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

Yunkai Yang; Xiaohan Guo; Bo Hu; Peng He; Xiaowu Jiang; Zuohuan Wang; Huaxing Zhu; Lina Hu; Minghua Yu; Meiqing Feng

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

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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 clinical 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 marrowderived DCs(BMDCs)were isolated,pulsed with SNU and maturated with cytokine cocktail.Then peripheral blood mononuclear cells(PBMCs)from C57 BL/6 mice inoculated intraperitoneally with DCSNU 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-γand 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 treatment.

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《药学学报：英文版》 |2021年第2期|P.476-487|共12页
作者
Yunkai Yang; Xiaohan Guo; Bo Hu; Peng He; Xiaowu Jiang; Zuohuan Wang; Huaxing Zhu; Lina Hu; Minghua Yu; Meiqing Feng;
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作者单位

Shanghai Engineering Research Center of ImmunoTherapeutics School of Pharmacy Fudan University Shanghai 201203 China;

Shanghai Engineering Research Center of ImmunoTherapeutics School of Pharmacy Fudan University Shanghai 201203 China;

Shanghai Novoprotein Biotechnology Co. Ltd. Shanghai 201203 China;

Shanghai Engineering Research Center of ImmunoTherapeutics School of Pharmacy Fudan University Shanghai 201203 China;

Medical School of Yichun University Yichun 336000 China;

Clinical Research Center 2nd Affiliated Hospital Medical College of Zhejiang University Hangzhou 310009 China;

Shanghai Novoprotein Biotechnology Co. Ltd. Shanghai 201203 China;

Department of Oncology Shanghai Pudong Hospital Fudan University Pudong Medicine Center Shanghai 201399 China;

Department of Oncology Shanghai Pudong Hospital Fudan University Pudong Medicine Center Shanghai 201399 China;

Shanghai Engineering Research Center of ImmunoTherapeutics School of Pharmacy Fudan University Shanghai 201203 China;

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原文格式 PDF
正文语种 chi
中图分类治疗实验;
关键词
Dendritic cells; Cancer vaccine; NY-ESO-1; SecPen; Ubiquitin;

机译：树突状细胞;癌症疫苗;NY-ESO-1;SECPEN;泛素;

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

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