Genetically-engineered“all-in-one”vaccine platform for cancer immunotherapy  

作　　者：Aihua Wu Yingzhi Chen Hairui Wang Ya Chang Meng Zhang Pengfei Zhao Yisi Tang Qin Xu Zhuangzhi Zhu Yang Cao Yongzhuo Huang 

机构地区：[1]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]Artemisinin Research Center,the First Affiliated Hospital,Guangzhou University of Chinese Medicine,Guangzhou 510450,China [3]National Pharmaceutical Engineering Research Center,China State Institute of Pharmaceutical Industry,Shanghai 201203,China [4]Zhongshan Institute for Drug Discovery,Institutes of Drug Discovery and Development,Chinese Academy of Sciences,Zhongshan 528437,China [5]University of Chinese Academy of Sciences,Beijing 100049,China [6]NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,Shanghai 201203,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第11期3622-3635,共14页药学学报（英文版）

基　　金：support of National Key Research and Development Program of China(2021YFE0103100,China);National Natural Science Foundation of China of China(81925035,81673382,and 81521005,China);National Special Project for Significant New Drugs Development(2018ZX09711002-010-002,China);Shanghai SciTech Innovation Initiative(19431903100,18430740800,China);Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations(SSMU-ZDCX20180701,China);Chinese Pharmaceutical Association-Yiling Pharm Joint Grants(CPAYLJ201901,China)for the support。

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"allin-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 vaccines at low cost and time-saving,and demonstrates the adjuvant application of TCSdan old drug for a new application.

关 键 词：TRICHOSANTHIN LEGUMAIN TRP2 Transcutaneous immunization ADJUVANT Cancer vaccine Protein engineering 

分 类 号：R392-3[医药卫生—免疫学]