Solid tumor therapy by selectively targeting stromal endothelial cells

Significance Anthrax toxin proteins engineered to require activation by tumor-associated proteases show high specificity and potency in suppression of solid tumor growth through actions on tumor endothelial cells. The toxin strongly inhibits proliferation of tumor endothelial cells. Importantly, an immunosuppressive regimen (pentostatin plus cyclophosphamide) not only prevents induction of toxin-neutralizing antibodies, allowing multiple courses of toxin treatment, but also has strong synergy with the toxin on solid tumors. The ability to give repeated doses of toxins, coupled with the specific targeting of tumor endothelium, suggests that our strategy should be efficacious for a wide range of solid tumors, meriting its clinical evaluation.