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A specific, glycomimetic Langerin ligand for human Langerhans cell targeting

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Wamhoff,  Eike-Christian
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Schulze,  Jessica
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Fuchsberger,  Felix F.
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

Rademacher,  Juliane
Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

Hartmann,  David
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Rademacher,  Christoph
Christoph Rademacher, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Wamhoff, E.-C., Schulze, J., Bellmann, L., Bachem, G., Fuchsberger, F. F., Rademacher, J., et al. (2018). A specific, glycomimetic Langerin ligand for human Langerhans cell targeting. bioRxiv.


Cite as: http://hdl.handle.net/21.11116/0000-0001-AAB5-3
Abstract
Langerhans cells are a subset of dendritic cells residing in the epidermis of the human skin. As such, they are key mediators of immune regulation and have emerged as prime targets for novel transcutaneous cancer vaccines. Importantly, 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 (CD207), an endocytic C-type lectin receptor. Here, we report the discovery of a specific, glycomimetic Langerin ligand employing a heparin-inspired design strategy that integrated NMR spectroscopy and molecular docking. The conjugation of these glycomimetics to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. This delivery platform provides superior versatility and scalability over antibody-based approaches and thus addresses current limitations of dendritic cell-based immunotherapies.