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.

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.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Bleomycin / analogs & derivatives*
  • Bleomycin / immunology*
  • Chromatography, Ion Exchange

Substances

  • Antibodies, Monoclonal
  • Bleomycin
  • talisomycin