Recombinant human CD137L for cancer immunotherapy: effects of different fusions and linkers on its activity
Recombinant human CD137L for cancer immunotherapy: effects of different fusions and linkers on its activity
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用于癌症免疫治疗的重组人 CD137L：不同融合体和接头对其活性的影响
DOI：
10.1007/s00262-011-1097-0
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Chen, Yijun
中科院分区：
文献类型：
--
作者：
Wang, Shuzhen;Lv, Junfang;Wang, Peng;Yin, Xiaojin;Tan, Aimin;Chen, Yijun
共刺激分子可以作为重组蛋白有效地生产出来。在免疫治疗领域有着广泛的应用前景。然而，关于不同的融合是否会影响它们的功能的分析很少。为了探讨不同的融合和连接子对CD137配体(CD137L)分子构象和活性的影响，构建了重组人CD137L蛋白(RhCD137L)文库，该文库由人CD137L的全胞外区通过不同的连接子与N端或C端的组氨酸标签融合而成，并分别在大肠杆菌中表达。携带伴侣质粒pG-TF2的ColiBL21(DE3)菌株。重组人CD137L经纯化后，能明显促进活化T细胞的生长，但对细胞因子产生的影响各不相同。目前的工作表明，尽管所有的重组人CD137L都具有预期的生物学活性，但不同的融合和连接子确实会影响它们的结构和功能。因此，合理设计文库是融合蛋白获得满意候选药物进行进一步开发的必要和可行的途径。
Co-stimulatory molecules can be efficiently produced as a recombinant protein inE. coliwith a large range of applications in the fields of immunotherapy. However, whether, different fusions that would affect their functions have rarely been analyzed. To explore the effects of different fusions and linkers on the molecular conformation and activity of CD137 ligand (CD137L), a recombinant human CD137L protein (rhCD137L) library, which consists of the entire extracellular domain of human CD137L fused to N- or C-terminal His-tag through different linkers, was constructed and all rhCD137Ls were, respectively, expressed inE. coliBL21 (DE3) strain carrying a chaperone plasmid pG-Tf2. After purification of the soluble rhCD137Ls, the recombinant fusion proteins could markedly promote the growth of activated T cells, but their effects on cytokine productions were different from each other. The present work indicated that, although all rhCD137Ls have desired biological activity, different fusions and linkers did affect their structures and functions. Consequently, rational design of a library is a necessary and feasible approach for fusion proteins in order to obtain a satisfactory drug candidate for further development.
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影响因子：
12.4
作者：
Zhong, Xiao-Song;Matsushita, Maiko;Sadelain, Michel
通讯作者：
Sadelain, Michel
影响因子：
6.4
作者：
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影响因子：
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作者：
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通讯作者：
GOODWIN, RG
影响因子：
5.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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