TY - JOUR
T1 - A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting
AU - Wamhoff, Eike-Christian
AU - Schulze, Jessica
AU - Bellmann, Lydia
AU - Rentzsch, Mareike
AU - Bachem, Gunnar
AU - Fuchsberger, Felix F.
AU - Rademacher, Juliane
AU - Hermann, Martin
AU - del Frari, Barbara
AU - van Dalen, Rob
AU - Hartmann, David
AU - van Sorge, Nina M.
AU - Seitz, Oliver
AU - Stoitzner, Patrizia
AU - Rademacher, Christoph
PY - 2019/5/22
Y1 - 2019/5/22
N2 - 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 and structural characterization by NMR spectroscopy and molecular docking. The conjugation of this glycomimetic to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. We further demonstrate the doxorubicin-mediated killing of a Langerin+ monocyte cell line, highlighting its therapeutic and diagnostic potential in Langerhans cell histiocytosis, caused by the abnormal proliferation of Langerin+ myeloid progenitor cells. Overall, our delivery platform provides superior versatility over antibody-based approaches and novel modalities to overcome current limitations of dendritic cell-targeted immuno- and chemotherapy.
AB - 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 and structural characterization by NMR spectroscopy and molecular docking. The conjugation of this glycomimetic to liposomes enabled the specific and efficient targeting of Langerhans cells in the human skin. We further demonstrate the doxorubicin-mediated killing of a Langerin+ monocyte cell line, highlighting its therapeutic and diagnostic potential in Langerhans cell histiocytosis, caused by the abnormal proliferation of Langerin+ myeloid progenitor cells. Overall, our delivery platform provides superior versatility over antibody-based approaches and novel modalities to overcome current limitations of dendritic cell-targeted immuno- and chemotherapy.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066129689&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31139717
U2 - https://doi.org/10.1021/acscentsci.9b00093
DO - https://doi.org/10.1021/acscentsci.9b00093
M3 - Article
C2 - 31139717
SN - 2374-7943
VL - 5
SP - 808
EP - 820
JO - ACS central science
JF - ACS central science
IS - 5
ER -