Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines

Shiwen Peng, Archana Monie, Xiaowu Pang, Chien-Fu Hung, Tzyy Choou Wu

Research output: Contribution to journalArticle

Abstract

Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6- dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.

Original languageEnglish (US)
Article number21
JournalJournal of Biomedical Science
Volume18
Issue number1
DOIs
StatePublished - 2011

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Papillomavirus Vaccines
DNA Vaccines
Therapeutic Uses
Acetic Acid
Blood Vessels
T-cells
Tumors
Vaccination
Bearings (structural)
vadimezan
DNA
Neoplasms
T-Lymphocytes
Antigens
Human papillomavirus 16
Cathode ray tubes
Histocompatibility Antigens Class II
Nitric Oxide Synthase Type II
Therapeutics
Immunotherapy

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 = "Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines",
abstract = "Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6- dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.",
author = "Shiwen Peng and Archana Monie and Xiaowu Pang and Chien-Fu Hung and Wu, {Tzyy Choou}",
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AU - Monie, Archana

AU - Pang, Xiaowu

AU - Hung, Chien-Fu

AU - Wu, Tzyy Choou

PY - 2011

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