PD-1 antibodies in combination with a cytokine-secreting cell and methods of use thereof

• US 8,287,856 B2
• Filed: 07/19/2010
• Issued: 10/16/2012
• Est. Priority Date: 07/23/2007
• Status: Expired due to Fees

• Current Assignee: ER Squibb & Sons LLC (Bristol-Myers Squibb Company)
• Original Assignee: BioSante Pharmaceuticals, Inc., Medarex Incorporated (Bristol-Myers Squibb Company)
• Inventors: Li, Betty, Jooss, Karin, Korman, Alan J.
• Primary Examiner(s): Goddard, Laura B
• Application Number:
  US12/839,163
• Publication Number:
  US 20100285013A1
• Time in Patent Office: 820 Days
• Field of Search: None
• US Class Current: 424/93.2
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/5152 Tumor cells
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2239/57 Skin; melanoma
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001136 Cytokines
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• 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 39/464456 Tyrosinase or tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/46449 Melanoma antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to a method of enhancing the anti-tumor response in a mammal. More particularly, the invention is concerned with combinations comprising a cytokine-secreting cell and an anti-PD-1 antibody, and methods of administering the combination for enhanced immune response to tumor cells in a patient with a cancer.

Claims

1. A composition for cancer therapy comprising:

a cytokine-expressing cellular immunotherapy comprising cells modified to express a cytokine and a single chain antibody that specifically binds to human Program Death 1 (anti-PD-1), wherein the cells of said cytokine-expressing cellular immunotherapy are rendered proliferation-incompetent by irradiation,

wherein administration of the composition to a subject with cancer results in enhanced therapeutic efficacy relative to administration of the cytokine-expressing cellular immunotherapy or the anti-PD-1 antibody alone.

2. The composition of claim 1, wherein the cells of said cytokine-expressing cellular immunotherapy are autologous to the subject.

3. The composition of claim 1, wherein the cells of said cytokine-expressing cellular immunotherapy are allogeneic to the subject.

4. The composition of claim 3, wherein said allogeneic cells are a tumor cell line selected from the group consisting of a prostate tumor line, a non-small cell lung carcinoma line and a pancreatic cancer line.

5. The composition of claim 1, wherein the cells of said cytokine-expressing cellular immunotherapy cells are bystander cells.

6. The composition of claim 1, wherein the anti-PD-1 antibody is mammalian.

7. The composition of claim 1, wherein the anti-PD-1 antibody is fully human.

8. The composition of claim 1, wherein the anti-PD-1 antibody is humanized.

9. The composition of claim 1, wherein enhanced therapeutic efficacy is measured by increased overall survival time.

10. The composition of claim 1, wherein enhanced therapeutic efficacy is measured by increased progression-free survival.

11. The composition of claim 1, wherein enhanced therapeutic efficacy is measured by decreased tumor size.

12. The composition of claim 1, wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF.

13. The composition of claim 1, wherein the cells comprise a single population of cells in which each cell of the population expresses both a cytokine and an anti-PD-1 antibody.

14. A kit comprising the composition of claim 1.

15. The kit of claim 14, further comprising instructions directing administration of the composition.

16. The kit of claim 15, wherein said instructions further direct administration of the composition on a biweekly basis.

17. The kit of claim 14, wherein the cytokine-expressing cellular immunotherapy expresses GM-CSF.

18. The kit of claim 14, wherein the cells comprise a single population of cells in which each cell of the population expresses both a cytokine and an anti-PD-1 antibody.