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

Zhuomin Huang, Shiwen Peng, Jayne Knoff, Sung Yong Lee, Benjamin Yang, Tzyy Choou Wu, Chien-Fu Hung

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalJournal of Biomedical Science
Volume22
Issue number1
DOIs
StatePublished - Jan 16 2015

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Proteasome Inhibitors
Histone Deacetylase Inhibitors
T-cells
Uterine Cervical Neoplasms
Tumors
T-Lymphocytes
Neoplasms
Bearings (structural)
Cells
Pharmaceutical Preparations
CD8 Antigens
Immune system
Mantle-Cell Lymphoma
Cutaneous T-Cell Lymphoma
Neoplasm Antigens
Multiple Myeloma
Immune System
Bortezomib
Immunity
Antigens

Keywords

  • Antitumor
  • Bortezomib
  • Host immunity
  • SAHA
  • Vorinostat

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

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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",
abstract = "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.",
keywords = "Antitumor, Bortezomib, Host immunity, SAHA, Vorinostat",
author = "Zhuomin Huang and Shiwen Peng and Jayne Knoff and Lee, {Sung Yong} and Benjamin Yang and Wu, {Tzyy Choou} and Chien-Fu Hung",
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T1 - Combination of proteasome and HDAC inhibitor enhances HPV16 E7-specific CD8+ T cell immune response and antitumor effects in a preclinical cervical cancer model

AU - Huang, Zhuomin

AU - Peng, Shiwen

AU - Knoff, Jayne

AU - Lee, Sung Yong

AU - Yang, Benjamin

AU - Wu, Tzyy Choou

AU - Hung, Chien-Fu

PY - 2015/1/16

Y1 - 2015/1/16

N2 - 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.

AB - 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.

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