Synergizing artificial intelligence with in vivo CAR-T cell generation: A new paradigm for democratized immunotherapy

In vivo CAR-T cell generation represents a paradigm shift in immunotherapy by transitioning the production of chimeric antigen receptor (CAR) T cells from external laboratories to the patient's own body. This innovative approach addresses the key limitations of conventional ex vivo CAR-T therapy, including prolonged manufacturing timelines, high costs, and restricted accessibility. The successful realization of this internalized manufacturing process is critically enabled by two interdependent pillars: advanced delivery platforms (viral vectors and non-viral lipid nanoparticle [LNP]-mRNA systems) and artificial intelligence (AI). AI acts as a transformative catalyst, accelerating the rational design of CAR constructs, optimizing the precision of targeted delivery systems, and enabling predictive safety modelling. Early clinical trials in oncology and autoimmune diseases provide compelling proof-of-concept, underscoring the potential of in vivo CAR-T strategies to substantially improve access and streamline treatment delivery. This review examines the mechanisms, comparative benefits, clinical progress, and future challenges of in vivo CAR-T generation, with a dedicated focus on the synergistic role of AI in shaping the next generation of safe, scalable, and intelligent cell-based immunotherapies.