The Evolution, Landscape, and Clinical Tradeoffs of In Vivo CAR-T Therapy
Chimeric antigen receptor (CAR)-T cell therapy has revolutionized hematological oncology, yet conventional ex vivo manufacturing imposes severe clinical and economic burdens. In vivo CAR-T therapy—programming endogenous T cells via systemic vector delivery—has emerged to overcome these limitations. This communication analyzes the 2026 inflection point in in vivo CAR-T development, comparing lentiviral versus mRNA-LNP platforms. Early candidates (ESO-T01, LB2501) show promising efficacy and reduced toxicities, but urgent challenges persist: variable transduction efficiency, vector immunogenicity, off-target risks, and regulatory harmonization. Resolving these hurdles is imperative to translate this paradigm-shifting modality into standard clinical practice.