Biomarkers for predicting therapeutic response to immunosuppressant cancer drugs and their applications

Abstract

To provide a method for predicting the therapeutic response to immunosuppressant drugs in cancer patients, a composition for predicting therapeutic response, and a kit for predicting therapeutic response. [Solution] The invention provides applications, compositions, and kits for predicting the therapeutic response to immunosuppressant drugs in cancer patients based on the expression levels of mRNA or proteins of one or more genes selected from the group consisting of OPN, POSTN, and IGFBP-3. Through this, it is possible to pre-classify patients who will respond to immunosuppressant drugs from those who will not, thereby greatly improving the efficiency of anticancer treatment using immunosuppressant drugs.

Claims

1. A composition for predicting the therapeutic response of cancer patients to immunosuppressant drugs, comprising a formulation capable of measuring the expression level of mRNA or protein thereof of one or more genes selected from the group consisting of OPN, POSTN, and IGFBP-3.

2. The composition according to claim 1, wherein the one or more genes include OPN.

3. The composition according to claim 1, wherein the one or more genes include OPN and POSTN.

4. The composition according to claim 1, wherein the one or more genes include OPN, POSTN, and IGFBP-3.

5. The composition according to claim 1, wherein the immunosuppressant inhibits the binding between PD-L1 and PD-1.

6. The composition according to claim 1, wherein the immunosuppressant is an anti-PD-L1 antibody.

7. The composition according to claim 6, wherein the anti-PD-L1 antibody comprises a heavy chain containing the amino acid sequence described in SEQ ID NO: 3 and a light chain containing the amino acid sequence described in SEQ ID NO:

4.

8. The composition according to claim 1, wherein the formulation capable of measuring the expression level of the mRNA is an antisense nucleotide, primer, or probe that binds complementarily to the gene.

9. The composition according to claim 1, wherein the formulation capable of measuring the expression level of the protein is an antibody that specifically binds to the protein of the gene.

10. The composition according to claim 1, wherein the cancer is a solid tumor.

11. The composition according to claim 1, wherein the cancer is one or more selected from the group consisting of bile duct cancer, colon cancer, adenocarcinoma, rectal cancer, breast cancer, synovial sarcoma, chondrosarcoma, thyroid cancer, stomach cancer, thymic cancer, cervical cancer, glioma, brain cancer, melanoma, lung cancer, bladder cancer, prostate cancer, leukemia, kidney cancer, liver cancer, colorectal cancer, pancreatic cancer, ovarian cancer, lymphoma, uterine cancer, oral cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, skin cancer, hematological cancer, parathyroid cancer, and ureteral cancer.

12. A kit for predicting the therapeutic response of cancer patients to immunosuppressant drugs, comprising a composition according to any one of claims 1 to 11.

13. A step of measuring the expression level of mRNA or protein of one or more genes selected from the group consisting of OPN, POSTN, and IGFBP-3 from a biological sample obtained from a cancer patient; and A method for providing information for predicting the therapeutic response of a cancer patient to an immunosuppressant drug, comprising the step of evaluating the patient's therapeutic response to the immunosuppressant drug based on the measured mRNA or protein expression level.

14. The method according to claim 13, wherein the one or more genes include OPN.

15. The method according to claim 13, wherein the one or more genes include OPN and POSTN.

16. The method according to claim 13, wherein the one or more genes include OPN, POSTN, and IGFBP-3.

17. The method according to claim 13, wherein the immunosuppressant inhibits the binding between PD-L1 and PD-1.

18. The method according to claim 13, wherein the immunosuppressant is an anti-PD-L1 antibody.

19. The method according to claim 13, further comprising the step of determining whether to treat the patient with an immunosuppressant drug or to continue treatment with the immunosuppressant drug based on the patient's response to the immunosuppressant drug.

20. The method according to claim 13, wherein the expression level is measured before administration, after administration, or before and after administration of the immunosuppressant.

21. The method according to claim 20, wherein the expression level is measured before and after administration of an immunosuppressant, and when the gene is OPN or POSTN, the patient's treatment response is evaluated as low if the measured expression level is significantly higher after administration of the immunosuppressant compared to before administration of the immunosuppressant.

22. The method according to claim 20, wherein the expression level is measured before administration of an immunosuppressant, and when the gene is OPN or POSTN, the patient is evaluated as having a low therapeutic response if the measured expression level is significantly higher than the expression level of other control cancer patients before administration of an immunosuppressant.

23. The method according to claim 20, wherein the expression level is measured before and after administration of an immunosuppressant, and when the gene is IGFBP-3, the patient's treatment response is evaluated as being low if the measured expression level is significantly lower after administration of the immunosuppressant compared to before administration of the immunosuppressant.

24. The method according to claim 20, wherein the expression level is measured before administration of an immunosuppressant, and when the gene is IGFBP-3, the patient is evaluated as having a low therapeutic response if the measured expression level is significantly lower than the expression level of other control cancer patients before administration of an immunosuppressant.

25. The method according to claim 13, wherein the expression level of the mRNA is measured by one or more methods selected from the group consisting of in situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR), competitive reverse transcriptase polymerase chain reaction (competitive RT-PCR), real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR), RNase protection assay (RPA), microarray, and northern blotting.

26. The expression level of the aforementioned protein is The method according to claim 13, wherein the measurement is performed by one or more methods selected from the group consisting of Western blotting, radioimmunoassay (RIA), radioimmunodiffusion, enzyme immunoassay (ELISA), immunoprecipitation, flow cytometry, immunofluorescence staining, octarony, complement fixation assay, and protein chip.

27. (i) the stage of administering immunosuppressant drugs to cancer patients; and (ii) A method for treating cancer based on the therapeutic response of a cancer patient to an immunosuppressant, comprising the step of measuring the expression level of mRNA or protein thereof of one or more genes selected from the group consisting of OPN, POSTN, and IGFBP-3 from a biological sample obtained from the cancer patient before, after, or before and after administration of the immunosuppressant.

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