Clinical applications of phage-derived sFvs and sFv fusion proteins

被引:17
作者
Chester, KA [1 ]
Bhatia, J [1 ]
Boxer, G [1 ]
Cooke, SP [1 ]
Flynn, AA [1 ]
Huhalov, A [1 ]
Mayer, A [1 ]
Pedley, RB [1 ]
Robson, L [1 ]
Sharma, SK [1 ]
Spencer, DIR [1 ]
Begent, RHJ [1 ]
机构
[1] UCL, Dept Oncol, Royal Free & Univ Coll Med Sch, CRC Targeting & Imaging Grp, London NW3 2PF, England
关键词
antibody targeting; cancer; ADEPT; CEA; sFv; fusion protein;
D O I
10.1155/2000/672706
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:53 / 62
页数:10
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