Novel antibodies targeting CD3 and other targets, and their use

Abstract

This disclosure provides novel antibodies targeting CD3 and one or more other targets, or antigen-binding fragments thereof, isolated polynucleotides encoding the same, pharmaceutical compositions comprising the same, and uses thereof.

Claims

1. i. A first binding site that binds to the conformational epitope of CD3, and ii. A second binding site that binds to a second target other than CD3. An antibody or an antigen-binding fragment thereof, An antibody or its antigen-binding fragment, wherein the first binding portion and the second binding portion are independently single-stranded Fv (scFv) or Fab domains.

2. The first joint portion is Sequence numbers 3, 7, 11, 21, 22, 23, 26, 27, 28, 29, 30, 80, 82, 83, 84, 85, 86, 119, 120, 122, 124, 125, 126, 128, 131, 134, 136, 138, 139, 145, 195, 196, 197, 200, 201, 202, 203, 204, 2 One, two, or three heavy chain complementarity determining regions (HCDR1, HCDR2, and / or HCDR3) contained within 05, 207, 208, 209, 210, 211, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, or 315; and / or One, two, or three light chain complementarity determining regions (LCDR1, LCDR2, and / or LCDR3) contained within sequence numbers 4, 8, 12, 24, 25, 81, 87, 88, 89, 90, 91, 92, 93, 94, 95, 141, 146, 198, 199, 206, 212, 213, 214, 215, 216, 217, 218, 219, 220, 233, 234, or 316 The antibody or antigen-binding fragment thereof according to claim 1, comprising:

3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the first binding portion is an anti-CD3 scFv domain and the second binding portion is a Fab domain; or the first binding portion is an anti-CD3 Fab domain and the second binding portion is an scFv domain.

4. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the first binding portion is linked to the second binding portion directly or via a linker.

5. The antibody or antigen-binding fragment according to claim 4, wherein the N-terminus of the first binding portion is linked to the C-terminus of the second binding portion via the linker.

6. The antibody or antigen-binding fragment according to claim 1 or 2, comprising a first chain from the N-terminus to the C-terminus that includes a VH region, a CH1 region from the second binding site, a VH region from the first binding site, and a VL region from the first binding site.

7. The antibody or antigen-binding fragment according to claim 6, wherein the VH region from the first binding portion and the VL region from the first binding portion are directly linked or linked via a linker.

8. The linker is a linker containing glycine and serine, for example (GGGGS) ２ A linker comprising an antibody or antigen-binding fragment thereof according to any one of claims 4 to 7.

9. The antibody or antigen-binding fragment according to any one of claims 6 to 8, further comprising a second chain including a VL region and a CL region from the second binding portion.

10. The antibody or antigen-binding fragment according to any one of the prior claims, further comprising a third binding portion that binds to a third target other than CD3.

11. The antibody or antigen-binding fragment thereof according to claim 10, wherein the second target is the same as the third target.

12. The antibody or antigen-binding fragment thereof according to claim 10 or 11, wherein the third binding portion is a Fab domain.

13. The antibody or antigen-binding fragment thereof according to any one of the prior claims, wherein the first binding portion comprises one, two, or three HCDR1, HCDR2, and HCDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 31-40, 44, 45, 46, 50, 51, 52, 96-106, 121, 123, 127, 129, 130, 132, 133, 135, 137, 140, 143, 144, 182, 183, 184, 307, 308, and 309.

14. The antibody or antigen-binding fragment thereof according to any one of the prior claims, wherein the first binding portion comprises one, two, or three LCDR1, LCDR2, and LCDR3, each containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 41, 42, 43, 47, 48, 49, 53, 54, 55, 107-118, 142, 149, 185, 186, 187, 310, 311, and 312.

15. The first joint portion is i. HCDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 31, 44, 50, 96, 97, 98, 132, 140, 182, and 307; ii. HCDR2 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 32, 33, 34, 45, 51, 99, 100, 101, 102, 121, 123, 129, 143, 183 and 308; and iii. HCDR3 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 35, 36, 37, 38, 39, 40, 46, 52, 103, 104, 105, 106, 127, 130, 133, 135, 137, 144, 184, and 309. An antibody or antigen-binding fragment thereof according to any one of the prior claims, comprising:

16. The first joint portion is i. LCDR1 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 41, 47, 53, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 185, and 310; ii. LCDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 42, 48, 54, 117, 186 and 311; and iii. LCDR3 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 43, 49, 55, 118, 142, 149, 187, and 312. An antibody or antigen-binding fragment thereof according to any one of the prior claims, comprising:

