Clinical applications of phage-derived sFvs and sFv fusion proteins

Single chain Fv antibodies (sFvs) have been produced from filamentous bacte riophage libraries obtained from immunised mice. R MFE-23, the most charact erised of these sFvs, is reactive with carcinoembryonic antigen (CEA), a gl ycoprotein that is highly expressed in colorectal adenocarcinomas. MFE-23 h as been expressed in bacteria and purified in our laboratory for two clinic al trials; a gamma camera imaging trial using I-123-MFE-23 and a radioimmun oguided surgery trial using I-125-MFE-23, where tumour deposits are detecte d by a hand-held probe during surgery. Both these trials show MFE-2.3 is sa fe and effective in localising tumour deposits in patients with cancer. We are now developing fusion proteins which use MFE-23 to deliver a therapeuti c moiety; MFE-23::CPG2 targets the enzyme carboxypeptidase G2 (CPG2) for us e in the ADEPT (antibody directed enzyme prodrug therapy) system and MFE::T NF alpha aims to reduce sequestration and increase tumor concentrations of systemically administered TNF alpha.