Methods of determining patient populations amenable to immunomodulatory treatment of cancer

Patent metadata

Field	Value
Publication number	US-11215616-B2
Application number	US-201615564704-A
Country	US
Kind code	B2
Filing date	Apr 8, 2016
Priority date	Apr 10, 2015
Publication date	Jan 4, 2022
Grant date	Jan 4, 2022

Abstract

The disclosure provides methods of determining patient populations amenable or suitable for immunomodulatory treatment of disease such as cancer by measuring the relative or absolute levels of T-cell sub-populations correlated with disease such as cancer.

First claim

What is claimed is:

1. A method of treating cancer in a human subject having cancer by determining if the subject is amenable to treatment with ipilimumab and administering to the subject determined to be amenable to treatment with ipilimumab an effective amount of ipilimumab to treat the cancer in the subject, said method comprising:
(a) isolating a population of peripheral blood mononuclear cells (PBMCs) from the subject having cancer and a population of PBMCs from a cancer-free human subject;
(b) quantifying the percentages of CD4 + CD3 + FoxP3 − T effector (T eff ) cells expressing PD1, PD-L1, and/or CTLA-4 in each of said populations;
(c) comparing the percentages of T eff cells expressing PD1, PD-L1, and/or CTLA-4 in the population of PBMCs from the subject having cancer and the percentages of T eff cells expressing PD1, PD-L1, and/or CTLA-4 in the population of PBMCs from the cancer-free subject;
(d) determining that the subject having cancer is amenable to treatment with ipilimumab if:
(1) the percentage of T eff cells expressing PD-1 in the population of PBMCs from the subject having cancer is lower than the percentage of T eff cells expressing PD-1 in the population of PBMCs from the cancer-free subject;
(2) the percentage of T eff cells expressing PD-L1 in the population of PBMCs from the subject having cancer is lower than the percentage of T eff cells expressing PD-L1 in the population of PBMCs from the cancer-free subject; and
(3) the percentage of T eff cells expressing CTLA-4 in the population of PBMCs from the subject having cancer is higher than the percentage of T eff cells expressing CTLA-4 in the population of PBMCs from the cancer-free subject; and

(e) if the subject having cancer is determined to be amenable to treatment with ipilimumab, administering to the subject an effective amount of ipilimumab to treat the cancer in the subject.

2. The method of claim 1 , wherein the cancer is an adenocarcinoma, a castration-resistant prostate cancer, a melanoma, a Head-and-Neck cancer, a lung cancer, a kidney cancer, a bladder cancer, a gastric cancer, a colorectal cancer, an ovarian cancer, a hepatocellular cancer, a hepatobiliary cancer, a breast cancer, or a blood cancer.

3. A method of inhibiting growth of cancer in a human subject having cancer by determining if the subject is amenable to treatment with ipilimumab and administering to the subject determined to be amenable to treatment with ipilimumab an effective amount of ipilimumab to inhibit growth of the cancer in the subject, said method comprising:
(a) isolating a population of peripheral blood mononuclear cells (PBMCs) from the subject having cancer and a population of PBMCs from a cancer-free human subject;
(b) quantifying the percentages of CD4 + CD3 + FoxP3 − T effector (T eff ) cells expressing PD1, PD-L1, and/or CTLA-4 in each of said populations;
(c) comparing the percentages of T eff cells expressing PD1, PD-L1, and/or CTLA-4 in the population of PBMCs from the subject having cancer and the percentages of T eff cells expressing PD1, PD-L1, and/or CTLA-4 in the population of PBMCs from the cancer-free subject;
(d) determining that the subject having cancer is amenable to treatment with ipilimumab if:
(1) the percentage of T eff cells expressing PD-1 in the population of PBMCs from the subject having cancer is lower than the percentage of T eff cells expressing PD-1 in the population of PBMCs from the cancer-free subject;
(2) the percentage of T eff cells expressing PD-L1 in the population of PBMCs from the subject having cancer is lower than the percentage of T eff cells expressing PD-L1 in the population of PBMCs from the cancer-free subject; and
(3) the percentage of T eff cells expressing CTLA-4 in the population of PBMCs from the subject having cancer is higher than the percentage of T eff cells expressing CTLA-4 in the population of PBMCs from the cancer-free subject; and

(e) if the subject having cancer is determined to be amenable to treatment with ipilimumab, administering to the subject an effective amount of ipilimumab to inhibit growth of the cancer in the subject.

4. The method of claim 3 , wherein the cancer is an adenocarcinoma, a castration-resistant prostate cancer, a melanoma, a Head-and-Neck cancer, a lung cancer, a kidney cancer, a bladder cancer, a gastric cancer, a colorectal cancer, an ovarian cancer, a hepatocellular cancer, a hepatobiliary cancer, a breast cancer, or a blood cancer.

5. A method of treating cancer in a human subject having cancer by determining if the subject is amenable to treatment with ipilimumab and administering to the subject determined to be amenable to treatment with ipilimumab an effective amount of ipilimumab to treat the cancer in the subject, said method comprising:
(a) isolating a population of peripheral blood mononuclear cells (PBMCs) from the subject having cancer and a population of PBMCs from a cancer-free human subject;
(b) quantifying the percentages of total CD4 + cells expressing PD1, PD-L1, and/or CTLA-4 in each of said populations;
(c) comparing the percentages of total CD4 + cells expressing PD1, PD-L1, and/or CTLA-4 in the population of PBMCs from the subject having cancer and the percentages of total CD4 + cells expressing PD1, PD-L1, and/or CTLA-4 in the population of PBMCs from the cancer-free subject;
(d) determining that the subject having cancer is amenable to treatment with ipilimumab if:
(1) the percentage of total CD4 + cells expressing PD-1 in the population of PBMCs from the subject having cancer is lower than the percentage of total CD4 + cells expressing PD-1 in the population of PBMCs from the cancer-free subject;
(2) the percentage of total CD4 + cells expressing PD-L1 in the population of PBMCs from the subject having cancer is lower than the percentage of total CD4 + cells expressing PD-L1 in the population of PBMCs from the cancer-free subject; and
(3) the percentage of total CD4 + cells expressing CTLA-4 in the population of PBMCs from the subject having cancer is higher than the percentage of total CD4 + cells expressing CTLA-4 in the population of PBMCs from the cancer-free subject; and

(e) if the subject having cancer is determined to be amenable to treatment with ipilimumab, administering to the subject an effective amount of ipilimumab to treat the cancer in the subject.

6. The method of claim 3 , wherein the cancer is an adenocarcinoma, a castration-resistant prostate cancer, a melanoma, a Head-and-Neck cancer, a lung cancer, a kidney cancer, a bladder cancer, a gastric cancer, a colorectal cancer, an ovarian cancer, a hepatocellular cancer, a hepatobiliary cancer, a breast cancer, or a blood cancer.

Assignees

• Univ California
• Nat Institutes Of Health Nih Dhhs U S Government

Inventors

• Fong Lawrence
• Macphee Serena Kwek
• Lewis Jera

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• G01N33/57555

  of the prostate · CPC title

• G01N33/5751

  of the skin, e.g. melanoma · CPC title

• G01N33/575 Primary

  for cancer · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title