17. The first joint portion is i. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 34, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 40; ii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35; iii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 36; iv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 37; v. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 38; vi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 33, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35; vii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 39; viiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 44, HCDR2 containing the amino acid sequence described in SEQ ID NO: 45, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 46; ix. HCDR1 containing the amino acid sequence described in SEQ ID NO: 50, HCDR2 containing the amino acid sequence described in SEQ ID NO: 51, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 52; x. HCDR1 containing the amino acid sequence described in SEQ ID NO: 98, HCDR2 containing the amino acid sequence described in SEQ ID NO: 102, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 106; xi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 99, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103; xi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103; xiiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 97, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103; xiv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 101, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103; xv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 104; xvi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 105; xvii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 132, HCDR2 containing the amino acid sequence described in SEQ ID NO: 143, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 144; xviiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 121, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35; xix. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 123, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35; xx. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 127; xxi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 129, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 130; xxii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 121, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 133; xxiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 135; xxiv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 137; xxv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 140, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35; xxvi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 182, HCDR2 containing the amino acid sequence described in SEQ ID NO: 183, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 184; or xxvii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 307, HCDR2 containing the amino acid sequence described in SEQ ID NO: 308, and HCDR3 containing the amino acid sequence described in SEQ ID NO:

309. An antibody or antigen-binding fragment thereof according to any one of the prior claims, comprising:

18. The first joint portion is i. LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; ii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 47, LCDR2 containing the amino acid sequence described in SEQ ID NO: 48, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 49; iii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 53, LCDR2 containing the amino acid sequence described in SEQ ID NO: 54, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 55; iv. LCDR1 containing the amino acid sequence described in SEQ ID NO: 116, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; v. LCDR1 containing the amino acid sequence described in SEQ ID NO: 107, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; vi. LCDR1 containing the amino acid sequence described in SEQ ID NO: 108, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; vii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 109, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; viiii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 110, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; ix. LCDR1 containing the amino acid sequence described in SEQ ID NO: 111, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; x. LCDR1 containing the amino acid sequence described in SEQ ID NO: 112, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xi. LCDR1 containing the amino acid sequence described in SEQ ID NO: 113, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xi. LCDR1 containing the amino acid sequence described in SEQ ID NO: 114, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xiiii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 115, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xiv. LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 142; xv. LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 149; xvi. LCDR1 containing the amino acid sequence described in SEQ ID NO: 185, LCDR2 containing the amino acid sequence described in SEQ ID NO: 186, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 187; or xvii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 310, LCDR2 containing the amino acid sequence described in SEQ ID NO: 311, and LCDR3 containing the amino acid sequence described in SEQ ID NO:

312. An antibody or antigen-binding fragment thereof according to any one of the prior claims, comprising:

19. The first joint portion is i. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 34, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 40, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; ii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; iii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 36, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; iv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 37, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; v. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 38, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; vi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 33, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; vii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 39, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; viiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 44, HCDR2 containing the amino acid sequence described in SEQ ID NO: 45, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 46, LCDR1 containing the amino acid sequence described in SEQ ID NO: 47, LCDR2 containing the amino acid sequence described in SEQ ID NO: 48, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 49; ix. HCDR1 containing the amino acid sequence described in SEQ ID NO: 50, HCDR2 containing the amino acid sequence described in SEQ ID NO: 51, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 52, LCDR1 containing the amino acid sequence described in SEQ ID NO: 53, LCDR2 containing the amino acid sequence described in SEQ ID NO: 54, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 55; x. HCDR1 containing the amino acid sequence described in SEQ ID NO: 98, HCDR2 containing the amino acid sequence described in SEQ ID NO: 102, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 106, LCDR1 containing the amino acid sequence described in SEQ ID NO: 116, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 99, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 107, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 97, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 107, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xiiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 101, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 107, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xiv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 104, LCDR1 containing the amino acid sequence described in SEQ ID NO: 107, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 105, LCDR1 containing the amino acid sequence described in SEQ ID NO: 107, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xvi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 108, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xvii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 109, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xviiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 110, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xix. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 111, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xx. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 112, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xxi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 113, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xxii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 114, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xxiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 96, HCDR2 containing the amino acid sequence described in SEQ ID NO: 100, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 103, LCDR1 containing the amino acid sequence described in SEQ ID NO: 115, LCDR2 containing the amino acid sequence described in SEQ ID NO: 117, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 118; xxiv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 121, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 123, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxvi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 127, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxvii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 129, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 130, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxviiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 121, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 133, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxx. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 135, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxx. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 137, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; xxxi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 140, HCDR2 containing the amino acid sequence described in SEQ ID NO: 32, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 35, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 43; or xxxii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 132, HCDR2 containing the amino acid sequence described in SEQ ID NO: 143, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 144, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 149; xxxiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 31, HCDR2 containing the amino acid sequence described in SEQ ID NO: 129, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 130, LCDR1 containing the amino acid sequence described in SEQ ID NO: 41, LCDR2 containing the amino acid sequence described in SEQ ID NO: 42, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 142; or xxxiv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 307, HCDR2 containing the amino acid sequence described in SEQ ID NO: 308, HCDR3 containing the amino acid sequence described in SEQ ID NO: 309, LCDR1 containing the amino acid sequence described in SEQ ID NO: 310, LCDR2 containing the amino acid sequence described in SEQ ID NO: 311, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 312 An antibody or antigen-binding fragment thereof according to any one of the prior claims, comprising:

