Antigen-specific T cell immunotherapy by in vivo mRNA delivery
Year: 2024
Type: preprint
Abstract: Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by in vivo mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis. In mouse models of type 1 diabetes and multiple myeloma, APNs selectively deplete autoreactive T cells leading to durable control of glycemia, and engineer virus-specific T cells with anti-cancer chimeric antigen receptors (CARs), achieving comparable therapeutic outcome as virally transduced ex vivo CAR. Overall, our work supports the use of APNs to engineer disease-relevant T cells in vivo as Ag-specific immunotherapy for autoimmune disorders and cancer.
Authors: Fang-Yi Su, Jamison C. Siebart, Ching S. Chan, Matthew Y. Wang, Xinyi Yao, Aaron Silva Trenkle, Avanti Sivakumar, Melanie Su, Rustin Harandi, Neha Shahrawat, Chi H. Nguyen, Anshika Goenka, Jinhee Mun, Madhav V. Dhodapkar, Gabriel A. Kwong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4404010388