Affiliations: CRC Targeting and Imaging Group, Department of
Oncology, RFUCMS, University College London, Royal Free Campus, London NW3 2PF,
UK
Note: [] CRC Targeting & Imaging Group, Department of Oncology,
Royal Free & University College Medical School, UCL, Royal Free Campus,
Rowland Hill Street, London NW3 2PF, UK. Tel.: +44 20 7794 5492; Fax: +44 20
7794 3341; E-mail: kac@rfhsm.ac.uk
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
^{123}I-MFE-23 and a radioimmunoguided surgery trial
using^{125}I-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.
Keywords: antibody targeting, cancer, ADEPT, CEA, sFv, fusion protein