20. The first binding portion is an amino acid sequence described in SEQ ID NOs: 3, 7, 11, 21, 22, 23, 26, 27, 28, 29, 30, 80, 82, 83, 84, 85, 86, 119, 120, 122, 124, 125, 126, 128, 131, 134, 136, 138, 139, 145, 195, 196, 197, 200, 201, 202, 203, 204, 205, 207, 208, 209, 210, 211, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232 or 315, or SEQ ID NOs: 3, 7, 11, 21, 22, 23, 2 An antibody or antigen-binding fragment according to any one of the prior claims, comprising a VH region having a homologous sequence having at least 80% sequence identity with 6, 27, 28, 29, 30, 80, 82, 83, 84, 85, 86, 119, 120, 122, 124, 125, 126, 128, 131, 134, 136, 138, 139, 145, 195, 196, 197, 200, 201, 202, 203, 204, 205, 207, 208, 209, 210, 211, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, or 315.

21. The first binding portion is an amino acid sequence as described in SEQ ID NOs: 4, 8, 12, 24, 25, 81, 87, 88, 89, 90, 91, 92, 93, 94, 95, 141, 146, 198, 199, 206, 212, 213, 214, 215, 216, 217, 218, 219, 220, 233, 234 or 316, or SEQ ID NOs: 4, 8, 12, 24, 25, 81, 8 An antibody or antigen-binding fragment according to any one of the prior claims, comprising a VL region having a homologous sequence having at least 80% sequence identity with 7, 88, 89, 90, 91, 92, 93, 94, 95, 141, 146, 198, 199, 206, 212, 213, 214, 215, 216, 217, 218, 219, 220, 233, 234, or 316.

22. The aforementioned first coupling portion is sequence numbers 3 / 4, 7 / 8, 11 / 12, 21 / 24, 22 / 24, 23 / 24, 21 / 25, 26 / 24, 27 / 24, 28 / 24, 29 / 24, 30 / 24, 80 / 81, 83 / 87, 84 / 87, 85 / 87, 86 / 87, 82 / 88, 82 / 89, 82 / 90, 82 / 91, 82 / 92, 82 / 93, 82 / 9 4, 82 / 95, 119 / 198, 120 / 198, 122 / 198, 124 / 198, 125 / 198, 126 / 198, 128 / 198, 131 / 198, 134 / 198, 136 / 198, 138 / 198, 139 / 198, 128 / 141, 195 / 198, 196 / 198, 197 / 198, 195 / 199, 200 / 198, 2 01 / 198, 202 / 198, 203 / 198, 204 / 198, 205 / 206, 208 / 212, 209 / 212, 210 / 212, 211 / 212, 207 / 213, 207 / 214, 207 / 215, 207 / 216, 207 / 217, 207 / 218, 207 / 219, 207 / 220, 221 / 233, 222 / 233, 22 An antibody or antigen-binding fragment according to any one of the prior claims, comprising a VH / VL amino acid sequence pair selected from the group consisting of 3 / 233, 224 / 233, 225 / 233, 226 / 233, 227 / 233, 227 / 234, 228 / 233, 229 / 233, 230 / 233, 231 / 233, 232 / 233, and 315 / 316.

23. The antibody or antigen-binding fragment according to any one of the prior claims, wherein the first binding portion further comprises one or more amino acid residue substitutions or modifications, but still retains specific binding affinity to CD3.

24. The antibody or antigen-binding fragment thereof according to claim 23, wherein at least one of the substitutions or modifications is located within one or more CDR sequences of the VH region or VL region of the first binding portion.

25. The antibody or antigen-binding fragment according to claim 23, wherein at least one of the substitutions or modifications is located within one or more non-CDR sequences of the VH region or VL region of the first binding portion.

26. An antibody or antigen-binding fragment thereof according to any one of the prior claims, further comprising one or more non-natural amino acid (NNAA) substitutions.

27. The antibody or antigen-binding fragment thereof according to claim 26, which can be conjugated to the aforementioned NNAA.

28. The antibody or antigen-binding fragment thereof according to any one of the prior claims, which is a chimeric, humanized, or human antibody or an antigen-binding fragment thereof.

29. An antibody or antigen-binding fragment thereof according to any one of the prior claims, which is a labeled antibody, a bivalent antibody, an anti-idiotype antibody, or a fusion protein.

30. An antibody or antigen-binding fragment according to any one of the prior claims, further comprising an Fc region, optionally an Fc region of human immunoglobulin (Ig), or optionally an Fc region of human IgG.

31. The antibody or antigen-binding fragment according to claim 30, wherein the Fc region is derived from human IgG1, IgG2, IgG3, or IgG4.

32. The antibody or antigen-binding fragment according to claim 31, wherein both the first binding portion and the third binding portion are linked to the Fc region.

33. The antibody or antigen-binding fragment thereof according to any one of the prior claims, wherein the light chain is a λ light chain or a κ light chain.

