antibody. In another embodiment, a method is provided for concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells, comprising: contacting CD4-expressing cells with a CD4 antibody provided herein; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells bound to the CD4 antibody. In some embodiments, the CD4-expressing cells are T cells. In some embodiments, the CD4-expressing cells are CD4+ T helper cells. In some embodiments, the CD4-expressing cells are provided as a sample containing a population of cells. In some embodiments, the cells are lymphocytes. In some embodiments, the cells are T cells. In some embodiments, the sample is a blood sample. In some embodiments, the sample is a tissue sample. In some embodiments, the CD4 antibody is a multispecific CD4 antibody provided herein.

[0036] In another embodiment, a multispecific antibody is provided comprising a first binding domain that binds to CD8 and a second binding domain that binds to CD4 (i.e., a multispecific CD4 / CD8 antibody). In a particular embodiment, the first binding domain that binds to CD8 is the CD8 antibody provided herein. In another embodiment, the second binding domain that binds to CD4 is the CD4 antibody provided herein. In a particular embodiment, the first binding domain that binds to CD8 is the CD8 antibody provided herein, and the second binding domain that binds to CD4 is the CD4 antibody provided herein. In a particular embodiment, the multispecific antibody further binds to a third target provided herein. In another embodiment, the multispecific antibody further binds to a third target and a fourth target provided herein.

[0037] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the amino acid sequences of VH CDR 1, VH CDR 2, VH CDR 3, VL CDR 1, VL CDR 2, and VL CDR 3 follow the Kabat numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Chothia numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the AbM numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the Contact numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the IMGT numbering system.

[0038] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In some embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody contains a kappa light chain. In some embodiments, the antibody contains a lambda light chain. In some embodiments, the antibody is a monoclonal antibody.

[0039] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the first binding domain binds to the CD8 antigen. In some embodiments, the first binding domain binds to the CD8 epitope. In some embodiments, the first binding domain specifically binds to CD8. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the first binding domain form binding sites for the CD8 antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the first binding domain form binding sites for the CD8 epitope. In some embodiments, CD8 is present on the surface of T cells.

[0040] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the second binding domain binds to the CD4 antigen. In some embodiments, the second binding domain binds to the CD4 epitope. In some embodiments, the second binding domain specifically binds to CD4. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the second binding domain form binding sites for the CD4 antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the second binding domain form binding sites for the CD4 epitope. In some embodiments, CD4 is present on the surface of T cells.

[0041] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the antibodies are polyvalent. In some embodiments, the antibodies can bind to at least three antigens. In some embodiments, the antibodies can bind to at least four antigens. In some embodiments, the antibodies can bind to at least five antigens.

[0042] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the antibody is a bispecific antibody. In some embodiments, the antibody is a triplicate antibody. In some embodiments, the antibody is a quadruplicate antibody.

[0043] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the multispecific antibody further comprises a third binding domain that binds to a third target. In some embodiments, the third target is a TCR complex. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the third target is CD28. In some embodiments, the third target is CTLA4. In some embodiments, the third target is ICOS. In some embodiments, the third target is 4-1BB. In some embodiments, the third target is GITR. In some embodiments, the third target is CD27. In some embodiments, the third target is OX40. In some embodiments, the third target is CD40L. In some embodiments, the third target is HVEM. In some embodiments, the third target is galectin-9. In some embodiments, the third target is TIM-1. In some embodiments, the third target is LFA1. In some embodiments, the third target is CD2. In some embodiments, the third target is PD1.

[0044] In some embodiments of the multispecific CD4 / CD8 antibodies provided herein, the multispecific antibody further comprises a third binding domain that binds to a third target and a fourth binding domain that binds to a fourth target. In some embodiments, the third target is a TCR complex. In some embodiments, the third target is CD3. In some embodiments, the third target is CD3ε. In some embodiments, the third target is CD3γ. In some embodiments, the third target is CD3δ. In some embodiments, the third target is CD3ζ. In some embodiments, the third target is a TCRα chain. In some embodiments, the third target is a TCRβ chain. In some embodiments, the third target is a TCRγ chain. In some embodiments, the third target is a TCRδ chain. In some embodiments, the fourth target is CD28. In some embodiments, the fourth target is CTLA4. In some embodiments, the fourth target is ICOS. In some embodiments, the fourth target is 4-1BB. In some embodiments, the fourth target is GITR. In some embodiments, the fourth target is CD27. In some embodiments, the fourth target is OX40. In some embodiments, the fourth target is CD40L. In some embodiments, the fourth target is HVEM. In some embodiments, the fourth target is galectin-9. In some embodiments, the fourth target is TIM-1. In some embodiments, the fourth target is LFA1. In some embodiments, the fourth target is CD2. In some embodiments, the fourth target is PD1.

[0045] In another embodiment, nucleic acids encoding the multispecific CD4 / CD8 antibodies provided herein are provided. Also provided are vectors containing nucleic acids encoding the multispecific CD4 / CD8 antibodies provided herein. Also provided are host cells containing a vector containing nucleic acids encoding the multispecific CD4 / CD8 antibodies provided herein. Also provided are kits containing a vector containing nucleic acids encoding the CD4 / CD8 antibodies provided herein and a package therefor.

[0046] In another embodiment, a kit is provided that includes a CD4 / CD8 antibody provided herein and a package therefor.

[0047] In another embodiment, a pharmaceutical composition is provided comprising a multispecific CD4 / CD8 antibody provided herein and a pharmaceutically acceptable carrier.

[0048] In another general embodiment, a method is provided for producing a pharmaceutical composition comprising a multispecific CD4 / CD8 antibody provided herein, the method comprising combining the CD4 / CD8 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0049] In another embodiment, a method is provided for concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and / or CD8-expressing cells, comprising: providing a sample containing CD4-expressing cells and / or CD8-expressing cells; contacting the sample with a multispecific antibody conjugated to a multispecific CD8 / CD4 antibody provided herein; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and / or CD8-expressing cells conjugated to the multispecific CD8 / CD4 antibody. In another embodiment, a method is provided for concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and / or CD8-expressing cells, comprising: contacting CD4-expressing cells and / or CD8-expressing cells with a multispecific CD4 / CD8 antibody provided herein; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and / or CD8-expressing cells conjugated to the multispecific CD4 / CD8 antibody. In another embodiment, a method is provided for enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting CD4-expressing cells and / or CD8-expressing cells, comprising contacting the CD4-expressing cells and / or CD8-expressing cells with a multispecific CD4 / CD8 antibody provided herein, and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and / or CD8-expressing cells based on their binding to the multispecific CD4 / CD8 antibody. In some embodiments, the CD4-expressing cells and / or CD8-expressing cells are T cells. In some embodiments, the CD4-expressing cells and / or CD8-expressing cells are CD4+ T helper cells. In some embodiments, the CD4-expressing cells and / or CD8-expressing cells are provided as a sample comprising a population of cells. In some embodiments, the cells are lymphocytes. In some embodiments, the cells are T cells. In some embodiments, the sample is a blood sample. In some embodiments, the sample is a tissue sample. In some embodiments, the multispecific CD4 / CD8 antibody is the multispecific CD4 / CD8 antibody provided herein. In some embodiments, the cells include CD4-expressing cells. In some embodiments, the cells include CD8-expressing cells.In some embodiments, the cells include CD4-expressing cells and CD8-expressing cells. [Modes for carrying out the invention]

[0050] In the "Background Art" section and throughout this specification, various publications, articles, and patents are cited or referenced, and each of these references is incorporated herein by reference in its entirety. The considerations of documents, operations, materials, devices, articles, etc., included herein are for the purpose of providing context for the present invention. Such considerations do not constitute an endorsement that any or all of these things constitute part of the prior art to any invention disclosed or claimed.

[0051] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present invention pertains. Otherwise, certain terms used herein have the meanings set forth herein.

[0052] When used herein and in the appended claims, it should be noted that the singular forms "a," "an," and "the" refer to multiple objects unless otherwise clearly indicated by the context.

[0053] Unless otherwise specified, all numerical values, such as concentrations or concentration ranges, described herein should be understood in all cases as being modified by the term “approximately.” Therefore, numerical 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, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). When used herein, the use of numerical ranges explicitly includes all possible subranges, including integers and fractions of values ​​within that range, and all individual numerical values ​​within that range, unless the context explicitly indicates otherwise.

[0054] Unless otherwise stated, the term "at least" preceding a set of elements should be understood to refer to all of those elements.

[0055] Those skilled in the art will be able to recognize or confirm many equivalents to the specific embodiments described herein simply by using ordinary experimental procedures. Such equivalents are intended to be encompassed by the present invention.

