Compositions and methods for inducing phagocytosis of MHC class I positive cells and countering anti-CD47/SIRPA resistance

Patent metadata

Field	Value
Publication number	US-10889649-B2
Application number	US-201916394411-A
Country	US
Kind code	B2
Filing date	Apr 25, 2019
Priority date	Oct 24, 2014
Publication date	Jan 12, 2021
Grant date	Jan 12, 2021

Abstract

Methods and compositions are provided for inducing phagocytosis of a target cell, treating an individual having cancer, treating an individual having an intracellular pathogen infection (e.g., a chronic infection), and/or reducing the number of inflicted cells (e.g., cancer cells, cells infected with an intracellular pathogen, etc.) in an individual. Methods and compositions are also provided for predicting whether an individual is resistant (or susceptible) to treatment with an anti-CD47/SIRPA agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent. In some cases, the subject methods and compositions include an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent (e.g., co-administration of an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent). Kits are also provided for practicing the methods of the disclosure.

First claim

What is claimed is:

1. A composition for increasing phagocytosis of a target cell, the composition comprising:
(a) an anti-MHC Class I/leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) agent; and
(b) at least one of:
(i) an agent that opsonizes the target cell, and
(ii) an anti-CD47/single regulatory protein alpha (SIRPA) agent.

2. The composition of claim 1 , wherein the anti-MHC Class I/LILRB1 agent specifically binds major histocompatibility complex (MHC) Class I.

3. The composition of claim 2 , wherein the anti-MHC Class I/LILRB1 agent is an antibody that specifically binds classical MHC Class I, wherein said classical MHC Class I lacks HLA-G and comprises at least one of HLA-A, HLA-B, and HLA-C.

4. The composition of claim 2 , wherein the anti-MHC Class I/LILRB1 agent is a soluble leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) peptide.

5. The composition of claim 1 , wherein the anti-MHC Class I/LILRB1 agent is an antibody that specifically binds leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) and does not activate signaling through LILRB1 upon binding.

6. The composition of claim 1 , wherein the composition comprises an anti-CD47/SIRPA agent.

7. The composition of claim 1 , wherein the agent that opsonizes the target cell is an antibody other than an anti-CD47 antibody.

8. The composition of claim 1 , wherein the composition comprises an agent that opsonizes the target cell and an anti-CD47/SIRPA agent.

9. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to CD20.

10. The composition according to claim 9 , wherein the antibody is rituximab, tositumomab or ibritumomab.

11. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to EGFR.

12. The composition according to claim 11 , wherein the antibody is cetuximab or panitumumab.

13. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to CD52.

14. The composition according to claim 13 , wherein the antibody is alemtuzumab.

15. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to CD22.

16. The composition according to claim 15 , wherein the antibody is ibritumomab.

17. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to 17-1A antigen.

18. The composition according to claim 17 , wherein the antibody is edrecolomab.

19. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to HER-2/neu antigen.

20. The composition according to claim 19 , wherein the antibody is trastuzumab or pertuzumab.

21. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to CD30.

22. The composition according to claim 21 , wherein the antibody is brentuximab.

23. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to CD33.

24. The composition according to claim 23 , wherein the antibody is gemtuzumab.

25. The composition according to claim 1 , wherein the agent that opsonizes the target cell is an antibody that binds to one of CD19, CD20, CD22, CD24, CD25, CD30, CD33, CD38, CD44, CD52, CD56, CD70, CD96, CD97, CD99, CD123, CD279 (PD-1), CD274 (PD-L1), EGFR, 17-1A, HER2, CD117, C-Met, PTHR2, and HAVCR2 (TIM3).

26. The composition of claim 1 , wherein the anti-CD47/SIRPA agent is an antibody that specifically binds to CD47 and does not activate CD47 upon binding.

27. The composition of claim 26 , wherein the antibody is Hu5F9-G4.

28. The composition of claim 5 , wherein the anti-LILRB1 antibody is selected from GHI/75, HP-F1, 3D3-1 D12, and VMP55.

29. A method of inducing phagocytosis of a target cell, the method comprising:
contacting a target cell with a macrophage in the presence of an anti-MHC Class I/LILRB1 agent and at least one of: an anti-CD47/SIRPA agent and an agent that opsonizes the target cell, for a period of time sufficient to induce phagocytosis of the target cell by the macrophage.

30. The method according to claim 29 , wherein the target cell is a cancer cell.

31. The method according to claim 29 , wherein the target cell is a cell infected with an intracellular pathogen.

32. The method according to claim 29 , wherein the target cell is a cancer cell of an individual having cancer, or an infected cell of an individual having a chronic intracellular pathogen infection.

33. The method according to claim 29 , wherein the contacting is in vivo.

34. The method according to claim 29 , wherein the anti-MHC Class I/LILRB1 agent specifically binds major histocompatibility complex (MHC) Class I.

35. The method according to claim 34 , wherein the anti-MHC Class I/LILRB1 agent specifically binds classical MHC Class I, wherein said classical MHC Class I lacks HLA-G and comprises at least one of HLA-A, HLA-B, and HLA-C.

36. The method according to claim 34 , wherein the anti-MHC Class I/LILRB1 agent is an antibody or a binding fragment thereof that specifically binds leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) and does not activate signaling through LILRB1 upon binding.

37. The method according to claim 34 , wherein the anti-MHC Class I/LILRB1 agent is a soluble leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) polypeptide.

38. The method according to claim 29 , wherein said contacting is in the presence of an anti-MHC Class I/LILRB1 agent and an anti-CD47/SIRPA agent.

39. The method according to claim 29 , wherein the agent that opsonizes the target cell is an antibody that binds to CD20.

40. The method according to claim 39 , wherein the antibody is rituximab, tositumomab or ibritumomab.

41. The method according to claim 29 , wherein the agent that opsonizes the target cell is an antibody that binds to EGFR.

42. The method according to claim 41 , wherein the antibody is cetuximab or panitumumab.

43. The method according to claim 29 , wherein the agent that opsonizes the target cell is an antibody that binds to CD52.

44. The method according to claim 43 , wherein the antibody is alemtuzumab.

45. The method according to claim 29 , wherein the agent that opsonizes the target cell is an antibody that binds to CD22.

46. The method according to claim 45 , wherein the antibody is ibritumomab.

47. The method according to claim 29 , wherein the agent that opsonizes the target cell is an antibody that binds to 17-1A antigen.

48. The method according to claim 47 , wherein the antibody is edrecolomab.

49. The method according to claim 29 , wherein the agent that opsonizes the target cell is an antibody that binds to HER-2/neu antigen.

50. The method according to claim 49 , wherein the antibody is trastuzumab

Assignees

• Univ Leland Stanford Junior

Inventors

• Maute Roy Louis
• Weiskopf Kipp Andrew
• Ring Aaron Michael
• Weissman Irving L

Classifications

• A61F2/945 Primary

  hardenable, e.g. stents formed in situ · CPC title

• C07K16/2863

  against receptors for growth factors, growth regulators · CPC title

• A61M2025/105

  having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes · CPC title

• A61B2017/00893

  pharmaceutically effective · CPC title

• A61F2250/0067

  Means for introducing or releasing pharmaceutical products into the body · CPC title