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. 2002 Jun 7;16(1-2):53–62. doi: 10.1155/2000/672706

Clinical Applications of Phage-Derived sFvs and sFv Fusion Proteins

K A Chester 1,*, J Bhatia 1, G Boxer 1, S P Cooke 1, A A Flynn 1, A Huhalov 1, A Mayer 1, R B Pedley 1, L Robson 1, S K Sharma 1, D I R Spencer 1, R H J Begent 1
PMCID: PMC3851051  PMID: 11360829

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.

Keywords: antibody targeting, cancer, ADEPT, CEA, sFv, fusion protein

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