[0056] When used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains,” or “containing,” or any other variation thereof, are intended to include the integer or set of integers mentioned, but not to exclude other integers or sets of integers, and are intended to be non-exclusive or non-restrictive. For example, a composition, mixture, process, method, article, or apparatus comprising a set of elements is not necessarily limited to those elements alone, and may include other elements not expressly enumerated or not inherently present in such composition, mixture, process, method, article, or apparatus. Furthermore, unless expressly otherwise indicated, “or” refers to an inclusive “or” and not an exclusive “or.” For example, condition A or B is satisfied by one of the following: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0057] When used herein, the connecting term "and / or" between multiple enumerated elements is understood to encompass both individual and combined options. For example, when two elements are connected by "and / or," the first option refers to the applicability of the first element without the second element. The second option refers to the applicability of the second element without the first element. The third option refers to the applicability of the first and second elements together. Any one of these options is included in the meaning and therefore, when used herein, satisfies the requirements of the term "and / or." The simultaneous applicability of two or more of the options is also included in the meaning and therefore, satisfies the requirements of the term "and / or."

[0058] When used herein, the term "consists of," or variations such as "consist of" or "consisting of," when used throughout the specification and claims, means that any enumerated integer or set of integers is included, but no additional integers or sets of integers are added to the specified method, structure, or composition.

[0059] When used herein, the terms "consists essentially of," or variations such as "consisting essentially of," when used throughout the specification and claims, include any enumerated integer or set of integers, and optionally also include any enumerated integer or set of integers that do not substantially alter the basic or novel properties of the specified method, structure, or composition. See MPEP §2111.03.

[0060] As used herein, “Subject” means any animal, preferably a mammal, most preferably a human. As used herein, the term “mammal” encompasses all mammals. Examples of mammals include, but are not limited to, cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, and humans. In certain embodiments, the subject is a human.

[0061] When referring to the dimensions or features of components of the embodiments provided herein, terms such as “about,” “approximately,” “generally,” and “substantially” used herein should be understood, as those skilled in the art will understand, to indicate that the described dimensions / features are not strict boundaries or parameters and do not exclude slight differences from them that are functionally the same or similar. At a minimum, such references involving numerical parameters will include variations in which the least significant digit remains unchanged when using mathematical and industrial principles accepted in the art (e.g., rounding, measurement, or other systematic errors, manufacturing tolerances, etc.).

[0062] The terms “identical” or “identity” percentage refer to two or more nucleic acid or polypeptide sequences (e.g., a CD8 antibody and the polynucleotide encoding it, a CD4 antibody and the polynucleotide encoding it, a multispecific CD4 / CD8 antibody and the polynucleotide encoding it) that, when compared and aligned to maximize the agreement using one of the following sequence comparison algorithms or by visual inspection, have two or more sequences or subsequences that are identical or identical by a certain percentage of amino acid residues or nucleotides.

[0063] For sequence comparison, typically one sequence acts as the reference sequence against which the test sequence is compared. When using a sequence comparison algorithm, the test and reference sequences are input into a computer, and sub-sequence coordinates and sequence algorithm program parameters are specified, if necessary. The sequence comparison algorithm then calculates the sequence identity percentage of the test sequence to the reference sequence based on the specified program parameters.

[0064] The optimal alignment of sequences for comparison can be achieved, for example, by the local homology algorithm in Smith & Waterman, Adv.Appl.Math.2:482 (1981), the homology alignment algorithm in Needleman & Wunsch, J.Mol.Biol.48:443 (1970), the similarity search method in Pearson & Lipman, Proc.Nat'l.Acad.Sci.USA85:2444 (1988), computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (generally, Current Protocols in Molecular Biology, FMAusubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995)). This can be done by (see Supplement)(Ausubel).

[0065] Examples of suitable algorithms for determining sequence identity percentage and sequence similarity are the BLAST and BLAST2.0 algorithms described in Altschul et al., (1990) J.Mol.Biol.215:403-410 and Altschul et al., (1997) Nucleic Acids Res.25:3389-3402, respectively. Software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information. This algorithm first involves identifying high-scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence that either match when aligned with words of the same length in the database sequence, or satisfy a threshold score T of some positive value. T is referred to as the adjacent word score threshold (Altschul et al., above). These initial adjacent word hits serve as seeds to initiate a search to find longer HSPs that contain them. Next, word hits are extended in both directions along each sequence, as long as the cumulative alignment score can be increased.

[0066] For nucleotide sequences, the cumulative score is calculated using parameter M (reward score for matching residue pairs, always greater than 0) and parameter N (penalty score for mismatched residues, always less than 0). For amino acid sequences, the cumulative score is calculated using a scoring matrix. The extension of word hits in each direction is stopped when the cumulative alignment score falls by amount X from its maximum value, when the cumulative score becomes zero or less due to the accumulation of alignments of one or more negative scoring residues, or when the end of either sequence is reached. The parameters W, T, and X of the BLAST algorithm determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses, by default, word length (word, W) 11, expectation (expectation, E) 10, M=5, N=-4, and comparison of both strands. For amino acid sequences, the BLASTP program uses a word length (W) of 3, an expected value (E) of 10, and the BLOSUM62 scoring matrix by default (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).

[0067] In addition to calculating the sequence identity percentage, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, for example, Karlin & Altschul, Proc. 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)), which provides an indicator of the probability that a match between two nucleotide sequences or two amino acid sequences occurs by chance. For example, a nucleic acid is considered similar to a reference sequence if the minimum sum probability in the comparison between the test nucleic acid and the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.

[0068] A further indicator that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross-reactive with the polypeptide encoded by the second nucleic acid, as described below. Thus, the polypeptide is typically substantially identical to the second polypeptide, for example, the two peptides differ only by conserved substitutions. Another indicator that two nucleic acid sequences are substantially identical is that the two molecules hybridize with each other under stringent conditions.

[0069] As used herein, the term “polynucleotide” is synonymous with “nucleic acid molecule,” “nucleotide,” or “nucleic acid,” and refers to any polyribonucleotide or polydeoxyribonucleotide that may be unmodified RNA or DNA, or modified RNA or DNA. “Polynucleotides” include, but are not limited to, 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, and hybrid molecules containing DNA and RNA which may be single-stranded or, more typically, double-stranded or a mixture of single-stranded and double-stranded regions. In addition, “polynucleotide” refers to a triple-stranded region containing RNA or DNA, or both RNA and DNA. The term polynucleotide also includes DNA or RNA containing one or more modified bases, and DNA or RNA having a backbone modified for stability or other reasons. “Modified” bases include, for example, tritylated bases and unusual bases, such as inosine. Various modifications can be made to DNA and RNA. Therefore, "polynucleotides" typically encompass chemically, enzymatically, or metabolically modified forms of naturally occurring polynucleotides, as well as chemical forms that possess the characteristics of viral and cellular DNA and RNA. "Polynucleotides" also encompass relatively short nucleic acid chains (often referred to as oligonucleotides).

[0070] As used herein, the term "vector" refers to a replicon that can replicate or express another nucleic acid segment by functionally inserting that segment.

[0071] As used herein, the term “host cell” refers to a cell containing the nucleic acid molecules provided herein. A “host cell” may be any type of cell, for example, a primary cell, a cell in culture, or a cell line derived from a cell line. In one embodiment, a “host cell” is a cell transfected with the nucleic acid molecules provided herein. In another embodiment, a “host cell” is a descendant or potential descendant of such a transfected cell. The progeny of a cell may or may not be identical to the parent cell, for example, due to mutations that may occur in subsequent generations, environmental influences, or the incorporation of the nucleic acid molecules into the host cell genome.

[0072] As used herein, the term “expression” refers to the biosynthesis of a gene product. This term encompasses the transcription of a gene into RNA. It also encompasses the translation of RNA into one or more polypeptides, and further includes all naturally occurring post-transcriptional and post-translational modifications. The expressed antibody may be present in the cytoplasm of a host cell, in an extracellular environment such as a cell culture growth medium, or immobilized on the cell membrane.

[0073] As used herein, the terms “peptide,” “polypeptide,” or “protein” may refer to a molecule composed of amino acids that can be recognized as a protein by those skilled in the art. Conventional one- or three-letter codes for amino acid residues are used herein. The terms “peptide,” “polypeptide,” and “protein” may be used interchangeably herein to refer to a polymer of amino acids of any length. The polymer may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acids. The term also encompasses amino acid polymers that are naturally modified or modified by intervention. Examples of interventions include, for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other operation or modification, such as conjugate with a labeling component. The definition also includes, for example, polypeptides containing one or more analogues of amino acids (including, for example, non-natural amino acids), as well as other modifications known in the art.

[0074] The peptide sequences described herein are written according to common convention, with the N-terminal region of the peptide on the left and the C-terminal region on the right. Although the isomer forms of amino acids are known, unless otherwise explicitly indicated, only the L-form of the amino acids is shown.

[0075] antibody CD8 antibodies or their antigen-binding fragments, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions comprising the antibodies are provided herein. Methods for producing such antibodies and methods for using such antibodies to treat diseases are also provided. The antibodies disclosed herein have one or more desirable functional properties, including but not limited to high affinity binding to CD8 or high specificity for CD8. In certain embodiments, the antibodies disclosed herein have the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies.

