Methods and compositions for localized agent delivery

Patent metadata

Field	Value
Publication number	US-9393199-B2
Application number	US-201313910937-A
Country	US
Kind code	B2
Filing date	Jun 5, 2013
Priority date	Nov 24, 2008
Publication date	Jul 19, 2016
Grant date	Jul 19, 2016

Abstract

The invention provides compositions and methods for delivering agents to localized regions, tissues, or organs in vivo by conjugating agent-loaded nanoparticles to cells having homing capability. The agents may be therapeutic or diagnostic agents such as cancer chemotherapeutic agents and imaging agents respectively.

First claim

What is claimed is:

1. A method for maintaining, stimulating or enhancing activity of a T cell, comprising administering to a subject a T cell that homes to a tumor and is covalently bound to a liposome that comprises an immunostimulatory cytokine that maintains, stimulates or enhances activity of a T cell, wherein the T cell does not significantly internalize the liposome and maintains the liposome on the cell surface, and wherein release of the immunostimulatory cytokine from the liposome maintains, stimulates or enhances activity of the T cell relative to an unmodified T cell.

2. The method of claim 1 , wherein the liposome is 20-500 nm in diameter.

3. The method of claim 1 , wherein the liposome comprises maleimide reactive groups on its surface.

4. The method of claim 1 , wherein the cytokine is IL-15/IL-15Rα.

5. The method of claim 1 , wherein the cytokine is IL-2.

6. The method of claim 1 , wherein the T cell is a tumor-reactive T cell.

7. The method of claim 1 , wherein the T cell is covalently bound to a plurality of liposomes.

8. The method of claim 1 , wherein release of the immunostimulatory cytokine enhances survival of the T cell.

9. The method of claim 1 , wherein release of the immunostimulatory cytokine enhances proliferation of the T cell.

10. The method of claim 1 , wherein covalent binding of the liposome to the T cell does not inhibit cytokine production of the T cell.

11. The method of claim 1 , wherein covalent binding of the liposome to the T cell does not inhibit cytolytic activity of the T cell.

12. A method for maintaining, stimulating or enhancing activity of a T cell located in the environment of a tumor, comprising administering to a subject having a tumor a carrier T cell that homes to the tumor and is covalently bound to a liposome that comprises an immunostimulatory cytokine that maintains, stimulates or enhances activity of a T cell, wherein the carrier T cell does not significantly internalize the liposome and maintains the liposome on the cell surface, and wherein release of the immunostimulatory cytokine from the liposome maintains, stimulates or enhances activity of a T cell located in the environment of the tumor.

13. The method of claim 12 , wherein the liposome is biodegradable.

14. The method of claim 12 , wherein the liposome is 20-500 nm in diameter.

15. The method of claim 12 , wherein the liposome comprises maleimide reactive groups on its surface.

16. The method of claim 12 , wherein the T cell is a tumor-reactive T cell.

17. The method of claim 12 , wherein the T cell is covalently bound to a plurality of liposomes.

18. The method of claim 12 , wherein the cytokine is IL-15/IL-15Rα.

19. The method of claim 12 , wherein the cytokine is IL-2.

20. The method of claim 12 , wherein release of the immunostimulatory cytokine enhances survival of the T cell.

21. The method of claim 12 , wherein release of the immunostimulatory cytokine enhances proliferation of the T cell.

22. The method of claim 12 , wherein covalent binding of the liposome to the T cell does not inhibit cytokine production of the T cell.

23. The method of claim 12 , wherein covalent binding of the liposome to the T cell does not inhibit cytolytic activity of the T cell.

24. A composition comprising a T cell that homes to a tumor and is covalently bound to a liposome that comprises an immunostimulatory cytokine that maintains, stimulates or enhances activity of a T cell, wherein the T cell does not significantly internalize the liposome and maintains the liposome on the cell surface, and wherein release of the immunostimulatory cytokine from the biodegradable liposome maintains, stimulates or enhances activity of the T cell relative to an unmodified T cell.

25. The composition of claim 24 , wherein the cytokine is IL-15/IL-15Rα.

26. The composition of claim 24 , wherein the cytokine is IL-2.

27. The composition of claim 24 , wherein the liposome is biodegradable.

28. The composition of claim 24 , wherein the liposome is 20-500 nm in diameter.

29. The composition of claim 24 , wherein the liposome comprises maleimide reactive groups on its surface.

30. The composition of claim 24 , wherein the T cell is a tumor-reactive T cell.

31. The composition of claim 24 , wherein the T cell is covalently bound to a plurality of liposomes.

32. The composition of claim 24 , wherein covalent binding of the liposome to the T cell does not inhibit cytokine production of the T cell.

33. The composition of claim 24 , wherein covalent binding of the lipo some to the T cell does not inhibit cytolytic activity of the T cell.

34. A method of maintaining, stimulating or enhancing activity of a T cell, comprising administering to a subject a population of T cells that home to a tumor and are covalently bound to a plurality of liposomes that comprise an immunostimulatory cytokine that maintains, stimulates or enhances activity of a T cell, wherein the T cells do not significantly internalize the liposomes and maintain the liposomes on the cell surface, and wherein release of the immunostimulatory cytokine from the liposomes maintains, stimulates or enhances activity of the T cells relative to unmodified T cells.

35. The method of claim 34 , wherein the liposomes are biodegradable.

36. The method of claim 34 , wherein the liposomes are 20-500 nm in diameter.

37. The method of claim 34 , wherein the liposomes comprise maleimide reactive groups on their surface.

38. The method of claim 34 , wherein the T cells are tumor-reactive T cells.

39. The method of claim 34 , wherein the cytokine is IL-15/IL-15Rα.

40. The method of claim 34 , wherein the cytokine is IL-2.

41. A method of maintaining, stimulating or enhancing activity of a T cell located in the environment of a tumor, comprising administering to a subject having a tumor a population of carrier T cells that home to a tumor and are covalently bound to a plurality of liposomes that comprise an immunostimulatory cytokine that maintains, stimulates or enhances activity of a T cell, wherein the carrier T cells do not significantly internalize the liposomes and maintain the liposomes on the cell surface, and wherein release of the immunostimulatory cytokine from the liposomes maintains, stimulates or enhances activity of T cells located in the environment of the tumor.

42. The method of claim 41 , wherein the liposomes are biodegradable.

43. The method of claim 41 , wherein the liposomes are 20-500 nm in diameter.

44. The method of claim 41 , wherein the liposomes comprise maleimide reactive groups on their surface.

45. The method of claim 41 , wherein the T cells are tumor-reactive T cells.

46. The method of claim 41 , wherein the cytokine is IL-15/IL-15Rα.

47. The method of claim 41 , wherein the cytokine is IL-2.

48. A composition comprising a population of T cells that home to a tumor and are covalently bound to a plurality of liposomes that comprise an immunostimulatory cytokine that maintains, stimulates or enhances activity of a T cell,

Assignees

• Massachusetts Inst Technology

Inventors

• Irvine Darrell J
• Stephan Matthias
• Moon Jaehyun
• Bershteyn Anna

Classifications

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K9/5146

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• A61K31/711

  Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title