Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists

Jana De Vrieze; Benoit Louage; Kim Deswarte; Zifu Zhong; Ruben De Coen; Simon Van Herck; Lutz Nuhn; Camilla Kaas Frich; Alexander N. Zelikin; Stefan Lienenklaus; Niek N. Sanders; Bart N. Lambrecht; Sunil A. David; Bruno G. De Geest

doi:10.1002/anie.201905687

Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists

Jana De Vrieze, Benoit Louage, Kim Deswarte, Zifu Zhong, Ruben De Coen, Simon Van Herck, Lutz Nuhn, Camilla Kaas Frich, Alexander N. Zelikin, Stefan Lienenklaus, Niek N. Sanders, Bart N. Lambrecht, Sunil A. David, Bruno G. De Geest^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

51 Citations (Scopus)

Abstract

Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum-protein-binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph-node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.

Original language	English
Journal	Angewandte Chemie - International Edition
Volume	58
Issue	43
Pages (from-to)	15390-15395
Number of pages	6
ISSN	1433-7851
DOIs	https://doi.org/10.1002/anie.201905687
Publication status	Published - Oct 2019

Keywords

immunomodulation
innate immunity
lipid amphiphiles
lymph nodes
polymers

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10.1002/anie.201905687

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De Vrieze, J., Louage, B., Deswarte, K., Zhong, Z., De Coen, R., Van Herck, S., Nuhn, L., Kaas Frich, C., Zelikin, A. N., Lienenklaus, S., Sanders, N. N., Lambrecht, B. N., David, S. A., & De Geest, B. G. (2019). Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists. Angewandte Chemie - International Edition, 58(43), 15390-15395. https://doi.org/10.1002/anie.201905687

@article{f41ae8f34e3f42f1b1be8340b313baef,

title = "Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists",

abstract = "Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum-protein-binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph-node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.",

keywords = "immunomodulation, innate immunity, lipid amphiphiles, lymph nodes, polymers",

author = "{De Vrieze}, Jana and Benoit Louage and Kim Deswarte and Zifu Zhong and {De Coen}, Ruben and {Van Herck}, Simon and Lutz Nuhn and {Kaas Frich}, Camilla and Zelikin, {Alexander N.} and Stefan Lienenklaus and Sanders, {Niek N.} and Lambrecht, {Bart N.} and David, {Sunil A.} and {De Geest}, {Bruno G.}",

year = "2019",

month = oct,

doi = "10.1002/anie.201905687",

language = "English",

volume = "58",

pages = "15390--15395",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley and Sons Ltd",

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}

De Vrieze, J, Louage, B, Deswarte, K, Zhong, Z, De Coen, R, Van Herck, S, Nuhn, L, Kaas Frich, C, Zelikin, AN, Lienenklaus, S, Sanders, NN, Lambrecht, BN, David, SA & De Geest, BG 2019, 'Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists', Angewandte Chemie - International Edition, vol. 58, no. 43, pp. 15390-15395. https://doi.org/10.1002/anie.201905687

Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists. / De Vrieze, Jana; Louage, Benoit; Deswarte, Kim et al.
In: Angewandte Chemie - International Edition, Vol. 58, No. 43, 10.2019, p. 15390-15395.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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AU - De Vrieze, Jana

AU - Louage, Benoit

AU - Deswarte, Kim

AU - Zhong, Zifu

AU - De Coen, Ruben

AU - Van Herck, Simon

AU - Nuhn, Lutz

AU - Kaas Frich, Camilla

AU - Zelikin, Alexander N.

AU - Lienenklaus, Stefan

AU - Sanders, Niek N.

AU - Lambrecht, Bart N.

AU - David, Sunil A.

AU - De Geest, Bruno G.

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N2 - Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum-protein-binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph-node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.

AB - Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes of small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage of the inherent serum-protein-binding property of lipid motifs and their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid–polymer conjugates that suppress systemic inflammation but provoke potent lymph-node immune activation. This work provides a rational basis for the design of lipid–polymer amphiphiles for optimized lymphoid targeting.

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KW - innate immunity

KW - lipid amphiphiles

KW - lymph nodes

KW - polymers

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JO - Angewandte Chemie - International Edition

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Potent Lymphatic Translocation and Spatial Control Over Innate Immune Activation by Polymer–Lipid Amphiphile Conjugates of Small-Molecule TLR7/8 Agonists

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