A novel approach for treatment of ovarian cancer involves using enhanced immune cells such as genetically engineered T cells that are targeted to tumor specific proteins on ovarian cancer cells. T cells can be forced to express an artificial receptor termed a chimeric antigen receptor (CAR) that recognizes a specific foreign protein on ovarian cancer cells. We have generated a CAR+ T cells that eradicate ovarian cancers in mice that lack an immune system. However, despite the ability of CAR+ T cells to localize to tumor targets, their activation in the clinical setting can be inhibited by a suppressive tumor microenvironment. To this end, we have found that CAR+ T cells further modified to secrete hormones called IL-12 exhibit enhanced killing of ovarian tumor cells in the mouse. This is partly due to resistance to the suppressive tumor microenvironment in a clinically relevant mouse that has an immune system. Given these preclinical experimental outcomes, in this application we propose to assess the safety as well as the anti-tumor efficacy of CAR+ T cells in a phase I clinical trial treating patients with relapsed ovarian cancers. In order to further study the anti-tumor response of the CAR+ T cells, we will assess the persistence of CAR+ T cells in patients and characterize the response of the patient’s own immune system to the CAR+ T cells. Additionally, the tumor microenvironment will be examined pre- and post-injection of CAR+ T cells for changes in various immune factors.
Dr. Oladapo Yeku is currently a Medical Oncology Fellow at Memorial Sloan Kettering Cancer Center. He is a laboratory research track fellow and will be investigating adoptive T Cell therapy for ovarian cancer. He graduated summa cum laude with a B.S degree in Biology from Medgar Evers College and was accepted to the Medical Scientist Training Program (MSTP) at Stony Brook University where he earned his combined M.D/Ph.D. degree. While there, he wrote for and was successfully awarded an F31 grant to fund his research. After completing his Internal Medicine Residency at University of Pittsburgh Medical Center, he was accepted to Memorial Sloan Kettering Cancer Center. His current research interests involve the use of genetically engineered T cells to target MUC-16ecto expressed on ovarian cancer cells. Given the promising preclinical studies, this research has led to a phase I clinical trial using this technology for patients with advanced ovarian cancer. He will analyze the patient samples for these modified T cells and further characterize the tumor microenvironment.