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Binding characteristics and tumor targeting of a covalently linked divalent CC49 single-chain antibody by Guy W. Beresford; Gabriela Pavlinkova; Barbara J.M. Booth; Surinder K. Batra; David Colcher is a Medicine article available to read on EtoBox.

What is Binding characteristics and tumor targeting of a covalently linked divalent CC49 single-chain antibody about?

Multivalency is a recognized means of increasing the functional affinity of single-chain Fvs (scFvs) for optimizing tumor uptake. A unique divalent single-chain Fv protein [sc(Fv)2], based on the variable regions of the monoclonal antibody (MAb) CC49, has been generated that differs from other dimeric single-chain constructs in that a linker sequence (L) is encoded between the repeated V(L) and V(H) domains (V(L)-L-V(H)-L-V(L)-L-V(H)). This construct was expressed in soluble form in Escherichia coli and purified by ion-exchange and gel-filtration chromatography. Purity and immunoreactivity were determined by SDS-PAGE, HPLC and competitive RIA. sc(Fv)2 exhibited a relative K(A) (3.34 x 10(7) M(-1)) similar to that of the native IgG (1.14 x 10(8) M(-1)) as determined by BIAcore analysis. Pharmacokinetic studies showed rapid blood clearance for sc(Fv)2, with a T(1/2) less than 40 min. Whole-body clearance analysis also revealed rapid clearance, suggesting no significant retention in the extravascular space or normal tissues. Biodistribution studies of radiolabeled sc(Fv)2 showed tumor uptake greater than 6% ID/g after 30 min, which remained at this level for 6 hr. High tumor uptake an

Who reads Binding characteristics and tumor targeting of a covalently linked divalent CC49 single-chain antibody?

Author

Guy W. Beresford; Gabriela Pavlinkova; Barbara J.M. Booth; Surinder K. Batra; David Colcher

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)

Published

1999

Language

EN

Field

Medicine (Health Sciences)