Control of Cervicovaginal HPV-16 E7-Expressing Tumors by the Combination of Therapeutic HPV Vaccination and Vascular Disrupting Agents

摘要: Abstract Antigen-specific immunotherapy and vascular disrupting agents, such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA), have emerged attractive approaches for the treatment of cancers. In current study, we tested combination DMXAA with therapeutic human papillomavirus type 16 (HPV-16) E7 peptide-based vaccination their ability to generate E7-specific CD8+ T-cell immune responses, well control E7-expressing tumors in a subcutaneous cervicovaginal tumor model. We found that long peptide (amino acids 43-62) mixed polyriboinosinic:polyribocytidylic generated significantly stronger responses antitumor effects compared alone or HPV Additionally, DMXAA-mediated enhancement by vaccine was dependent on timing administration DMXAA. Treatment tumor-bearing mice also shown lead increased dendritic cell maturation production inflammatory cytokines tumor. Furthermore, observed HPV-16 significant TC-1 growth model, which closely resembles microenvironment cervical cancer. Taken together, our data demonstrated agent, DMXAA, enhances vaccine-induced cytotoxic T-lymphocyte against two different locations. Our study has implications future clinical translation.