Glycan modification of the tumor antigen gp100 targets DC-SIGN to enhance dendritic cell induced antigen presentation to T cells.
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.
Aarnoudse
Corlien A
CA
Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands.
Bax
Marieke
M
Sánchez-Hernández
Marta
M
García-Vallejo
Juan J
JJ
van Kooyk
Yvette
Y
D017951:Antigen Presentation; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008358:Mannose / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008358:Mannose; D008562:Membrane Glycoproteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D058951:gp100 Melanoma Antigen; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C548637:PMEL protein, human