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Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety. / Van der Jeught, Kevin; De Koker, Stefaan; Bialkowski, Lukasz; Heirman, Carlo; Tjok Joe, Patrick; Perche, Federico; Maenhout, Sarah; Bevers, Sanne; Broos, Katrijn; Deswarte, Kim; Malard, Virginie; Hammad, Hamida; Baril, Patrick; Benvegnu, Thierry; Jaffrès, Paul-Alain; Kooijmans, Sander A A; Schiffelers, Raymond; Lienenklaus, Stefan; Midoux, Patrick; Pichon, Chantal; Breckpot, Karine; Thielemans, Kris.

In: ACS Nano, Vol. 12, No. 10, 01.10.2018, p. 9815-9829.

Research output: Contribution to journalArticleResearchpeer-review

Harvard

Van der Jeught, K, De Koker, S, Bialkowski, L, Heirman, C, Tjok Joe, P, Perche, F, Maenhout, S, Bevers, S, Broos, K, Deswarte, K, Malard, V, Hammad, H, Baril, P, Benvegnu, T, Jaffrès, P-A, Kooijmans, SAA, Schiffelers, R, Lienenklaus, S, Midoux, P, Pichon, C, Breckpot, K & Thielemans, K 2018, 'Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety' ACS Nano, vol. 12, no. 10, pp. 9815-9829. https://doi.org/10.1021/acsnano.8b00966

APA

Vancouver

Author

Van der Jeught, Kevin ; De Koker, Stefaan ; Bialkowski, Lukasz ; Heirman, Carlo ; Tjok Joe, Patrick ; Perche, Federico ; Maenhout, Sarah ; Bevers, Sanne ; Broos, Katrijn ; Deswarte, Kim ; Malard, Virginie ; Hammad, Hamida ; Baril, Patrick ; Benvegnu, Thierry ; Jaffrès, Paul-Alain ; Kooijmans, Sander A A ; Schiffelers, Raymond ; Lienenklaus, Stefan ; Midoux, Patrick ; Pichon, Chantal ; Breckpot, Karine ; Thielemans, Kris. / Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety. In: ACS Nano. 2018 ; Vol. 12, No. 10. pp. 9815-9829.

BibTeX

@article{7083768792c744de96dcdf92ce68a732,
title = "Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety",
abstract = "In vitro transcribed mRNA constitutes a versatile platform to encode antigens and to evoke CD8 T-cell responses. Systemic delivery of mRNA packaged into cationic liposomes (lipoplexes) has proven particularly powerful in achieving effective antitumor immunity in animal models. Yet, T-cell responses to mRNA lipoplexes critically depend on the induction of type I interferons (IFN), potent pro-inflammatory cytokines, which inflict dose-limiting toxicities. Here, we explored an advanced hybrid lipid polymer shell mRNA nanoparticle (lipopolyplex) endowed with a trimannose sugar tree as an alternative delivery vehicle for systemic mRNA vaccination. Like mRNA lipoplexes, mRNA lipopolyplexes were extremely effective in conferring antitumor T-cell immunity upon systemic administration. Conversely to mRNA lipoplexes, mRNA lipopolyplexes did not rely on type I IFN for effective T-cell immunity. This differential mode of action of mRNA lipopolyplexes enabled the incorporation of N1 methyl pseudouridine nucleoside modified mRNA to reduce inflammatory responses without hampering T-cell immunity. This feature was attributed to mRNA lipopolyplexes, as the incorporation of thus modified mRNA into lipoplexes resulted in strongly weakened T-cell immunity. Taken together, we have identified lipopolyplexes containing N1 methyl pseudouridine nucleoside modified mRNA as potent yet low-inflammatory alternatives to the mRNA lipoplexes currently explored in early phase clinical trials.",
keywords = "cancer therapy, lipopolyplexes, modified nucleosides, mRNA, T cell, type I interferon",
author = "{Van der Jeught}, Kevin and {De Koker}, Stefaan and Lukasz Bialkowski and Carlo Heirman and {Tjok Joe}, Patrick and Federico Perche and Sarah Maenhout and Sanne Bevers and Katrijn Broos and Kim Deswarte and Virginie Malard and Hamida Hammad and Patrick Baril and Thierry Benvegnu and Paul-Alain Jaffr{\`e}s and Kooijmans, {Sander A A} and Raymond Schiffelers and Stefan Lienenklaus and Patrick Midoux and Chantal Pichon and Karine Breckpot and Kris Thielemans",
year = "2018",
month = "10",
day = "1",
doi = "10.1021/acsnano.8b00966",
language = "English",
volume = "12",
pages = "9815--9829",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Dendritic Cell Targeting mRNA Lipopolyplexes Combine Strong Antitumor T-Cell Immunity with Improved Inflammatory Safety

