Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response

Rica R, Klein K, Johnson L, Carta G, Sarcevic M, Langer F, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. Molecular Therapy.

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Author
Rica, Ramona; Klein, Klara; Johnson, Litty; Carta, Gabriele; Sarcevic, Mirza; Langer, FreyjaISTA; Rademacher, Christoph; Wawrzinek, Robert; Quattrone, Federica; Sparber, Florian
Abstract
Targeted antigen delivery to immune cells, particularly dendritic cells, has emerged as a promising strategy to enhance therapeutic efficacy of vaccines, while minimizing adverse effects associated with conventional immunization. In this study, we use our previously described small glycomimetic molecule that is selectively recognized by the Langerhans cell (LC)-specific surface receptor Langerin and demonstrate specific delivery of protein antigens to these specialized dendritic cells. Our results show that Langerin-mediated antigen delivery significantly enhances the immune response in vivo, resulting in increased expansion and activation of antigen-specific T cells, compared to immunization with unmodified antigen. We demonstrate the feasibility of our LC-targeted platform for immune cell-specific immunization with protein antigen and underscore the potential of LCs as an access point for next-generation vaccines and immunotherapies.
Publishing Year
Date Published
2025-10-04
Journal Title
Molecular Therapy
Publisher
Elsevier
Acknowledgement
This project was generously supported by Seedfinancing (grant no. P2282679) of the Austrian Bundesministerium für Digitalisierung und Wirtschaftsstandort and the Bundesministerium für Klimaschutz, Umwelt, Energie, Mobilität, Innovation, und Technologie, handled by the Austrian Wirtschaftsservice (aws), as well as by Life Science Call 2022 (grant no. FO999896442) of the Austrian Research Promotion Agency (FFG). We thank Mag. Michael Schunn from the PCF of the Institute of Science and Technology Austria for his continuous technical support.
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eISSN
IST-REx-ID

Cite this

Rica R, Klein K, Johnson L, et al. Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. Molecular Therapy. doi:10.1016/j.ymthe.2025.10.008
Rica, R., Klein, K., Johnson, L., Carta, G., Sarcevic, M., Langer, F., … Sparber, F. (n.d.). Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. Molecular Therapy. Elsevier. https://doi.org/10.1016/j.ymthe.2025.10.008
Rica, Ramona, Klara Klein, Litty Johnson, Gabriele Carta, Mirza Sarcevic, Freyja Langer, Christoph Rademacher, Robert Wawrzinek, Federica Quattrone, and Florian Sparber. “Langerhans Cell-Targeted Protein Delivery Enhances Antigen-Specific Cellular Immune Response.” Molecular Therapy. Elsevier, n.d. https://doi.org/10.1016/j.ymthe.2025.10.008.
R. Rica et al., “Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response,” Molecular Therapy. Elsevier.
Rica R, Klein K, Johnson L, Carta G, Sarcevic M, Langer F, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans cell-targeted protein delivery enhances antigen-specific cellular immune response. Molecular Therapy.
Rica, Ramona, et al. “Langerhans Cell-Targeted Protein Delivery Enhances Antigen-Specific Cellular Immune Response.” Molecular Therapy, Elsevier, doi:10.1016/j.ymthe.2025.10.008.
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