Glycan-modified melanoma-derived apoptotic extracellular vesicles as antigen source for anti-tumor vaccination
| Autor: | Sandra J. van Vliet, Sophie A. Dusoswa, Juan J. Garcia-Vallejo, Rienk Nieuwland, Dorian A. Stolk, Rieneke van de Ven, Sanne Duinkerken, Arjan A. van de Loosdrecht, Bert van het Hof, Sophie K. Horrevorts, Myrthe Hulst, Yvette van Kooyk, Marieke H. Heineke, Wenbin Ma, Tanja D. de Gruijl |
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| Přispěvatelé: | CCA - Cancer biology and immunology, ACS - Microcirculation, Laboratory Specialized Diagnostics & Research, AII - Cancer immunology, Molecular cell biology and Immunology, Otolaryngology / Head & Neck Surgery, Neurosurgery, Hematology, Medical oncology laboratory, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research dendritic cell medicine.medical_treatment T cell Priming (immunology) Major histocompatibility complex 03 medical and health sciences 0302 clinical medicine Antigen medicine glycan modification biology Chemistry Immunotherapy Dendritic cell apoptotic extracellular vesicles Immune checkpoint 3. Good health Cell biology T cell priming C-type lectin 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis biology.protein cancer vaccine CD8 |
| Zdroj: | Cancers, 11(9):1266. Multidisciplinary Digital Publishing Institute (MDPI) Horrevorts, S K, Stolk, D A, van de Ven, R, Hulst, M, van Het Hof, B, Duinkerken, S, Heineke, M H, Ma, W, Dusoswa, S A, Nieuwland, R, Garcia-Vallejo, J J, van de Loosdrecht, A A, de Gruijl, T D, van Vliet, S J & van Kooyk, Y 2019, ' Glycan-modified melanoma-derived apoptotic extracellular vesicles as antigen source for anti-tumor vaccination ', Cancers, vol. 11, no. 9, 1266 . https://doi.org/10.3390/cancers11091266 Cancers Volume 11 Issue 9 |
| ISSN: | 2072-6694 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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