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Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model

BACKGROUND: Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved for the treatment of cutaneous T cell lymphoma and multipl...

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Autores principales: Huang, Zhuomin, Peng, Shiwen, Knoff, Jayne, Lee, Sung Yong, Yang, Benjamin, Wu, Tzyy-Choou, Hung, Chien-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298946/
https://www.ncbi.nlm.nih.gov/pubmed/25591912
http://dx.doi.org/10.1186/s12929-014-0111-1
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author Huang, Zhuomin
Peng, Shiwen
Knoff, Jayne
Lee, Sung Yong
Yang, Benjamin
Wu, Tzyy-Choou
Hung, Chien-Fu
author_facet Huang, Zhuomin
Peng, Shiwen
Knoff, Jayne
Lee, Sung Yong
Yang, Benjamin
Wu, Tzyy-Choou
Hung, Chien-Fu
author_sort Huang, Zhuomin
collection PubMed
description BACKGROUND: Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved for the treatment of cutaneous T cell lymphoma and multiple myeloma/mantle cell lymphoma, respectively. Furthermore, the combination of the bortezomib and SAHA has been tested in a variety of preclinical models and in clinical trials and may be ideal for the treatment of cancer. However, it remains unclear how this treatment strategy affects the host immune response against tumors. RESULTS: Here, we used a well-defined E6/E7-expressing tumor model to examine how the immune system can be motivated to act against tumor cells expressing tumor antigens. We demonstrate that the combination of bortezomib and SAHA elicits potent antitumor effects in TC-1 tumor-bearing mice. Additionally, we are the first to show that treatment with bortezomib and SAHA leads to tumor-specific immunity by rendering tumor cells more susceptible to killing by antigen-specific CD8+ T cells than treatment with either drug alone. CONCLUSIONS: The current study serves an important foundation for the future clinical application of both drugs for the treatment of cervical cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-014-0111-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-42989462015-01-21 Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model Huang, Zhuomin Peng, Shiwen Knoff, Jayne Lee, Sung Yong Yang, Benjamin Wu, Tzyy-Choou Hung, Chien-Fu J Biomed Sci Research BACKGROUND: Bortezomib, a proteasome inhibitor and suberoylanilide hydroxamic acid (SAHA, also known as Vorinostat), a histone deacetylase inhibitor, have been recognized as potent chemotherapeutic drugs. Bortezomib and SAHA are FDA-approved for the treatment of cutaneous T cell lymphoma and multiple myeloma/mantle cell lymphoma, respectively. Furthermore, the combination of the bortezomib and SAHA has been tested in a variety of preclinical models and in clinical trials and may be ideal for the treatment of cancer. However, it remains unclear how this treatment strategy affects the host immune response against tumors. RESULTS: Here, we used a well-defined E6/E7-expressing tumor model to examine how the immune system can be motivated to act against tumor cells expressing tumor antigens. We demonstrate that the combination of bortezomib and SAHA elicits potent antitumor effects in TC-1 tumor-bearing mice. Additionally, we are the first to show that treatment with bortezomib and SAHA leads to tumor-specific immunity by rendering tumor cells more susceptible to killing by antigen-specific CD8+ T cells than treatment with either drug alone. CONCLUSIONS: The current study serves an important foundation for the future clinical application of both drugs for the treatment of cervical cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12929-014-0111-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-16 /pmc/articles/PMC4298946/ /pubmed/25591912 http://dx.doi.org/10.1186/s12929-014-0111-1 Text en © Huang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Huang, Zhuomin
Peng, Shiwen
Knoff, Jayne
Lee, Sung Yong
Yang, Benjamin
Wu, Tzyy-Choou
Hung, Chien-Fu
Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model
title Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model
title_full Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model
title_fullStr Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model
title_full_unstemmed Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model
title_short Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8(+) T cell immune response and antitumor effects in a preclinical cervical cancer model
title_sort combination of proteasome and hdac inhibitor enhances hpv16 e7-specific cd8(+) t cell immune response and antitumor effects in a preclinical cervical cancer model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4298946/
https://www.ncbi.nlm.nih.gov/pubmed/25591912
http://dx.doi.org/10.1186/s12929-014-0111-1
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