Development and in vitro validation of anti-mesothelin biobodies that prevent CA125/mesothelin-dependent cell attachment
Development and in vitro validation of anti-mesothelin biobodies that prevent CA125/mesothelin-dependent cell attachment
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DOI：
10.1016/j.canlet.2007.04.012
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发表时间：
2007-10-08
期刊：
影响因子：
9.7
通讯作者：
Scholler, Nathalie
中科院分区：
文献类型：
--
作者：
Bergan, Lindsay;Gross, Jennifer A.;Scholler, Nathalie
预防癌细胞腹膜种植可延长卵巢癌患者的缓解期和生存期。腹膜细胞组成型表达间皮素，间皮素是由肿瘤细胞表达的CA 125的配体。因此，阻断CA 125/间皮素依赖性细胞附着可以预防或延迟腹膜转移复发。我们开发了一种高通量筛选系统，用于能够以灵敏的定量读数阻断CA 125/间皮素依赖性细胞附着的试剂。使用一种新的酵母表达系统，以产生分泌的，在体内生物素化的蛋白质和生物抗体（Bbs），我们产生了抗间皮素Bbs。来源于高亲和力酵母展示scFv的抗间皮素Bbs检测膜结合和可溶性间皮素两者，并抑制CA 125/间皮素依赖性细胞附着。出版社：Elsevier爱尔兰Ltd.
Preventing peritoneal implantation of carcinoma cells could prolong ovarian cancer patient remission and survival. Peritoneal cells constitutively express mesothelin, a ligand for CA 125 that is expressed by tumor cells. Thus blocking CA 125/ mesothelin-dependent cell attachment may prevent or delay peritoneal metastatic recurrence. We developed a high-throughput screening system for reagents able to block CA125/mesothelin-dependent cell attachment with a sensitive quantitative readout. Using a novel yeast-expression system to produce secreted, in vivo biotinylated proteins and biobodies (Bbs), we generated anti-mesothelin Bbs. Anti-mesothelin Bbs derived from high affinity yeast-display scFv detected both membrane-bound and soluble mesothelins and inhibited CA125/mesothelin-dependent cell attachment. Published by Elsevier Ireland Ltd.