2. Academic Validation
  3. Monoclonal antibody mediated intracellular targeting of tallysomycin S(10b)

Monoclonal antibody mediated intracellular targeting of tallysomycin S(10b)

  • Bioorg Med Chem Lett. 2004 Aug 16;14(16):4323-7. doi: 10.1016/j.bmcl.2004.05.089.
Michael A Walker 1,  H Dalton King,  Richard A Dalterio,  Pamela Trail,  Raymond Firestone,  Gene M Dubowchik
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Pharmaceutical Research Institute, Medicinal Chemistry, PO Box 5100, 5 Research Parkway, Wallingford, CT 06492, USA. [email protected]
PMID: 15261295 DOI: 10.1016/j.bmcl.2004.05.089
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.

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