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An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model
BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22–24 months. Some immunoth...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037582/ https://www.ncbi.nlm.nih.gov/pubmed/27669687 http://dx.doi.org/10.1186/s12865-016-0172-x |
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author | Ju, Huanyu Xing, Wenjing Yang, Jinfeng Zheng, Yang Jia, Xiuzhi Zhang, Benning Ren, Huan |
author_facet | Ju, Huanyu Xing, Wenjing Yang, Jinfeng Zheng, Yang Jia, Xiuzhi Zhang, Benning Ren, Huan |
author_sort | Ju, Huanyu |
collection | PubMed |
description | BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22–24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy. METHODS: In this study, the experiments were designed including prevention and therapeutic stages in order to attain effect against tumor recurrence in clinical settings. The anti-tumor efficacy of a novel cytokine adjuvant vaccine that contained cytokines GM-CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse tumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the expression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow cytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and the lactic dehydrogenates (LDH) release assays. IFN-γ, IL-2 and GM-CSF secretion in serum was assayed by ELISA. RESULTS: Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended the survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were significantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells play a key role in anti-tumor response. CONCLUSIONS: The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response and represented a promising immunotherapeutic approach for patients with colon cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-016-0172-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5037582 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50375822016-10-05 An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model Ju, Huanyu Xing, Wenjing Yang, Jinfeng Zheng, Yang Jia, Xiuzhi Zhang, Benning Ren, Huan BMC Immunol Research Article BACKGROUND: Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22–24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy. METHODS: In this study, the experiments were designed including prevention and therapeutic stages in order to attain effect against tumor recurrence in clinical settings. The anti-tumor efficacy of a novel cytokine adjuvant vaccine that contained cytokines GM-CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse tumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the expression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow cytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and the lactic dehydrogenates (LDH) release assays. IFN-γ, IL-2 and GM-CSF secretion in serum was assayed by ELISA. RESULTS: Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended the survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were significantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells play a key role in anti-tumor response. CONCLUSIONS: The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response and represented a promising immunotherapeutic approach for patients with colon cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-016-0172-x) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-26 /pmc/articles/PMC5037582/ /pubmed/27669687 http://dx.doi.org/10.1186/s12865-016-0172-x Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Ju, Huanyu Xing, Wenjing Yang, Jinfeng Zheng, Yang Jia, Xiuzhi Zhang, Benning Ren, Huan An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model |
title | An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model |
title_full | An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model |
title_fullStr | An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model |
title_full_unstemmed | An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model |
title_short | An effective cytokine adjuvant vaccine induces autologous T-cell response against colon cancer in an animal model |
title_sort | effective cytokine adjuvant vaccine induces autologous t-cell response against colon cancer in an animal model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037582/ https://www.ncbi.nlm.nih.gov/pubmed/27669687 http://dx.doi.org/10.1186/s12865-016-0172-x |
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