34. The second target is GPRC5D, GD2, CD16a, CD33, CD38, CD45, CD123, CD146, CD228, CLL-1, FLT3, FLT3L, TAF1, TgPRF, HVCN1, IL-6R, IL-11R, IL17A, IL-23R, IL-33, ILDR2, LAP, TSLP, TREM-1, ANGPT2, APOE, IFNAR, CypA, DOG-1, NKp30, CSF-1R, CCR2, LRRC15, Mesothelin, Dickkopf2, DLL3, HER-2, C10orf54, TrkA, M EKK1, KRAS, ERK, XPO1, mTORC1 / 2, PAK4, NAMPT, ATR, EGFR, FGFR, VEGF, LI LRB (e.g. LILRB1, LILRB2, LILRB3, LILRB4, LILRB5), c-MET, Her2, Her3, C TLA4, GITA, CD112R, CD2, CD7, CD16, CD19, CD20, CD24, CD27, CD30, CD34, C D37, CD39, CD70, CD73, CD83, CD28, CD80 (B7-1), CD86 (B7-2), CD40, CD40L (CD154), CD47, SIRPα, CD122, CD137, CD137L, OX40 (CD134), OX40L (CD25 2), BCMA (e.g. BCMA02), PSMA, CLDN18 (e.g. CLDN18.2), NKG2C, 4-1BB, LIG HT, PVRIG, SLAMF7, HVEM, BAFFR, ICAM-1, 2B4, LFA-1, GITR, ICOS (CD278), ICOSLG (CD275), LAG3 (CD223), A2AR, B7-H3 (CD276), B7-H4 (VTCN1), B7-H 5. An antibody or antigen-binding fragment thereof according to any one of the prior claims, selected from the group consisting of BTLA (CD272), CD160, CTLA-4 (CD152), IDO (e.g., IDO1, IDO2), ILT3, TDO, KIR, LAIR-1, NOX2, PD-1, PD-L1, PD-L2, TIM-3, VISTA, SIGLEC-7 (CD328), SIGLEC-9 (CD329), SIGLEC-15, TIGIT, PVR (CD155), TLR3, CLEC9A, DEC-205, STING, and TGFβ.

35. The antibody or antigen-binding fragment thereof according to claim 34, wherein the second target is GPRC5D, GD2, LILRB4, CD19, or CD20.

36. The second connecting portion is One, two, or three heavy chain complementarity-determining regions (HCDR1, HCDR2, and / or HCDR3) contained within any one heavy chain variable (VH) region sequence selected from the group consisting of SEQ ID NOs: 1, 5, 9, 13, 14, 15, 16, 19, 147, 243, 257, 270, 282, 294, 313, and 326; and / or One, two, or three light chain complementarity-determining regions (LCDR1, LCDR2, and / or LCDR3) contained within any one of the light chain variable (VL) region sequences selected from the group consisting of SEQ ID NOs: 2, 6, 10, 17, 18, 20, 148, 247, 258, 271, 283, 295, 314, and 327. The antibody or antigen-binding fragment thereof according to claim 35, comprising:

37. The second combined portion described above corresponds to sequence numbers 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 188, 189, 190, 191, 192, 193, 251, 252, 253, 254, 255, 256, 264, 265, 266, 267, 268, 269, 276, 277 The antibody or antigen-binding fragment thereof according to claim 36, comprising at least one heavy chain or light chain complementarity-determining region (CDR) containing an amino acid sequence selected from the group consisting of 278, 279, 280, 281, 288, 289, 290, 291, 292, 293, 301, 302, 303, 304, 305, 306, 320, 321, 322, 323, 324, and 325.

38. The antibody or antigen-binding fragment thereof according to claim 36 or 37, wherein the second binding portion comprises one, two, or three HCDR1, HCDR2, and HCDR3 having amino acid sequences selected from the group consisting of SEQ ID NOs: 56, 57, 58, 62, 63, 64, 68, 69, 70, 74, 75, 76, 188, 189, 190, 251, 252, 253, 264, 265, 266, 276, 277, 278, 288, 289, 290, 301, 302, 303, 320, 321, and 322.

39. The antibody or antigen-binding fragment thereof according to any one of claims 36 to 38, wherein the second binding portion comprises one, two, or three LCDR1, LCDR2, and LCDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 59, 60, 61, 65, 66, 67, 71, 72, 73, 77, 78, 79, 191, 192, 193, 254, 255, 256, 267, 268, 269, 279, 280, 281, 291, 292, 293, 304, 305, 306, 323, 324, and 325.

