Selective tumor antigen vaccine delivery to human CD169 <sup>+</sup> antigen-presenting cells using ganglioside-liposomes
Alsya J. Affandi, Joanna Grabowska, Katarzyna Olesek, Miguel Lopez Venegas, Arnaud Barbaria, Ernesto Rodríguez, Patrick P. G. Mulder, Helen J. Pijffers, Martino Ambrosini, Hakan Kalay, Tom O’Toole, Eline S. Zwart, Geert Kazemier, Kamran Nazmi, Floris J. Bikker, Johannes Stöckl, Alfons J.M. van den Eertwegh, Tanja D. de Gruijl, Gert Storm, Yvette van Kooyk, Joke M. M. den Haan
Abstract
Significance Current immunotherapies only benefit a minority of all cancer patients, so it is necessary to develop other strategies to boost patients’ antitumor CD8 + T cell responses. Here, we formulated a liposomal vaccine carrier that selectively delivers tumor antigens and Toll-like receptor agonists to human CD169/Siglec-1 + antigen-presenting cells (APCs) through the incorporation of gangliosides that are natural ligands of CD169. This liposomal vaccine binds to a variety of human CD169 + APCs, including monocyte-derived dendritic cells (moDCs) and the recently described Axl + DCs. Uptake of the vaccine results in robust cross-presentation and activation of tumor antigen-specific CD8 + T cells. Our findings demonstrate a unique vaccination platform by targeting human CD169 + DCs to stimulate antitumor T cell responses.