biostudies-literatureStock SThomas Kirch StiftungUniversitätsklinik MünchenBavarian Center for Cancer ResearchHector StiftungBruno und Helene Jöster StiftungBayerische ForschungsstiftungBavarian Ministry for Economical AffairsElse Kröner-Fresenius-StiftungLudwig-Maximilians-Universität MünchenSFB-TRR 338German Excellence InitiativeWilhelm Sander-StiftungEuropean Research CouncilDeutsche ForschungsgemeinschaftDeutsche KrebshilfeBavarian Elite Graduate Training NetworkElitenetzwerk BayernFritz-Bender-StiftungEuropean UnionDeutschen Konsortium für Translationale KrebsforschungErnst-Jung-StiftungMarie Sklodowska-Curie Program Training NetworkMelanoma Research AllianceJosé Carreras Leukämie-StiftungBundesministerium für Bildung und ForschungGo-Bio Initiative100https://www.ebi.ac.uk/biostudies/studies/S-EPMC11024081biostudies-literatureUnknown73(6)In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs. CD8TM.41BBIC-based anti-BCMA CAR vectors with either a long linker or a short linker between the light and heavy scFv chain, CD28TM.41BBIC-based and CD28TM.CD28IC-baCancer immunology, immunotherapy : CIIComparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma.PMC11024081756017101100460101124203Endres SCordas Dos Santos DMTheurich SSubklewe MKobold SMajed LStock SGrunmeier RDorr JFertig Lvon Bergwelt-Baildon MGottschlich AMenkhoff VDRejeski KMarkl FfalseComparative performance of scFv-based anti-BCMA CAR formats for improved T cell therapy in multiple myeloma.In multiple myeloma (MM), B cell maturation antigen (BCMA)-directed CAR T cells have emerged as a novel therapy with potential for long-term disease control. Anti-BCMA CAR T cells with a CD8-based transmembrane (TM) and CD137 (41BB) as intracellular costimulatory domain are in routine clinical use. As the CAR construct architecture can differentially impact performance and efficacy, the optimal construction of a BCMA-targeting CAR remains to be elucidated. Here, we hypothesized that varying the constituents of the CAR structure known to impact performance could shed light on how to improve established anti-BCMA CAR constructs. CD8TM.41BBIC-based anti-BCMA CAR vectors with either a long linker or a short linker between the light and heavy scFv chain, CD28TM.41BBIC-based and CD28TM.CD28IC-ba2024-01-01T00:00:00Z2024 Apr2026-06-01T21:55:38.646Z2025-04-06T03:18:01.832ZS-EPMC110240813863029110.1007/s00262-024-03688-4