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Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant

BACKGROUND: Human Papillomavirus is responsible for over 99 % of cervical cancers and is associated with cancers of the head and neck. The currently available prophylactic vaccines against HPV do not generate therapeutic effects against established HPV infections and associated lesions and disease....

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Autores principales: Yang, Ming-Chieh, Yang, Andrew, Qiu, Jin, Yang, Benjamin, He, Liangmei, Tsai, Ya-Chea, Jeang, Jessica, Wu, T.-C., Hung, Chien-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778350/
https://www.ncbi.nlm.nih.gov/pubmed/26949512
http://dx.doi.org/10.1186/s13578-016-0083-9
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author Yang, Ming-Chieh
Yang, Andrew
Qiu, Jin
Yang, Benjamin
He, Liangmei
Tsai, Ya-Chea
Jeang, Jessica
Wu, T.-C.
Hung, Chien-Fu
author_facet Yang, Ming-Chieh
Yang, Andrew
Qiu, Jin
Yang, Benjamin
He, Liangmei
Tsai, Ya-Chea
Jeang, Jessica
Wu, T.-C.
Hung, Chien-Fu
author_sort Yang, Ming-Chieh
collection PubMed
description BACKGROUND: Human Papillomavirus is responsible for over 99 % of cervical cancers and is associated with cancers of the head and neck. The currently available prophylactic vaccines against HPV do not generate therapeutic effects against established HPV infections and associated lesions and disease. Thus, the need for a therapeutic vaccine capable of treating HPV-induced malignancies persists. Synthetic long peptides vaccination is a popular antigen delivery method because of its safety, stability, production feasibility, and its need to be processed by professional antigen presenting cells before it can be presented to cytotoxic CD8+ T lymphocytes. Cancers in the buccal mucosa have been shown to elicit cancer-related inflammations that are capable of recruiting inflammatory and immune cells to generate antitumor effects. In the current study, we evaluated the therapeutic potential of synthetic HPV long peptide vaccination in the absence of adjuvant in the TC-1 buccal tumor model. RESULT: We show that intratumoral vaccination with E7 long peptide alone effectively controls buccal TC-1 tumors in mice. Furthermore, we observed an increase in systemic as well as local E7-specific CD8+ T cells in buccal tumor-bearing mice following the vaccination. Finally, we show that induction of immune responses against buccal tumors by intratumoral E7 long peptide vaccination is independent of CD4+ T cells, and that the phenomenon may be related to the unique environment associated with mucosal tissues. CONCLUSION: Our results suggest the possibility for clinical translation of the administration of adjuvant free therapeutic long peptide vaccine as a potentially effective and safe strategy for mucosal HPV-associated tumor treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13578-016-0083-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-47783502016-03-05 Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant Yang, Ming-Chieh Yang, Andrew Qiu, Jin Yang, Benjamin He, Liangmei Tsai, Ya-Chea Jeang, Jessica Wu, T.-C. Hung, Chien-Fu Cell Biosci Research BACKGROUND: Human Papillomavirus is responsible for over 99 % of cervical cancers and is associated with cancers of the head and neck. The currently available prophylactic vaccines against HPV do not generate therapeutic effects against established HPV infections and associated lesions and disease. Thus, the need for a therapeutic vaccine capable of treating HPV-induced malignancies persists. Synthetic long peptides vaccination is a popular antigen delivery method because of its safety, stability, production feasibility, and its need to be processed by professional antigen presenting cells before it can be presented to cytotoxic CD8+ T lymphocytes. Cancers in the buccal mucosa have been shown to elicit cancer-related inflammations that are capable of recruiting inflammatory and immune cells to generate antitumor effects. In the current study, we evaluated the therapeutic potential of synthetic HPV long peptide vaccination in the absence of adjuvant in the TC-1 buccal tumor model. RESULT: We show that intratumoral vaccination with E7 long peptide alone effectively controls buccal TC-1 tumors in mice. Furthermore, we observed an increase in systemic as well as local E7-specific CD8+ T cells in buccal tumor-bearing mice following the vaccination. Finally, we show that induction of immune responses against buccal tumors by intratumoral E7 long peptide vaccination is independent of CD4+ T cells, and that the phenomenon may be related to the unique environment associated with mucosal tissues. CONCLUSION: Our results suggest the possibility for clinical translation of the administration of adjuvant free therapeutic long peptide vaccine as a potentially effective and safe strategy for mucosal HPV-associated tumor treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13578-016-0083-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-03 /pmc/articles/PMC4778350/ /pubmed/26949512 http://dx.doi.org/10.1186/s13578-016-0083-9 Text en © Yang et al. 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
Yang, Ming-Chieh
Yang, Andrew
Qiu, Jin
Yang, Benjamin
He, Liangmei
Tsai, Ya-Chea
Jeang, Jessica
Wu, T.-C.
Hung, Chien-Fu
Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant
title Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant
title_full Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant
title_fullStr Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant
title_full_unstemmed Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant
title_short Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant
title_sort buccal injection of synthetic hpv long peptide vaccine induces local and systemic antigen-specific cd8+ t-cell immune responses and antitumor effects without adjuvant
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778350/
https://www.ncbi.nlm.nih.gov/pubmed/26949512
http://dx.doi.org/10.1186/s13578-016-0083-9
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