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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1819289897410756608 |
---|---|
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. |
first_indexed | 2024-12-24T03:14:09Z |
format | Article |
id | doaj.art-97a3dda06b3a473ca728f11b7161a1cc |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-24T03:14:09Z |
publishDate | 2013-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT wenfangcheng fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects AT mingchengchang fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects AT weizensun fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects AT yuweijen fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects AT chaoweiliao fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects AT yunyuanchen fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects AT chianchen fusionproteinvaccinestargetingtwotumorantigensgeneratesynergisticantitumoreffects |