血管生成
融合蛋白
生物
表位
重组DNA
质粒
嵌合基因
抗原
大肠杆菌
免疫系统
基因
微生物学
癌症研究
分子生物学
免疫学
遗传学
基因表达
作者
Feng‐Ying Huang,Ling Li,Quan Liu,Yue‐Nan Li,Ruizhen Bai,Yonghao Huang,Huange Zhao,Junli Guo,Songlin Zhou,Hua Wang,Yingying Lin,Guang‐Hong Tan
摘要
Various angiogenesis-related self-molecules have been considered to be therapeutic targets. However, the direct use of self-molecules as vaccines is not recommended because of the inherent ability of the host to develop immune tolerance. Antigen 43 (Ag43) is a surface protein found in E. coli and contains an α and a β subunits, which contains multiple T epitopes in α subunit. Here we construct a novel Ag43 surface display system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune tolerance against self-molecules. The Ag43 system was constructed from an Escherichia coli strain Tan109, derived from JM109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43′) expressing a partial Ag43 gene was introduced. The extracellular domain of angiogenesis-related endoglin gene was then subcloned into plasmid pETAg43′, resulting in a recombinant plasmid pETAg43′/ENDe which was then used to transform Tan109 for protein expression. We found that Ag43 and endoglin chimeric protein (Ag43′/ENDe) was expressed on the bacterial surface. The chimeric protein could be separated from the bacterial surface by heating to 60°C and yet retain activity. We used Ag43′/ENDe as a protein vaccine and found that it could disrupt immune tolerance against endoglin by inducing significant antitumor activities and inhibit angiogenesis in several tumor models without significant side effects. These data suggest that Ag43′/ENDe chimeric protein is a potential model vaccine for active tumor immunotherapy, and that Ag43 system could be an effective tool for novel vaccine preparation to break immune tolerance to other angiogenesis-related self-molecules for cancer therapy.
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