High-affinity recombinant phage antibodies to the pan-carcinoma marker epithelial glycoprotein-2 for tumour targeting

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作者：

R Roovers，P Henderikx，W Helfrich，dLE Van，A Reurs，A De Bru?Ne，J Arends，L De Leij，H Hoogenboom

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摘要：

The -associated antigen -2 (-2) is a promising target for detection and treatment of a variety of . Antibodies to this antigen have been successfully used in patients for imaging of and for adjuvant treatment of of . We describe here the isolation and complete characterization of high-affinity single-chain variable fragments (scFv) to the -2 antigen. First, the kinetics of four whole antibodies directed to -2 (17-1A, 323/A3, MOC-31 and MOC-161) were determined using surface plasmon resonance (SPR). The MOC-31 antibody has the lowest apparent off-rate, followed by MOC-161 and 323/A3. The V-genes of the two MOC hybridomas were cloned as scFv in a phage display vector and phage were selected by panning on recombinant antigen. The scFvs compete with the original hybridoma antibodies for to antigen and specifically bind to in immunohistochemistry. MOC-31 scFv has an off-rate which is better than those of the bivalent 17-1A and 323/A3 whole antibodies, providing it with an essential characteristic for retention in vivo. The availability of these high-affinity anti--2 antibody fragments and of their encoding V-genes creates a variety of possibilities for their future use as -targeting vehicles.

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关键词：

epithelial glycoprotein-2 tumour targeting single-chain Fv affinity phage display

DOI：

10.1038/bjc.1998.700

被引量：

110