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2024 Recipient — Sarah Gitto, PhD

Sarah Gitto, PhD

PARP-targeted PET imaging to measure response to PARP inhibitor and immunotherapy in ovarian cancer

Project Summary

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 our 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 synergize with immunotherapy, even PARPi-resistant ovarian cancer, and FTT imaging can predict response to combination therapy. 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.

Bio

Dr. Sarah Gitto is an Instructor of Pathology and Laboratory Medicine in the Division of Diagnostic Innovation at the University of Pennsylvania. Her research laboratory focuses on immune modulating and molecular therapeutic strategies for the treatment of ovarian cancer. Her work further utilizes novel imaging modalities to predict and monitor treatment efficacy and outcomes. Dr. Gitto holds four degrees from the University of Central Florida (UCF) - BS in microbiology and Molecular Microbiology, BS in Health Sciences, MS in Biomedical Sciences, and PhD in Biomedical Sciences. Her graduate research focused on the role of the tumor microenvironment of pancreatic cancer onset and progression and NK cell-based therapies for the treatment of ovarian cancer. She was recognized for her graduate research through numerous institutional awards most notably, induction into the Order of the Pegasus and UCF Alumni 30 under 30. Dr. Gitto completed her post-doctoral research under the mentorship of Dr. Daniel J. Powell at the University of Pennsylvania (UPenn) and earned an MS in Translational Research from UPenn. As a postdoctoral researcher she developed a novel autologous humanized preclinical platform for evaluating immunotherapies for the treatment of ovarian cancer, which has been the cornerstone of her ongoing research. Her research has been funded by the Ovarian Cancer Research Alliance, Rivkin Center for Ovarian Cancer, and the NIH Clinical and Translational Science Award.