Powerful therapies that utilize a patient’s immune system (Immunotherapies) are being developed to treat ovarian cancer. Ovarian cancer tumors contain bad cells (tumor cells) and good cells (cells of the immune system). One type of good cell found within the tumor is called a tumor-infiltrating lymphocyte (TIL). TILs contain properties that enable them to destroy cancer cells. However, the cancer cells and the TIL also have properties that can result in suppression of the TIL’s ability to maintain tumor control, allowing the cancer cells to grow. Our lab recently identified a subset of TIL, CD137+ TIL, which contains superior properties that enable this subset to maintain tumor control. Although the discovery of this tumor-reactive TIL subset was promising, the CD137+ TIL failed to completely ablate the ovarian cancer, suggesting that the tumor cell and TIL inhibitory properties may still be playing an active role to initiate the survival and growth of the ovarian cancer.
In our study, we will be the first researchers to thoroughly investigate what inhibitory properties the CD137+ TIL contain and determine the effects of obstructing the inhibitory properties on the ovarian cancer and TIL. We hypothesize that blocking the inhibitory properties will facilitate the TIL, specifically the CD137+ subset, to completely annihilate the ovarian cancer. We will test our hypothesis by investigating three objectives. Our first objective will elucidate the expression of a wide range of co-inhibitory molecules on ovarian cancer TIL. Our second objective determines whether blocking inhibitory molecules modulates TIL function in vitro (in the dish). Our final objective investigates the role of inhibitory molecules using an ovarian cancer mouse model in vivo (in the body). Through our objectives, we will evaluate and optimize the effects of blocking inhibitory molecules on the TIL and other immune cells activation status, phenotype, migration and anti-tumor activity.
The Powell lab is involved in a soon to open ovarian cancer phase II clinical trial utilizing reagents that block the inhibitory molecules expressed on TIL and ovarian cancer cells. Our study may provide further, innovative insights for this and other clinical trials by specifically investigating parameters that might otherwise limit the tumor-reactive CD137+ subset. The infrastructure for this project and mentorship is established to ensure project completion and potential future clinical translation.
This grant is made possible in part through a generous donation from Frances and Leon Hyman in memory of Barbara Skydel, and Tell Every Amazing Lady About Ovarian Cancer Louisa McGregor Ovarian Cancer Foundation also known as ®T.E.A.L.
Dr. Jessica Chacon is currently a postdoctoral fellow in the Ovarian Cancer Research Center at the University of Pennsylvania in Philadelphia, PA. Dr. Chacon received her Bachelor of Science degree in Biological Sciences from the University of Texas at El Paso and completed her Ph.D. in Biomedical Sciences, specializing in Immunology at the University of Texas Health Science Center/ M.D. Anderson Cancer Center, under the mentorship of Dr. Laszlo Radvanyi. Her Ph.D. research focused on improving the quality of the tumor-infiltrating lymphocytes (TIL) used in Adoptive T-cell therapy by understanding the role of 4-1BB co-stimulation during the expansion of the tumor-infiltrating lymphocytes (TIL). As a result of Jessica’s scientific work, she received the Fadine Jackson Roquemore Scholarship in Cancer Research award, University of Texas Health Innovation for Cancer Prevention Research Pre-doctoral Fellowship and was invited to present her research at RIKEN, Center for Integrative Medical Sciences in Yokohama, Japan. Jessica’a doctoral work focused on melanoma immunology but she has transitioned to the challenge of ovarian cancer research, which she is determined to succeed in under the mentorship of Dr. Daniel Powell, Jr., who followed a similar path to ovarian cancer immunology. Jessica has been a recipient of the University of Pennsylvania’s Postdoctoral Opportunities in Research and Teaching IRACDA fellowship and the T32 Immunobiology of normal and neoplastic lymphocytes fellowship. Her current research focuses on elucidating the immune profile of bona fide tumor-reactive TILs in ovarian cancer. Jessica’s work establishes for the first time a fundamental approach by which new cancer immunotherapy trials for ovarian cancer may be rationally designed, thus resulting in a paradigm shift for ovarian cancer.