Simultaneously Targeting Ovarian Cancer and Tumor Microenvironment Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells
Adoptive cellular therapy has recently transformed the field of cancer immunotherapy, specifically the treatment of hematological malignancies, through the application of chimeric antigen receptor (CAR) T cells. While a tremendous step forward for cell therapy, current CAR T products face barriers to patient accessibility and clinical benefit. Their autologous nature renders the therapies patient selective and costly, and mechanisms of resistance to CAR T cells, including antigen downregulation/antigen-negative relapse, limit long-term therapeutic efficacy. In this letter, we report novel ex vivo HSC-derived mesothelin- CAR engineered NKT (AlloMCAR-iNKT) cell products that are pure, potent, and safe allogeneic cell therapies. AlloMCAR-iNKT cells execute ovarian cancer killing through a CAR-TCR-NK triple-mechanism, do not cause GvHD, and are resistant to allorejection. Our feeder- free, serum-free culture method promotes the speedy clinical translation of HSC engineered cells, and here we validate our system as a versatility platform for the development of designer “off-the-shelf” cellular products with high therapeutic potential to ovarian cancer patients. Overall design: Gene expression profiling of primary ovarian cancer (OC) patient samples