biostudies-literatureDas RCSB Development FundNational Cancer InstituteKarin Grunebaum Cancer Research FoundationNCI NIH HHSe2400633https://www.ebi.ac.uk/biostudies/studies/S-EPMC11740962biostudies-literatureUnknown9(1)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 NFkBSmall methodsLipid Nanoparticle-mRNA Engineered Dendritic Cell Based Adoptive Cell Therapy Enhances Cancer Immune Response.PMC11740962T32 CA079443T32CA079443R33 CA277820Parvanian SDas RGarris CSWeissleder RGe XFei FfalseLipid Nanoparticle-mRNA Engineered Dendritic Cell Based Adoptive Cell Therapy Enhances Cancer Immune Response.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 NFkB2025-01-01T00:00:00Z2025 Jan2026-06-06T07:38:26.238Z2026-05-27T03:11:46.525ZS-EPMC117409623903999510.1002/smtd.202400633