Development and in vitro validation of anti-mesothelin biobodies that prevent CA125/mesothelin-dependent cell attachment

被引:59
作者
Bergan, Lindsay [1 ]
Gross, Jennifer A. [1 ]
Nevin, Barry [1 ]
Urban, Nicole [1 ]
Scholler, Nathalie [1 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Mol Diagnost Progarm, Seattle, WA 98109 USA
关键词
mesothelin; CA125; biobody; tumor cell attachment; ovarian cancer; peritoneal metastasis;
D O I
10.1016/j.canlet.2007.04.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:263 / 274
页数:12
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