Clinical applications of phage-derived sFvs and sFv fusion proteins.
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.
Chester
K A
KA
CRC Targeting & Imaging Group, Department of Oncology, Royal Free & University College Medical School, UCL, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. kac@rfhsm.ac.uk
Bhatia
J
J
Boxer
G
G
Cooke
S P
SP
Flynn
A A
AA
Huhalov
A
A
Mayer
A
A
Pedley
R B
RB
Robson
L
L
Sharma
S K
SK
Spencer
D I
DI
Begent
R H
RH
D002986:Clinical Trials as Topic; D005803:Genes, Immunoglobulin; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D019151:Peptide Library; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D011993:Recombinant Fusion Proteins