CD169/Sialoadhesin-expressing macrophages are present in lymphoid organs at the site of antigen entrance and are essential in the activation of innate as well as adaptive immune responses. Our aim is to target tumor antigens to these CD169+ macrophages for the activation of anti-cancer immune responses and have investigated two approaches.
First, using antiCD169 antibody-antigen conjugates we have shown that CD169+ macrophages present antigen to B cells and stimulate strong germinal center B cell and antibody responses. Furthermore, antigens targeted to CD169+ macrophages were transferred to cross-presenting dendritic cells and this led to strong cytotoxic and helper T cell responses. Both (melanoma) peptide as well as protein antigen targeting to CD169 resulted in strong primary and recall immune responses and protective immunity against melanoma outgrowth in mice.
Second, we used liposomes containing CD169-binding ganglioside ligands to target antigens to CD169+ antigen presenting cells in mice and man. These liposomes specifically bound to CD169+ macrophages in mice and led to B and T cell responses against antigen present in the liposome. In addition, CD169 ligand-containing liposomes bound to human monocyte-derived dendritic cells and peripheral blood CD169+ dendritic cells and will be further evaluated for their capacity to stimulate T cell responses.
In conclusion, different approaches to target tumor antigens to CD169+ antigen presenting cells demonstrate a strong capacity to stimulate immune responses and should be further explored as a vaccination strategy for cancer.
Biography Joke den Haan
Joke den Haan received her PhD in 1997 at the University in Leiden with a thesis titled ‘Identification of human minor histocompatibility antigens’. Next she performed a post-doc in the lab of Prof.dr. Mike Bevan at the University of Washington from 1998 till 2003 in which she investigated the cross-presentation capacities of different types of murine splenic dendritic cells. She started her own group in 2004 at the department of Molecular Cell Biology and Immunology at the VU University Medical Center. Her research focuses on the function of different macrophages and dendritic cells and aims to utilize this knowledge to develop vaccines that stimulate anti-cancer immune responses.