Glycan-Modified Melanoma-Derived Apoptotic 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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Veröffentlicht in:Cancers Jg. 11; H. 9
Hauptverfasser: Horrevorts, Sophie K, Stolk, Dorian A, Ven, Rieneke van de, Hulst, Myrthe, Hof, Bert van Het, Duinkerken, Sanne, Heineke, Marieke H, Ma, Wenbin, Dusoswa, Sophie A, Nieuwland, Rienk, Garcia-Vallejo, Juan J, Loosdrecht, Arjan A van de, de Gruijl, Tanja D, Vliet, Sandra J van, van Kooyk, Yvette
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland 01.09.2019
Schlagworte:
T cell priming
cancer vaccine
glycan modification
dendritic cell
apoptotic extracellular vesicles
C-type lectin
ISSN:2072-6694, 2072-6694
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Abstract 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.
AbstractList 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.
Author Vliet, Sandra J van
de Gruijl, Tanja D
Hof, Bert van Het
van Kooyk, Yvette
Ven, Rieneke van de
Heineke, Marieke H
Horrevorts, Sophie K
Garcia-Vallejo, Juan J
Nieuwland, Rienk
Duinkerken, Sanne
Ma, Wenbin
Stolk, Dorian A
Loosdrecht, Arjan A van de
Hulst, Myrthe
Dusoswa, Sophie A
Author_xml – sequence: 1
  givenname: Sophie K
  surname: Horrevorts
  fullname: Horrevorts, Sophie K
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 2
  givenname: Dorian A
  surname: Stolk
  fullname: Stolk, Dorian A
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 3
  givenname: Rieneke van de
  surname: Ven
  fullname: Ven, Rieneke van de
  organization: Department of Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 4
  givenname: Myrthe
  surname: Hulst
  fullname: Hulst, Myrthe
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 5
  givenname: Bert van Het
  surname: Hof
  fullname: Hof, Bert van Het
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 6
  givenname: Sanne
  surname: Duinkerken
  fullname: Duinkerken, Sanne
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 7
  givenname: Marieke H
  surname: Heineke
  fullname: Heineke, Marieke H
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 8
  givenname: Wenbin
  surname: Ma
  fullname: Ma, Wenbin
  organization: De Duve Institute, Université Catholique de Louvain, B-1200 Brussels, Belgium
– sequence: 9
  givenname: Sophie A
  surname: Dusoswa
  fullname: Dusoswa, Sophie A
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 10
  givenname: Rienk
  surname: Nieuwland
  fullname: Nieuwland, Rienk
  organization: Laboratory of Experimental Clinical Chemistry, and Vesicle Observation Centre, Amsterdam UMC, Academic Medical Centre, 1081 HV Amsterdam, The Netherlands
– sequence: 11
  givenname: Juan J
  surname: Garcia-Vallejo
  fullname: Garcia-Vallejo, Juan J
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 12
  givenname: Arjan A van de
  surname: Loosdrecht
  fullname: Loosdrecht, Arjan A van de
  organization: Department of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 13
  givenname: Tanja D
  surname: de Gruijl
  fullname: de Gruijl, Tanja D
  organization: Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 14
  givenname: Sandra J van
  surname: Vliet
  fullname: Vliet, Sandra J van
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
– sequence: 15
  givenname: Yvette
  surname: van Kooyk
  fullname: van Kooyk, Yvette
  email: y.vankooyk@amsterdamumc.nl
  organization: Department of Molecular Cell Biology and Immunology, Amsterdam Infection and Immunity Institute, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands. y.vankooyk@amsterdamumc.nl
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Keywords T cell priming
cancer vaccine
glycan modification
dendritic cell
apoptotic extracellular vesicles
C-type lectin
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Snippet 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...
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