Abstract:
Chimeric antigen receptor T-cell therapy has shown significant clinical benefit, particularly in hematologic malignancies; however, conventional CAR-T platforms still face important limitations, including fixed antigen specificity, antigen escape, limited controllability, and safety-related toxicities. Modular universal CAR-T cell systems have emerged as a strategy to address some of these challenges by separating the signaling component of the CAR from the tumor-targeting module. In this presentation, recent updates in the development and application of modular universal CAR-T cell therapies in cancer will be discussed, with a focus on adaptor-based designs, switchable targeting systems, and approaches that enable more flexible control of CAR-T cell activity. Particular attention will be given to antibody fragment- and nanobody-based targeting modules, which can be engineered to redirect a universal CAR-T cell toward different tumor-associated antigens without redesigning the cellular product itself. The talk will also highlight recent progress in modular CAR-T platforms for hematologic malignancies, including our recent work on the development of universal modular CAR-T cells using target-specific nanobodies. These strategies may provide a more adaptable framework for cellular immunotherapy, although further optimization, preclinical validation, and clinical evaluation are still required to define their safety, efficacy, and translational potential.