40. The second connecting portion is i. HCDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 56, 62, 68, 74, 188, 251, 264, 276, 288, 301, and 320; ii. HCDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 57, 63, 69, 75, 189, 252, 265, 277, 289, 302 and 321; and iii. HCDR3 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 58, 64, 70, 76, 190, 253, 266, 278, 290, 303, and 322. An antibody or antigen-binding fragment thereof according to any one of claims 36 to 39, comprising:

41. The second connecting portion is i. LCDR1 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 59, 65, 71, 77, 191, 254, 267, 279, 291, 304, 323; ii. LCDR2 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 60, 66, 72, 78, 192, 255, 268, 280, 292, 305 and 324; and iii. LCDR3 containing an amino acid sequence selected from the group consisting of SEQ ID NOs: 61, 67, 73, 79, 193, 256, 269, 281, 293, 306, 325 An antibody or antigen-binding fragment thereof according to any one of claims 36 to 40, comprising:

42. The second connecting portion is i. HCDR1 containing the amino acid sequence described in SEQ ID NO: 56, HCDR2 containing the amino acid sequence described in SEQ ID NO: 57, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 58; ii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 62, HCDR2 containing the amino acid sequence described in SEQ ID NO: 63, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 64; iii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 68, HCDR2 containing the amino acid sequence described in SEQ ID NO: 69, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 70; iv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 74, HCDR2 containing the amino acid sequence described in SEQ ID NO: 75, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 76; v. HCDR1 containing the amino acid sequence described in SEQ ID NO: 188, HCDR2 containing the amino acid sequence described in SEQ ID NO: 189, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 190; vi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 251, HCDR2 containing the amino acid sequence described in SEQ ID NO: 252, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 253; vii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 264, HCDR2 containing the amino acid sequence described in SEQ ID NO: 265, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 266; viiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 276, HCDR2 containing the amino acid sequence described in SEQ ID NO: 277, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 278; ix. HCDR1 containing the amino acid sequence described in SEQ ID NO: 288, HCDR2 containing the amino acid sequence described in SEQ ID NO: 289, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 290; x. HCDR1 containing the amino acid sequence described in SEQ ID NO: 301, HCDR2 containing the amino acid sequence described in SEQ ID NO: 302, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 303; or xi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 320, HCDR2 containing the amino acid sequence described in SEQ ID NO: 321, and HCDR3 containing the amino acid sequence described in SEQ ID NO:

322. An antibody or antigen-binding fragment thereof according to any one of claims 36 to 41, comprising:

43. The second connecting portion is i. LCDR1 containing the amino acid sequence described in SEQ ID NO: 59, LCDR2 containing the amino acid sequence described in SEQ ID NO: 60, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 61; ii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 65, LCDR2 containing the amino acid sequence described in SEQ ID NO: 66, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 67; iii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 71, LCDR2 containing the amino acid sequence described in SEQ ID NO: 72, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 73; iv. LCDR1 containing the amino acid sequence described in SEQ ID NO: 77, LCDR2 containing the amino acid sequence described in SEQ ID NO: 78, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 79; v. LCDR1 containing the amino acid sequence described in SEQ ID NO: 191, LCDR2 containing the amino acid sequence described in SEQ ID NO: 192, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 193; vi. LCDR1 containing the amino acid sequence described in SEQ ID NO: 254, LCDR2 containing the amino acid sequence described in SEQ ID NO: 255, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 256; vii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 267, LCDR2 containing the amino acid sequence described in SEQ ID NO: 268, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 269; viiii. LCDR1 containing the amino acid sequence described in SEQ ID NO: 279, LCDR2 containing the amino acid sequence described in SEQ ID NO: 280, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 281; ix. LCDR1 containing the amino acid sequence described in SEQ ID NO: 291, LCDR2 containing the amino acid sequence described in SEQ ID NO: 292, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 293; x. LCDR1 containing the amino acid sequence described in SEQ ID NO: 304, LCDR2 containing the amino acid sequence described in SEQ ID NO: 305, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 306; or xi. LCDR1 containing the amino acid sequence described in SEQ ID NO: 323, LCDR2 containing the amino acid sequence described in SEQ ID NO: 324, and LCDR3 containing the amino acid sequence described in SEQ ID NO:

