Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes
Menée à l'aide de lignées cellulaires et d'échantillons sanguins de patients atteints d'un cancer gastro-intestinal ou d'un mélanome métastatique, cette étude met en évidence l'intérêt thérapeutique d'un vaccin à base de liposomes contenant des antigènes tumoraux et présentant à leur surface des gangliosides ciblant l'antigène CD169 des cellules présentatrices de l'antigène
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.Priming of CD8+ T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+ antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+ CD169+ monocytes and Axl+ CD169+ DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+ moDCs and Axl+ CD169+ DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+ T cells. Finally, Axl+ CD169+ DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+ DCs to drive antitumor T cell responses.All study data are included in the article and supporting information.