Enhancement of Immune Responses By 4-1BB-Binding Agents

• US 20100266611A1
• Filed: 11/06/2009
• Published: 10/21/2010
• Est. Priority Date: 10/09/2001
• Status: Active Grant

• Current Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Original Assignee: Mayo Foundation For Medical Education And Research (Mayo Clinic)
• Inventors: Strome, Scott E., Chen, Lieping
• Granted Patent: US 8,163,550 B2
• Time in Patent Office: Days
• US Class Current: 424/158.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/5154 Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/585 wherein the target is cancer
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4615 Dendritic cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/464499 Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: C07K 16/2878 : against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C12N 2710/20034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

This invention features methods of enhancing immune responses in mammalian subjects and in vitro methods of enhancing the response of a T cell. Also embodied by the invention are methods of receiving and preventing the induction of energy in T cells.

Claims

1. A method of generating an enhanced immune response in a subject, the method comprising administering to the subject:

(a) an immunogenic stimulus; and

(b) an agonistic 4-1BB-binding agent.

2. The method of claim 1, wherein the agonistic 4-1BB binding agent is an antibody that binds to 4-1BB.

7. The method of claim 1, wherein the immunogenic stimulus is a molecule produced by an infectious microorganism.

8. The method of claim 7, wherein the infectious microorganism is a virus.

9. The method of claim 8, wherein the virus is a retrovirus.

10. The method of claim 7, wherein the infectious microorganism is selected from the group consisting of a bacterium, a fungus, and a protozoan parasite.

15. The method of claim 1, wherein the immune response is a response of a T cell.

20. The method of claim 1, wherein the immunogenic stimulus is a tumor cell, a tumor cell lysate, a TAA, a peptide-epitope of a TAA, or a heat shock protein bound to peptide-epitope of protein expressed by a tumor cell.

22. The method of claim 20, wherein the tumor cell is transfected with or transformed with a nucleic acid encoding a cytokine or a growth factor.

23. The method of claim 22, wherein the cytokine is granulocyte macrophage-colony stimulating factor (GM-CSF).

3-6. -6. (canceled)

11-14. -14. (canceled)

16-19. -19. (canceled)

21. (canceled)

24. (canceled)

25. A method of preventing induction of anergy or of reversing anergy in a T cell, the method comprising contacting the T cell with:

(a) an immunogenic stimulus; and

(b) an agonistic 4-1BB-binding agent.

32. The method of claim 25, wherein the agonistic 4-1BB binding agent is an antibody that binds to 4-1BB.

37. The method of claim 25, wherein the immunogenic stimulus is a molecule produced by an infectious microorganism.

38. The method of claim 37, wherein the infectious microorganism is a virus.

39. The method of claim 38, wherein the virus is a retrovirus.

40. The method of claim 37, wherein the infectious microorganism is selected from the group consisting of a bacterium, a fungus, and a protozoan parasite.

48. The method of claim 25, wherein the immunogenic stimulus is a tumor cell, a tumor cell lysate, a TAA, a peptide-epitope of a TAA, or a heat shock protein bound to peptide-epitope of protein expressed by a tumor cell.

50. The method of claim 48, wherein the tumor cell is transfected with or transformed with a nucleic acid encoding a cytokine or a growth factor.

51. The method of claim 50, wherein the cytokine is granulocyte macrophage-colony stimulating factor (GM-CSF).

26-31. -31. (canceled)

33-36. -36. (canceled)

41-47. -47. (canceled)

49. (canceled)