Next-generation BCMA-targeted chimeric antigen receptor CARTemis-1: the impact of manufacturing procedure on CAR T-cell features

• DOI: 10.1007/s13402-024-00984-0
• Publication Date: 2024-08-27T16:01:56Z
• Authors: Belén Sierro-Mart...; Virginia Escamill...; Laura Pérez-Ortega; Beatriz Guijarro-...; Paola Hernández-Díaz; María de la Rosa-...; Maribel Lara-Chica; Alfonso Rodríguez...; Juan Luis Reguera...; Luzalba Sanoja-Fl...; Blanca Arribas-Ar...; Miguel Ángel Mont...; Gloria Carmona; Maria Jose Robles; Teresa Caballero-...; Javier Briones; Hermann Einsele; Michael Hudecek; Jose Antonio Pére...; Estefanía García-...

CAR therapy targeting BCMA is under investigation as treatment for multiple myeloma. However, given the lack of plateau in most studies, pursuing more effective alternatives imperative. We present preclinical and clinical validation a new optimized anti-BCMA (CARTemis-1). In addition, we explored how manufacturing process could impact CAR-T cell product quality fitness. CARTemis-1 optimizations were evaluated at level both, vitro vivo. generation was validated GMP conditions, studying dynamics immunophenotype from leukapheresis to final product. Here, studied on cells define optimal culture protocol expansion time increase Two different versions with spacers compared. The longer version showed increased cytotoxicity. incorporation safety-gene EGFRt into structure can be used monitoring marker. no inhibition by soluble presents potent antitumor effects both Expansion IL-2 or IL-7/IL-15 compared, revealing greater proliferation, less differentiation, exhaustion IL-7/IL-15. Three consecutive batches produced guidelines meeting all required specifications. manufactured conditions memory subpopulations, reduced markers selective efficacy against MM lines primary myeloma cells. release points obtaining best fit > 6 < 10 days (days 8-10). has been rationally designed efficacy, overcome sBCMA inhibition, incorporate expression safety-gene. successfully standards. A phase I/II trial patients will conducted (EuCT number 2022-503063-15-00).