- 作者: Chi-Mu Chuang; Archana Monie; Chien-Fu Hung; T.-c. Wu
- 作者服務機構: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
- 中文摘要: --
- 英文摘要:
Background: There 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.
Methods: In 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.
Results: We 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.
Conclusions: Thus, 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. - 中文關鍵字: --
- 英文關鍵字: --