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Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes

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. Gangliosid...

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Autores principales: Affandi, Alsya J., Grabowska, Joanna, Olesek, Katarzyna, Lopez Venegas, Miguel, Barbaria, Arnaud, Rodríguez, Ernesto, Mulder, Patrick P. G., Pijffers, Helen J., Ambrosini, Martino, Kalay, Hakan, O’Toole, Tom, Zwart, Eline S., Kazemier, Geert, Nazmi, Kamran, Bikker, Floris J., Stöckl, Johannes, van den Eertwegh, Alfons J. M., de Gruijl, Tanja D., Storm, Gert, van Kooyk, Yvette, den Haan, Joke M. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959579/
https://www.ncbi.nlm.nih.gov/pubmed/33067394
http://dx.doi.org/10.1073/pnas.2006186117
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author Affandi, Alsya J.
Grabowska, Joanna
Olesek, Katarzyna
Lopez Venegas, Miguel
Barbaria, Arnaud
Rodríguez, Ernesto
Mulder, Patrick P. G.
Pijffers, Helen J.
Ambrosini, Martino
Kalay, Hakan
O’Toole, Tom
Zwart, Eline S.
Kazemier, Geert
Nazmi, Kamran
Bikker, Floris J.
Stöckl, Johannes
van den Eertwegh, Alfons J. M.
de Gruijl, Tanja D.
Storm, Gert
van Kooyk, Yvette
den Haan, Joke M. M.
author_facet Affandi, Alsya J.
Grabowska, Joanna
Olesek, Katarzyna
Lopez Venegas, Miguel
Barbaria, Arnaud
Rodríguez, Ernesto
Mulder, Patrick P. G.
Pijffers, Helen J.
Ambrosini, Martino
Kalay, Hakan
O’Toole, Tom
Zwart, Eline S.
Kazemier, Geert
Nazmi, Kamran
Bikker, Floris J.
Stöckl, Johannes
van den Eertwegh, Alfons J. M.
de Gruijl, Tanja D.
Storm, Gert
van Kooyk, Yvette
den Haan, Joke M. M.
author_sort Affandi, Alsya J.
collection PubMed
description 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.
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spelling pubmed-79595792021-03-22 Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes Affandi, Alsya J. Grabowska, Joanna Olesek, Katarzyna Lopez Venegas, Miguel Barbaria, Arnaud Rodríguez, Ernesto Mulder, Patrick P. G. Pijffers, Helen J. Ambrosini, Martino Kalay, Hakan O’Toole, Tom Zwart, Eline S. Kazemier, Geert Nazmi, Kamran Bikker, Floris J. Stöckl, Johannes van den Eertwegh, Alfons J. M. de Gruijl, Tanja D. Storm, Gert van Kooyk, Yvette den Haan, Joke M. M. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-11-03 2020-10-16 /pmc/articles/PMC7959579/ /pubmed/33067394 http://dx.doi.org/10.1073/pnas.2006186117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Affandi, Alsya J.
Grabowska, Joanna
Olesek, Katarzyna
Lopez Venegas, Miguel
Barbaria, Arnaud
Rodríguez, Ernesto
Mulder, Patrick P. G.
Pijffers, Helen J.
Ambrosini, Martino
Kalay, Hakan
O’Toole, Tom
Zwart, Eline S.
Kazemier, Geert
Nazmi, Kamran
Bikker, Floris J.
Stöckl, Johannes
van den Eertwegh, Alfons J. M.
de Gruijl, Tanja D.
Storm, Gert
van Kooyk, Yvette
den Haan, Joke M. M.
Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes
title Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes
title_full Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes
title_fullStr Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes
title_full_unstemmed Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes
title_short Selective tumor antigen vaccine delivery to human CD169(+) antigen-presenting cells using ganglioside-liposomes
title_sort selective tumor antigen vaccine delivery to human cd169(+) antigen-presenting cells using ganglioside-liposomes
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959579/
https://www.ncbi.nlm.nih.gov/pubmed/33067394
http://dx.doi.org/10.1073/pnas.2006186117
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