In Vivo Engineered CAR-T Cell Therapy: Lessons Built from COVID-19 mRNA Vaccines.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized cancer immunotherapy but continues to face significant challenges that limit its broader application, such as antigen targeting, the tumor microenvironment, and cell persistence, especially in solid tumors. Meanwhile, the global implementation of mRNA vaccines during the COVID-19 pandemic has highlighted the transformative potential of mRNA and lipid nanoparticle (LNP) technologies. These innovations, characterized by their swift development timelines, precise antigen design, and efficient delivery mechanisms, provide a promising framework to address some limitations of CAR-T therapy. Recent advancements, including mRNA-based CAR engineering and optimized LNP delivery, have demonstrated the capacity to enhance CAR-T efficacy, particularly in the context of solid tumors. This review explores how mRNA-LNP technology can drive the development of in vivo engineered CAR-T therapies to address current limitations and discusses future directions, including advancements in mRNA design, LNP optimization, and strategies for improving in vivo CAR-T functionality and safety. By bridging these technological insights, CAR-T therapy may evolve into a versatile and accessible treatment paradigm across diverse oncological landscapes.