2025-06-13 マサチューセッツ工科大学（MIT）
＜関連情報＞
- https://news.mit.edu/2026/new-approach-cancer-vaccination-yields-more-powerful-t-cells-0513
- https://www.nature.com/articles/s41587-026-03115-2
IRF8またはNIKを発現する免疫リモデリングmRNAは、複数の癌モデルにおいて持続的な抗腫瘍免疫を誘導する Immune-remodeling mRNAs expressing IRF8 or NIK generate durable antitumor immunity in multiple cancer models
A. Gupta,R. Das,K. Reed,T. Jeon,Q. T. C. Nguyen,A. Rudra,X. Ge,S. Trongjit,Y. S. Vanrobaeys,R. Langer,R. Weissleder,C. Garris & D. G. Anderson
Nature Biotechnology Published:13 May 2026
DOI:https://doi.org/10.1038/s41587-026-03115-2
Abstract
Although immunotherapy has benefited a subset of persons with cancer, its broader efficacy remains limited, primarily because of an immunosuppressive tumor microenvironment characterized by insufficient numbers of functional tumor-specific T cells, antigen-presenting cells (APCs) and tumor-infiltrating lymphocytes. Here we engineer immune cells in the tumor microenvironment using lipid nanoparticles (LNPs) to deliver immune-remodeling mRNAs (IR-mRNAs) encoding NF-κB-inducing kinase or interferon regulatory factor 8. These IR-mRNAs activate APCs in tumors, significantly increasing activated type 1 conventional dendritic cells, immunostimulatory cytokines and priming antitumor CD8+ T cells. IR-mRNAs encapsulated in LNPs elicited durable antitumor responses in multiple syngeneic mouse tumor models through both intratumoral and intravenous delivery. Coadministration of IR-mRNA and ovalbumin mRNA elicited a ~10-fold increase in antigen-specific CD8+ T cell responses, sustained long-term memory and effectively prevented tumor growth in vaccinated mice. Additionally, coadministration of IR-mRNA and hemagglutinin mRNA enhanced the humoral response ~5-fold and the cellular response ~15-fold, underscoring their potential as adjuvants for boosting adaptive immunity.
