2019 Mentored Investigator Grant Recipient — Alba Rodriguez-Garcia, PhD

Project Summary

Ovarian cancer ranks 5th among cancer-related deaths in women and is the most lethal of all gynecologic malignancies, with an overall 5-year survival rate of 46%. Therefore, there is a dire need for effective therapies. Chimeric antigen receptor (CAR) T cell therapy consists in engineering T cells from patients in order to express a CAR that comprises an extracellular portion based on a fragment of antibody that recognizes a tumor antigen, coupled to the intracellular signaling domains of the T cell receptor. This modification allow the T cells to specifically recognize and kill tumor cells that express the selected antigen on their surface upon reinfusion to the patient. CAR T cells targeting CD19 had shown great success in the treatment of hematologic cancers, and had been recently approved by the FDA. However, effective CAR T cell therapy for ovarian cancer has not yet been achieved. The selection of a target antigen that is overexpressed in malignant cells but not present in normal cells is crucial for the safety and efficacy of the treatment. Here we propose the Müllerian Inhibiting Substance type 2 Receptor (MISIIR) as an ideal target since it is overexpressed in the majority of ovarian cancers while has limited expression in normal tissues. Also, the natural ligand of this receptor, MIS, inhibits the growth of ovarian cancer cells, rationalizing our approach of targeting this relevant pathway with CAR T cells to kill ovarian cancer cells in an efficient manner.

Bio

Dr. Rodriguez-Garcia is currently a postdoctoral fellow in the laboratory of Dr. Daniel Powell Jr. at the Ovarian Cancer Research Center and the Center for Cellular Immunotherapies at the University of Pennsylvania. She earned her degree in Biotechnology in 2009 from the Autonomous University of Barcelona and received her PhD in Biomedicine from the University of Barcelona in 2015. Her doctoral studies were conducted in the laboratory of Dr. Ramon Alemany and focused on the development of novel anticancer therapies in the area of oncolytic adenoviruses, using them as tools to elicit antitumor immune responses. In 2015, Dr. Rodriguez-Garcia joined Dr. Powell’s laboratory, which has a strong background and expertise in the field of cancer immunotherapy. Since then, her research has focused on developing chimeric antigen receptor (CAR) T-cell therapies for ovarian cancer, exploring different tumor antigen targets and strategies to overcome current limitations in the field. In 2016, she was awarded the Stand Up to Cancer Ovarian Cancer Dream Team Grant by the Sandy Rollman Ovarian Cancer Foundation, and in 2018 she received a Meritorious Abstract Travel Award from the American Society Gene and Cell Therapy. The OCRA Ann and Sol Schreiber Mentored Investigator Award will greatly contribute to Dr. Rodriguez-Garcia’s goal of becoming an independent researcher in the field of immunotherapy for ovarian cancer.