System and methods for deriving gene signature biomarkers of response to PD-1 antagonists
A gene expression platform, which is a combination of a set of genes that are correlated with response to a PD-1 antagonist in multiple tumor types and a normalization gene set, is disclosed. A method and system of using the gene expression platform to derive gene signature biomarkers of anti-tumor response to a PD-1 antagonist and to test patient samples for predictive gene signature biomarkers are also disclosed.
1. A method for treating a patient having a tumor which comprises determining if a sample of the tumor is positive or negative for a gene signature biomarker based on a gene signature score, wherein the gene signature score is calculated based on a combination of gene expression values for all of the genes in the gene signature biomarker, and administering to the patient a PD-1 antagonist if the tumor is positive for the biomarker or administering to the subject a cancer treatment that does not include a PD-1 antagonist if the tumor is negative for the biomarker, wherein the gene signature biomarker is for a gene signature that comprises the 18-Gene Up-Down Signature in Table 2 below:
TABLE 2
18 Gene Up-
Down
Signature
1
CCL5
2
CD27
3
CD274
4
CD276
5
CD8A
6
CMKLR1
7
CXCL9
8
CXCR6
9
HLA.DQA1
10
HLA.DRB1
11
HLA.E
12
IDO1
13
LAG3
14
NKG7
15
PDCD1LG2
16
PSMB10
17
STAT1
18
TIGIT
2. The method of claim 1 , wherein the PD-1 antagonist administered to the patient if the tumor is positive is an antibody that blocks binding of both human PD-L1 and PD-L2 to human PD-1.
3. The method of claim 2 , wherein the tumor is bladder cancer, colorectal cancer, gastric cancer, head and neck cancer, melanoma, non-small cell lung cancer, ovarian cancer, prostate cancer, anal cancer, biliary cancer, triple negative breast cancer, esophageal, or renal cancer.
4. The method of claim 3 , wherein the tumor is colorectal cancer.
5. The method of claim 4 , wherein the PD-1 antagonist administered to the patient if the tumor is positive is pembrolizumab.
6. The method of claim 3 , wherein the PD-1 antagonist administered to the patient if the tumor is positive is pembrolizumab.
7. The method of claim 2 , wherein the PD-1 antagonist administered to the patient if the tumor is positive is pembrolizumab.