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CN-122029197-A - Anti-CTLA-4 antibodies and related binding molecules and methods and uses thereof

CN122029197ACN 122029197 ACN122029197 ACN 122029197ACN-122029197-A

Abstract

Novel monoclonal antibodies or antibody fragments directed against protein cytotoxic T lymphocyte-associated protein 4 (CTLA-4) are provided. The disclosed antibodies or antibody fragments can be used to provide an effective agent for the treatment of cancer by modulating human immune function.

Inventors

  • A. Pantal

Assignees

  • 阿巴利泰克肿瘤学公司

Dates

Publication Date
20260512
Application Date
20240809
Priority Date
20230811

Claims (20)

  1. 1. An anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (V H ) region and a light chain variable (V L ) region, wherein: The V H region comprises heavy chain complementarity determining region 1 (CDR-H1), heavy chain complementarity determining region 2 (CDR-H2) and heavy chain complementarity determining region 3 (CDR-H3) contained within any one of SEQ ID NOS: 1-27 and 112, and the V L region comprises light chain complementarity determining region 1 (CDR-L1), light chain complementarity determining region 2 (CDR-L2) and light chain complementarity determining region 3 (CDR-L3) contained within any one of SEQ ID NOS: 28-48 and 118, wherein the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are not listed in SEQ ID NOS: 49, 57, 68, 74, 89 and 98, respectively.
  2. 2. The anti-CTLA-4 antibody or antigen-binding fragment thereof of claim 1, wherein: The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 1 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 2 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO.3 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 4 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 5 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 6 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 7 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 8 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 9 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 10 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 11 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 12 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 13 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 14 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 15 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 16 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 17 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 18 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 19 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 20 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 21 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 22 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 28; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 30; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 31; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO 32; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 33; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO 34; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 35; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 36; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 37; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO 38; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 39; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 40; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 42; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 43; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 44; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 45; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO 112 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO 46; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 23 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO.24 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 25 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 26 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 22 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 27 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 41; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 23 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 47; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 24 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 47; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 25 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 47; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 26 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 47; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 22 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 47; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO 27 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO 47; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 23 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 24 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 25 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 26 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 22 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 27 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 29; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 23 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 39; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 24 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 39; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 25 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 39; The V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 26 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 39; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 22 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 39; the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO: 27 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO: 39, or The V H region comprises CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO. 5 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO. 48.
  3. 3. An anti-CTLA-4 antibody or antigen-binding fragment thereof, comprising a heavy chain variable (V H ) region and a light chain variable (V L ) region, wherein: The V H region includes heavy chain complementarity determining region 1 (CDR-H1) comprising the sequence set forth in any one of SEQ ID NOS: 49-56, heavy chain complementarity determining region 2 (CDR-H2) comprising the sequence set forth in any one of SEQ ID NOS: 57-67, heavy chain complementarity determining region 3 (CDR-H3) comprising the sequence set forth in any one of SEQ ID NOS: 68-73, and The V L region includes a light chain complementarity determining region 1 (CDR-L1) comprising the sequence set forth in any one of SEQ ID NOS: 74-88, a light chain complementarity determining region 2 (CDR-L2) comprising the sequence set forth in any one of SEQ ID NOS: 89-97, and a light chain complementarity determining region 3 (CDR-L3) comprising the sequence set forth in any one of SEQ ID NOS: 98-100, wherein the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 are not set forth in SEQ ID NOS: 49, 57, 68, 74, 89 and 98, respectively.
