Clinical applications of phage-derived sFvs and sFv fusion proteins |
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Authors: | Chester K A Bhatia J Boxer G Cooke S P Flynn A A Huhalov A Mayer A Pedley R B Robson L Sharma S K Spencer D I Begent R H |
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Affiliation: | CRC Targeting & Imaging Group, Department of Oncology, Royal Free & University College Medical School, UCL, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. kac@rfhsm.ac.uk |
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Abstract: | Single chain Fv antibodies (sFvs) have been produced from filamentous bacteriophage libraries obtained from immunised mice. 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 123I-MFE-23 and a radioimmunoguided surgery trial using 125I-MFE-23, where tumour deposits are detected by a hand-held probe during surgery. Both these trials show MFE-23 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. |
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