Abstract 6100: Point-of-care manufacturing of FOLR1-directed CAR T cells for the treatment of ovarian cancer

Abstract Treatment options for ovarian cancer patients are limited, highlighting a significant unmet need for targeted, durable, and effective therapies. In recent years, adoptive cell transfer therapies have made tremendous progress in the past years. Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are promising drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in different indications. Recently, we have reported the preclinical evaluation of a novel FOLR1-targeting CAR directed against ovarian cancer and potentially other FOLR1-expressing tumors. Despite advancements in T cell therapy, producing a functional and robust cell product in the necessary quantities remains challenging. Currently available processes for the preparation of CAR T are laborious and include numerous manual handling steps, which increase the risk of errors and may impose safety risks. This underscores the need for reliable and automated manufacturing processes to ensure high-quality cellular products for immunotherapy. This study aimed to develop an automated, closed, and good manufacturing practice (GMP)-compliant process for FOLR1-specific CAR T cells. Using the CliniMACS Prodigy® Platform, we established a streamlined process in a closed system that meets stringent regulatory requirements while reducing hands-on time. We optimized culture conditions to reduce the process time to 7 days. Starting from a cryopreserved leukapheresis we achieved a clinically relevant yield of FOLR1-specific CAR-engineered T cells. The cellular product mainly consisted of highly viable CAR-expressing T cells with an early memory phenotype. FOLR1-specific CAR T cells manufactured with the optimized process showed specific killing of ovarian cancer cells in vitro and in an ovarian cancer xenograft model in vivo. Moreover, the automated CliniMACS Prodigy Platform enables point-of-care (POC) manufacturing. In conclusion, we developed a robust, rapid, and efficient process for manufacturing anti-FOLR1 CAR T cells. This platform is well-suited for automated and decentralized POC manufacturing and can be adapted for the production of other CAR T cell therapies. Citation Format: Christoph Herbel, Manuel Martinez-Osuna, Larissa Steiner, Maria Bethke, Leon Osinski, Katrin Krischer, Janina Brauner, Cathrin Bleilevens, Jens Kopatz, Katja Petry, Dominik Eckardt. Point-of-care manufacturing of FOLR1-directed CAR T cells for the treatment of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6100.