Biomarkers and combination therapies using oncolytic virus and immunomodulation
The invention disclosed herein describes biomarkers useful for prognosis, selection and monitoring of oncolytic virus therapy for patients with various types of cancer. In particular, the present invention provides identification of proteins whose expression patterns are strongly predictive of the outcome of oncolytic virus therapy in a patient with cancer. The present invention provides a method for identifying and selecting cancer patients who are likely to be non-responsive to onocolytic virus therapy. These patients can be co-administered an agent that stimulates a cell-mediated immune response in the patient with the oncolytic virus or can be administered a therapy other than oncolytic virus therapy.
1. A method for treating cancer in a patient having or suspected of having cancer comprising (a) administering a Delta-24 oncolytic adenovirus for a treatment period, (b) measuring the level of one or more Th1 biomarkers at a first time point and at a subsequent second time point, and (c) comparing the level of one or more Th1 biomarkers at the first time point and the second time point, wherein a decrease in one or more Th1 biomarkers at the second time point compared to the first time point indicates that the patient is non-responsive to treatment with the Delta-24 oncolytic adenovirus.
2. The method of claim 1 , further comprising administering a Th1 stimulating agent to the patient with the Delta-24 oncolytic adenovirus if the patient is determined to be non-responsive.
3. The method of claim 1 , wherein said Delta-24 oncolytic adenovirus is a Delta-24-RGD oncolytic adenovirus.
4. The method of claim 1 , wherein the cancer is selected from the group consisting of primary brain cancer, metastatic brain cancer, lung cancer, breast cancer and prostate cancer.
5. The method of claim 4 , wherein the cancer is low-grade or high-grade glioma.
6. The method of claim 5 , wherein the cancer is high-grade glioma.