tailieunhanh - Báo cáo y học: "Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines | Peng et al. Journal of Biomedical Science 2011 18 21 http content 18 1 21 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines Shiwen Peng1 Archana Monie1 Xiaowu Pang5 Chien-Fu Hung1 4 T-C Wu1 2 3 4 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. Introduction Advanced stage cancers are difficult to control using conventional therapies such as chemotherapy surgery and radiation. Therefore new innovative therapies are urgently required in order to combat