CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity.

Autor: Ye T; Department of Pharmaceutics, Ghent University, Ghent, Belgium., Zhong Z; Department of Pharmaceutics, Ghent University, Ghent, Belgium., Cappellesso F; Lab of Cellular and Molecular Immunology, Brussel Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium., Deswarte K; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium., Chen Y; Department of Pharmaceutics, Ghent University, Ghent, Belgium., Lauwers H; Department of Pharmaceutics, Ghent University, Ghent, Belgium., De Lombaerde E; Department of Pharmaceutics, Ghent University, Ghent, Belgium., Gontsarik M; Department of Pharmaceutics, Ghent University, Ghent, Belgium., Lienenklaus S; Institute of Laboratory Animal Science, Hannover Medical School, Hannover, Germany., Van Lysebetten D; Department of Pharmaceutics, Ghent University, Ghent, Belgium., Sanders NN; Laboratory of Gene Therapy, Department of Veterinary and Biosciences, Ghent University, Merelbeke, Belgium., Lambrecht BN; Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands., De Koker S; etherna, Niel, Belgium., Laoui D; Lab of Cellular and Molecular Immunology, Brussel Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Lab of Dendritic Cell Biology and Cancer Immunotherapy, VIB Center for Inflammation Research, Brussels, Belgium. Electronic address: dlaoui@vub.be., De Geest BG; Department of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: br.degeest@ugent.be.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2024 Dec; Vol. 311, pp. 122693. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1016/j.biomaterials.2024.122693
Abstrakt: Cancer vaccines aim at generating cytotoxic CD8 + T cells that kill cancer cells and confer durable tumor regression. Hereto, CD8 + peptide epitopes should be presented by antigen presenting cells to CD8 + T cells in lymphoid tissue. Unfortunately, in unformulated soluble form, peptide antigens are poorly taken up by antigen presenting cells and do not efficiently reach lymph nodes. Hence, the lack of efficient delivery remains a major limitation for successful clinical translation of cancer vaccination using peptide antigens. Here we propose a generic peptide nanoformulation strategy by extending the amino acid sequence of the peptide antigen epitope with 10 glutamic acid residues. The resulting overall anionic charge of the peptide allows encapsulation into lipid nanoparticles (peptide-LNP) by electrostatic interaction with an ionizable cationic lipid. We demonstrate that intravenous injection of peptide-LNP efficiently delivers the peptide to immune cells in the spleen. Peptide-LNP that co-encapsulate an imidazoquinoline TLR7/8 agonist (IMDQ) induce robust innate immune activation in a broad range of immune cell subsets in the spleen. Peptide-LNP containing the minimal CD8 + T cell epitope of the HPV type 16 E7 oncoprotein and IMDQ induces high levels of antigen-specific CD8 + T cells in the blood, and can confer protective immunity against E7-expressing tumors in both prophylactic and therapeutic settings.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bruno De Geest and Yong Chen have patent #WO2022136641A1 licensed to etherna. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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