  4. 4. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-3, wherein the V H region comprises heavy chain complementarity determining region 1 (CDR-H1) comprising the sequence set forth in any one of SEQ ID NOs 50-56, heavy chain complementarity determining region 2 (CDR-H2) comprising the sequence set forth in any one of SEQ ID NOs 58-67, and heavy chain complementarity determining region 3 (CDR-H3) comprising the sequence set forth in any one of SEQ ID NOs 69-73.
  5. 5. The anti-CTLA-4 antibody or antigen-binding fragment thereof of claims 1-4, wherein the V L region comprises light chain complementarity determining region 1 (CDR-L1) comprising the sequence set forth in any one of SEQ ID NOs 75-88, light chain complementarity determining region 2 (CDR-L2) comprising the sequence set forth in any one of SEQ ID NOs 90-97, and light chain complementarity determining region 3 (CDR-L3) comprising the sequence set forth in any one of SEQ ID NOs 99-100.
  6. 6. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-5, wherein: The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 58 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 69, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 51, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 50, 59 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 60 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 61 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 51, 62 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 50, 63 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 50, 57 and 69, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 53, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 53, 57 and 70, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 54, 57 and 71, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS: 55, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS: 74, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 56, 57 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 64 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 60 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 66 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 71, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 73, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 75, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 77, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 78, 90 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 79, 90 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 80, 91 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 78, 89 and 99, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 81, 92 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 82, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 82, 93 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 83, 92 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 100, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 86, 94 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 87, 95 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 96 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 88, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 74, 97 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 73, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 60 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 85, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 73, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 60 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 73, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 60 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 76, 89 and 98, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 73, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 60 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 67 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively; The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 57 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively; the V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 49, 65 and 72, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 84, 89 and 99, respectively, or The V H region includes CDR-H1, CDR-H2 and CDR-H3 comprising the sequences set forth in SEQ ID NOS 52, 60 and 68, respectively, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 comprising the sequences set forth in SEQ ID NOS 88, 89 and 100, respectively.
  7. 7. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-6, wherein: The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 1, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 2, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 3, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 4, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 5, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 6, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 7, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 8, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The VH region is or comprises an amino acid sequence having at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID No. 9, and the VL region is or comprises an amino acid sequence having at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 10, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 11, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 12, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 13, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 14, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 15, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 16, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 17, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 18, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 19, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 20, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 21, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 22, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 118; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 28; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 30; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 31; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 32; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 33; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 34; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112 