PARP-Targeted PET Imaging to Measure Response to PARP Inhibitor and Immunotherapy in Ovarian Cancer

Project summary

PARP inhibitors (PARPi) increase the expression of proteins on tumor cells that directly prohibit immune cells from targeting and eliminating tumor cells. Combination of PARPi with immunotherapy agents that block inhibitory interactions can enhance the patient’s immune system to better target tumor cells. This proposal first aims to comprehensively understand what effects PARPi have on ovarian cancer, and how these changes can be exploited to increase the activity of immunotherapy. Second, we will test combination PARPi-immunotherapy strategies using humanized models that we developed from human ovarian cancer and patient-matched immune cells. These models are unique since they can mimic the donor’s specific activity and response to therapies. Finally, we will evaluate a non-invasive PET imaging ligand that measures PARP expression ([18F]FluorThanatrace, FTT) to evaluate its ability to predict patient response to combination therapies. The overall hypothesis is that PARPi provide immune modulatory effects and can synergize with immunotherapy. And, that PARPi and FTT imaging can predict response to combination therapy, even with PARPi-resistant ovarian cancer. This project will provide insights into combination strategies and imaging biomarkers aimed to improve ovarian cancer outcomes. This work can be directly translated into clinical trials of PARPi/immunotherapy combinations. Also, data obtained from the FTT imaging studies will have an immediate impact on our understanding of our ongoing FTT clinical trial.