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

Proceedings of the National Academy of Sciences of the United States of America
Edmund A RossiChien-Hsing Chang

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.

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