clinical applications of phage-derived sfvs and sfv fusion proteins
;K. A. Chester;J. Bhatia;G. Boxer;S. P. Cooke;A. A. Flynn;A. Huhalov;A. Mayer;R. B. Pedley;L. Robson;S. K. Sharma;D. I. R. Spencer;R. H. J. Begent
international journal of psychology : journal international de psychologie2000Vol. 16pp. 53-62
118
chester2000diseaseclinical
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::TNFα aims to reduce sequestration and increase tumor concentrations of systemically administered TNFα.