From Ex Vivo to In Vivo: The Next Generation of CAR-T Therapy

Chimeric antigen receptor T cell (CAR-T) therapy has transformed hematological cancer treatment, but its broader clinical application remains constrained by the exorbitant costs and complex procedures of ex vivo manufacturing. To overcome these limitations, in vivo CAR-T engineering strategies are emerging as compelling alternatives, enabling direct reprogramming of T cells within the patients. Recent studies indicate that in vivo CAR-T therapy is evolving from a delivery-centered concept into an integrated engineering framework that should coordinate cell-selective targeting, controllable CAR expression, T-cell fitness, and long-term safety. Looking forward, this field is likely to move beyond vector innovation alone toward multidimensional platform design, which is comprehensively discussed in this perspective.