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A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist

A single-protein or -peptide vaccine is not sufficient to arouse immune responses in cancer therapy. A whole-tumor-cell vaccine with complete cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this s...

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Autores principales: Chi, Huju, Hao, Yue, Wang, Xia, Tang, Li, Deng, Yongqiang, Chen, Xianxiong, Gao, Feng, Sha, Ou, Jin, Guangyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266217/
https://www.ncbi.nlm.nih.gov/pubmed/35805071
http://dx.doi.org/10.3390/cells11131986
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author Chi, Huju
Hao, Yue
Wang, Xia
Tang, Li
Deng, Yongqiang
Chen, Xianxiong
Gao, Feng
Sha, Ou
Jin, Guangyi
author_facet Chi, Huju
Hao, Yue
Wang, Xia
Tang, Li
Deng, Yongqiang
Chen, Xianxiong
Gao, Feng
Sha, Ou
Jin, Guangyi
author_sort Chi, Huju
collection PubMed
description A single-protein or -peptide vaccine is not sufficient to arouse immune responses in cancer therapy. A whole-tumor-cell vaccine with complete cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this study, we used 5-azacitidine to stimulate B16-F10 melanoma cells to express toll-like receptor (TLR) 3 on the cell surface and then chemically linked SZU-106, a small-molecule TLR7 agonist, to the cell surface with a pegylated linker to produce a novel whole-tumor-cell vaccine, abbreviated as Aza-BFcell-106. The vaccine stimulated mouse splenic lymphocytes and bone marrow-derived dendritic cells to secrete cytokines, promoted the maturation of dendritic cells and enhanced the capability of dendritic cells to present antigens. In a mouse model of melanoma, the vaccine effectively inhibited tumor growth, decreased tumor volume and prolonged survival. Further combination of the vaccine with a chemokine inhibitor, reparixin, significantly increased the infiltration of CD4+ and CD8+ T cells into the tumor environment, while the antitumor effect was significantly enhanced. The whole-tumor-cell vaccine Aza-BFcell-106 induced immune-activating responses in both in vitro and in vivo experiments, indicating that this vaccine has great potential to treat advanced malignant tumors.
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spelling pubmed-92662172022-07-09 A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist Chi, Huju Hao, Yue Wang, Xia Tang, Li Deng, Yongqiang Chen, Xianxiong Gao, Feng Sha, Ou Jin, Guangyi Cells Article A single-protein or -peptide vaccine is not sufficient to arouse immune responses in cancer therapy. A whole-tumor-cell vaccine with complete cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this study, we used 5-azacitidine to stimulate B16-F10 melanoma cells to express toll-like receptor (TLR) 3 on the cell surface and then chemically linked SZU-106, a small-molecule TLR7 agonist, to the cell surface with a pegylated linker to produce a novel whole-tumor-cell vaccine, abbreviated as Aza-BFcell-106. The vaccine stimulated mouse splenic lymphocytes and bone marrow-derived dendritic cells to secrete cytokines, promoted the maturation of dendritic cells and enhanced the capability of dendritic cells to present antigens. In a mouse model of melanoma, the vaccine effectively inhibited tumor growth, decreased tumor volume and prolonged survival. Further combination of the vaccine with a chemokine inhibitor, reparixin, significantly increased the infiltration of CD4+ and CD8+ T cells into the tumor environment, while the antitumor effect was significantly enhanced. The whole-tumor-cell vaccine Aza-BFcell-106 induced immune-activating responses in both in vitro and in vivo experiments, indicating that this vaccine has great potential to treat advanced malignant tumors. MDPI 2022-06-21 /pmc/articles/PMC9266217/ /pubmed/35805071 http://dx.doi.org/10.3390/cells11131986 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chi, Huju
Hao, Yue
Wang, Xia
Tang, Li
Deng, Yongqiang
Chen, Xianxiong
Gao, Feng
Sha, Ou
Jin, Guangyi
A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist
title A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist
title_full A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist
title_fullStr A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist
title_full_unstemmed A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist
title_short A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist
title_sort therapeutic whole-tumor-cell vaccine covalently conjugated with a tlr7 agonist
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266217/
https://www.ncbi.nlm.nih.gov/pubmed/35805071
http://dx.doi.org/10.3390/cells11131986
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