A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting

Langerhans cells are a subset of dendritic cells residing in the epidermis of the human skin. They mediate immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. The induction of protective T cell immunity by these vaccines requires the efficient and specific delivery of both tumor-associated antigens and adjuvants. Langerhans cells uniquely express Langerin, an endocytic C-type lectin receptor. An heparin-inspired strategy comforted by structural characterization by NMR spectroscopy and molecular docking yield the discovery of a specific glycomimetic Langerin ligand. The conjugation of this glycomimetic to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. The doxorubicin-mediated killing of a Langerin+ monocyte cell line was further demonstrated. This result highlights the therapeutic and diagnostic potential in Langerhans cell histiocytosis, caused by the abnormal proliferation of Langerin+ myeloid progenitor cells. This delivery platform provides superior versatility over antibody-based approaches and novel modalities to overcome current limitations of dendritic cell-targeted Immuno- and chemotherapy.