New strategies for targeting ovarian tumors using CAR T cells

High-grade serous carcinoma (HGSC) is a type of epithelial ovarian cancer (EOC). EOC is the fourth most common cause of cancer-related death in women in the developed world and the leading cause of death from gynecological malignancies. EOC is often diagnosed at advanced-stage disease with an overall 5-year survival rate of <40%. While a significant progress has been made in surgical and chemotherapeutic treatments for EOC, the survival rates for this disease have only modestly improved. We constructed a ‘dual-Chimeric Antigen Receptor’ (dCAR) for ovarian cancer. The dCAR represent a new approach that addresses the major challenge of `off-tumor on-target` toxicity in CAR therapy, namely, the risk of damage to healthy tissues of the patient which express the target antigen of the selected CAR. The underlying idea is that restricting the activity of CAR T cells against a combination of two antigens which are co-expressed by the tumor, but not by normal tissues, can prevent off target toxicity. We analyzed the potential efficacy and safety of the dual CAR in vitro. Additionally, we compared the administration of CAR T cells locally to intra venues injection and compared it to i.v injections. We show that intra- tumoral injection have significant superior effect in vivo.