mRNA lipid nanoparticles in CAR-T therapy: a novel strategy to improve efficacy

Abstract Chimeric antigen receptor T cells (CAR-T) immunotherapy has achieved remarkable progress in the treatment of hematological malignancies. However, it encounters challenges including complex manufacturing processes, high cost, and safety issues. Lipid nanoparticle (LNP) technology, as an advanced gene delivery platform, offers significant advancements to CAR-T therapy through its high efficiency, low immunogenicity, and safety. LNP enable in vivo production of CAR-T cells, thereby improving delivery efficiency, reducing the risks of immunogenicity and insertional mutations, simplifying the production process and reducing costs. The scalability and rapid optimization ability of LNP position them as promising candidates for CAR-T cell production. LNP technology is expected to further promote the development of CAR-T immunotherapy and provide safer and more economical treatment options. Therefore, this paper aims to provide a comprehensive and systematic review of the application of LNP in CAR-T therapy. In this review, we initially outline the fundamental design, process, and current challenges of CAR-T therapy. Subsequently, we present the characteristics of LNP, their advantages as a gene delivery vectors, and how they improve the efficacy of CAR-T therapy. Finally, we summarize the current research landscape of LNP applications in CAR-T therapy. This includes enhancing in vitro transfection of T cells, programming T cells in situ , facilitating T-cell activation, alleviating the side effects of CAR-T therapy, and combining CAR-T therapy with other immunotherapies. These advancements will aid in the design of mRNA delivery systems based on LNP, thereby promoting the development of CAR-T therapy.