Generated SecPen_NY-ESO-1_ubiquitin-pulsed dendritic cell cancer vaccine elicits stronger and specific T cell immune responses

• 作者: Yunkai Yang Xiaohan Guo Bo Hu Peng He Xiaowu Jiang Zuohuan Wang Huaxing Zhu Lina Hu Minghua Yu Meiqing Feng
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（2）
• 所属期刊栏目: Original articles
• 页码范围: 476-487
• 页数: 12页
• 语种: 英文

摘要

Dendritic cell-based cancer vaccines(DC vaccines)have been proved efficient and safe in immunotherapy of various cancers,including melanoma,ovarian and prostate cancer.However,the clin-ical responses were not always satisfied.Here we proposed a novel strategy to prepare DC vaccines.In the present study,a fusion protein SNU containing a secretin-penetratin(SecPen)peptide,NY-ESO-1 and ubiquitin was designed and expressed.To establish the DC vaccine(DC-SNU),the mouse bone marrow-derived DCs(BMDCs)were isolated,pulsed with SNU and maturated with cytokine cocktail.Then pe-ripheral blood mononuclear cells(PBMCs)from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38NY-ESO-1 tumor cells or DC vaccines.The results show that SNU was successfully expressed.This strategy made NY-ESO-1 entering cytoplasm of BMDCs more efficiently and degraded mainly by proteasome.As we expected,mature BMDCs expressed higher CD40,CD80 and CD86 than immature BMDCs.Thus,the PBMCs released more IFN-γ and TNF-αwhen stimulated with DC-SNU in vitro again.What's more,the PBMCs induced stronger and specific cytotoxicity towards MC38NY-ESO-1 tumor cells.Given the above,it demonstrated that DC-SNU loaded with SecPen and ubiquitin-fused NY-ESO-1 could elicit stronger and specific T cell immune responses.This strategy can be used as a platform for DC vaccine preparation and applied to various cancers treat-ment.