Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination

作者: Chi-Mu Chuang , Archana Monie , Chien-Fu Hung , T.-c. Wu

DOI: 10.1186/1423-0127-17-32

关键词:

摘要: There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination antigen-specific immunotherapy with employment immunomodulatory agents has emerged as a potentially plausible approach In current study, we explored DNA vaccine encoding calreticulin (CRT) linked human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) TLR7 agonist imiquimod their ability generate E7-specific immune responses and antitumor effects in tumor-bearing mice. We observed that treatment CRT/E7 leads enhancement CD8+ T cell decrease number myeloid-derived suppressor cells tumor microenvironment Furthermore, significantly improved prolonged survival treated addition, led increased NK1.1+ F4/80+ microenvironment. Macrophages were found play important role mediated by imiquimod. Thus, our data suggests therapeutic HPV vaccination topical enhances immunity induced vaccination. study significant implications future clinical translation.

参考文章(28)
Thomas Bieber, Natalija Novak, Chun-Feng Yu, Jean-Pierre Allam, Toll-like receptor 7 agonists and skin. Drug News & Perspectives. ,vol. 21, pp. 158- 165 ,(2008)
Drew M. Pardoll, Richard A. Young, Tian Li Wang, Chien Fu Hung, T. C. Wu, Yanqin Yang, Chien Hung Chen, Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. Cancer Research. ,vol. 60, pp. 1035- 1042 ,(2000)
Andreas M Kaufmann, Malcolm Adams, Julian K Hickling, John St C Roberts, Uwe Wagner, Jantien Wanders, Karlijn Kroon, Volkmar Nuessler, Jennifer Gillard, Elaine M Rankin, Thomas Bauknecht, Heinz Zwierzina, Simon N Stacey, Christopher M Boswell, Achim Schneider, Harald Sommer, Peter L Stern, Henry C Kitchener, Toli S Onon, Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer. Clinical Cancer Research. ,vol. 8, pp. 3676- 3685 ,(2002)
Orla M. Hart, Veronica Athie-Morales, Geraldine M. O’Connor, Clair M. Gardiner, TLR7/8-Mediated Activation of Human NK Cells Results in Accessory Cell-Dependent IFN-γ Production Journal of Immunology. ,vol. 175, pp. 1636- 1642 ,(2005) , 10.4049/JIMMUNOL.175.3.1636
Hyam I. Levitsky, J. Thomas August, Tzyy Choou Wu, Kevin F. Staveley-O'Carroll, Frank G. Guarnieri, Ken Yu Lin, Drew M. Pardoll, Treatment of Established Tumors with a Novel Vaccine That Enhances Major Histocompatibility Class II Presentation of Tumor Antigen Cancer Research. ,vol. 56, pp. 21- 26 ,(1996)
Tae Woo Kim, Jin Hyup Lee, Chien-Fu Hung, Shiwen Peng, Richard Roden, Mei-Cheng Wang, Raphael Viscidi, Ya-Chea Tsai, Liangmei He, Pei-Jer Chen, David AK Boyd, T-C Wu, None, Generation and Characterization of DNA Vaccines Targeting the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus Journal of Virology. ,vol. 78, pp. 4638- 4645 ,(2004) , 10.1128/JVI.78.9.4638-4645.2004
Hiroaki Hemmi, Tsuneyasu Kaisho, Osamu Takeuchi, Shintaro Sato, Hideki Sanjo, Katsuaki Hoshino, Takao Horiuchi, Hideyuki Tomizawa, Kiyoshi Takeda, Shizuo Akira, Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nature Immunology. ,vol. 3, pp. 196- 200 ,(2002) , 10.1038/NI758
Shiwen Peng, Hongxiu Ji, Cornelia Trimble, Liangmei He, Ya-Chea Tsai, Jessica Yeatermeyer, David A. K. Boyd, Chien-Fu Hung, T.-C. Wu, Development of a DNA Vaccine Targeting Human Papillomavirus Type 16 Oncoprotein E6 Journal of Virology. ,vol. 78, pp. 8468- 8476 ,(2004) , 10.1128/JVI.78.16.8468-8476.2004
Wen Fang Cheng, Morris Ling, Liangmei He, Chien Fu Hung, T. C. Wu, Keng Fu Hsu, Chee Yin Chai, Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. Journal of Clinical Investigation. ,vol. 108, pp. 669- 678 ,(2001) , 10.1172/JCI12346
R.L Miller, J.F Gerster, M.L Owens, H.B Slade, M.a Tomai, Review Article Imiquimod applied topically: a novel immune response modifier and new class of drug International Journal of Immunopharmacology. ,vol. 21, pp. 1- 14 ,(1999) , 10.1016/S0192-0561(98)00068-X