Lipid Nanoparticle‐mRNA Engineered Dendritic Cell Based Adoptive Cell Therapy Enhances Cancer Immune Response

Abstract: Lipid nanoparticles encapsulating mRNA (LNP‐mRNA) revolutionized medicine over the past several years. While clinically approved indications currently focus on infectious disease vaccination, LNP‐mRNA based treatments also hold promise for cancer immunotherapy. However, the route of dosing may impact treatment efficacy, safety, and dose. To minimize adverse effects, it is hypothesized that LNP‐mRNA can be used to activate and engineer dendritic cells (DC) ex vivo before re‐administration of these cells. Here, it is shown that LNP‐mRNA engineered DCs can indeed vaccinate recipient mice. Vaccinated mice showed strong anti‐tumor T cell responses, rejected tumor challenge, and displayed no evidence of toxicity. Further, it is found that DC specific ablation of the immune activating kinase NFkB inducing kinase (NIK) abrogated vaccination efficacy, demonstrating that adoptively transferred DCs can be functionally modified in addition to their antigen presentation capacity. Collectively, these studies show that ex vivo LNP‐mRNA engineering of DCs is a feasible and robust therapeutic strategy for cancer.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Lipid Nanoparticle‐mRNA Engineered Dendritic Cell Based Adoptive Cell Therapy Enhances Cancer Immune Response ; day:23 ; month:07 ; year:2024 ; extent:9
Small Methods ; (23.07.2024) (gesamt 9)

Urheber
Das, Riddha
Ge, Xinying
Fei, Fan
Parvanian, Sepideh
Weissleder, Ralph
Garris, Christopher S.

DOI
10.1002/smtd.202400633
URN
urn:nbn:de:101:1-2407231429586.413460566148
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:59 MESZ

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Beteiligte

  • Das, Riddha
  • Ge, Xinying
  • Fei, Fan
  • Parvanian, Sepideh
  • Weissleder, Ralph
  • Garris, Christopher S.

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