This proposed project aims to test our recently defined combination immune therapy against metastatic castration-resistant prostate cancer (mCRPC), an unmet medical need and FY19 PCRP Overarching Challenge. If our defined combination regimen works in a novel bone metastatic animal model, it will likely lead to direct translation into mCRPC clinical care. All compounds we propose to test are clinical grade and are in various phases of clinical trials for cancer patients; therefore, the risk of unknown toxicities will be low and can be quickly incorporated into clinical trials for mCRPC patients. We will initially test immune checkpoint blockade using a double PD1 and CTLA4 combination, a current clinical practice, although it is clear that some patients may not tolerate to this combination. We therefore propose to remove CTLA4 late in our preclinical trials and replacing with potential novel immune regulators identified through our detailed analysis of the bone metastatic microenvironment. By the end of the three year proposal, our best combination regimens will likely enter clinical trials for mCRPC patients given all tested compounds are clinical grade. |
