title: Monoclonal antibody mediated intracellular targeting of tallysomycin S(10b).
abstract: The potency of tallysomycin S(10b) (TLM S(10b)) an analogue bleomycin was enhanced by up to 875-fold when it was conjugated to the internalizing antibody BR96. Attachment to the antibody is achieved via a Cathepsin B cleavable linker. The enhancement in potency is believed to be a result of cellular uptake of the conjugate upon antigen binding followed by rapid release of the drug inside the lysosome. This method provides a novel approach for increasing the potency and therapeutic index of nominally moderately-active cytotoxic agents.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Medicinal Chemistry, PO Box 5100, 5 Research Parkway, Wallingford, CT 06492, USA. michael.a.walker@bms.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Walker
authors.forename: H Dalton
authors.initials: HD
authors.lastname: King
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dalterio
authors.forename: Pamela
authors.initials: P
authors.lastname: Trail
authors.forename: Raymond
authors.initials: R
authors.lastname: Firestone
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000276:immunology*; D002852:Chromatography, Ion Exchange
chemical_list: D000911:Antibodies, Monoclonal; D001761:Bleomycin; C016126:talisomycin