and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 35; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 36; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 37; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 38; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 39; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 40; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 42; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 43; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 44; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 45; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 112, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 46; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 23, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 24, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 25, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 26, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 22, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 27, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 41; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 23, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 47; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 24, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 47; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 25, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 47; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 26, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 47; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 22, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 47; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 27, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 47; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 23, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 24, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 25, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 26, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 22, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; the V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 27, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 29; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 23, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 39; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 24, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 39; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 25, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 39; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 26, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 39; The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 22, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 39; The V H region is or comprises an amino acid sequence having at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 27, and the V L region is or comprises an amino acid sequence having at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 39, or The V H region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 5, and the V L region is or comprises an amino acid sequence that is at least or about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID No. 48.
  8. 8. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-7, wherein the V H region and the V L region are or comprise the sequences set forth in SEQ ID NOs 1 and 118, respectively; the sequences listed in SEQ ID NO 2 and 118, the sequences listed in SEQ ID NO 3 and 118, the sequences listed in SEQ ID NO 4 and 118, the sequences listed in SEQ ID NO 5 and 118, the sequences listed in SEQ ID NO 6 and 118, the sequences listed in SEQ ID NO 7 and 118, the sequences listed in SEQ ID NO 8 and 118, the sequences listed in SEQ ID NO 9 and 118, the sequences listed in SEQ ID NO 10 and 118, the sequences listed in SEQ ID NO 11 and 118, the sequences listed in SEQ ID NO 12 and 118, the sequences listed in SEQ ID NO 13 and 118, the sequences listed in SEQ ID NO 14 and 118, the sequences listed in SEQ ID NO 15 and 118, the sequences listed in SEQ ID NO 16 and 118, the sequences listed in SEQ ID NO 17 and 118, the sequences listed in SEQ ID NO 18 and 118, the sequences listed in SEQ ID NO 19 and 118, the sequences listed in SEQ ID NO 12 and 118, the sequences listed in SEQ ID NO 13 and 118, the sequences listed in SEQ ID NO 14 and 118, the sequences listed in SEQ ID NO 15 and 112, and the sequences listed in SEQ ID NO 16 and 118, respectively, the sequences listed in SEQ ID NO 19 and 112, and the sequences listed in SEQ ID NO 14 and 118, respectively, and the sequences listed in SEQ ID NO 14 and 112, respectively, and SEQ ID NO 14 and 112, respectively The sequences shown, the sequences shown in SEQ ID NO 112 and 31, the sequences shown in SEQ ID NO 112 and 32, the sequences shown in SEQ ID NO 112 and 33, the sequences shown in SEQ ID NO 112 and 34, the sequences shown in SEQ ID NO 112 and 35, the sequences shown in SEQ ID NO 112 and 36, the sequences shown in SEQ ID NO 112 and 37, the sequences shown in SEQ ID NO 112 and 38, the sequences shown in SEQ ID NO 112 and 39, the sequences shown in SEQ ID NO 112 and 40, the sequences shown in SEQ ID NO 112 and 41, the sequences shown in SEQ ID NO 112 and 42, the sequences shown in SEQ ID NO 112 and 43, the sequences shown in SEQ ID NO 112 and 44, the sequences shown in SEQ ID NO 112 and 45, the sequences shown in SEQ ID NO 112 and 46, the sequences shown in SEQ ID NO 23 and 41, the sequences shown in SEQ ID NO 24 and 38, the sequences shown in SEQ ID NO 112 and 41, the sequences shown in SEQ ID NO 112 and 42, the sequences shown in SEQ ID NO 112 and 43, the sequences shown in SEQ ID NO 112 and 47, the sequences shown in SEQ ID NO 22 and 47, and the sequences shown in SEQ ID NO 22 and 47, respectively Sequences listed separately, sequences listed in SEQ ID Nos. 23 and 29, sequences listed in SEQ ID Nos. 24 and 29, sequences listed in SEQ ID Nos. 25 and 29, sequences listed in SEQ ID Nos. 26 and 29, sequences listed in SEQ ID Nos. 22 and 29, sequences listed in SEQ ID Nos. 27 and 29, sequences listed in SEQ ID Nos. 23 and 39, sequences listed in SEQ ID Nos. 24 and 39, sequences listed in SEQ ID Nos. 25 and 39, sequences listed in SEQ ID Nos. 26 and 39, sequences listed in SEQ ID Nos. 22 and 39, sequences listed in SEQ ID Nos. 27 and 39, or sequences listed in SEQ ID Nos. 5 and 48, respectively.
