Identification of VSIG8 as the putative VISTA receptor (V-R) and use thereof to produce VISTA/VSIG8 agonists and antagonists
The receptor for VISTA is identified (VSIG8) as well as the use of this receptor in the identification or synthesis of agonist or antagonist compounds, preferably antibodies, polypeptides and fusion proteins which agonize or antagonize the effects of VSIG8 and/or VISTA and/or the VSIG8/VISTA binding interaction. These antagonists may be used to suppress VISTA's suppressive effects on T cell immunity, and more particularly used in the treatment of cancer, or infectious disease. These agonist compounds may be used to potentiate or enhance VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity, such as in the treatment of autoimmunity, allergy or inflammatory conditions. Screening assays for identifying these agonists and antagonist compounds are also provided.
1. A method of treating cancer which method comprises the administration to a subject in need thereof a therapeutically effective amount of at least one antibody or antigen binding antibody fragment that binds to a VSIG8 polypeptide which has a sequence selected from SEQ ID NO: 1, 2, and 3, and wherein said antibody or antigen binding antibody fragment potentiates CD8 + T cell mediated anti-tumor immunity in said subject.
2. A method of treating an infectious disease, which method comprises the administration to a subject in need thereof of a therapeutically effective amount of at least one antibody or antigen binding antibody fragment that binds to a VSIG8 polypeptide having an amino acid sequence selected from SEQ ID NO: 1, 2, and 3, and wherein said antibody or antigen binding antibody fragment potentiates CD8 + T cell mediated killing of infected cells in said subject.
3. The method of claim 1 , wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:1.
4. The method of claim 1 , wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:2.
5. The method of claim 1 , wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:3.
6. The method of claim 2 , wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:1.
7. The method of claim 2 , wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:2.
8. The method of claim 2 , wherein said antibody or antigen binding antibody fragment binds to the VSIG polypeptide of SEQ ID NO:3.
9. The method of claim 1 , wherein said antibody or antigen binding antibody fragment comprises a human IgG1, IgG2, IgG3 or IgG4.
10. The method of claim 2 , wherein said antibody or antigen binding antibody fragment comprises a human IgG1, IgG2, IgG3 or IgG4.
11. The method of claim 1 , wherein said antibody or antigen binding antibody fragment comprises an IgG1, IgG2, IgG3 or IgG4 which is mutated to impair FcR and/or complement binding.
12. The method of claim 2 , wherein said antibody or antigen binding antibody fragment comprises an IgG1, IgG2, IgG3 or IgG4 which is mutated to impair FcR and/or complement binding.
13. The method of claim 1 , which further comprises the administration of an anti-human VISTA antibody.
14. The method of claim 2 , which further comprises the administration of an anti-human VISTA antibody.