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Updated: Aug 12, 2026

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Synthesis of an immunoconjugate of camptothecin
Michael A Walker1, Gene M Dubowchik, Sandra J Hofstead
1Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5100, 5 Research Parkway, Wallingford, CT 06492, USA. michael.a.walker@bms.com
Abstract:
The first immunoconjugate of camptothecin has been synthesized wherein the drug is attached to the tumor-recognizing antibody BR96 via a Cathepsin B cleavable linker. Endocytosis of the immunoconjugate upon binding to the tumor cell followed by enzymatic cleavage of the linker inside the endosome ensures tumor-specific release of the drug. In this way, it is hoped that the dose-limiting side effects associated with camptothecin can be eliminated while the antitumor activity is preserved.
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