METHODS FOR TREATING CANCER

• US 20170198039A1
• Filed: 07/07/2015
• Published: 07/13/2017
• Est. Priority Date: 07/07/2014
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Wong, Kwok-Kin
• Granted Patent: US 10,501,537 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/70503 Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
• CPC Class Codes: G01N 33/574 for cancer

Abstract

The present invention provides methods of treating cancer, particularly cancers that had developed resistance to PD-1 and PDL-1 blockade. Also included are methods of identifying therapeutic targets for the treatment of cancer.

Claims

1. A method of treating or preventing PD-1 or PDL-1 resistance in a subject comprising administering to said subject a compound that inhibits the expression or activity of a T cell immunoglobulin and mucin protein 3 (Tim3).

2. The method of claim 1, wherein the cancer is a KRAS or EGFR mutant cancer.

3. The method of claim 2, wherein the cancer has a EGFR T790M L858R mutation.

4. The method of claim 1, wherein said cancer is a lung cancer, melanoma, kidney cancer, a head and neck cancer, bladder cancer or an upper gastrointestinal cancer.

5. The method of claim 1, wherein the kidney cancer is a renal cell cancer.

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

7. The method of claim 1, wherein the compound is a nucleic acid, an antibody or a small molecule.

8. The method of claim 7, wherein in the antibody is bi-specific.

9. The method of claim 1, wherein the subject has received PD-1 or PDL-1 therapy.

10. The method of claim 1, further comprising administering to the subject PD-1 or PDL-1 therapy.

11. The method of claim 10, wherein the PD-1 or PDL-1 therapy is administered concurrently or sequentially with the Tim3 inhibitor.

12. The method of claim 10, wherein the PD-1 or PDL-1 therapy is immunotherapy.

13. The method of claim 1, further comprising administering a chemotherapeutic agent or radiation therapy.

14. The method of claim 13, wherein the chemotherapeutic agent is a targeted therapy.

15. The method of claim 13, wherein the chemotherapeutic agent is an EGFR tyrosine kinase inhibitor.

16. The method of claim 15, wherein the EGFR tyrosine kinase inhibitor is WZ4002.

17. A method of determining whether a subject has acquired PD-1 or PDL-1 resistance comprising detecting the expression level of Tim3 in a subject sample, wherein an increase of expression of Tim3 compared to a normal control cell indicates that the subject has PD-1 or PDL-1 resistance.

19. The method of claim 17 or 18, wherein the normal control cell is T cells from cancer associated tissues that has not been exposed to PD-1 or PDL-1 blockade.

20. The method of claim 19, wherein the T cells are derived from the subject before PD-1 or PDL-1 blockade.

18. A method of selecting a subject whom would derive a benefit from PD-1 or PDL-1 therapy, comprising detecting the expression level of Tim3 in a subject sample, wherein a similarity of expression of Tim3 compared to a normal control cell indicates that the subject would derive a benefit from PD-1 or PDL-1 therapy.