Current Developments of CAR-T and CAR-NK Cell Therapies for Ovarian Cancer

Ovarian cancer (OC) remains the deadliest gynecological malignancy, characterized by late diagnosis, tumor heterogeneity, and chemotherapy resistance, contributing to poor survival rates. This comprehensive review explores the potential of chimeric antigen receptor (CAR)-T and CAR-natural killer (NK) cell therapies as emerging immunotherapies for OC. We examine key tumor-associated antigens, including folate receptor alpha (FRα), mesothelin (MSLN), HER2, EpCAM, MUC16, Tn-glycopeptide, TAG-72, and LGR5, which are overexpressed in OC and have shown promise in preclinical studies and early clinical trials for inducing tumor regression without MHC restrictions. While CAR-T cells have demonstrated significant antitumor cytotoxicity in preclinical models, their application in solid tumors like OC faces challenges, including immunosuppressive tumor microenvironments, antigen escape, cytokine release syndrome, and neurotoxicity. CAR-NK cells offer potential advantages, such as reduced toxicity, off-the-shelf availability, and efficacy against heterogeneous tumors, making them a promising complementary approach. This review discusses current research on dosing regimens and combination strategies involving checkpoint inhibitors, chemotherapy, and radiotherapy, as well as responses across histological subtypes. Drawing from ongoing early-phase trials and innovative approaches like CRISPR editing and dual-targeting, we highlight the progress and challenges in developing CAR-based therapies, underscoring their potential while emphasizing the need for further research to establish clinical efficacy in OC.