Promises and potential pitfalls of in vivo CAR gene therapy

ABSTRACT: Genetically modified T cells expressing chimeric antigen receptors (CARs) manufactured ex vivo have demonstrated high efficacy in patients with lymphoid hematologic malignancies, but their logistic complexity limits patient access. In vivo approaches generate the CAR-expressing T cells within the body but may have their own challenges. Recent clinical reports provide proof of concept for the feasibility and therapeutic potential of in vivo CAR gene delivery. We summarize clinical evidence and discuss the critical technical, biological, and safety considerations of this approach.