Shihui Liu (NIAID)
Thomas Bugge (NIDCR)
This technology relates to multimeric bacterial protein toxins which can be used to specifically target cells. Specifically, this is a modified recombinant anthrax toxin protective antigen (PrAg) that has been modified in several ways. First, the PrAg can be activated both by a metalloproteinase (MMP) and by urokinase plasminogen activator (uPA). Second, the native PrAg lethal factor (LF) binding site has been modified so that only a modified PrAg comprising two different monomers can bind anthrax LF. When administered with an effector component, the recombinant anthrax toxins are toxic only to cells expressing both a MMP and uPA on their surface. This technology is therefore useful for selective methods of treating cancers, because many cancer cells express multiple cell-surface proteases.