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

• US 8,580,247 B2
• Filed: 09/14/2012
• Issued: 11/12/2013
• Est. Priority Date: 07/23/2007
• Status: Active Grant

• Current Assignee: Healthcare, Inc.
• Original Assignee: Medarex Incorporated (Bristol-Myers Squibb Company), Aduro Gvax, Inc. (Novartis Ag)
• Inventors: Li, Betty, Jooss, Karin, Korman, Alan J.
• Primary Examiner(s): Goddard, Laura B
• Application Number:
  US13/619,699
• Publication Number:
  US 20130022600A1
• Time in Patent Office: 424 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 method of cancer immunotherapy comprising:

administering a cytokine-expressing cellular immunotherapy comprising cells modified to express GM-CSF and a single chain antibody that specifically binds to human Programmed Death 1 (anti-PD-1) to a subject with cancer,

wherein the modified cells are rendered proliferation-incompetent by irradiation, and

wherein administration of the cells modified to express GM-CSF and the single chain antibody results in enhanced therapeutic efficacy relative to administration of an anti-PD-1 antibody alone or cells modified to express GM-CSF alone.

2. The method of claim 1, wherein the cytokine-expressing cellular immunotherapy comprises cells that are autologous to the subject.

3. The method of claim 1, wherein the cytokine-expressing cellular immunotherapy comprises cells that are allogeneic to the subject.

4. The method of claim 3, wherein the 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 method of claim 1, wherein the cytokine-expressing cellular immunotherapy comprises bystander cells.

6. The method of claim 1, wherein the subject is a human.

7. The method of claim 1, wherein the cancer is a prostate cancer.

8. The method of claim 1, wherein the cancer is a non-small cell lung carcinoma.

9. The method of claim 1, wherein the cancer is a melanoma.

10. The method of claim 1, wherein the cancer is a colorectal cancer.

11. The method of claim 1, wherein the cancer is a renal cell carcinoma.

12. The method of claim 1, wherein the cancer is an ovarian cancer.

13. The method of claim 1, wherein the cytokine-expressing cellular immunotherapy is administered subcutaneously.

14. The method of claim 1, wherein the cytokine-expressing cellular immunotherapy is administered intratumorally.

15. The method of claim 1, wherein the cytokine-expressing cellular immunotherapy is intradermally.

16. The method of claim 1, wherein the cytokine-expressing cellular immunotherapy is administered intravenously.

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

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

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