Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity Klein, Klara Johnson, Litty Rîca, Ramona Sarcevic, Mirza Carta, Gabriele Seiser, Saskia Elbe-Bürger, Adelheid Langer, Freyja Rahhal, Nowras Rademacher, Christoph Wawrzinek, Robert Quattrone, Federica Sparber, Florian Despite the success of mRNA therapeutics, challenges remain in optimizing immune responses and minimizing side effects. Cell-specific antigen delivery may help reduce required doses and improve vaccine efficacy. In this study, we report on a targeted delivery system for mRNA to a specific subset of skin-resident antigen-presenting cells: Langerhans cells. By functionalizing lipid nanoparticles with a langerin-specific glycomimetic ligand, we achieve selective mRNA delivery to both murine and human primary Langerhans cells with minimal off-target uptake, at the same time resulting in significantly increased mRNA translation. This targeted mRNA delivery not only enhances antigen presentation and T-cell responses but also enables dose-sparing and superior antitumor immunity compared with conventional immunization in a B16-OVA tumor model. Importantly, our platform’s high compatibility with various lipid nanoparticle formulations offers a flexible and precise tool for skin-directed mRNA delivery. Elsevier 2026 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/21848 Klein K, Johnson L, Rîca R, et al. Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. <i>Journal of Investigative Dermatology</i>. doi:<a href="https://doi.org/10.1016/j.jid.2026.03.026">10.1016/j.jid.2026.03.026</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jid.2026.03.026 info:eu-repo/semantics/altIdentifier/issn/0022-202X info:eu-repo/semantics/altIdentifier/e-issn/1523-1747 info:eu-repo/semantics/openAccess