Anti-human VISTA antibodies and use thereof
The invention provides antagonistic and agonistic anti-human VISTA antibodies and antibody fragments. These antagonist antibodies and antibody fragments may be used to inhibit or block VISTA's suppressive effects on T cell immunity and thereby promote T cell immunity. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These antagonist antibodies and antibody fragments are especially useful in the treatment of cancer and infectious conditions. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.
1. An anti-human antibody or antibody fragment thereof comprising an antigen binding region that specifically binds to human V-domain Ig Suppressor of T cell Activation (human VISTA), wherein the variable heavy (VH) polypeptide of the antibody or antibody fragment comprises the VH complementarity determining region-1 (CDR1), CDR2 and CDR3 polypeptides of SEQ ID NO: 400, 401 and 402, respectively, and the variable light (VL) polypeptide of the antibody or antibody fragment comprises the VL CDR1, CDR2 and CDR3 polypeptides of SEQ ID NO: 403, 404 and 405, respectively.
2. The anti-human antibody or antibody fragment of claim 1 , which comprises a VH polypeptide possessing at least 90% sequence identity to SEQ ID NO: 406.
3. The anti-human antibody or antibody fragment of claim 1 , which comprises a VH polypeptide possessing at least 95% sequence identity to SEQ ID NO: 406.
4. The anti-human antibody or antibody fragment of claim 1 , which comprises a VH polypeptide possessing sequence identity to SEQ ID NO: 406.
5. The anti-human antibody or antibody fragment of claim 1 , which comprises a VL polypeptide possessing at least 90% sequence identity to SEQ ID NO: 408.
6. The anti-human antibody or antibody fragment of claim 1 , which comprises a VL polypeptide possessing at least 95% sequence identity to SEQ ID NO: 408.
7. The anti-human antibody or antibody fragment of claim 1 , which comprises a VL polypeptide possessing sequence identity to SEQ ID NO: 408.
8. The anti-human antibody or antibody fragment of claim 1 , which comprises a VH polypeptide possessing at least 90% sequence identity to SEQ ID NO: 406, and a VL polypeptide possessing at least 90% sequence identity to SEQ ID NO: 408.
9. The anti-human antibody or antibody fragment of claim 1 , which comprises a VH polypeptide possessing at least 95% sequence identity to SEQ ID NO: 406, and a VL polypeptide possessing at least 95% sequence identity to SEQ ID NO: 408.
10. The anti-human antibody or antibody fragment of claim 1 , which comprises a VH polypeptide possessing sequence identity to SEQ ID NO: 406, and a VL polypeptide possessing identity to SEQ ID NO: 408.
11. The anti-human antibody or antibody fragment of claim 1 , which comprises a human constant region.
12. The anti-human antibody or antibody fragment of claim 1 , which comprises a human IgG1, IgG2, IgG3 or IgG4 constant region.
13. The anti-human antibody or antibody fragment of claim 1 , which comprises a human IgG1, IgG2, IgG3 or IgG4 constant region which comprises a mutation which impairs FcR binding.
14. The anti-human antibody or antibody fragment of claim 1 , which comprises a human IgG1, IgG2, IgG3 or IgG4 constant region which comprises a mutation which impairs complement binding.
15. The anti-human antibody or antibody fragment of claim 1 , which comprises a human IgG1, IgG2, IgG3 or IgG4 constant region which comprises a mutation which impairs FcR binding and a mutation which impairs complement binding.
16. The anti-human antibody or antibody fragment of claim 1 , which comprises a human IgG2 constant region which is not modified.
17. A composition comprising an anti-human antibody or antibody fragment according to claim 1 , and a pharmaceutically acceptable carrier.
18. A composition comprising an anti-human antibody or antibody fragment according to claim 12 , and a pharmaceutically acceptable carrier.
19. A composition comprising an anti-human antibody or antibody fragment according to claim 15 , and a pharmaceutically acceptable carrier.
20. A composition comprising an anti-human antibody or antibody fragment according to claim 16 , and a pharmaceutically acceptable carrier.