AU - Van der Jeught, Kevin

AU - De Koker, Stefaan

AU - Bialkowski, Lukasz

AU - Heirman, Carlo

AU - Tjok Joe, Patrick

AU - Perche, Federico

AU - Maenhout, Sarah

AU - Bevers, Sanne

AU - Broos, Katrijn

AU - Deswarte, Kim

AU - Malard, Virginie

AU - Hammad, Hamida

AU - Baril, Patrick

AU - Benvegnu, Thierry

AU - Jaffrès, Paul-Alain

AU - Kooijmans, Sander A A

AU - Schiffelers, Raymond

AU - Lienenklaus, Stefan

AU - Midoux, Patrick

AU - Pichon, Chantal

AU - Breckpot, Karine

AU - Thielemans, Kris

PY - 2018/10/1

Y1 - 2018/10/1

N2 - In vitro transcribed mRNA constitutes a versatile platform to encode antigens and to evoke CD8 T-cell responses. Systemic delivery of mRNA packaged into cationic liposomes (lipoplexes) has proven particularly powerful in achieving effective antitumor immunity in animal models. Yet, T-cell responses to mRNA lipoplexes critically depend on the induction of type I interferons (IFN), potent pro-inflammatory cytokines, which inflict dose-limiting toxicities. Here, we explored an advanced hybrid lipid polymer shell mRNA nanoparticle (lipopolyplex) endowed with a trimannose sugar tree as an alternative delivery vehicle for systemic mRNA vaccination. Like mRNA lipoplexes, mRNA lipopolyplexes were extremely effective in conferring antitumor T-cell immunity upon systemic administration. Conversely to mRNA lipoplexes, mRNA lipopolyplexes did not rely on type I IFN for effective T-cell immunity. This differential mode of action of mRNA lipopolyplexes enabled the incorporation of N1 methyl pseudouridine nucleoside modified mRNA to reduce inflammatory responses without hampering T-cell immunity. This feature was attributed to mRNA lipopolyplexes, as the incorporation of thus modified mRNA into lipoplexes resulted in strongly weakened T-cell immunity. Taken together, we have identified lipopolyplexes containing N1 methyl pseudouridine nucleoside modified mRNA as potent yet low-inflammatory alternatives to the mRNA lipoplexes currently explored in early phase clinical trials.

AB - In vitro transcribed mRNA constitutes a versatile platform to encode antigens and to evoke CD8 T-cell responses. Systemic delivery of mRNA packaged into cationic liposomes (lipoplexes) has proven particularly powerful in achieving effective antitumor immunity in animal models. Yet, T-cell responses to mRNA lipoplexes critically depend on the induction of type I interferons (IFN), potent pro-inflammatory cytokines, which inflict dose-limiting toxicities. Here, we explored an advanced hybrid lipid polymer shell mRNA nanoparticle (lipopolyplex) endowed with a trimannose sugar tree as an alternative delivery vehicle for systemic mRNA vaccination. Like mRNA lipoplexes, mRNA lipopolyplexes were extremely effective in conferring antitumor T-cell immunity upon systemic administration. Conversely to mRNA lipoplexes, mRNA lipopolyplexes did not rely on type I IFN for effective T-cell immunity. This differential mode of action of mRNA lipopolyplexes enabled the incorporation of N1 methyl pseudouridine nucleoside modified mRNA to reduce inflammatory responses without hampering T-cell immunity. This feature was attributed to mRNA lipopolyplexes, as the incorporation of thus modified mRNA into lipoplexes resulted in strongly weakened T-cell immunity. Taken together, we have identified lipopolyplexes containing N1 methyl pseudouridine nucleoside modified mRNA as potent yet low-inflammatory alternatives to the mRNA lipoplexes currently explored in early phase clinical trials.

KW - cancer therapy

KW - lipopolyplexes

KW - modified nucleosides

KW - mRNA

KW - T cell

KW - type I interferon

UR - http://www.scopus.com/inward/record.url?scp=85054377308&partnerID=8YFLogxK

U2 - 10.1021/acsnano.8b00966

DO - 10.1021/acsnano.8b00966

M3 - Article

VL - 12

SP - 9815

EP - 9829

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 10

ER -

ID: 40493019