Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.

INTRODUCTION: Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these...

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Main Authors: Wen-Fang Cheng, Ming-Cheng Chang, Wei-Zen Sun, Yu-Wei Jen, Chao-Wei Liao, Yun-Yuan Chen, Chi-An Chen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3772923?pdf=render
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author Wen-Fang Cheng
Ming-Cheng Chang
Wei-Zen Sun
Yu-Wei Jen
Chao-Wei Liao
Yun-Yuan Chen
Chi-An Chen
author_facet Wen-Fang Cheng
Ming-Cheng Chang
Wei-Zen Sun
Yu-Wei Jen
Chao-Wei Liao
Yun-Yuan Chen
Chi-An Chen
author_sort Wen-Fang Cheng
collection DOAJ
description INTRODUCTION: Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. MATERIALS AND METHODS: In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. RESULTS: PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone. CONCLUSION: Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies.
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spelling doaj.art-97a3dda06b3a473ca728f11b7161a1cc2022-12-21T17:17:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7121610.1371/journal.pone.0071216Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.Wen-Fang ChengMing-Cheng ChangWei-Zen SunYu-Wei JenChao-Wei LiaoYun-Yuan ChenChi-An ChenINTRODUCTION: Human papillomavirus (HPV) has been consistently implicated in causing several kinds of malignancies, and two HPV oncogenes, E6 and E7, represent two potential target antigens for cancer vaccines. We developed two fusion protein vaccines, PE(ΔIII)/E6 and PE(ΔIII)/E7 by targeting these two tumor antigens to test whether a combination of two fusion proteins can generate more potent anti-tumor effects than a single fusion protein. MATERIALS AND METHODS: In vivo antitumor effects including preventive, therapeutic, and antibody depletion experiments were performed. In vitro assays including intracellular cytokine staining and ELISA for Ab responses were also performed. RESULTS: PE(ΔIII)/E6+PE(ΔIII)/E7 generated both stronger E6 and E7-specific immunity. Only 60% of the tumor protective effect was observed in the PE(ΔIII)/E6 group compared to 100% in the PE(ΔIII)/E7 and PE(ΔIII)/E6+PE(ΔIII)/E7 groups. Mice vaccinated with the PE(ΔIII)/E6+PE(ΔIII)/E7 fusion proteins had a smaller subcutaneous tumor size than those vaccinated with PE(ΔIII)/E6 or PE(ΔIII)/E7 fusion proteins alone. CONCLUSION: Fusion protein vaccines targeting both E6 and E7 tumor antigens generated more potent immunotherapeutic effects than E6 or E7 tumor antigens alone. This novel strategy of targeting two tumor antigens together can promote the development of cancer vaccines and immunotherapy in HPV-related malignancies.http://europepmc.org/articles/PMC3772923?pdf=render
spellingShingle Wen-Fang Cheng
Ming-Cheng Chang
Wei-Zen Sun
Yu-Wei Jen
Chao-Wei Liao
Yun-Yuan Chen
Chi-An Chen
Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
PLoS ONE
title Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
title_full Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
title_fullStr Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
title_full_unstemmed Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
title_short Fusion protein vaccines targeting two tumor antigens generate synergistic anti-tumor effects.
title_sort fusion protein vaccines targeting two tumor antigens generate synergistic anti tumor effects
url http://europepmc.org/articles/PMC3772923?pdf=render
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