Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy

doi:10.1016/j.apsb.2021.06.001

	Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy
	Wu, Aihua 1,2; Chen, Yingzhi 1; Wang, Hairui 1,2; Chang, Ya 1; Zhang, Meng 1; Zhao, Pengfei 1; Tang, Yisi 1,2; Xu, Qin 2; Zhu, Zhuangzhi 3; Cao, Yang 2
刊名	ACTA PHARMACEUTICA SINICA B
	2021-11-01
卷号	11 期号:11 页码:3622-3635
关键词	Trichosanthin Legumain TRP2 Transcutaneous immunization Adjuvant Cancer vaccine Protein engineering
ISSN号	2211-3835
DOI	10.1016/j.apsb.2021.06.001
通讯作者	Xu, Qin(xuqin@gzucm.edu.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要	An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an "all-in-one" vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared via a facile recombinant method. The vaccines induced the maturation of DCs that subsequently primed CD8(+) T cells. The TCS-based immunostimulation was associated with the STING pathway. The general applicability of this genetic engineering strategy was demonstrated with various tumor antigens (i.e., legumain and TRP2 antigenic peptides) and tumor models (i.e., colon tumor and melanoma). These findings represent a useful protocol for developing cancer vac-cines at low cost and time-saving, and demonstrates the adjuvant application of TCS-an old drug for a new application. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
资助项目	National Key Research and Development Program of China (China)[2021YFE0103100] ; Na-tional Natural Science Foundation of China of China (China)[81925035] ; Na-tional Natural Science Foundation of China of China (China)[81673382] ; Na-tional Natural Science Foundation of China of China (China)[81521005] ; National Special Project for Significant New Drugs Development (China)[2018ZX09711002-010-002] ; Shanghai SciTech Innovation Initiative (China)[19431903100] ; Shanghai SciTech Innovation Initiative (China)[18430740800] ; Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations (China)[SSMU-ZDCX20180701] ; Chinese Pharmaceutical Association-Yiling Pharm Joint Grants (China)[CPAYLJ201901]
WOS关键词	TUMOR-ASSOCIATED MACROPHAGES ; DENDRITIC CELLS ; PRODRUG-LIKE ; TGF-BETA ; TRICHOSANTHIN ; DELIVERY ; PROTEIN ; EXPRESSION ; LEGUMAIN ; MICROENVIRONMENT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
WOS记录号	WOS:000725263500008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299190]
专题	中国科学院上海药物研究所
通讯作者	Xu, Qin; Huang, Yongzhuo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Guangzhou Univ Chinese Med, Affiliated Hosp 1, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China 3.Natl Pharmaceut Engn Res Ctr, China State Inst Pharmaceut Ind, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery, Zhongshan 528437, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wu, Aihua,Chen, Yingzhi,Wang, Hairui,et al. Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy[J]. ACTA PHARMACEUTICA SINICA B,2021,11(11):3622-3635.
APA	Wu, Aihua.,Chen, Yingzhi.,Wang, Hairui.,Chang, Ya.,Zhang, Meng.,...&Huang, Yongzhuo.(2021).Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy.ACTA PHARMACEUTICA SINICA B,11(11),3622-3635.
MLA	Wu, Aihua,et al."Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy".ACTA PHARMACEUTICA SINICA B 11.11(2021):3622-3635.