Methods and Compositions Involving NKG2D Inhibitors and Cancer

• US 20140377266A1
• Filed: 09/07/2012
• Published: 12/25/2014
• Est. Priority Date: 09/09/2011
• Status: Active Grant

• Current Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Original Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Inventors: Spies, Thomas, Spies, Veronika
• Granted Patent: US 10,040,853 B2
• Time in Patent Office: Days
• US Class Current: 424/135.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2815 against CD8
• CPC Class Codes: C07K 16/2833 against MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2330/51 Specially adapted vectors

Abstract

Embodiments methods and compositions involving inhibitors of the immunoreceptor Natural Killer Group 2, Member D, (NKG2D) for inhibiting tumor progression and treating cancer.

Claims

1. A method for inhibiting tumor progression in a cancer patient comprising administering to the patient a composition comprising an NKG2D inhibitor.

2. The method of claim 1, wherein the NKG2D inhibitor directly binds NKG2D receptor on a cancer cell.

3. The method of claim 2, wherein the NKG2D inhibitor inhibits formation of an NKG2D-DAP10 complex on a cancer cell.

4. The method of claim 1, wherein the NKG2D inhibitor directly binds an NKG2D-DAP10 complex on a cancer cell.

5. The method of claim 1, wherein the NKG2D inhibitor inhibits NKG2D receptor expression in a tumor cell.

6. The method of claim 1, wherein the NKG2D inhibitor is a nucleic acid, polypeptide, or small molecule.

19. The method of claim 6, wherein the polypeptide is an isolated antibody.

20. The method of claim 19, wherein the isolated antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, or a single chain antibody.

21. The method of claim 19, wherein the isolated antibody is a human antibody.

22. The method of claim 21, wherein the human antibody is MS, 21F2, 16F1g or 16F31.

7-18. -18. (canceled)

23-30. -30. (canceled)

31. A method for inhibiting tumor progression in a cancer patient comprising administering to the patient a composition comprising an isolated human NKG2D antibody that prevents NKG2D-DAP10 signaling in tumor cells of the patient.

32. The method of claim 31, wherein the human NKG2D antibody is MS, 21F2, 16F1g or 16F31.

33. A method for inhibiting tumor progression in a cancer patient comprising administering to the patient a composition comprising a nucleic acid that inhibits NKG2D expression in cancer cells, wherein the nucleic acid is 15-100 nucleotides in length and comprises at least one strand whose sequence is at least 80% complementary to a region of an NKG2D transcript.

34. A method for treating cancer in a patient comprising administering to NKG2D-expressing cancer cells in the patient a composition comprising an NKG2D inhibitor.

35. The method of claim 34, wherein the NKG2D inhibitor directly binds NKG2D receptor on a cancer cell.

40. The method of claim 34, wherein the NKG2D inhibitor is a nucleic acid, polypeptide, or small molecule.

53. The method of claim 40, wherein the polypeptide is an isolated antibody.

54. The method of claim 53, wherein the isolated antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, or a single chain antibody.

55. The method of claim 53, wherein the isolated antibody is a human antibody.

56. The method of claim 55, wherein the human antibody is MS, 21F2, 16F1g or 16F31.

36-39. -39. (canceled)

41-52. -52. (canceled)

57-63. -63. (canceled)