Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity
Klein K, Johnson L, Rîca R, Sarcevic M, Carta G, Seiser S, Elbe-Bürger A, Langer F, Rahhal N, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. Journal of Investigative Dermatology.
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Author
Klein, Klara;
Johnson, Litty;
Rîca, Ramona;
Sarcevic, Mirza;
Carta, Gabriele;
Seiser, Saskia;
Elbe-Bürger, Adelheid;
Langer, FreyjaISTA;
Rahhal, Nowras;
Rademacher, Christoph;
Wawrzinek, Robert;
Quattrone, Federica
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All
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Abstract
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.
Publishing Year
Date Published
2026-04-07
Journal Title
Journal of Investigative Dermatology
Publisher
Elsevier
Acknowledgement
We thank Mareike Rentzsch for her intellectual contributions during the course of our discussions. We thank Michael Schunn from the Preclinical Facility of the Institute of Science and Technology Austria for his continuous technical support. Guarantor of the work is FS. This project was supported by “Seedfinancing” (P2282679) of the Austrian Federal Ministry of Digital and Economic Affairs and the Ministry of Climate Action and Energy, handled by the Austrian Wirtschaftsservice, as well as by...
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eISSN
IST-REx-ID
Cite this
Klein K, Johnson L, Rîca R, et al. Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. Journal of Investigative Dermatology. doi:10.1016/j.jid.2026.03.026
Klein, K., Johnson, L., Rîca, R., Sarcevic, M., Carta, G., Seiser, S., … Sparber, F. (n.d.). Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. Journal of Investigative Dermatology. Elsevier. https://doi.org/10.1016/j.jid.2026.03.026
Klein, Klara, Litty Johnson, Ramona Rîca, Mirza Sarcevic, Gabriele Carta, Saskia Seiser, Adelheid Elbe-Bürger, et al. “Langerhans Cell–Targeted MRNA Delivery: A Strategy for Dose-Sparing and Enhanced Antitumor Immunity.” Journal of Investigative Dermatology. Elsevier, n.d. https://doi.org/10.1016/j.jid.2026.03.026.
K. Klein et al., “Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity,” Journal of Investigative Dermatology. Elsevier.
Klein K, Johnson L, Rîca R, Sarcevic M, Carta G, Seiser S, Elbe-Bürger A, Langer F, Rahhal N, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor immunity. Journal of Investigative Dermatology.
Klein, Klara, et al. “Langerhans Cell–Targeted MRNA Delivery: A Strategy for Dose-Sparing and Enhanced Antitumor Immunity.” Journal of Investigative Dermatology, Elsevier, doi:10.1016/j.jid.2026.03.026.
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