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

Journal of Biomedical Science

Research

Archana Monie¹  Shiwen Peng¹  T-C Wu²  Chien-Fu Hung³  Xiaowu Pang⁴ 

[1] Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA;University College of Dentistry, Washington, DC, USA;

关键词: Severe Acute Respiratory Syndrome;    Cell Immune Response;    Intracellular Cytokine Staining;    Tumor Bearing Mouse;    Therapeutic Antitumor Effect;   

DOI  :  10.1186/1423-0127-18-21

 received in 2010-11-24, accepted in 2011-03-08,  发布年份 2011

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Peng et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. 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 cited.