[0076] Furthermore, CD8 multispecific antibodies or their antigen-binding fragments, nucleic acids encoding multispecific antibodies and expression vectors, recombinant cells containing vectors, and compositions comprising multispecific antibodies are also provided herein. Methods for producing antibodies and methods for using multispecific antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein have one or more desirable functional properties. In some embodiments, the multispecific antibodies provided herein have high affinity binding to CD8. In some embodiments, the multispecific antibodies provided herein have high affinity binding to a second target antigen. In some embodiments, the multispecific antibodies provided herein have high specificity to CD8. In some embodiments, the multispecific antibodies provided herein have high specificity to a second target antigen. In some embodiments, the multispecific antibodies provided herein, when administered alone, have the ability to treat or prevent a disease or disorder. In some embodiments, the multispecific antibodies provided herein, when administered in combination with other therapies, have the ability to treat or prevent a disease or disorder. In certain embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the multispecific antibody is a tripspecific antibody. In some embodiments, the multispecific antibody is a quadrispecific antibody. In certain embodiments, the second target is CD4.

[0077] Also provided herein are CD4 antibodies or their antigen-binding fragments, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions comprising the antibodies. Methods for producing such antibodies and methods for using such antibodies to treat diseases are also provided. The antibodies disclosed herein have one or more desirable functional properties, including but not limited to high affinity binding to CD4 or high specificity for CD4. In certain embodiments, the antibodies disclosed herein have the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies.

[0078] Also provided herein are CD4 multispecific antibodies or their antigen-binding fragments, nucleic acids encoding multispecific antibodies and expression vectors, recombinant cells containing vectors, and compositions comprising multispecific antibodies. Methods for producing antibodies and methods for using multispecific antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein have one or more desirable functional properties. In some embodiments, the multispecific antibodies provided herein have high affinity binding to CD4. In some embodiments, the multispecific antibodies provided herein have high affinity binding to a second target antigen. In some embodiments, the multispecific antibodies provided herein have high specificity to CD4. In some embodiments, the multispecific antibodies provided herein have high specificity to a second target antigen. In some embodiments, the multispecific antibodies provided herein, when administered alone, have the ability to treat or prevent a disease or disorder. In some embodiments, the multispecific antibodies provided herein, when administered in combination with other therapies, have the ability to treat or prevent a disease or disorder. In certain embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the multispecific antibody is a tripspecific antibody. In some embodiments, the multispecific antibody is a quadruplespecific antibody. In certain embodiments, the second target is CD8.

[0079] As used herein, the term “antibody” is used broadly and includes immunoglobulins or antibody molecules, as well as antibody fragments that are monoclonal or polyclonal, including human, humanized, complex, and chimeric antibodies. Generally, an antibody is a protein or peptide chain that exhibits binding specificity to a particular antigen. The structure of antibodies is well known. Immunoglobulins can be assigned to five main classes (i.e., IgA, IgD, IgE, IgG, and IgM) depending on the amino acid sequence of the heavy chain constant domain. IgA and IgG are further subdivided as isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Thus, the antibodies provided herein may be of any of the five main classes or their corresponding subclasses. In certain embodiments, the antibodies provided herein are IgG1, IgG2, IgG3, or IgG4. The antibody light chains of vertebrate species can be assigned to one of two distinct types, namely κ and λ, based on the amino acid sequence of their constant domain. Therefore, the antibodies provided herein may, in certain embodiments, contain kappa or lambda light chain constant domains. The antibodies provided herein may also, in certain embodiments, contain lambda light chain constant domains. According to certain embodiments, the antibodies provided herein contain heavy chain and / or light chain constant regions derived from rat or human antibodies. In certain embodiments, the constant region is a human constant region.

[0080] In addition to the heavy and light chain constant domains, the antibody contains an antigen-binding region composed of a light chain variable region (VL) and a heavy chain variable region (VH), each of which contains three domains (i.e., complementarity determining region 1 (CDR1), CDR2, and CDR3). "CDR" refers to one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) within the non-framework region of the immunoglobulin (Ig or antibody) VH β-sheet framework, or one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) within the non-framework region of the antibody VL β-sheet framework. Therefore, CDRs are variable region sequences scattered within the framework region sequence. The CDR region is well known to those skilled in the art and, for example, defined by Kabat as the most variable region within the antibody variable (V) domain (Kabat et al., J. Biol. Chem. 252:6609-6616 (1977), Kabat, Adv. Prot. Chem. 32:1-75 (1978)). The CDR region sequence is also structurally defined by Chothia as a residue that can adapt to various higher-order structures because it is not part of the conserved β-sheet framework (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terms are well recognized in the art. The CDR region sequence is also defined by AbM, Contact, and IMGT. Exemplary CDR region sequences are illustrated herein, for example, in the table provided in the following examples. The location of the CDR within the variable region of a standard antibody has been determined by comparing numerous structures (Al-Lazikani et al., J.Mol.Biol.273:927-948 (1997), Morea et al., Methods 20:267-279 (2000)).Since the number of residues in the hypervariable region varies between antibodies, additional residues at standard positions are conventionally numbered by adding a, b, c, etc., after the residue number in the standard variable region numbering scheme (Al-Lazikani et al., above (1997)). Such nomenclature is well known to those skilled in the art.

[0081] The light chain variable region CDR1 domain is referred to herein interchangeably as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is referred to herein interchangeably as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is referred to herein interchangeably as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is referred to herein interchangeably as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is referred to herein interchangeably as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is referred to herein interchangeably as HCDR3 or VH CDR3.

[0082] As used herein, the terms VH or VL, etc., “hypervariable region,” refer to regions of antibody variable regions that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies contain six hypervariable regions, namely three VH (HCDR1, HCDR2, HCDR3) and three VL (LCDR1, LCDR2, LCDR3). Numerous descriptions of hypervariable regions are used and are incorporated herein. “Kabat” CDR is based on sequence variability and is the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). “Chothia” instead refers to the location of structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The end of the Chothia CDR-HCDR1 loop, when numbered using Kabat's numbering rules, varies from H32 to H34 depending on the loop length (this is because Kabat's numbering scheme places insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; and if both 35A and 35B are present, the loop ends at 34). The "AbM" hypervariable region represents a compromise between Kabat CDR and Chothia structural loops and is used by Oxford Molecular's AbM antibody modeling software (see, for example, Martin, in Antibody Engineering, Vol. 2, Chapter 3, Springer Verlag). The "Contact" hypervariable region is based on the analysis of available composite crystal structures.

[0083] Recently, a universal numbering system has been developed and widely adopted: the ImMunoGeneTics (IMGT) Information System (registered trademark) (Lafranc et al., Dev.Comp.Immunol.27(1):55-77(2003)). IMGT is an integrated information system specializing in immunoglobulins (IG), T cell receptors (TR), and major histocompatibility complexes (MHC) of humans and other vertebrates. In this specification, CDRs are referred to in terms of both their amino acid sequence and their position within the light or heavy chain. Because the "position" of CDRs within the structure of immunoglobulin variable domains is conserved across species and exists in structures referred to as loops, CDRs and framework residues can be easily identified by using a numbering system that aligns variable domain sequences according to their structural features. This information can be used to transplant and replace CDR residues from immunoglobulins of one species into acceptor frameworks, typically from human antibodies. Further numbering systems (AHon) have been developed by Honegger and Pluckthun, J.Mol.Biol.309:657-670 (2001). For example, correspondences between numbering systems, including Kabat numbering and IMGT-specific numbering systems, are well known to those skilled in the art (see, e.g., Kabat, above; Chothia and Lesk, above; Martin, above; Lefranc et al., above). The exemplary systems shown herein combine Kabat and Chothia.

[0084] [Table 1]

[0085] The hypervariable region may include the following “extended hypervariable regions”: 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2), and 89-97 or 89-96 (LCDR3) within the VL, and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102, or 95-102 (HCDR3) within the VH. CDR sequences reflecting each of the above numbering schemes are provided herein, as included in the table of the following examples.

[0086] The term "constant region" or "constant domain" refers to the carboxyl-terminal portions of the light and heavy chains that do not directly participate in antibody binding to an antigen but exhibit various effector functions, such as interaction with the Fc receptor. This term refers to a portion of the immunoglobulin molecule that has a more conserved amino acid sequence compared to other parts of the immunoglobulin, which are variable regions containing the antigen-binding site. The constant region may include the CH1, CH2, and CH3 regions of the heavy chain, as well as the CL region of the light chain.

[0087] The term "framework" or "FR" residue refers to a variable region residue adjacent to a CDR. FR residues are found, for example, in chimeric antibodies, humanized antibodies, human antibodies, domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are variable domain residues other than hypervariable region residues or CDR residues.

[0088] As used herein, the term “isolated antibody” refers to an antibody that substantially contains no other antibodies with different antigen specificities (for example, an isolated antibody that specifically binds to CD8 substantially contains no antibodies that do not bind to CD8; an isolated antibody that specifically binds to CD4 substantially contains no antibodies that do not bind to CD4). Furthermore, an isolated antibody substantially contains no other cellular material and / or chemical substances.

