- 作者: Shiwen Peng; Archana Monie; Xiaowu Pang; Chien-Fu Hung; T.-c. Wu
- 作者服務機構: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: --