Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination
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-specifi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/9/1266 |
| _version_ | 1797711406956544000 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sophie K. Horrevorts |
| collection | DOAJ |
| description | 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 apoptotic tumor cell-derived 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<sup>+</sup> and CD4<sup>+</sup> 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<sup>+</sup> T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer. |
| first_indexed | 2024-03-12T07:06:37Z |
| format | Article |
| id | doaj.art-e2594e8dfa1c426ca3484fdcd933343d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:06:37Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e2594e8dfa1c426ca3484fdcd933343d2023-09-02T23:25:05ZengMDPI AGCancers2072-66942019-08-01119126610.3390/cancers11091266cancers11091266Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor VaccinationSophie K. Horrevorts0Dorian A. Stolk1Rieneke van de Ven2Myrthe Hulst3Bert van Het Hof4Sanne Duinkerken5Marieke H. Heineke6Wenbin Ma7Sophie A. Dusoswa8Rienk Nieuwland9Juan J. Garcia-Vallejo10Arjan A. van de Loosdrecht11Tanja D. de Gruijl12Sandra J. van Vliet13Yvette van Kooyk14Amsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsLudwig Institute for Cancer Research, B-1200 Brussels, BelgiumAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Laboratory of Experimental Clinical Chemistry, and Vesicle Observation Centre, Academic Medical Centre, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Hematology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Medical Oncology, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsAmsterdam UMC, Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The NetherlandsTumors 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 apoptotic tumor cell-derived 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<sup>+</sup> and CD4<sup>+</sup> 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<sup>+</sup> T cells. This approach thus presents a promising vaccination strategy in support of T cell-based immunotherapy of cancer.https://www.mdpi.com/2072-6694/11/9/1266dendritic cellapoptotic extracellular vesiclesT cell primingcancer vaccineglycan modificationC-type lectin |
| spellingShingle | 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 Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination Cancers dendritic cell apoptotic extracellular vesicles T cell priming cancer vaccine glycan modification C-type lectin |
| title | Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination |
| title_full | Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination |
| title_fullStr | Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination |
| title_full_unstemmed | Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination |
| title_short | Glycan-Modified Apoptotic Melanoma-Derived Extracellular Vesicles as Antigen Source for Anti-Tumor Vaccination |
| title_sort | glycan modified apoptotic melanoma derived extracellular vesicles as antigen source for anti tumor vaccination |
| topic | dendritic cell apoptotic extracellular vesicles T cell priming cancer vaccine glycan modification C-type lectin |
| url | https://www.mdpi.com/2072-6694/11/9/1266 |
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