Tumor suppressor and oncogene biomarkers predictive of anti-immune checkpoint inhibitor response

Patent metadata

Field	Value
Publication number	US-11624093-B2
Application number	US-201515305498-A
Country	US
Kind code	B2
Filing date	Apr 24, 2015
Priority date	Apr 24, 2014
Publication date	Apr 11, 2023
Grant date	Apr 11, 2023

Abstract

The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies.

First claim

What is claimed is:

1. A method of treating a subject afflicted with a lung cancer, wherein i) the lung cancer is selected from the group consisting of adenocarcinoma, lung squamous cell carcinoma (SCC), adeno-squamous carcinoma, or mixed tumors thereof, and ii) the lung cancer comprises at least one mutation selected from the group consisting of an activating KRAS mutation, an activating NRAS mutation, an activating HRAS mutation, an inhibiting LKB1 mutation, and an inhibiting PTEN mutation, comprising administering to the subject an agent that inhibits the copy number, amount, and/or activity of arginase 1 without administration of an additional immunotherapy, thereby treating the subject afflicted with the lung cancer.

2. The method of claim 1 , wherein the agent is administered in a pharmaceutically acceptable formulation.

3. The method of claim 1 , wherein the agent directly binds arginase 1.

4. The method of claim 1 , wherein the arginase 1 is human arginase 1.

5. The method of claim 1 , wherein the agent is selected from the group consisting of a blocking antibody, small molecule, antisense nucleic acid, interfering RNA, shRNA, siRNA, aptamer, ribozyme, dominant-negative protein, and combinations thereof.

6. The method of claim 1 , wherein the lung cancer comprises at least one inhibiting LKB1 mutation and at least one inhibiting PTEN mutation.

7. The method of claim 1 , wherein the lung cancer comprises at least one activating RAS mutation selected from the group consisting of KRAS, NRAS, HRAS, and any combination thereof.

8. The method of claim 1 , wherein the lung cancer comprises 1) at least one inhibiting LKB1 mutation and at least one inhibiting PTEN mutation and 2) at least one activating RAS mutation selected from the group consisting of KRAS, NRAS, HRAS, and any combination thereof.

9. The method of claim 1 , wherein the subject is a mammal, an animal model of cancer, or a human.

10. The method of claim 1 , further comprising administering one or more additional anti-cancer agents.

11. A method of inhibiting hyperproliferative growth of a lung cancer cell or cells, wherein i) the lung cancer is selected from the group consisting of adenocarcinoma, lung squamous cell carcinoma (SCC), adeno-squamous carcinoma, or mixed tumors thereof, and ii) the lung cancer cell or cells comprise at least one mutation selected from the group consisting of an activating KRAS mutation, an activating NRAS mutation, an activating HRAS mutation, an inhibiting LKB1 mutation, and an inhibiting PTEN mutation, the method comprising contacting the cancer cell or cells with an agent that inhibits the copy number, amount, and/or activity of arginase 1 without contacting the cells with an additional immunotherapy, thereby inhibiting hyperproliferative growth of the cancer cell or cells.

12. The method of claim 11 , wherein the step of contacting occurs in vivo, ex vivo, or in vitro.

13. The method of claim 11 , wherein the agent is administered in a pharmaceutically acceptable formulation.

14. The method of claim 11 , wherein the agent directly binds arginase 1.

15. The method of claim 11 , wherein the arginase 1 is human arginase 1.

16. The method of claim 11 , wherein the agent is selected from the group consisting of a blocking antibody, small molecule, antisense nucleic acid, interfering RNA, shRNA, siRNA, aptamer, ribozyme, dominant-negative protein, and combinations thereof.

17. The method of claim 11 , wherein the lung cancer comprises at least one inhibiting LKB1 mutation and at least one inhibiting PTEN mutation.

18. The method of claim 11 , wherein the lung cancer comprises at least one activating RAS mutation selected from the group consisting of KRAS, NRAS, HRAS, and any combination thereof.

19. The method of claim 11 , wherein the lung cancer comprises 1) at least one inhibiting LKB1 mutation and at least one inhibiting PTEN mutation and 2) at least one activating RAS mutation selected from the group consisting of KRAS, NRAS, HRAS, and any combination thereof.

20. The method of claim 11 , wherein the subject is a mammal, an animal model of cancer, or a human.

21. The method of claim 11 , further comprising administering one or more additional anti-cancer agents.

Assignees

• Dana Farber Cancer Inst Inc
• Childrens Medical Center

Inventors

• Wong Kwok-Kin
• Xu Chunxiao
• Brainson Christine F
• Kim Carla F
• Dranoff Glenn
• Hammerman Peter

Classifications

• G01N33/5752

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