Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy

Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy

© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 26 vom: 28. Juni, Seite e2313226
1. Verfasser: Metzloff, Ann E (VerfasserIn)
Weitere Verfasser: Padilla, Marshall S, Gong, Ningqiang, Billingsley, Margaret M, Han, Xuexiang, Merolle, Maria, Mai, David, Figueroa-Espada, Christian G, Thatte, Ajay S, Haley, Rebecca M, Mukalel, Alvin J, Hamilton, Alex G, Alameh, Mohamad-Gabriel, Weissman, Drew, Sheppard, Neil C, June, Carl H, Mitchell, Michael J
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CAR T cells biomimicry cancer immunotherapy lipid nanoparticles mRNA Receptors, Chimeric Antigen RNA, Messenger Lipid Nanoparticles Lipids Liposomes
Beschreibung
Zusammenfassung:© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.
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
Beschreibung:Date Completed 26.06.2024
Date Revised 22.07.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202313226