[0089] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies constituting the population are identical except for trace amounts of spontaneous variation. The monoclonal antibodies provided herein can be produced by hybridoma, phage display, single lymphocyte gene cloning, or recombinant DNA methods. For example, a monoclonal antibody may be produced by a hybridoma containing B cells obtained from a transgenic non-human animal, such as a transgenic mouse or rat, and having a genome containing human heavy chain and light chain transgenes.

[0090] As used herein, the term “antigen-binding fragment” refers to an antibody fragment such as a diabody, Fab, Fab', F(ab')2, Fv fragment, disulfide-stabilized Fv fragment (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabody (dsdiabody), single-chain antibody molecule (scFv), single-domain antibody (sdAb)scFv dimer (bivalent diabody), multispecific antibody formed from an antibody portion containing one or more CDRs, camelized single-domain antibody, nanobody, domain antibody, bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not contain a complete antibody structure. An antigen-binding fragment can bind to the same antigen to which a parent antibody or parent antibody fragment binds. According to a particular embodiment, an antigen-binding fragment comprises a light chain variable region, a light chain constant region, and a heavy chain Fd fragment. According to other specific embodiments, the antigen-binding fragment comprises Fab and F(ab').

[0091] As used herein, the term "single-chain antibody" refers to a single-chain antibody conventionally known in the art, comprising a heavy-chain variable region and a light-chain variable region linked by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single-domain antibody" refers to a single-domain antibody conventionally known in the art, comprising a heavy-chain variable region and a heavy-chain constant region, or comprising only the heavy-chain variable region.

[0092] As used herein, the term “human antibody” means an antibody produced by a human, or an antibody having an amino acid sequence corresponding to a human-produced antibody, prepared using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and / or antibodies comprising at least one human heavy chain and / or light chain polypeptide.

[0093] As used herein, the term "humanized antibody" refers to a non-human antibody that has been modified to increase sequence homology to a human antibody, while retaining the antigen-binding properties of the antibody, thereby reducing the antigenicity of the antigen in the human body.

[0094] As used herein, the term “chimeric antibody” refers to an antibody whose immunoglobulin molecule’s amino acid sequence originates from two or more species. The variable regions of both the light and heavy chains often correspond to the variable regions of an antibody derived from one species of mammal (e.g., mouse, rat, rabbit) that possesses the desired specificity, affinity, and capability, while the constant region corresponds to the sequence of an antibody derived from another species of mammal (e.g., human) to avoid inducing an immune response in that species.

[0095] As used herein, the term “multispecific antibody” refers to an antibody comprising multiple immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence has binding specificity to a first epitope, and a second immunoglobulin variable domain sequence has binding specificity to a second epitope. In some embodiments, the first and second epitopes do not overlap or substantially overlap. In some embodiments, the first and second epitopes are on different antigens, for example, on different proteins (or different subunits of a polymer protein). In some embodiments, the multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain. In some embodiments, the multispecific antibody is a bispecific antibody molecule, a triplicate antibody molecule, or a quadruplicate antibody molecule.

[0096] As used herein, the term “bispecific antibody” refers to a multispecific antibody that binds to two or fewer epitopes or two or fewer antigens. A bispecific antibody is characterized by a first immunoglobulin variable domain sequence having binding specificity to a first epitope (e.g., an epitope on a target antigen) and a second immunoglobulin variable domain sequence having binding specificity to a second epitope. In some embodiments, the first and second epitopes are on different antigens, e.g., different proteins (or different subunits of a polymer protein). In some embodiments, the bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence having binding specificity to a first epitope, and a heavy chain variable domain sequence and a light chain variable domain sequence having binding specificity to a second epitope. In some embodiments, the bispecific antibody comprises a semi-antibody or fragment thereof having binding specificity to a first epitope and a semi-antibody or fragment thereof having binding specificity to a second epitope. In one embodiment, a bispecific antibody comprises an scFv or fragment thereof having binding specificity to a first epitope and an scFv or fragment thereof having binding specificity to a second epitope. A "triplespecific antibody" refers to a multispecific antibody that binds to three different antigens, or to three different epitopes within the same antigen. A "quadrispecific antibody" is a multispecific antibody that binds to four different antigens, or to four different epitopes within the same antigen.

[0097] As used herein, the term “CD4” refers to a polypeptide that, when expressed on the surface of a T cell, can form a co-receptor with the T cell receptor (TCR). The term “CD4” includes any CD4 variant, isoform, and species homologue that are naturally expressed by cells (including T cells) or that can be expressed on cells transfected with a gene or cDNA encoding the polypeptide. In certain embodiments, CD4 is human CD4. An exemplary human CD4 amino acid sequence is provided by GenBank accession number NP_000607.1.

[0098] As used herein, the term "CD8" refers to a polypeptide capable of forming a coreceptor with the T cell receptor (TCR) when expressed on the surface of T cells. The term "CD8" includes any CD8 variants, isoforms, and species homologs that are naturally expressed by cells (including T cells) or can be expressed on cells transfected with the gene or cDNA encoding the polypeptide. In certain embodiments, CD8 is human CD8. CD8 may comprise a CD8α chain or a CD8β chain. In certain embodiments, CD8 comprises a CD8αβ heterodimer. In certain embodiments, CD8 comprises a CD8αα homodimer. In certain embodiments, CD8 comprises a CD8ββ homodimer. An exemplary human CD8α amino acid sequence is provided by GenBank Accession No. AAH25715. An exemplary human CD8β amino acid sequence is provided by GenBank Accession No. AAI00912.

[0099] As used herein, an antibody that "specifically binds to CD8" binds to CD8 with a K -7 D of 1 × 10 -8 −7 M or less, for example, 1 × 10 -9 −8 M or less, 5 × 10 -9 −9 M or less, 1 × 10 -10 −9 M or less, 5 × 10 -10 −10 M or less, or 1 × 10−10 M or less, to CD8, preferably human CD8. As used herein, an antibody that "specifically binds to CD4" binds to CD4, preferably human CD4, with a KD of 1×10-7 M or less, 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 M or less. As used herein, an antibody that "specifically binds to a second target antigen" binds to the second target antigen with a K -7 D of 1 × 10 -8 −7 M or less, for example, 1 × 10 -9 −8 M or less, 5 × 10 -9 −9 M or less, 1 × 10 -10 −9 M or less, 5 × 10 -10This refers to antibodies with a KD of M or less that bind to a second target antigen. When used herein, antibodies that "specifically bind to a third target antigen" are defined as 1 × 10⁶ antibodies. -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 antibodies with a KD of M or less that bind to the third target antigen. When used herein, antibodies that "specifically bind to the fourth target antigen" are defined as 1 × 10⁶ antibodies. -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 antibodies with a KD of M or lower that bind to the fourth target antigen.

[0100] The term "KD" refers to the dissociation constant, which is derived from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as molar concentration (M). The KD value of an antibody can be determined using methods in the art in consideration of this disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, by using a biosensor system such as the Biacore® system, or by using biolayer interferometry techniques such as the Octet RED96 system. A lower KD value of an antibody indicates a higher affinity for binding to the target antigen.

[0101] In one embodiment, an antibody that binds to CD8 is provided herein. In some embodiments, the CD8 antibody binds to CD8α. In some embodiments, the CD8 antibody binds to CD8β. In some embodiments, the CD8 antibody binds at the interface between CD8α and CD8β. In some embodiments, an antibody that binds to the CD8 antigen is provided herein. In some embodiments, the CD8 antibody is the CD8α antigen. In some embodiments, the CD8 antibody is the CD8β antigen. In some embodiments, the CD8 antibody binds to the antigen at the interface between CD8α and CD8β. In some embodiments, an antibody that binds to the CD8 epitope is provided herein. In some embodiments, the CD8 antibody is the CD8α epitope. In some embodiments, the CD8 antibody binds to the CD8β epitope. In some embodiments, the CD8 antibody binds to the epitope at the interface between CD8α and CD8β.

[0102] In some embodiments, the antibody includes a heavy chain variable region and a light chain variable region. In some embodiments, the CD8 antibody is not a single-domain antibody or a nanobody. In some embodiments, the CD8 antibody is a humanized antibody. In some embodiments, the CD8 antibody is a fully humanized antibody.

[0103] In certain embodiments, CD8 antibodies comprising any one of the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising any one of the VH region of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising any one of the VL region of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising any one of the VH region of the antibodies described herein and any one of the VL region of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising any one of the VH region of the antibodies described herein and any one of the VL region of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising any one of the VH CDR1, VH CDR2, and VH CDR3 of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising any one of the VL CDR1, VL CDR2, and VL CDR3 of the antibodies described herein are provided herein. In some embodiments, CD8 antibodies comprising one of the antibodies described herein, VH CDR1, VH CDR2, and VH CDR3, and one of the antibodies described herein, VL CDR1, VL CDR2, and VL CDR3, are provided herein. Representative VH and VL amino acid sequences, including the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the CD8 antibodies provided herein, are provided in Tables 2 to 7.

