Description

Clinical Phase I

CEA is a 180 kDa tumour-associated antigen expressed in the developing foetus and a wide variety of tumours, including those of the GI tract (e.g. colon, rectum, pancreas, liver), breast, lung and prostate.

A high-affinity anti-CEA single chain Fv (scFv), MFE-23, has been developed by phage display technology (1). MFE-23 has exceptional specificity for CEA and appears to have no nonspecific reactivity with human tissues. Furthermore, preclinical and clinical studies indicate that MFE-23 localisation to CEA-expressing tumours is not affected by CEA protein being shed into the circulation. A humanised MFE-23 variant (hMFE) has been engineered by using a resurfacing technique and higher-affinity hMFE variants (improved off-rates) generated by mutagenesis and screening yeast surface-displayed libraries. One of these variants, sm3E, has a dissociation halftime of several days and retains approximately 80% anti-CEA binding activity after incubation for 9 days under physiological conditions (37oC). MFE antibodies have been successfully radiolabelled with 123Iodine, 125Iodine, 131Iodine and 99mTc. Economical methods of producing recombinant MFE antibodies and MFE fusion proteins to clinical grade have been developed comprising expression in bacteria or pichia pastoris and purification by immobilised metal affinity chromatography (IMAC) by virtue of an engineered hexahistidine tag.

Extensive preclinical and clinical studies of the Inventors and others indicate that these antibodies are potentially useful imaging agents and have considerable therapeutic potential when linked to a suitable moiety.

Download the PDF of CEA Antibodies

For more information please contact

Dr Hanane Gouizi

+44 (0) 20 3469 6300 .(JavaScript must be enabled to view this email address)