Glycan-modified melanoma-derived apoptotic extracellular vesicles as antigen source for anti-tumor vaccination

Sophie K. Horrevorts, Dorian A. Stolk, Rieneke van de Ven, Myrthe Hulst, Bert van Het Hof, Sanne Duinkerken, Marieke H. Heineke, Wenbin Ma, Sophie A. Dusoswa, Rienk Nieuwland, Juan J. Garcia-Vallejo, Arjan A. van de Loosdrecht, Tanja D. de Gruijl, Sandra J. van Vliet, Yvette van Kooyk

Research output: Contribution to journalArticleAcademicpeer-review


Tumors that lack T cell infiltration are less likely to respond to immune checkpoint inhibition and could benefit from cancer vaccination for the initiation of anti-tumor T cell responses. An attractive vaccine strategy is in vivo targeting of dendritic cells (DCs), key initiators of antigen-specific T cell responses. In this study we generated tumor-derived apoptotic extracellular vesicles (ApoEVs), which are potentially an abundant source of tumor-specific neo-antigens and other tumor-associated antigens (TAAs), and which can be manipulated to express DC-targeting ligands for efficient antigen delivery. Our data demonstrates that by specifically modifying the glycocalyx of tumor cells, high-mannose glycans can be expressed on their cell surface and on extracellular vesicles derived after the induction of apoptosis. High-mannose glycans are the natural ligands of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a dendritic cell associated C-type lectin receptor (CLR), which has the ability to efficiently internalize its cargo and direct it to both major histocompatibility complex (MHC)-I and MHC-II pathways for the induction of CD8+ and CD4+ T cell responses, respectively. Compared to unmodified ApoEVs, ApoEVs carrying DC-SIGN ligands are internalized to a higher extent, resulting in enhanced priming of tumor-specific CD8+ T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer.
Original languageEnglish
Article number1266
Issue number9
Publication statusPublished - 1 Sep 2019

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