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Proc Natl Acad Sci U S A. 2006 May 2;103(18):6841-6. Epub 2006 Apr 24.

Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting.

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  • 1IBC Pharmaceuticals, Inc., 300 American Road, Morris Plains, NJ 07950, USA.

Abstract

We describe a platform technology, termed the dock and lock method, which uses a natural binding between the regulatory subunits of cAMP-dependent protein kinase and the anchoring domains of A kinase anchor proteins for general application in constructing bioactive conjugates of different protein and nonprotein molecules from modular subunits on demand. This approach could allow quantitative and site-specific coupling of many different biological substances for diverse medical applications. The dock and lock method is validated herein by producing bispecific, trivalent-binding complexes composed of three stably linked Fab fragments capable of selective delivery of radiotracers to human cancer xenografts, resulting in rapid, significantly improved cancer targeting and imaging, providing tumor/blood ratios from 66 +/- 5 at 1 h to 395 +/- 26 at 24 h.

PMID:
16636283
[PubMed - indexed for MEDLINE]
PMCID:
PMC1447525
Free PMC Article
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