# Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8+ T cells Article · Gold MJ, Millar DG, Liu J, Menon H, Karpov Y, Olsen K, Oliveira LT, Dubé C, Tran CW, Elford AR, Schwartz JA, Gopalakrishna Panicker RK, Marcusson EG, Ohashi PS, Martin Orozco N - Archive id: doi:10.1016/j.omtn.2026.103076 - Published: 2026-08-27 - Venue: Molecular therapy. Nucleic acids - DOI: https://doi.org/10.1016/j.omtn.2026.103076 - PMID: 42774904 - PMCID: PMC13594926 - Citations: 0 - Source URL: https://doi.org/10.1016/j.omtn.2026.103076 - PDF: https://europepmc.org/articles/PMC13594926/pdf - Provenance: europepmc ## Abstract mRNA based vaccines utilizing lipid-based delivery systems have been used for cancer therapy with some success targeting tumor-associated antigens (TAAs) or neoantigens. However, in many patients, T cell exhaustion or tumor suppression impedes the induction of a protective anti-tumor T cell response, which suggests that additional activation signals are required to reduce antagonistic tumor effects and reinvigorate the T cells. Here we sought to evaluate novel ionizable lipids for lipid nanoparticle (LNP)-formulations containing a tumor antigen mRNA as a therapeutic treatment for solid tumors and identify key immunogenic features of successful ionizable lipid candidates. Focusing on the induction of a tissue-destructive immune response became the ideal in vivo screening to compare two novel ionizable lipids, INTENT-1 and INTENT-2. Both LNPs carrying the same mRNA- encoded antigen induced similar CD8 + T cell responses, but only INTENT-2.1 LNPs could cause tissue destruction. Mechanism-of-action studies revealed that INTENT-2.1, but not INTENT-1.1 LNP, induced type I interferons independently of the mRNA to enhance anti-tissue CD8 + T cell responses. These results demonstrate the efficacy of INTENT-2.1 LNP for cancer vaccines, shed light on its mechanism of action, and support its use in clinical trials to treat solid tumors. _Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._ Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines) Cited in dossiers: - [mRNA Therapeutics & Cancer Vaccines: State of the Field (October 2026)](https://space-kitty.com/dossiers/mrna-cancer-vaccines) --- Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.