Glycan modification of the tumor antigen gp100 targets DC‐SIGN to enhance dendritic cell induced antigen presentation to T cells

• Published in: International journal of cancer 2008-02, Vol.122 (4), p.839-846
• Main Authors: Aarnoudse, Corlien A., Bax, Marieke, Sánchez‐Hernández, Marta, García‐Vallejo, Juan J., van Kooyk, Yvette
• Format: Article
• Language: English
• Subjects: Antigen Presentation; Antineoplastic agents; Biological and medical sciences; Blotting, Western; CD4-Positive T-Lymphocytes - immunology; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell Communication; C‐type lectins; DC‐SIGN; dendritc cell targeting; dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Enzyme-Linked Immunosorbent Assay; glycans; gp100 Melanoma Antigen; Humans; Immunotherapy; Lectins, C-Type - immunology; Lectins, C-Type - metabolism; Lymphocyte Activation; Mannose - metabolism; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Monocytes - cytology; Monocytes - metabolism; Neoplasms - immunology; Neoplasms - metabolism; Pharmacology. Drug treatments; Polysaccharides - pharmacology; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23101

Dendritic cells (DC) have gained much interest in the field of anticancer vaccine development because of their central function in immune regulation. However, the clinical application of ex vivo cultured DC has significant disadvantages. A vaccine that targets dendritic cells in vivo and enhances antigen presentation would be of great benefit. Because of its DC‐restricted expression pattern, and its function as an antigen uptake receptor, DC‐SIGN is an interesting candidate target structure for human immature DC. Here, we studied whether modification of the melanoma differentiation antigen gp100 with DC‐SIGN‐interacting glycans enhances targeting to human DC. A high‐mannose form of gp100, as protein or as tumor lysate, not only interacted specifically with DC through DC‐SIGN but also resulted in an enhanced antigen presentation to gp100‐specific CD4+ T cells. Our results indicate that glycan modification of tumor antigens to target C‐type lectin receptors, such as DC‐SIGN, is a new way to develop in vivo targeting DC strategies that simultaneously enhance the induction of tumor‐specific T cells. © 2007 Wiley‐Liss, Inc.