[0104] In certain embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein, specifically a VH region, a VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3. In some embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein, specifically a VH region. In some embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein, specifically a VL region. In some embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein, specifically a VH region and any one of the antibodies described herein, specifically a VL region. In some embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein, specifically a VH region and a VL region. In some embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein as VL CDR1, VL CDR2, and VL CDR3. In some embodiments, CD8 multispecific antibodies are provided herein, comprising a binding domain that binds to CD8 having any one of the antibodies described herein as VH CDR1, VH CDR2, and VH CDR3 and any one of the antibodies described herein as VL CDR1, VL CDR2, and VL CDR3. In certain embodiments, the CD8 antibody is a bispecific antibody. In certain embodiments, the CD8 antibody is a triplicate antibody. In certain embodiments, the CD8 antibody is a quadruplicate antibody.

[0105] In some embodiments, the antibody specifically binds to CD8. In other embodiments, CD8 is present on the surface of T cells.

[0106] In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In some embodiments, the antibody is a triplicate antibody. In some embodiments, the antibody is a quadruplicate antibody. In certain embodiments, 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 four antigens. In some embodiments, the antibody can bind to at least five antigens.

[0107] In certain embodiments, an intact CD8 antibody is provided. In other embodiments, a CD8 antibody is provided that is an antigen-binding fragment of the CD8 antibody. In some embodiments, the antigen-binding fragment of the CD8 antibody is a functional fragment.

[0108] In some embodiments, the antigen-binding fragment is a diabody. In some embodiments, the antigen-binding fragment is Fab. In some embodiments, the antigen-binding fragment is Fab'. In some embodiments, the antigen-binding fragment is F(ab')2. In some embodiments, the antigen-binding fragment is an Fv fragment. In some embodiments, the antigen-binding fragment is a disulfide-stabilized Fv fragment (dsFv). In some embodiments, the antigen-binding fragment is (dsFv)2. In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen-binding fragment is a disulfide-stabilized diabody (ds diabody). In some embodiments, the antigen-binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen-binding fragment is a single-domain antibody (sdAb). In some embodiments, the antigen-binding fragment is an scFv dimer (bivalent diabody). In some embodiments, the antigen-binding fragment 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 camelidized single-domain antibody. In some embodiments, the antigen-binding fragment is a nanobody. In some embodiments, the antigen-binding fragment is a domain antibody. In some embodiments, the antigen-binding fragment is a bivalent domain antibody. In some embodiments, the antigen-binding fragment is an antibody fragment that binds to an antigen but does not contain a complete antibody structure.

[0109] In certain embodiments, the CD8 antibody includes a VH region and a VL region. In some embodiments, the CD8 antibody is a single-chain antibody. In some embodiments, the CD8 antibody is a single-domain antibody. In some embodiments, the CD8 antibody is a nanobody. In certain embodiments, the CD8 antibody is a VHH antibody. In certain embodiments, the CD8 antibody is a llama antibody. In some embodiments, the CD8 antibody is not a single-chain antibody. In some embodiments, the CD8 antibody is not a single-domain antibody. In some embodiments, the CD8 antibody is not a nanobody. In some embodiments, the CD8 antibody is not a VHH antibody. In some embodiments, the CD8 antibody is not a llama antibody. In some embodiments, the CD8 antibody is a multispecific antibody. In other embodiments, the CD8 antibody is a bispecific antibody. In other embodiments, the CD8 antibody is a triplicate antibody. In other embodiments, the CD8 antibody is a quadruplicate antibody. In certain embodiments, the multispecific antibody includes an antigen-binding fragment of the CD8 antibody provided herein. In other embodiments, the bispecific antibody includes an antigen-binding fragment of the CD8 antibody provided herein. In other embodiments, the triplicate antibody comprises an antigen-binding fragment of the CD8 antibody provided herein. In other embodiments, the quadruplicate antibody comprises an antigen-binding fragment of the CD8 antibody provided herein. In some embodiments, the CD8 antibody is an agonist antibody. In certain embodiments, the CD8 antibody activates T cells. In other embodiments, the CD8 antibody is an antagonist antibody. In certain embodiments, the CD8 antibody inactivates T cells. In some embodiments, the CD8 antibody blocks T cell activation. In some embodiments, the CD8 antibody modulates T cell activity. In some embodiments, the CD8 antibody neither activates nor inactivates T cell activity. In certain embodiments, the T cells are human T cells.

[0110] In some embodiments, the sequence of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follows the Kabat numbering system. In some embodiments, the sequence of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follows the Chothia numbering system. In some embodiments, the sequence of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follows the exemplary numbering system. In some embodiments, the sequence of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follows the Contact numbering system. In some embodiments, the sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the IMGT numbering system. In some embodiments, the sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 follow the AbM numbering system. An exemplary set of six CDRs (VH CDR1-3 and VL CDR1-3) for a particular antibody embodiment is provided herein. Other sets of CDRs are also conceived and are within the scope of the antibody embodiments provided herein.

[0111] In one embodiment, an antibody that binds to CD8 is provided herein. In one embodiment, antibodies having VH CDR1, VH CDR2, and VH CDR3 of the CD8 antibody provided herein are provided. In one embodiment, antibodies having VL CDR1, VL CDR2, and VL CDR3 of the CD8 antibody provided herein are provided. In one embodiment, antibodies having VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the CD8 antibody provided herein are provided. In one embodiment, an antibody having VH of the CD8 antibody provided herein is provided. In one embodiment, an antibody having VL of the CD8 antibody provided herein is provided. In one embodiment, antibodies having VH and VL of the CD8 antibody provided herein are provided. In one embodiment, an antibody having the heavy chain of the CD8 antibody provided herein is provided. In one embodiment, an antibody having the light chain of the CD8 antibody provided herein is provided. In one embodiment, antibodies having the heavy chain and light chain of the CD8 antibody provided herein are provided.

