Details

Autor(en) / Beteiligte

• Metzloff, Ann E.
• 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.

Titel

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

Ist Teil von

• Advanced materials (Weinheim), 2024-06, Vol.36 (26), p.e2313226-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2024

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. Activating lipid nanoparticles (aLNPs) combine the antigen presenting cell‐mimetic character of commonly used T cell activating beads with the mRNA transfecting capabilities of LNPs. aLNPs facilitate rapid, one‐step activation and transfection of primary human T cells with chimeric antigen receptor (CAR) mRNA without requiring activating beads, potentially reducing the complexity, cost, and time of mRNA CAR T cell production.