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

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. © 2011 peng et al; licensee biomed central ltd.