1. Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy.
- Author
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Metzloff AE, Padilla MS, Gong N, Billingsley MM, Han X, Merolle M, Mai D, Figueroa-Espada CG, Thatte AS, Haley RM, Mukalel AJ, Hamilton AG, Alameh MG, Weissman D, Sheppard NC, June CH, and Mitchell MJ
- Subjects
- Humans, Animals, Mice, Neoplasms therapy, Neoplasms immunology, Immunotherapy methods, Cell Line, Tumor, Lipids chemistry, Transfection methods, Liposomes, Nanoparticles chemistry, Receptors, Chimeric Antigen, Antigen-Presenting Cells immunology, Immunotherapy, Adoptive methods, T-Lymphocytes immunology, RNA, Messenger genetics, RNA, Messenger metabolism
- Abstract
Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in the treatment of hematological malignancies. However, producing these bespoke cancer-killing cells is a complicated ex vivo process involving leukapheresis, artificial T cell activation, and CAR construct introduction. The activation step requires the engagement of CD3/TCR and CD28 and is vital for T cell transfection and differentiation. Though antigen-presenting cells (APCs) facilitate activation in vivo, ex vivo activation relies on antibodies against CD3 and CD28 conjugated to magnetic beads. While effective, this artificial activation adds to the complexity of CAR T cell production as the beads must be removed prior to clinical implementation. To overcome this challenge, this work develops activating lipid nanoparticles (aLNPs) that mimic APCs to combine the activation of magnetic beads and the transfection capabilities of LNPs. It is shown that aLNPs enable one-step activation and transfection of primary human T cells with the resulting mRNA CAR T cells reducing tumor burden in a murine xenograft model, validating aLNPs as a promising platform for the rapid production of mRNA CAR T cells., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)
- Published
- 2024
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