Harnessing pre-existing measles immunity: mRNA-Lipid nanoparticle-mediated measles hemagglutinin expression boosts antitumor CD8⁺ T cell responsesDownload PDF Download PDF LetterOpen accessPublished: 04 May 2026Javier Martínez-Latorre ORCID: orcid.org/0000-0001-5421-53711,2,3 na1,Paula M. Soriano-Teruel1,2,3,4 na1,Vicente Candela-Noguera1,2,3,Rita C. Acúrcio5,Helena F. Florindo ORCID: orcid.org/0000-0002-4006-58405,Alba García-Fernández1,2,3,4 &…Ramón Martínez-Máñez ORCID: orcid.org/0000-0001-5873-96741,2,3,4 Signal Transduction and Targeted Therapy volume 11, Article number: 164 (2026) Cite this articleSubjectsGene deliveryTumour immunologyDear Editor,Cancer immunotherapy has revolutionized oncology by leveraging immune mechanisms to eliminate tumors. However, many cancers evade immune detection due to the absence of recognizable antigens, limiting the efficacy of current therapies.1 Redirecting pre-existing antiviral immunity toward tumors by introducing exogenous viral antigens offers a promising solution. Here, we present a novel clinically translatable approach that uses lipid nanoparticles (LNPs) to deliver mRNA encoding the measles virus hemagglutinin (H) protein directly into tumors (Fig. 1a). Prior approaches have largely relied on antibody-recruiting molecules or the delivery of defined viral peptides, thereby engaging only limited immune pathways.2 In contrast, inducing de novo expression of a full-length viral surface antigen on tumor cells enables activation of both humoral and cellular immunity through recruitment of pre-existing antibodies and presentation of multiple epitopes to CD8⁺ T cells. Compared with other viral antigens explored in mRNA–LNP-based strategies, such as the SARS-CoV-2 spike protein,3,4 measles H provides a distinct translational advantage due to the high durability and near ubiquity of measles immunity,5 supporting a robust and broadly applicable approach for redirecting antiviral immune memory toward cancer. Together, this work introduces a previously unexplored and clinically relevant framework that combines LNP-mediated mRNA delivery with a highly conserved viral antigen to broadly redirect antiviral immunity toward cancer.Fig. 1The alternative text for this image may have been generated using AI.Full size imageExpression of measles hemagglutinin via mRNA–LNP induces a potent CD8⁺ antitumor response in a melanoma model. a Illustration of the LNP H strategy and in vivo validation of LNP-mediated expression. Tumor cells are treated with lipid nanoparticles (LNPs) containing mRNA encoding the measles virus hemagglutinin (H) protein. Expression of H protein in cancer cells promotes immune recruitment, particularly of measles-specific CD8⁺ cytotoxic T lymphocytes, leading to tumor cell death. Bioluminescence images of B16-BL6 tumor-bearing mice at 6, 12, 24, and 48 h after intratumoral administration of LNP Luc confirm effective LNP-mediated expression at the tumor site. b LNP-mediated tumor expression of H protein drives a therapeutic response in vaccinated mice. Tumor volume progression in B16-BL6 tumors after the first intratumoral treatment (n ≥ 19). Since no therapeutic effect was observed in non-vaccinated mice regardless of treatment (NV–Vehicle, NV–LNP Luc, and NV–LNP H), we used NV–LNP H as the representative non-vaccinated control group in the current study for clarity. Tumor growth in these groups was similar to that in the vaccinated vehicle group (V–Vehicle), indicating that vaccination alone does not influence tumor growth. The vaccinated V-LNP H group exhibited significantly reduced tumor growth, whereas no effect was observed in the control groups. Statistical analysis was performed using two-way ordinary ANOVA followed by Tukey’s multiple comparison test. c LNP H treatment drives tumor cell apoptosis and a marked shift in the CD8⁺:CD4⁺ ratio. Percentage of TUNEL-positive cells in tumors (left axis, n ≥ 4 per group) and tumor-infiltrating CD8⁺:CD4⁺ ratio (right axis, n ≥ 4). Statistical analysis was performed using the Kruskal-Wallis test followed by Dunn’s multiple comparison test (TUNEL⁺ cells) and one-way ordinary ANOVA followed by Tukey’s multiple comparison test (CD8⁺:CD4⁺ ratio). Significance is shown relative to the V–LNP H group. d LNP H elicits effective antitumor activity through cytotoxic T lymphocytes. Ex vivo immune cell killing assay showing the activation of isolated splenocytes from treated mice measured via CD107b after stimulation with 16 μg/mL H protein for 5 days and co-culture with B16-BL6 cells treated with LNP H for 18 h (left axis, n = 6) and the cytotoxic activity of these splenocytes against B16-BL6 LNP H–treated cells (right axis, n = 6). Statistical analysis was performed using one-way ordinary ANOVA followed by Tukey’s multiple comparison test. Significance is shown relative to the V–LNP H group. In all subfigures, data are presented as the mean ± SEM (*p