[0112] In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 31. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR3, having the amino acid sequence of SEQ ID NO: 32. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 32. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 66. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 65, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 66. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 99.In one embodiment, the CD8 antibody includes VLs, each having the amino acid sequences of VLs VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 100, respectively. In one embodiment, the CD8 antibody includes VHs, each having the amino acid sequences of VHs VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VHs In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 133. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 134. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 133, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 134. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs, VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs VL CDR1, VL CDR2, and VL CDR3, respectively, which have the amino acid sequence of SEQ ID NO: 168.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 167, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 168. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 201. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 202. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 201, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of SEQ ID NO: 202. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 235. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 236.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 235, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 236. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 270. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 269, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of SEQ ID NO: 270. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 303. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR3, having the amino acid sequence of SEQ ID NO: 304.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 303, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 304. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 338. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 337, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 338. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 371. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR3, having the amino acid sequence of SEQ ID NO: 372.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 371, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 372. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 405. In one embodiment, the CD8 antibody includes VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of SEQ ID NO: 406. In one embodiment, the CD8 antibody includes VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 405, and (ii) VL having the amino acid sequence of VL, VL CDR1, VL. The CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of L CDR2 and VL CDR3, respectively. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH, which comprises VH CDR1, VH CDR2, and VL CDR3, each having the amino acid sequences of VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL, which comprises VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 439, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 440. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 474. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 474.In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 507. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 508. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 507, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 508. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 542. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 541, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 542. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 575.In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 576. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 575, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 576. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 609. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 610. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 609, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 610. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs, VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs VL CDR1, VL CDR2, and VL CDR3, respectively, which have the amino acid sequence of SEQ ID NO: 644.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 643, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 644. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 678. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VHs In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 711. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR3, having the amino acid sequence of SEQ ID NO: 712.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 711, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 712. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 746. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 746. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 779. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR3, having the amino acid sequence of SEQ ID NO: 780.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 779, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 780. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of SEQ ID NO: 814. In one embodiment, the CD8 antibody includes VH CDR1, VH CDR2, and VH CDR3, having the amino acid sequence of VH, having the amino acid sequence of SEQ ID NO: 813. (ii) VH includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of VL having the amino acid sequence of SEQ ID NO: 814, each having VL CDR1, VL CDR2, and VL CDR3. In one embodiment, the CD8 antibody includes VH including VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of VH having the amino acid sequence of SEQ ID NO: 847. In one embodiment, the CD8 antibody includes VL including VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of VL having the amino acid sequence of SEQ ID NO: 848. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 847, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 848. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs, VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs having the amino acid sequence of SEQ ID NO: 882.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 881, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 882. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 915. In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 916. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VHs VHs VHs VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 915, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 916. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 949. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 950.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 949, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 950. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 984. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 983, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 984. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1017. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 1018.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1017, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1018. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1052. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1051, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1052. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 1085. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1086, having VL CDR1, VL CDR2, and VL CDR3.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH having the amino acid sequence of SEQ ID NO: 1085, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL having the amino acid sequence of SEQ ID NO: 1086. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH having the amino acid sequence of SEQ ID NO: 1119. In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1120. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1119, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1120. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH, VH CDR1, VH CDR2, and VH CDR3, respectively. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1153, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of SEQ ID NO: 1154. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 1187. In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1188. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1187, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1188. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1221. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1222. (ii) The CD8 antibody includes VL, which includes CDR1, VL CDR2, and VL CDR3. In one embodiment, the CD8 antibody includes VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH having the amino acid sequence of SEQ ID NO: 1221, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL having the amino acid sequence of SEQ ID NO: 1222. In one embodiment, the CD8 antibody includes VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH having the amino acid sequence of SEQ ID NO: 1255. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1256. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1256. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 1289. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1290.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1289, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1290. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1324. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1323, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1324. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1357. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence having the amino acid sequence of SEQ ID NO: 1358.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1357, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1358. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1392. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1391, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1392. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH, VH CDR1, VH CDR2, and VH CDR3, respectively. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1425, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1426. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH CDR3 having the amino acid sequence of SEQ ID NO: 1459. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1460. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1459, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1460. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1493. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1493, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1494. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1528. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1527, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1528. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1561. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 1562.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH having the amino acid sequence of SEQ ID NO: 1561, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL having the amino acid sequence of SEQ ID NO: 1562. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH having the amino acid sequence of SEQ ID NO: 1595. In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1596. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1595, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1596. In one embodiment, the CD8 antibody comprises VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH VH CDR1, VH CDR2, and VH CDR3. (ii) The CD8 antibody includes VH, which has VH CDR1, VH CDR2, and VH CDR3, respectively. In one embodiment, the CD8 antibody includes VL, which has VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1630. In one embodiment, the CD8 antibody includes VH, which has VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1630. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 1663. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1664, having VL CDR1, VL CDR2, and VL CDR3. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1663, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1664. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VHIn one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1698. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1698. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1731. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1731, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1732. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs, VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VLs having the amino acid sequence of SEQ ID NO: 1766.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 1765, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 1766. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 1799. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1800. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1799, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1800. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH, VH CDR1, VH CDR2, and VH CDR3, respectively. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1833, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1834. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1868. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1867, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1868. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1901. In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1901, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1902. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1936. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1936. In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 1969. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NO: 1970.In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 1969, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 1970. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 2003. In one embodiment, the CD8 antibody includes VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which have the amino acid sequence of SEQ ID NO: 2004. In one embodiment, the CD8 antibody includes VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which have the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 2003, and (ii) VL having VL CDR1, VL CDR2, and VL C. The CD8 antibody includes VLs, each having the amino acid sequence of DR3, and VL CDR1, VL CDR2, and VL CDR3. In one embodiment, the CD8 antibody includes VHs, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which have the amino acid sequence of VHs, which have the amino acid sequence of SEQ ID NO: 2037. In one embodiment, the CD8 antibody includes VLs, each having the amino acid sequences of VLs, which have the amino acid sequence of VLs, which have the amino acid sequence of VLs, which have the amino acid sequence of SEQ ID NO: 2038, and VL CDR1, VL CDR2, and VL CDR3. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 2037, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2038. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2072. In one embodiment, the CD8 antibody includes VHs comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 2071, and (ii) VLs comprising VLs comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2072.In one embodiment, the CD8 antibody includes VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of VH, VH CDR1, VH CDR2, and VH CDR3, respectively. In one embodiment, the CD8 antibody includes VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL, VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 2105, and VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2106. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH VH In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2140. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2139, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2140. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 2173.In one embodiment, the CD8 antibody includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2174. In one embodiment, the CD8 antibody includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH VH1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 2173, and VL, which comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 2174. In some embodiments, the CD8 antibody is a multispecific antibody. In some embodiments, the CD8 antibody is a bispecific antibody. In some embodiments, the CD8 antibody is a tripspecific antibody. In some embodiments, the CD8 antibody is a quadruspecific antibody. In certain embodiments, the CD8 antibody is a multispecific antibody whose second target is CD4. In certain embodiments, the CD8xCD4 multispecific antibody comprises the CD8 antibody and the CD4 antibody provided herein.

[0113] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 4, 5, and 6, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs: 7, 8, and 9, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 10, 11, and 12, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 13, 14, and 15, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 16, 17, and 18, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 19, 20, and 21, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 22, 23, and 24, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 25, 26, and 27, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 28, 29, and 30, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 31. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 32. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 31 and VL having the amino acid sequence of SEQ ID NO: 32. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 33. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 34, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 33 and a light chain having the amino acid sequence of SEQ ID NO: 34, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 31, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 32, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 31 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 32, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 33, is provided herein.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 33 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34.

[0114] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 35, 36, and 37, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 38, 39, and 40, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 41, 42, and 43, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 44, 45, and 46, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 47, 48, and 49, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 50, 51, and 52, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 53, 54, and 55, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 56, 57, and 58, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 59, 60, and 61, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 62, 63, and 64, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and CD8. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 65. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 66. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 65 and VL having the amino acid sequence of SEQ ID NO: 66. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 67. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 68, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 67 and a light chain having the amino acid sequence of SEQ ID NO: 68, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 67, is provided herein.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 68. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 67 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 68.

[0115] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 69, 70, and 71, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 72, 73, and 74, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 75, 76, and 77, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 78, 79, and 80, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 81, 82, and 83, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 84, 85, and 86, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 87, 88, and 89, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 90, 91, and 92, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 93, 94, and 95, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 96, 97, and 98, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 99. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 100. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 99 and VL having the amino acid sequence of SEQ ID NO: 100. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 101, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 102, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 101 and a light chain having the amino acid sequence of SEQ ID NO: 102, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 99, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 100, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 99 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 100, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 101.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 102. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 101 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 102.

[0116] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 103, 104, and 105, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 106, 107, and 108, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 109, 110, and 111, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 112, 113, and 114, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 115, 116, and 117, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 118, 119, and 120, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 121, 122, and 123, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 124, 125, and 126, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 127, 128, and 129, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 130, 131, and 132, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 133. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 134. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 133 and VL having the amino acid sequence of SEQ ID NO: 134. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 135, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 136, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 135 and a light chain having the amino acid sequence of SEQ ID NO: 136, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 135.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 136. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 135 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 136.

[0117] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 137, 138, and 139, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 140, 141, and 142, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 143, 144, and 145, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 146, 147, and 148, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 149, 150, and 151, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 152, 153, and 154, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 155, 156, and 157, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 158, 159, and 160, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 161, 162, and 163, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 164, 165, and 166, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 167. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 168. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 167 and VL having the amino acid sequence of SEQ ID NO: 168. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 169, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 170, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 169 and a light chain having the amino acid sequence of SEQ ID NO: 170, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 167, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 168, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 167 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 168, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 169.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 170. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 169 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 170.

[0118] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 171, 172, and 173, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 174, 175, and 176, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 177, 178, and 179, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 180, 181, and 182, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 183, 184, and 185, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 186, 187, and 188, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 189, 190, and 191, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 192, 193, and 194, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 195, 196, and 197, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 198, 199, and 200, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 201. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 202. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 201 and VL having the amino acid sequence of SEQ ID NO: 202. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 203, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 204, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 203 and a light chain having the amino acid sequence of SEQ ID NO: 204, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 201, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 202, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 201 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 202, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 203.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 204. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 203 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 204.

[0119] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 205, 206, and 207, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 208, 209, and 210, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 211, 212, and 213, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 214, 215, and 216, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 217, 218, and 219, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 220, 221, and 222, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 223, 224, and 225, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 226, 227, and 228, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 229, 230, and 231, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 232, 233, and 234, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 235. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 236 and VL having the amino acid sequence of SEQ ID NO: 236. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 237, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 238, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 237 and a light chain having the amino acid sequence of SEQ ID NO: 238, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 235, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 236, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 235 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 236, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 237.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 238. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 237 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 238.

[0120] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 239, 240, and 241, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 242, 243, and 244, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 245, 246, and 247, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 248, 249, and 250, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 251, 252, and 253, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 254, 255, and 256, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 257, 258, and 259, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 260, 261, and 262, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 263, 264, and 265, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 266, 267, and 268, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 269. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 270. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 269 and VL having the amino acid sequence of SEQ ID NO: 270. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 271, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 272, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 271 and a light chain having the amino acid sequence of SEQ ID NO: 272, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 269, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 270, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 269 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 270, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 271.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 272. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 271 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 272.

[0121] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 273, 274, and 275, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 276, 277, and 278, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 279, 280, and 281, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 282, 283, and 284, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 285, 286, and 287, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 288, 289, and 290, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 291, 292, and 293, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 294, 295, and 296, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 297, 298, and 299, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 300, 301, and 302, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 303. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 304. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 303 and VL having the amino acid sequence of SEQ ID NO: 304. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 305, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 306, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 305 and a light chain having the amino acid sequence of SEQ ID NO: 306, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 303, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 304, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 303 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 304, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 305.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 306. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 305 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 306.

