Rewiring immunity with in vivo CAR T cell engineering

Ex vivo engineered chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of certain hematologic malignancies, yet manufacturing complexities and limited patient accessibility constrain its impact. In vivo CAR T cell engineering seeks to overcome these limitations by generating CAR T cells directly within an individual. This Perspective examines the rapidly evolving field of in vivo CAR T cell generation in oncology, outlines principles of lymphocyte targeting, discusses pharmacology and biodistribution and assesses emerging safety issues. We conclude with a translational outlook, highlighting both the opportunities and the outstanding questions that will define the path to clinical implementation.