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

Alsya J Affandi; Joanna Grabowska; Katarzyna Olesek; Miguel Lopez Venegas; Arnaud Barbaria; Ernesto Rodríguez; Patrick P G Mulder; Helen J Pijffers; Martino Ambrosini; Hakan Kalay; Tom O'Toole; Eline S Zwart; Geert Kazemier; Kamran Nazmi; Floris J Bikker; Johannes Stöckl; Alfons J M van den Eertwegh; Tanja D de Gruijl; Gert Storm; Yvette van Kooyk; Joke M M den Haan

doi:10.1073/pnas.2006186117

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

Alsya J Affandi, Joanna Grabowska, Katarzyna Olesek, Miguel Lopez Venegas, Arnaud Barbaria, Ernesto Rodríguez, Patrick P G Mulder, Helen J Pijffers, Martino Ambrosini, Hakan Kalay, Tom O'Toole, Eline S Zwart, Geert Kazemier, Kamran Nazmi, Floris J Bikker, Johannes Stöckl, Alfons J M van den Eertwegh, Tanja D de Gruijl, Gert Storm, Yvette van KooykJoke M M den Haan

Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands.
DC4U, 3621 ZA Breukelen, The Netherlands.
Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam and University of Amsterdam, 1081 LA Amsterdam, The Netherlands.
Institute of Immunology, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands; [email protected].

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	27528-27539
Number of pages	12
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	117
Issue number	44
DOIs	https://doi.org/10.1073/pnas.2006186117
Publication status	Published - 3 Nov 2020

Keywords

Siglec-1
CD169
dendritic cells
CD8+ T cells
vaccination
Gangliosides
Humans
Immunogenicity, Vaccine
Leukocytes, Mononuclear
Liposomes
Macrophages/immunology
Neoplasms/immunology
Primary Cell Culture
Proto-Oncogene Proteins/metabolism
Receptor Protein-Tyrosine Kinases/metabolism
Sialic Acid Binding Ig-like Lectin 1/metabolism
THP-1 Cells
Vaccination/methods
Vaccines, Subunit/administration & dosage

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10.1073/pnas.2006186117

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Affandi, A. J., Grabowska, J., Olesek, K., Lopez Venegas, M., Barbaria, A., Rodríguez, E., Mulder, P. P. G., Pijffers, H. J., Ambrosini, M., Kalay, H., O'Toole, T., Zwart, E. S., Kazemier, G., Nazmi, K., Bikker, F. J., Stöckl, J., van den Eertwegh, A. J. M., de Gruijl, T. D., Storm, G., ... den Haan, J. M. M. (2020). Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes. Proceedings of the National Academy of Sciences of the United States of America, 117(44), 27528-27539. https://doi.org/10.1073/pnas.2006186117

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title = "Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes",

abstract = "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.",

keywords = "Siglec-1, CD169, dendritic cells, CD8+ T cells, vaccination, Gangliosides, Humans, Immunogenicity, Vaccine, Leukocytes, Mononuclear, Liposomes, Macrophages/immunology, Neoplasms/immunology, Primary Cell Culture, Proto-Oncogene Proteins/metabolism, Receptor Protein-Tyrosine Kinases/metabolism, Sialic Acid Binding Ig-like Lectin 1/metabolism, THP-1 Cells, Vaccination/methods, Vaccines, Subunit/administration & dosage",

author = "Affandi, {Alsya J} and Joanna Grabowska and Katarzyna Olesek and {Lopez Venegas}, Miguel and Arnaud Barbaria and Ernesto Rodr{\'i}guez and Mulder, {Patrick P G} and Pijffers, {Helen J} and Martino Ambrosini and Hakan Kalay and Tom O'Toole and Zwart, {Eline S} and Geert Kazemier and Kamran Nazmi and Bikker, {Floris J} and Johannes St{\"o}ckl and {van den Eertwegh}, {Alfons J M} and {de Gruijl}, {Tanja D} and Gert Storm and {van Kooyk}, Yvette and {den Haan}, {Joke M M}",

note = "Copyright {\textcopyright} 2020 the Author(s). Published by PNAS.",

year = "2020",

month = nov,

day = "3",

doi = "10.1073/pnas.2006186117",

language = "English",

volume = "117",

pages = "27528--27539",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "44",

}

Affandi, AJ, Grabowska, J, Olesek, K, Lopez Venegas, M, Barbaria, A, Rodríguez, E, Mulder, PPG, Pijffers, HJ, Ambrosini, M, Kalay, H, O'Toole, T, Zwart, ES, Kazemier, G, Nazmi, K, Bikker, FJ, Stöckl, J, van den Eertwegh, AJM, de Gruijl, TD, Storm, G, van Kooyk, Y & den Haan, JMM 2020, 'Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 44, pp. 27528-27539. https://doi.org/10.1073/pnas.2006186117

Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes. / Affandi, Alsya J; Grabowska, Joanna; Olesek, Katarzyna et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 117, No. 44, 03.11.2020, p. 27528-27539.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes

AU - Affandi, Alsya J

AU - Grabowska, Joanna

AU - Olesek, Katarzyna

AU - Lopez Venegas, Miguel

AU - Barbaria, Arnaud

AU - Rodríguez, Ernesto

AU - Mulder, Patrick P G

AU - Pijffers, Helen J

AU - Ambrosini, Martino

AU - Kalay, Hakan

AU - O'Toole, Tom

AU - Zwart, Eline S

AU - Kazemier, Geert

AU - Nazmi, Kamran

AU - Bikker, Floris J

AU - Stöckl, Johannes

AU - van den Eertwegh, Alfons J M

AU - de Gruijl, Tanja D

AU - Storm, Gert

AU - van Kooyk, Yvette

AU - den Haan, Joke M M

PY - 2020/11/3

Y1 - 2020/11/3

N2 - 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.

AB - 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.

KW - Siglec-1

KW - CD169

KW - dendritic cells

KW - CD8+ T cells

KW - vaccination

KW - Gangliosides

KW - Humans

KW - Immunogenicity, Vaccine

KW - Leukocytes, Mononuclear

KW - Liposomes

KW - Macrophages/immunology

KW - Neoplasms/immunology

KW - Primary Cell Culture

KW - Proto-Oncogene Proteins/metabolism

KW - Receptor Protein-Tyrosine Kinases/metabolism

KW - Sialic Acid Binding Ig-like Lectin 1/metabolism

KW - THP-1 Cells

KW - Vaccination/methods

KW - Vaccines, Subunit/administration & dosage

U2 - 10.1073/pnas.2006186117

DO - 10.1073/pnas.2006186117

M3 - Article

C2 - 33067394

SN - 0027-8424

VL - 117

SP - 27528

EP - 27539

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 44

ER -

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

Abstract

Keywords

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