Clinical applications of phage-derived sFvs and sFv fusion proteins

Dis Markers. 2000;16(1-2):53-62. doi: 10.1155/2000/672706.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Fragments / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Peptide Library*
  • Recombinant Fusion Proteins / therapeutic use*

Substances

  • Immunoglobulin Fragments
  • Immunoglobulin Variable Region
  • Peptide Library
  • Recombinant Fusion Proteins