Synthesis of an immunoconjugate of camptothecin.
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.
Walker
Michael A
MA
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5100, 5 Research Parkway, Wallingford, CT 06492, USA. michael.a.walker@bms.com
Dubowchik
Gene M
GM
Hofstead
Sandra J
SJ
Trail
Pamela A
PA
Firestone
Raymond A
RA
D002166:Camptothecin / Q000737:chemistry* / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D004705:Endocytosis; D018796:Immunoconjugates / Q000737:chemistry* / Q000378:metabolism
D018796:Immunoconjugates; D002401:Cathepsin B; D002166:Camptothecin