325. An antibody or antigen-binding fragment thereof according to any one of claims 36 to 42, comprising:

44. The second connecting portion is i. HCDR1 containing the amino acid sequence described in SEQ ID NO: 56, HCDR2 containing the amino acid sequence described in SEQ ID NO: 57, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 58, LCDR1 containing the amino acid sequence described in SEQ ID NO: 59, LCDR2 containing the amino acid sequence described in SEQ ID NO: 60, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 61; ii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 62, HCDR2 containing the amino acid sequence described in SEQ ID NO: 63, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 64, LCDR1 containing the amino acid sequence described in SEQ ID NO: 65, LCDR2 containing the amino acid sequence described in SEQ ID NO: 66, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 67; iii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 68, HCDR2 containing the amino acid sequence described in SEQ ID NO: 69, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 70, LCDR1 containing the amino acid sequence described in SEQ ID NO: 71, LCDR2 containing the amino acid sequence described in SEQ ID NO: 72, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 73; iv. HCDR1 containing the amino acid sequence described in SEQ ID NO: 74, HCDR2 containing the amino acid sequence described in SEQ ID NO: 75, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 76, LCDR1 containing the amino acid sequence described in SEQ ID NO: 77, LCDR2 containing the amino acid sequence described in SEQ ID NO: 78, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 79; v. HCDR1 containing the amino acid sequence described in SEQ ID NO: 188, HCDR2 containing the amino acid sequence described in SEQ ID NO: 189, and HCDR3 containing the amino acid sequence described in SEQ ID NO: 190, LCDR1 containing the amino acid sequence described in SEQ ID NO: 191, LCDR2 containing the amino acid sequence described in SEQ ID NO: 192, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 193; vi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 251, HCDR2 containing the amino acid sequence described in SEQ ID NO: 252, HCDR3 containing the amino acid sequence described in SEQ ID NO: 253, LCDR1 containing the amino acid sequence described in SEQ ID NO: 254, LCDR2 containing the amino acid sequence described in SEQ ID NO: 255, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 256; vii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 264, HCDR2 containing the amino acid sequence described in SEQ ID NO: 265, HCDR3 containing the amino acid sequence described in SEQ ID NO: 266, LCDR1 containing the amino acid sequence described in SEQ ID NO: 267, LCDR2 containing the amino acid sequence described in SEQ ID NO: 268, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 269; viiii. HCDR1 containing the amino acid sequence described in SEQ ID NO: 276, HCDR2 containing the amino acid sequence described in SEQ ID NO: 277, HCDR3 containing the amino acid sequence described in SEQ ID NO: 278, LCDR1 containing the amino acid sequence described in SEQ ID NO: 279, LCDR2 containing the amino acid sequence described in SEQ ID NO: 280, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 281; ix. HCDR1 containing the amino acid sequence described in SEQ ID NO: 288, HCDR2 containing the amino acid sequence described in SEQ ID NO: 289, HCDR3 containing the amino acid sequence described in SEQ ID NO: 290, LCDR1 containing the amino acid sequence described in SEQ ID NO: 291, LCDR2 containing the amino acid sequence described in SEQ ID NO: 292, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 293; x. HCDR1 containing the amino acid sequence described in SEQ ID NO: 301, HCDR2 containing the amino acid sequence described in SEQ ID NO: 302, HCDR3 containing the amino acid sequence described in SEQ ID NO: 303, LCDR1 containing the amino acid sequence described in SEQ ID NO: 304, LCDR2 containing the amino acid sequence described in SEQ ID NO: 305, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 306; or xi. HCDR1 containing the amino acid sequence described in SEQ ID NO: 320, HCDR2 containing the amino acid sequence described in SEQ ID NO: 321, HCDR3 containing the amino acid sequence described in SEQ ID NO: 322, LCDR1 containing the amino acid sequence described in SEQ ID NO: 323, LCDR2 containing the amino acid sequence described in SEQ ID NO: 324, and LCDR3 containing the amino acid sequence described in SEQ ID NO: 325 An antibody or antigen-binding fragment thereof according to any one of claims 36 to 43, comprising:

45. The antibody or antigen-binding fragment according to any one of claims 36 to 44, wherein the second binding portion includes an amino acid sequence described in SEQ ID NOs: 1, 5, 9, 13, 14, 15, 16, 19, 147, 243, 257, 270, 282, 294, 313 or 326, or a VH region having a homologous sequence having at least 80% sequence identity with SEQ ID NOs: 1, 5, 9, 13, 14, 15, 16, 19, 147, 243, 257, 270, 282, 294, 313 or 326.

46. The antibody or antigen-binding fragment according to any one of claims 36 to 45, wherein the second binding portion includes an amino acid sequence described in SEQ ID NOs: 2, 6, 10, 17, 18, 20, 148, 247, 258, 271, 283, 295, 314, or 327, or a VL region having a homologous sequence having at least 80% sequence identity with SEQ ID NOs: 2, 6, 10, 17, 18, 20, 148, 247, 258, 271, 283, 295, 314, or 327.

47. The antibody or antigen-binding fragment according to any one of claims 36 to 46, wherein the second binding portion comprises a VH / VL amino acid sequence pair selected from the group consisting of SEQ ID NOs: 1 / 2, 5 / 6, 9 / 10, 15 / 18, 13 / 18, 16 / 17, 14 / 18, 19 / 20, 147 / 148, 243 / 247, 257 / 258, 270 / 271, 282 / 283, 294 / 295, 313 / 314, and 326 / 327.

48. The antibody or antigen-binding fragment according to any one of claims 36 to 47, wherein the second binding portion further comprises one or more amino acid residue substitutions or modifications, but still retains specific binding affinity to the second target.

49. The antibody or antigen-binding fragment according to claim 48, wherein at least one of the substitutions or modifications is located within one or more of the CDR sequences in the VH region or VL region of the second binding portion.

50. The antibody or antigen-binding fragment according to claim 48, wherein at least one of the substitutions or modifications is located within one or more of the non-CDR sequences in the VH region or VL region of the second binding portion.

51. The antibody or antigen-binding fragment thereof according to claims 36 to 50, further comprising one or more non-natural amino acid (NNAA) substitutions.

52. An antibody or antigen-binding fragment thereof according to any one of the prior claims, which is linked to one or more conjugate portions.

