Methods of identifying and treating patient populations amenable to cancer immunotherapy

Patent metadata

Field	Value
Publication number	US-11699503-B2
Application number	US-201816479211-A
Country	US
Kind code	B2
Filing date	Jan 19, 2018
Priority date	Jan 19, 2017
Publication date	Jul 11, 2023
Grant date	Jul 11, 2023

Abstract

Methods for identifying cancer patients amenable to anti-cancer immunotherapy are provided along with methods of monitoring cancer therapy. Also provided are methods of treating cancer patients amenable to anti-cancer immunotherapy. The methods involve determining the level of CD127 <low> PD-1 <low> T cells. The patients are treated with an immune checkpoint inhibitor, such as an anti-CTLA-4 antibody, e.g. ipilimumab.

First claim

What is claimed is:

1. A method of treating cancer in a human subject having cancer comprising:
(a) generating a first scaffold map from a first population of blood leukocytes isolated from the human subject having cancer, wherein the cancer is melanoma, and a second scaffold map from a second population of blood leukocytes isolated from a control, wherein the control is the human subject having cancer at an earlier time, a distinct human subject having cancer that is unresponsive to anti-cancer immunotherapy, or a healthy human subject, wherein the cancer is melanoma;
(b) generating a first cell population expression profile from the first scaffold map, and a second cell population expression profile from the second scaffold map;
(c) comparing the first cell population expression profile and the second cell population expression profile to determine expression level of CD127 low PD-1 low T cells in the human subject having cancer and the control;
(d) administering a therapeutically effective amount of a composition comprising an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is ipilumimab, to the human subject having cancer, if the expression level of CD127 low PD-1 low T cells in the human subject having cancer is greater than the expression level of CD127 low PD-1 low T cells in the control, thereby treating the cancer in the human subject having cancer.

2. The method of claim 1 , further comprising administering a soluble growth factor to the human subject having cancer.

3. The method of claim 2 , wherein the soluble growth factor is granulocyte-macrophage colony stimulating factor (GM-CSF).

4. The method of claim 1 , wherein the T cells are CD4 positive cells.

5. The method of claim 4 , wherein the CD4 positive cells are regulatory T cells.

6. The method of claim 1 , wherein the control is the human subject having cancer at an earlier time.

7. The method of claim 6 , wherein the earlier time is prior to a cancer treatment.

8. The method of claim 1 , wherein the human subject having cancer has a tumor and the first population of blood leukocytes is obtained intratumorally.

9. The method of claim 1 , wherein the first population of blood leukocytes is obtained from a secondary lymphoid organ or from peripheral blood.

10. The method of claim 1 , wherein the immune checkpoint inhibitor inhibits the growth of cancer cells.

11. The method of claim 1 , wherein the immune checkpoint inhibitor inhibits the migration of cancer cells.

12. The method of claim 1 , wherein the generating a first and second scaffold map comprises obtaining, from a third party, a dataset comprising data representing the level(s) of CD127 low PD-1 low cells.

13. The method of claim 1 , wherein the generating a first and second scaffold map comprises processing, using flow cytometry, a sample from the human subject having cancer and/or control to experimentally determine a dataset comprising data representing the level(s) of CD127 low PD-1 low cells.

14. The method of claim 5 , wherein the CD4 positive cells are CD4 + CD25 + regulatory T cells.

Assignees

• Univ California

Inventors

• Spitzer Matthew
• Fong Lawrence

Classifications

• G16B5/10

  Boolean models · CPC title

• G01N2333/70596

  Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 · CPC title

• A61K38/193

  Colony stimulating factors [CSF] · CPC title

• C07K16/2818

  against CD28 or CD152 · CPC title

• G16B45/00

  ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks · CPC title