[0122] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 307, 308, and 309, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 310, 311, and 312, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 313, 314, and 315, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 316, 317, and 318, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 319, 320, and 321, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 322, 323, and 324, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 325, 326, and 327, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 328, 329, and 330, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 331, 332, and 333, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 334, 335, and 336, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 337. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 338 and VL having the amino acid sequence of SEQ ID NO: 338. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 337 and VL having the amino acid sequence of SEQ ID NO: 338. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 339, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 340, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 339 and a light chain having the amino acid sequence of SEQ ID NO: 340, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 337, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 338, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 337 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 338, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 339.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 340. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 339 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 340.

[0123] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 341, 342, and 343, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 344, 345, and 346, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 347, 348, and 349, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 350, 351, and 352, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 353, 354, and 355, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 356, 357, and 358, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 359, 360, and 361, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 362, 363, and 364, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 365, 366, and 367, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 368, 369, and 370, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 371. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 372. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 371 and VL having the amino acid sequence of SEQ ID NO: 372. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 373, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 374, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 373 and a light chain having the amino acid sequence of SEQ ID NO: 374, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 371, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 372, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 371 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 372, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 373.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 374. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 373 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 374.

[0124] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 375, 376, and 377, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 378, 379, and 380, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 381, 382, ​​and 383, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 384, 385, and 386, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 387, 388, and 389, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 390, 391, and 392, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 393, 394, and 395, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 396, 397, and 398, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 399, 400, and 401, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 402, 403, and 404, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 405. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 406. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 405 and VL having the amino acid sequence of SEQ ID NO: 406. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 407, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 408, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 407 and a light chain having the amino acid sequence of SEQ ID NO: 408, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 405, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 406, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 405 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 406, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 407.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 408. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 407 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 408.

[0125] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 409, 410, and 411, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 412, 413, and 414, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 415, 416, and 417, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 418, 419, and 420, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 421, 422, and 423, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 424, 425, and 426, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 427, 428, and 429, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 430, 431, and 432, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 433, 434, and 435, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 436, 437, and 438, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 439. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 440. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 439 and VL having the amino acid sequence of SEQ ID NO: 440. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 441, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 442, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 441 and a light chain having the amino acid sequence of SEQ ID NO: 442, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 439, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 440, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 439 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 440, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 441.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 442. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 441 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 442.

[0126] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 443, 444, and 445, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 446, 447, and 448, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 449, 450, and 451, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 452, 453, and 454, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 455, 456, and 457, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 458, 459, and 460, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 461, 462, and 463, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 464, 465, and 466, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 467, 468, and 469, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 470, 471, and 472, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 473. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 474. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 473 and VL having the amino acid sequence of SEQ ID NO: 474. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 475, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 476, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 475 and a light chain having the amino acid sequence of SEQ ID NO: 476, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 473, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 474, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 473 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 474, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 475.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 476. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 475 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 476.

[0127] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 477, 478, and 479, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 480, 481, and 482, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 483, 484, and 485, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 486, 487, and 488, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 489, 490, and 491, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 492, 493, and 494, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 495, 496, and 497, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 498, 499, and 500, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 501, 502, and 503, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 504, 505, and 506, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 507. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 508 and VL having the amino acid sequence of SEQ ID NO: 508. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 509, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 510, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 509 and a light chain having the amino acid sequence of SEQ ID NO: 510, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 507, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 508, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 507 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 508, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 509.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 510. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 509 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 510.

[0128] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 511, 512, and 513, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 514, 515, and 516, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 517, 518, and 519, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 520, 521, and 522, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 523, 524, and 525, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 526, 527, and 528, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 529, 530, and 531, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 532, 533, and 534, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 535, 536, and 537, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 538, 539, and 540, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 541. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 542. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 541 and VL having the amino acid sequence of SEQ ID NO: 542. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 543, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 544, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 543 and a light chain having the amino acid sequence of SEQ ID NO: 544, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 541, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 542, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 541 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 542, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 543.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 544. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 543 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 544.

[0129] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 545, 546, and 547, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 548, 549, and 550, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 551, 552, and 553, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 554, 555, and 556, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 557, 558, and 559, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 560, 561, and 562, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 563, 564, and 565, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 566, 567, and 568, respectively. In one embodiment, the Specified Reference Indicators provide a CD8-binding antibody comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 569, 570, and 571, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 572, 573, and 574, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 575. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 576 and VL having the amino acid sequence of SEQ ID NO: 576. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 577, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 578, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 577 and a light chain having the amino acid sequence of SEQ ID NO: 578, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 575, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 576, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 575 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 576, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 577.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 578. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 577 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 578.

[0130] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 579, 580, and 581, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 582, 583, and 584, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 585, 586, and 587, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 588, 589, and 590, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 591, 592, and 593, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 594, 595, and 596, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 597, 598, and 599, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 600, 601, and 602, respectively. In one embodiment, the Specified Reference Indicators provide a CD8-binding antibody comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 603, 604, and 605, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 606, 607, and 608, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 609. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 610. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 609 and VL having the amino acid sequence of SEQ ID NO: 610. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 611, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 612, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 611 and a light chain having the amino acid sequence of SEQ ID NO: 612, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 609, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 610, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 609 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 610, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 611.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 612. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 611 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 612.

[0131] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 613, 614, and 615, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 616, 617, and 618, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 619, 620, and 621, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 622, 523, and 624, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 625, 626, and 627, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 628, 629, and 630, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 631, 632, and 633, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 634, 635, and 636, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 637, 638, and 639, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 640, 641, and 642, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 643. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 644. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 643 and VL having the amino acid sequence of SEQ ID NO: 644. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 645, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 646, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 645 and a light chain having the amino acid sequence of SEQ ID NO: 646, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 643, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 644, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 643 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 644, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 645.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 646. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 645 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 646.

[0132] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 647, 648, and 649, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 650, 651, and 652, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 653, 654, and 655, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 656, 657, and 658, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 659, 660, and 661, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 662, 663, and 664, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 665, 666, and 667, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 668, 669, and 670, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 671, 672, and 673, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 674, 675, and 676, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 677. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 678. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 677 and VL having the amino acid sequence of SEQ ID NO: 678. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 679, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 680, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 679 and a light chain having the amino acid sequence of SEQ ID NO: 680, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 677, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 678, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 677 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 678, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 679.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 680. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 679 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 680.

[0133] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 681, 682, and 683, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 684, 685, and 686, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 687, 688, and 689, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 690, 691, and 692, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 693, 694, and 695, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 696, 697, and 698, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 699, 700, and 701, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 702, 703, and 704, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 705, 706, and 707, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 708, 709, and 710, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 711. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 712. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 711 and VL having the amino acid sequence of SEQ ID NO: 712. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 713, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 714, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 713 and a light chain having the amino acid sequence of SEQ ID NO: 714, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 711, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 712, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 711 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 712, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 713.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 714. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 713 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 714.

[0134] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 715, 716, and 717, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 718, 719, and 720, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 721, 722, and 723, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 724, 725, and 726, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 727, 728, and 729, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 730, 731, and 732, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 733, 734, and 735, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 736, 737, and 738, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 739, 740, and 741, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 742, 743, and 744, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 745. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 746 and VL having the amino acid sequence of SEQ ID NO: 746. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 747, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 748, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 747 and a light chain having the amino acid sequence of SEQ ID NO: 748, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 745, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 746, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 745 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 746, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 747.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 748. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 747 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 748.

[0135] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 749, 750, and 751, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 752, 753, and 754, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 755, 756, and 757, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 758, 759, and 760, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 761, 762, and 763, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 764, 765, and 766, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 767, 768, and 769, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 770, 771, and 772, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 773, 774, and 775, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 776, 777, and 778, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 779. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 780. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 779 and VL having the amino acid sequence of SEQ ID NO: 780. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 781, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 782, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 781 and a light chain having the amino acid sequence of SEQ ID NO: 782, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 779, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 780, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 779 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 780, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 781.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 782. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 781 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 782.

[0136] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 783, 784, and 785, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 786, 787, and 788, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 789, 790, and 791, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 792, 793, and 794, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 795, 796, and 797, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 798, 799, and 800, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 801, 802, and 803, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 804, 805, and 806, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 807, 808, and 809, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 810, 811, and 812, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 813. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VL having the amino acid sequence of SEQ ID NO: 814. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 813 and VL having the amino acid sequence of SEQ ID NO: 814. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 815, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 816, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 815 and a light chain having the amino acid sequence of SEQ ID NO: 816, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 813, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 814, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 813 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 814, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 815.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 816. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 815 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 816.