  9. 9. An anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody or antigen-binding fragment thereof comprising a heavy chain variable (V H ) region and a light chain variable (V L ) region, wherein said V H region and said V L region are or comprise the sequences set forth in SEQ ID NOS.1 and 118, the sequences set forth in SEQ ID NOS.2 and 118, the sequences set forth in SEQ ID NOS.3 and 118, the sequences set forth in SEQ ID NOS.4 and 118, the sequences set forth in SEQ ID NOS.5 and 118, the sequences set forth in SEQ ID NOS.6 and 118, the sequences set forth in SEQ ID NOS.7 and 118, the sequences set forth in SEQ ID NOS.8 and 118, the sequences set forth in SEQ ID NOS.9 and 118, the sequences set forth in SEQ ID NOS.10 and 118, the sequences set forth in SEQ ID NOS.12 and 118, the sequences set forth in SEQ ID NOS.13 and 118, the sequences set forth in SEQ ID NOS.14 and 118, the sequences set forth in SEQ ID NO. 14 and the sequences set forth in SEQ ID NO. 16 and 118, and the sequences set forth in SEQ ID NO. 14 and 118, respectively, and the sequences set forth in SEQ ID NO. 14 and 118 and the sequences set forth in SEQ ID NO and 16 and in SEQ ID NO and 14 and respectively The sequences listed in SEQ ID NO 112 and 29, the sequences listed in SEQ ID NO 112 and 30, the sequences listed in SEQ ID NO 112 and 31, the sequences listed in SEQ ID NO 112 and 32, the sequences listed in SEQ ID NO 112 and 34, the sequences listed in SEQ ID NO 112 and 35, the sequences listed in SEQ ID NO 112 and 36, the sequences listed in SEQ ID NO 112 and 37, the sequences listed in SEQ ID NO 112 and 38, the sequences listed in SEQ ID NO 112 and 39, the sequences listed in SEQ ID NO 112 and 40, the sequences listed in SEQ ID NO 112 and 42, the sequences listed in SEQ ID NO 112 and 43, the sequences listed in SEQ ID NO 112 and 44, the sequences listed in SEQ ID NO 112 and 45, the sequences listed in SEQ ID NO 112 and 46, the sequences listed in SEQ ID NO 112 and 24, the sequences listed in SEQ ID NO 41 and 47, the sequences listed in SEQ ID NO 112 and 41, and the sequences listed in SEQ ID NO 24 and 25 and 47, respectively Sequences set forth in SEQ ID NOS.22 and 47, sequences set forth in SEQ ID NOS.27 and 47, sequences set forth in SEQ ID NOS.23 and 29, sequences set forth in SEQ ID NOS.24 and 29, sequences set forth in SEQ ID NOS.25 and 29, sequences set forth in SEQ ID NOS.26 and 29, sequences set forth in SEQ ID NOS.22 and 29, sequences set forth in SEQ ID NOS.27 and 29, sequences set forth in SEQ ID NOS.23 and 39, sequences set forth in SEQ ID NOS.24 and 39, sequences set forth in SEQ ID NOS.25 and 39, sequences set forth in SEQ ID NOS.26 and 39, sequences set forth in SEQ ID NOS.22 and 39, sequences set forth in SEQ ID NOS.27 and 39, or sequences set forth in SEQ ID NOS.5 and 48.
  10. 10. The anti-CTLA-4 antibody or antigen-binding fragment of claim 1 to 9, wherein the V H region comprises one or more amino acid residues selected from the group consisting of histidine (H) at position 98, arginine (R) at position 31, glutamic acid (E) or histidine (H) at position 53, histidine (H) at position 58 and histidine (H) at position 97, or any combination thereof, and/or the V L region comprises one or more amino acid residues selected from the group consisting of histidine (H) at position 27a, histidine (H) at position 30, histidine (H) and histidine (H) at position 90, or any combination thereof, wherein the numbering of the amino acid residues is by Kabat numbering.
  11. 11. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the V H region comprises CDR-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 52, 60, and 72, respectively, and the V L region comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 85, 89, and 98, respectively, optionally wherein the V H region comprises the sequence of the amino acids set forth in SEQ ID NO 25, and the V L region comprises the sequence of the amino acids set forth in SEQ ID NO 41.
  12. 12. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the V H region comprises CDR-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 49, 67, and 68, respectively, and the V L region comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 84, 89, and 98, respectively, optionally wherein the V H region comprises the sequence of the amino acids set forth in SEQ ID NO 23, and the V L region comprises the sequence of the amino acids set forth in SEQ ID NO 47.
  13. 13. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the V H region comprises CDR-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 52, 60, and 72, respectively, and the V L region comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 76, 89, and 98, respectively, optionally wherein the V H region comprises the sequence of the amino acids set forth in SEQ ID NO 25, and the V L region comprises the sequence of the amino acids set forth in SEQ ID NO 29.
  14. 14. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the V H region comprises CDR-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 49, 67, and 68, respectively, and the V L region comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 84, 89, and 99, respectively, optionally wherein the V H region comprises the sequence of the amino acids set forth in SEQ ID NOs 23, and the V L region comprises the sequence of the amino acids set forth in SEQ ID NOs 39.
  15. 15. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the V H region comprises CDR-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 52, 60, and 72, respectively, and the V L region comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 84, 89, and 99, respectively, optionally wherein the V H region comprises the sequence of the amino acids set forth in SEQ ID NO 25, and the V L region comprises the sequence of the amino acids set forth in SEQ ID NO 39.
  16. 16. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-10, wherein the V H region comprises CDR-H1, CDR-H2, and CDR-H3 comprising the sequences set forth in SEQ ID NOs 52, 67, and 68, respectively, and the V L region comprises CDR-L1, CDR-L2, and CDR-L3 comprising the sequences set forth in SEQ ID NOs 84, 89, and 99, respectively, optionally wherein the V H region comprises the sequence of the amino acids set forth in SEQ ID NOs 26, and the V L region comprises the sequence of the amino acids set forth in SEQ ID NOs 39.
  17. 17. The anti-CTLA-4 antibody or antigen-binding fragment thereof of any one of claims 1-16, wherein the antibody is a full-length antibody.
  18. 18. The anti-CTLA-4 antibody or antigen-binding fragment thereof of claim 17, wherein the full-length antibody comprises a constant region (Fc) from IgA1, igA2, igD, igE, igG1, igG2, igG3, igG4, or IgM.
  19. 19. The anti-CTLA-4 antibody or antigen-binding fragment thereof of claim 18, wherein the constant region is a human IgG1 heavy chain constant region.
  20. 20. The anti-CTLA-4 antibody or antigen-binding fragment thereof of claim 19, wherein the human IgG1 heavy chain constant region comprises one or more mutations selected from the group consisting of G236A, S239D, M252Y, S T, T256E, A330L, I332E, M428L and N434S, numbered according to the EU numbering system.

