CMC considerations on <i>in vivo</i> CAR-T

“In the rapidly evolving landscape of in vivo CAR-T cell therapies, viral-based approaches, such as those utilizing lentiviral vectors, offer robust integration and persistent CAR expression... Ex vivo CAR-T therapy requires weeks of manufacturing and release testing, resulting in high costs and prolonged vein-to-vein times. In vivo CAR-T eliminates patient-specific processing, making scalable vector production and CMC maturity the key bottleneck. Non-viral mRNA-LNP systems enable rapid, vaccine-like, fully synthetic manufacturing at commercial scale with lower costs, simpler QC, and enhanced safety due to transient expression without genomic integration. In contrast, lentiviral vectors provide durable CAR expression but face complex, expensive production, limited scalability, and extensive safety testing for replication-competent virus and insertional mutagenesis. Non-viral mRNA-LNP platforms currently offer superior manufacturability and faster clinical translation, while viral systems remain preferred when long-term efficacy is essential.