[0137] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 817, 818, and 819, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 820, 821, and 822, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 823, 824, and 825, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 826, 827, and 828, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 829, 830, and 831, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 832, 833, and 834, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 835, 836, and 837, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 838, 839, and 840, respectively. In one embodiment, the Specified Reference Indicators provide an antibody that binds to CD8, comprising (i) VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 841, 842, and 843, respectively, and (ii) VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 844, 845, and 846, respectively.In one embodiment, an antibody that binds to CD8 is provided herein, comprising (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 847. In one embodiment, an antibody that binds to CD8 is provided herein, comprising VH having the amino acid sequence of SEQ ID NO: 848 and VL having the amino acid sequence of SEQ ID NO: 848. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 849, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a light chain having the amino acid sequence of SEQ ID NO: 850, is provided herein. In one embodiment, an antibody that binds to CD8, comprising a heavy chain having the amino acid sequence of SEQ ID NO: 849 and a light chain having the amino acid sequence of SEQ ID NO: 850, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 847, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 848, is provided herein. In one embodiment, an antibody that binds to CD8, comprising VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 847 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 848, is provided herein. In one embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 849.In one embodiment, an antibody that binds to CD8 is provided herein, comprising a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 850. In another embodiment, an antibody that binds to CD8 is provided herein, comprising a heavy chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 849 and a light chain having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 850.

[0138] In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 851, 852, and 853, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 854, 855, and 856, respectively. In another embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 857, 858, and 859, respectively, and (ii) VL including VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs. 860, 861, and 862, respectively. In one embodiment, an antibody constituting CD8 is provided herein, comprising (i) VH including VH CDR1, VH CDR2, and VH CDR3...

Claims

1. An antibody that binds to CD8, or a multispecific antibody that binds to CD8 and CD4, wherein the antibody is (A) An antibody that binds to CD8, (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, and VH including VH CDR1, VH CDR2, and VH CDR3, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, and VL including VL CDR1, VL CDR2, and VL CDR3, A CD8-binding antibody containing, or (B) A multispecific antibody that binds to CD8 and CD4, comprising a first binding domain that binds to CD8 and a second binding domain that binds to CD4, (a) The first binding domain that binds to CD8 is (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, Includes, (b) The second binding domain that binds to CD4 is (1) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (2) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (3) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (4) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (5) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3 respectively, and (ii) VL having the amino acid sequence of VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3 respectively, and VL having VL CDR1, VL CDR2, and VL CDR3 (6) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (7) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (8) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (9) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (10) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (11) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (12) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (13) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (14) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (15) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (16) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (17) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (18) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (19) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (20) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (21) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (22) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (23) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (24) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (25) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3 respectively, and (ii) VL having the amino acid sequence of VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3 respectively, and VL having VL CDR1, VL CDR2, and VL CDR3 (26) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (27) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3 respectively, and (ii) VL having the amino acid sequence of VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3 respectively, and VL having VL CDR1, VL CDR2, and VL CDR3 (28) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (29) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (30) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (31) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (iii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (32) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (33) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (34) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (35) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (36) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (37) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (38) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (39) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (40) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (41) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (42) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (43) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (44) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (45) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3 respectively, including VH CDR1, VH CDR2, and VH CDR3, and (ii) VL having the amino acid sequence of VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3 respectively, including VL CDR1, VL CDR2, and VL CDR3, (46) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (47) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (48) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (49) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (50) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (51) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (52) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (53) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (54) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (55) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (56) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (57) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (58) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (59) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (60) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (61) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (62) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (63) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (64) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (65) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (66) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (67) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (68) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (69) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (70) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (71) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (72) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (73) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, (74) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4689, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4690, respectively, and VL having VL CDR1, VL CDR2, and VL CDR3, (75) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4723, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4724, respectively, and VL having VL CDR1, VL CDR2, and VL CDR3, (76) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4757, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4758, respectively, and VL having VL CDR1, VL CDR2, and VL CDR3, (77) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4791, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4792, and VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, (78) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4825, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4826, respectively, and VL having VL CDR1, VL CDR2, and VL CDR3, (79) (i) VH containing VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4859, and (ii) VL containing VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4860, (80) (i) VH having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4893, respectively, and (ii) VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4894, respectively, and VL having VL CDR1, VL CDR2, and VL CDR3, (81) (i) VH containing VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4927, and (ii) VL containing VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4928, or (82) (i) VH containing VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 4961, and (ii) VL containing VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 4962 It is a multispecific antibody containing a first binding domain that binds to CD8 and a second binding domain that binds to CD4. The antibody.

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

3. The antibody according to claim 1, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 conform to Chothia's numbering system.

4. The antibody according to claim 1, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 conform to the AbM numbering system.

5. The antibody according to claim 1, wherein the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 conform to the Contact numbering system.

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

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

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

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

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

11. The antibody according to any one of claims 1 to 9, wherein the antibody comprises a λ light chain.

12. The antibody according to any one of claims 1 to 11, wherein the antibody is a monoclonal antibody.

13. An antibody according to any one of claims 1 to 12, (i) An antibody that binds to CD8 binds to the CD8 antigen or CD8 epitope, or (ii) The multispecific antibody that binds to CD8 and CD4 comprises a first binding domain that binds to a CD8 antigen or CD8 epitope and a second binding domain that binds to a CD4 antigen or CD4 epitope.

14. An antibody according to any one of claims 1 to 13, (i) The CD8 is present on the surface of the T cell, (ii) The CD4 is present on the surface of the T cell, or (iii) Both CD8 and CD4 are present on the surface of the T cell, The antibody.

15. An antibody according to any one of claims 1 to 14, (i) Antibodies that bind to CD8, (a) Binds to CD8α, (b) Binding to CD8β, or (c) bonded at the interface between CD8α and CD8β, or (ii) The first binding domain of a multispecific antibody that binds to CD8 and CD4, (a) Binds to CD8α, (b) Binding to CD8β, or (c) Bonded at the interface between CD8α and CD8β, The antibody.

16. The antibody according to any one of claims 1 to 15, wherein the antibody is polyvalent.

17. The antibody according to any one of claims 1 to 16, wherein the antibody is a multispecific antibody.

18. An antibody according to any one of claims 1 to 17, (A) The antibody that binds to CD8 is a multispecific CD8 antibody, and the multispecific CD8 antibody is (a) A first binding domain that binds to CD8, and a second binding domain that binds to a second target, (b) A first binding domain that binds to CD8, a second binding domain that binds to a second target, and a third binding domain that binds to a third target, or (c) comprising a first binding domain that binds to CD8, a second binding domain that binds to a second target, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target, (B) Multispecific antibodies that bind to CD8 and CD4, (a) a first binding domain that binds to CD8, a second binding domain that binds to CD4, and a third binding domain that binds to a third target, or (b) A first binding domain that binds to CD8, a second binding domain that binds to CD4, a third binding domain that binds to a third target, and a fourth binding domain that binds to a fourth target, The antibody.

19. A nucleic acid encoding an antibody according to any one of claims 1 to 18.

20. A vector comprising the nucleic acid described in claim 19.

21. A host cell comprising the vector according to claim 20.

22. A kit comprising the vector according to claim 20 and a package therefor.

23. A kit comprising an antibody according to any one of claims 1 to 18 and a package thereof.

24. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 18 and a pharmaceutically acceptable carrier.

25. A method for producing the pharmaceutical composition described in claim 24, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

26. An in vitro method for activating T cells, comprising contacting the T cells with an antibody according to any one of claims 1 to 18.

27. A method for concentrating, isolating, separating, purifying, sorting, selecting, capturing, or detecting cells, (A) The cells are CD8-expressing cells, and the method is (i) Contacting a sample containing the CD8-expressing cells with an antibody that binds to CD8 as described in any one of claims 1 to 18; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cells bound to the antibody that binds to CD8. (ii) Contacting CD8-expressing cells with an antibody that binds to CD8 as described in any one of claims 1 to 18; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cells bound to the antibody that binds to CD8, or (iii) Contacting CD8-expressing cells with an antibody that binds to CD8 as described in any one of claims 1 to 18; and enriching, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD8-expressing cells based on the binding of the CD8-expressing cells to the antibody that binds to CD8. Includes, (B) The cells are CD4-expressing cells and / or CD8-expressing cells, and the method is (i) Contacting a sample containing the CD4-expressing cells and / or CD8-expressing cells with a multispecific antibody that binds to CD8 and CD4 as described in any one of claims 1 to 18; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and / or CD8-expressing cells bound to the multispecific antibody. (ii) Contacting CD4-expressing cells and / or CD8-expressing cells with a multispecific antibody that binds to CD8 and CD4 as described in any one of claims 1 to 18; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and / or CD8-expressing cells bound to the multispecific antibody, or (iii) Contacting CD4-expressing cells and / or CD8-expressing cells with a multispecific antibody that binds to CD8 and CD4 as described in any one of claims 1 to 18; and concentrating, isolating, separating, purifying, sorting, selecting, capturing or detecting the CD4-expressing cells and / or CD8-expressing cells based on their binding to the multispecific antibody. The method, including the method described above.

28. The method according to claim 27, wherein the cells are provided as a sample containing a population of cells.

29. The method according to claim 27 or 28, wherein the sample is a blood sample or a tissue sample.

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