Description

Anti-CTLA-4 antibodies and related binding molecules and methods and uses thereof Cross Reference to Related Applications The present application claims priority from U.S. provisional patent application No. 63/532,336, filed 8/11 2023, entitled "anti-CTLA-4 antibodies and related binding molecules, and methods and uses thereof," the contents of which are incorporated by reference in their entirety. The sequence listing is incorporated by reference The present application is submitted in electronic format along with the sequence listing. The sequence listing is provided in file form, and is named 281632000240.XML, created at 8/2024, and is 169,088 bytes in size. The information in the sequence listing in electronic format is incorporated by reference in its entirety. Technical Field The present disclosure provides novel monoclonal antibodies or antibody fragments directed against protein cytotoxic T lymphocyte-associated protein 4 (CTLA-4). CTLA-4 is a cell surface protein that is expressed primarily on T cells and plays a vital role in regulating immune responses. The novel antibodies or antibody fragments described may provide an effective moiety for the modulation of human immune function, with potential therapeutic applications in a variety of diseases including cancer. Background Cancer therapy includes a number of therapeutic approaches including surgery, radiation therapy, and chemotherapy. While various approaches provide a broad choice of cancer treatment options, many therapies suffer from drawbacks such as lack of selectivity for targeted cancer cells over normal healthy cells and resistance of the cancer to treatment. Because of encouraging results from both preclinical and clinical trials, immunotherapy targeting checkpoint molecules has become one of the most attractive approaches to treat cancer patients. Despite this prospect, certain immunotherapies, including antibodies that target CTLA-4, show limited efficacy in a substantial number of patients and are associated with undesirable toxicities, including immune-related adverse events. Thus, there is a need to provide improved immunotherapy. The disclosure provided herein addresses this need. Disclosure of Invention In some embodiments, provided herein is an anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody, or antigen-binding fragment thereof, comprising a heavy chain variable (V H) region and a light chain variable (V L) region, wherein the V H region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) comprised in any one of SEQ ID NOS: 28-48 and 118, and the V L region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2), and a light chain complementarity determining region 3 (CDR-L3) comprised in any one of SEQ ID NOS: 49, 57, 68, 74, 89, and 98, respectively, wherein the CDR-H1, CDR-H3, CDR-L1, and CDR-L3 are not listed in any one of SEQ ID NOS: 1-27 and 112. In some embodiments, the V H region comprises CDR-H1, CDR-H2 and CDR-H3 comprised within SEQ ID NO. 1 and the V L region comprises CDR-L1, CDR-L2 and CDR-L3 comprised within SEQ ID NO. 118 and the V H region comprises CDR-H1, CDR-L3 comprised within SEQ ID NO. 2, CDR-H2 and CDR-H3, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO: 118, the V H region includes CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO: 3, and the V L region includes CDR-L1, CDR-L2, CDR-H3 contained within SEQ ID NO: 118, CDR-L2 and CDR-L3, the V H region comprising CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO: 4 and the V L region comprising CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO: 118, the V H region comprising CDR-H1, CDR-H2 and CDR-L3 contained within SEQ ID NO: 5, CDR-H2 and CDR-H3, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO: 118, the V H region includes CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO: 6, and the V L region includes CDR-L1, CDR-L2, CDR-H3 contained within SEQ ID NO: 118, CDR-L2 and CDR-L3, the V H region comprising CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO: 7 and the V L region comprising CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO: 118, the V H region comprising CDR-H1, CDR-H2 and CDR-L3 contained within SEQ ID NO: 8, CDR-H2 and CDR-H3, and the V L region includes CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO: 118, the V H region includes CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO: 9, and the V L region includes CDR-L1, CDR-L2, CDR-H3 contained within SEQ ID NO: 118, CDR-L2 and CDR-L3, the V H region comprising CDR-H1, CDR-H2 and CDR-H3 contained within SEQ ID NO: 10 and the V L region comprising CDR-L1, CDR-L2 and CDR-L3 contained within SEQ ID NO: 118, the V H region comprising CDR-H1, CDR-H2 and CDR-L3 c