53. The antibody or antigen-binding fragment thereof according to claim 52, wherein the conjugate portion comprises a clearance modifier, a chemotherapeutic agent, a toxin, a radioisotope, a lantanide, a detectable label, a DNA alkylating agent, a topoisomerase inhibitor, a tubulin binder, a purified portion, or other anticancer agents.

54. The antibody or antigen-binding fragment thereof according to claim 52 or 53, wherein the conjugate portion is covalently bound directly or via a linker.

55. The antibody or antigen-binding fragment according to claim 52 or 53, wherein the sequence of the second binding portion is the same as the sequence of the third binding portion.

56. A chimeric antigen receptor comprising an antibody or its antigen-binding fragment, a transmembrane region, and an intracellular signaling region according to any one of claims 1 to 55.

57. The chimeric antigen receptor according to claim 56, wherein the transmembrane region includes a transmembrane region of CD3, CD4, CD8, or CD28.

58. The chimeric antigen receptor according to claim 56, wherein the intracellular signaling region is selected from the group consisting of intracellular signaling region sequences of CD3, FcγRI, CD27, CD28, CD137, CD134, MyD88, CD40, CD278, TLR, or combinations thereof.

59. A chimeric antigen receptor according to any one of claims 56 to 58, which is grafted onto allogeneic cells, autologous cells, or heterogeneous cells.

60. A chimeric antigen receptor according to any one of claims 56 to 59, grafted onto immune effector cells.

61. A chimeric antigen receptor according to any one of claims 56 to 60, grafted onto a T cell, natural killer cell, macrophage cell, or tumor-infiltrating lymphocyte.

62. A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof according to any one of claims 1 to 55, or a chimeric antigen receptor according to any one of claims 56 to 61, and one or more pharmaceutically acceptable carriers.

63. An antibody or an antigen-binding fragment thereof according to any one of claims 1 to 55, and / or an isolated polynucleotide encoding a chimeric antigen receptor according to any one of claims 56 to 61.

64. A vector comprising an isolated polynucleotide as described in claim 63.

65. A host expression system comprising the vector described in claim 64, or having the polynucleotide described in claim 63 incorporated into its genome.

66. The host expression system according to claim 65, wherein the host is a microorganism, yeast, or mammalian cell, wherein the microorganism is optionally selected from the group consisting of Escherichia coli and Bacillus subtilis, the yeast is optionally selected to be Saccharomyces, and the mammalian cell is optionally selected from the group consisting of COS, CHO-S, CHO-K1, HEK-293, and 3T3 cells.

67. A virus comprising the vector described in claim 64.

68. A kit comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 62, and a second therapeutic agent.

69. A method for expressing an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, or a chimeric antigen receptor according to any one of claims 56 to 61, comprising culturing the host expression system according to claim 62 under conditions in which the antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, or the chimeric antigen receptor according to any one of claims 56 to 61, is expressed.

70. A method for treating, preventing, or alleviating a disease, disorder, or condition in a subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof as described in any one of claims 1 to 55, and / or a chimeric antigen receptor as described in any one of claims 56 to 61, and / or a pharmaceutical composition as described in claim 62.

71. The method according to claim 70, wherein the disease, disorder, or condition is an immune disease, an autoimmune disease (e.g., autoimmune encephalomyelitis, systemic lupus erythematosus, etc.), an inflammatory disease, cancer, or a neurological disease.

