Clinical applications of phage-derived sFvs and sFv fusion proteins
Clinical applications of phage-derived sFvs and sFv fusion proteins
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DOI：
10.1155/2000/672706
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发表时间：
2000-01-01
期刊：
影响因子：
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通讯作者：
Begent, RHJ
中科院分区：
文献类型：
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作者：
Chester, KA;Bhatia, J;Begent, RHJ
单链Fv抗体（sFvs）已经从获自免疫小鼠的丝状噬菌体文库产生。这些sFvs中最具特征的R MFE-23与癌胚抗原（CEA）反应，癌胚抗原是一种在结肠直肠腺癌中高度表达的糖蛋白。MFE-23已在细菌中表达并在我们的实验室中纯化用于两项临床试验;使用I-123-MFE-23的伽马相机成像试验和使用I-125-MFE-23的放射免疫导向手术试验，其中在手术期间通过手持式探针检测肿瘤沉积物。这两项试验都表明，MFE-2.3在定位癌症患者的肿瘤沉积物方面是安全有效的。我们现在正在开发融合蛋白，其使用MFE-23来递送治疗部分; MFE-23：：CPG 2靶向酶羧肽酶G2（CPG 2）用于ADEPT（抗体导向酶前药治疗）系统，MFE：：TNF α旨在减少螯合并增加全身施用的TNF α的肿瘤浓度。
Single chain Fv antibodies (sFvs) have been produced from filamentous bacteriophage libraries obtained from immunised mice. R MFE-23, the most characterised of these sFvs, is reactive with carcinoembryonic antigen (CEA), a glycoprotein that is highly expressed in colorectal adenocarcinomas. MFE-23 has been expressed in bacteria and purified in our laboratory for two clinical trials; a gamma camera imaging trial using I-123-MFE-23 and a radioimmunoguided surgery trial using I-125-MFE-23, where tumour deposits are detected by a hand-held probe during surgery. Both these trials show MFE-2.3 is safe and effective in localising tumour deposits in patients with cancer. We are now developing fusion proteins which use MFE-23 to deliver a therapeutic moiety; MFE-23::CPG2 targets the enzyme carboxypeptidase G2 (CPG2) for use in the ADEPT (antibody directed enzyme prodrug therapy) system and MFE::TNF alpha aims to reduce sequestration and increase tumor concentrations of systemically administered TNF alpha.