{"id":"doi:10.1016/j.omtn.2026.103076","kind":"article","title":"Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8<sup>+</sup> T cells","authors":["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"],"author_count":15,"year":2026,"published":"2026-08-27","venue":"Molecular therapy. Nucleic acids","cited_by":0,"doi":"10.1016/j.omtn.2026.103076","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.omtn.2026.103076","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.omtn.2026.103076","updated":null,"pmid":"42774904","pmcid":"PMC13594926","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13594926/pdf","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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Novel lipid nanoparticle in a mRNA cancer vaccine drives tumor control via type I IFNs and effector CD8<sup>+</sup> T cells\" by Gold MJ, Millar DG, Liu J et al., https://doi.org/10.1016/j.omtn.2026.103076, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[{"slug":"mrna-cancer-vaccines","title":"mRNA Therapeutics & Cancer Vaccines: State of the Field (October 2026)","url":"https://space-kitty.com/dossiers/mrna-cancer-vaccines"}]}