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

Journal of Biomedical Science

Research

Archana Monie¹  Chien-Fu Hung²  T-C Wu³  Chi-Mu Chuang⁴ 

[1] Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA;Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan;School of Medicine, National Yang-Ming University, Taipei, Taiwan;

关键词: Imiquimod;    Cell Immune Response;    Taipei Veteran General Hospital;    Clodronate Liposome;    Topical Imiquimod;   

DOI  :  10.1186/1423-0127-17-32

 received in 2010-01-11, accepted in 2010-04-28,  发布年份 2010

来源: Springer

【 摘 要 】

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

【 授权许可】

Unknown   
© Chuang et al; licensee BioMed Central Ltd. 2010. 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.