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Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation half-time at 37 degrees C

Graff, CP; Chester, K; Begent, R; Wittrup, KD; (2004) Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation half-time at 37 degrees C. PROTEIN ENG DES SEL , 17 (4) 293 - 304. 10.1093/protein/gzh038.

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Abstract

An scFv has been engineered to bind carcinoembryonic antigen (CEA) with a dissociation half-time >4 days at 37degreesC. Two mutations responsible for this affinity increase were isolated by screening yeast surface-displayed mutant libraries by flow cytometry. Soluble expression of the mutant scFv in a yeast secretion system was increased 100-fold by screening mutant libraries for improved yeast surface display level. This scFv will be useful as a limiting case for evaluating the significance of affinity in tumor targeting to noninternalizing antigens.

Type: Article
Title: Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation half-time at 37 degrees C
DOI: 10.1093/protein/gzh038
Keywords: affinity, carcinoembryonic antigen, directed evolution, scFv, tumor targeting, SINGLE-CHAIN FV, PHAGE DISPLAY LIBRARY, CARCINOEMBRYONIC ANTIGEN, MONOCLONAL-ANTIBODIES, AFFINITY MATURATION, POLYPEPTIDE LIBRARIES, CLINICAL-APPLICATIONS, MOLECULAR EVOLUTION, RANDOM MUTAGENESIS, THERMAL-STABILITY
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/467
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