72. The method according to claim 71, wherein the cancer is a solid tumor or a hematological malignancy.

73. The aforementioned disease, disorder, or condition is lung cancer (e.g., non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), lung adenocarcinoma, or lung squamous cell carcinoma), abdominal cancer, carcinoid cancer, bone cancer, pancreatic cancer, undifferentiated neuroectodermal tumor, skin cancer, gallbladder cancer, head or neck cancer, squamous cell carcinoma, uterine cancer, ovarian cancer, rectal cancer, prostate cancer, bladder cancer (e.g., urothelial carcinoma), anal cancer (e.g., anal squamous cell carcinoma), gastric cancer, or stomach cancer. Cancer (e.g., gastrointestinal cancer), esophageal cancer, colon cancer, breast cancer, uterine cancer, liver cancer (e.g., hepatoblastoma, hepatocellular carcinoma / hepatoma, or liver cancer), bile duct cancer, sarcoma, colorectal cancer, fallopian tube cancer, salivary gland cancer, cervical cancer, endometrial cancer or uterine cancer, osteosarcoma, vaginal cancer, vulvar cancer, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, nasopharyngeal cancer, soft tissue sarcoma, polycythemia vera, urethral cancer, penile cancer, kidney cancer or ureteral cancer (e.g., renal rhabdoid tumor), cutaneous T-cell lymphoma, medulloblastoma, nephroblastoma, myelodysplastic syndrome, chronic and non-chronic myeloproliferative disorders, choroid plexus papilloma, renal cell carcinoma, renal pelvis cancer, central nervous system (CNS) neoplasms, soft tissue sarcomas (e.g., rhabdomyosarcoma, fibrosarcoma, Kaposi's sarcoma), spinal axial tumors, gliomas (e.g., ependymoma, astrocytoma, anaplastic astrocytoma, oligodendroglioma), eye cancers (e.g., retinoblastoma), brainstem gliomas, or mixed gliomas, e.g., oligodendroglioma. Astrocytoma, brain tumors (e.g., glioblastoma / glioblastoma multiforme (GBM), non-glioblastomatous brain tumors, or meningiomas), melanoma (e.g., cutaneous or intraocular melanoma), thrombocytosis, mesothelioma, mycosis fungoides, Sézary syndrome, idiopathic myelofibrosis, solitary plasmacytoma, vestibular schwannoma, Ewing's sarcoma, chondrosarcoma, MYH-associated polyposis, pituitary adenoma, childhood cancers, such as childhood sarcomas (e.g., neuroblastoma, rhabdomyosarcoma, and osteosarcoma), hematological malignancies, Hodg Kinkin lymphoma, non-Hodgkin lymphoma, leukemia (e.g., lymphocytic / lymphoblastic leukemia), chronic or acute leukemia, mast cell leukemia, lymphocytic lymphoma, primary CNS lymphoma, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), chronic lymphoblastic leukemia, acute lymphoblastic leukemia, hairy cell leukemia (HCL),The method according to any one of claims 70 to 72, selected from the group consisting of Burkitt lymphoma (BL), multiple myeloma (e.g., relapsed or refractory multiple myeloma), T or B-cell lymphoma, mantle cell lymphoma (MCL) (e.g., relapsed or refractory mantle cell lymphoma), malignant melanoma, diffuse large B-cell lymphoma (DLBCL), DLBCL resulting from follicular lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, follicular lymphoma (FL), and primary mediastinal B-cell lymphoma.

74. The method according to any one of claims 70 to 72, wherein the subject is a human.

75. The method according to any one of claims 70 to 74, wherein the administration is carried out via a parenteral route including subcutaneous, intraperitoneal, intravenous, intramuscular, or intradermal injection; or via a route other than a parenteral route including transdermal, oral, intranasal, intraocular, sublingual, rectal, or local surface.

76. The method according to any one of claims 70 to 75, further comprising administering an additional therapeutic agent to the subject in need thereof.

77. The method according to claim 76, wherein the additional therapeutic agent is selected from the group consisting of activators, contrast agents, cytotoxic agents, angiogenesis inhibitors, kinase inhibitors, costimulatory molecule agonists, coinhibitory molecule blockers, adhesion molecule blockers, anticytokine antibodies or their functional fragments, detectable labels or reporters, antibacterial agents, gene editing agents, beta-agonists, viral RNA inhibitors, polymerase inhibitors, interferons, and microRNAs.

78. The method according to claim 76, wherein the additional therapeutic agent is administered to the subject in need of it before, after, or concurrently with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or the chimeric antigen receptor according to any one of claims 56 to 61, and / or the pharmaceutical composition according to claim 62.

79. A method for activating T cells expressing CD3 or another target other than CD3 in vivo or in vitro, comprising contacting the T cells with an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 59.

80. A method for modulating the activity of CD3 or another target other than CD3 in cells expressing CD3 or another target other than CD3, comprising exposing the cells to an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 59.

81. A method for promoting in vivo or in vitro processing of a second antigen by CD3-expressing T cells, comprising contacting CD3-expressing T cells with an antibody or antigen-binding fragment described in any one of claims 1 to 55, wherein the antibody or antigen-binding fragment binds to both the CD3-expressing T cells and the second antigen, thereby bringing them into close proximity.

82. A method for detecting the presence or amount of CD3 or another target other than CD3 in a sample, comprising contacting the sample with an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 62, and determining the presence or amount of CD3 or another target other than CD3 in the sample.

83. A method for diagnosing a disease, disorder, or condition in a subject that is associated with CD3 or another target other than CD3, comprising: a) contacting a sample obtained from the subject with an antibody or antigen-binding fragment thereof as described in any one of claims 1 to 55, and / or a chimeric antigen receptor as described in any one of claims 56 to 61, and / or a pharmaceutical composition as described in claim 62; b) determining the presence or amount of CD3 or another target other than CD3 in the sample; and c) correlating the presence or amount of CD3 or another target other than CD3 with the presence or circumstances of a disease, disorder, or condition in the subject.

84. Use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 62, in the manufacture of a pharmaceutical for treating a disease, disorder, or condition related to CD3 or another target other than CD3 in a subject.

85. Use of an antibody or antigen-binding fragment thereof according to any one of claims 1 to 55, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 62, in the manufacture of a diagnostic reagent for diagnosing a disease, disorder, or condition associated with CD3 or another target other than CD3.

86. A kit comprising an antibody or antigen-binding fragment thereof according to any one of claims 1 to 54, and / or a chimeric antigen receptor according to any one of claims 56 to 61, and / or a pharmaceutical composition according to claim 62, useful for detecting CD3 or another target other than CD3, optionally recombinant CD3, CD3 expressed on the cell surface, or CD3-expressing cells.

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