Immunoregulation by anti-ILT5 antibodies and ILT5-binding antibody fragments
View Patent ↗Disclosed herein are methods of using anti-ILT5 antibodies and ILT5-binding fragments thereof to induce an immunostimulatory effect in a T cell when such a T cell is contacted with an antigen presenting cell (APC) that has been previously contacted with the anti-ILT5 antibody or ILT5-binding fragment. Also disclosed herein are methods of using anti-ILT5 antibodies and ILT5-binding fragments thereof to inhibit a response in a T cell (e.g., a pro-liferative response) when such a T cell is concomitantly contacted, or has previously been contacted, with an APC, which APC is simultaneously contacted with the anti-ILT5 antibody or ILT5-binding fragment. Also disclosed herein are methods of using anti-ILT5 antibodies and ILT5-binding fragments thereof for the treatment of various diseases and for use as immunostimulatory adjuvants.
1. A method of inducing an immunostimulatory effect in a T cell, the method comprising contacting the T cell with an antigen-presenting cell (“APC”) that has been contacted with or is in contact with a monovalent antibody against human immunoglobulin-like transcript 5 (“ILT-5”) or an antigen binding fragment of the antibody.
2. The method of claim 1 , wherein the T cell is a naïve T cell and the method results in
inducing the naïve cell to express NKG2D on its surface.
3. The method of claim 1 wherein the immunostimulatory effect in a T cell is a proliferative response.
4. The method of claim 1 , wherein the response in the T cell does not require recognition of a MHC molecule by a T cell receptor.
5. A method of inducing an immunostimulatory effect in a T cell, the method comprising contacting the T cell with an antigen-presenting cell (“APC”) that has been contacted with or is in contact with a monovalent antibody against human immunoglobulin-like transcript 5 (“ILT-5”) or an antigen binding fragment of the antibody, and further comprising contacting the T cell with an antigen from a tumor cell or from a cell that is infected with a bacterium, a virus, a fungus, a protozoan, or a parasite; wherein the T cell becomes cytotoxic when it binds or recognizes the antigen on a cell.
6. The method of claim 1 , wherein the contacting is done in vitro.
7. The method of claim 1 , wherein the T cell is in a subject and the contacting is done in vivo.
8. The method of claim 1 , wherein the T cell is a CD4+ T cell or a CD8+ T cell.
9. The method of claim 7 , wherein the inducing of an immunostimulatory effect in the T cell comprises inducing or enhancing an immune response in the subject and the method comprises administering to the subject the anti-ILT5 antibody or the ILT5-binding fragment of the antibody.
10. The method of claim 9 , wherein the response does not require recognition of a MHC molecule by a T cell receptor.
11. The method of claim 9 , wherein the T cell in the subject is endowed with cytotoxic potential upon contact with the APC that has been contacted with or is in contact with the administered anti-ILT5 antibody or the administered ILT5-binding fragment of the antibody.
12. The method of claim 11 , wherein the T cell or its progeny, having gained cytotoxic potential, becomes cytotoxic when it binds or recognizes an antigen.
13. The method of claim 12 , wherein the antigen is selected from one or both of an exogenous antigen and an endogenous antigen.
14. The method of claim 13 , wherein the exogenous antigen is selected from the group consisting of: a tumor antigen, a viral antigen, a bacterial antigen, a fungal antigen, a protozoan antigen, and a parasite antigen.
15. The method of claim 14 , wherein the exogenous antigen is administered to the subject.
16. The method of claim 15 , wherein;
the anti-ILT5 antibody or the ILT5-binding fragment of the antibody is administered at least once before, together with, or very close in time to the administration of the exogenous antigen; or
the anti-ILT5 antibody or the ILT5-binding fragment of the antibody is administered at least once after, together with, or very close in time to the administration of the exogenous antigen.
17. The method of claim 12 , wherein the antigen is a cellular antigen.
18. The method of claim 12 , wherein the T cell becomes cytotoxic when it binds or recognizes the antigen on a cell.
19. The method of claim 11 , wherein the T cell is a CD4+ T cell or a CD8+ T cell.
20. The method of claim 1 , wherein the method results in the upregulation of the expression of a T cell receptor:CD3 complex on the T cell.
21. The method of claim 1 , wherein the method results inducing the T cell to secret Fas ligand.
22. The method of claim 1 , wherein the method results is endowing the T cell with cytotoxic potential.