Human cancer therapy using engineered matrix metalloproteinase-activated anthrax lethal toxin that targets tumor vasculatuture

A method of inhibiting tumor associated angiogenesis in a subject, the method comprising the steps of:

• (1) administering to the subject a therapeutically effective amount of a mutant PA protein comprising a matrix metalloproteinase 2-recognized cleavage site in place of the native PA furin-recognized cleavage site, wherein the mutant PA is cleaved by a matrix metalloproteinase;
• and
• (ii) administering to the subject a therapeutically effective amount of an LF polypeptide comprising a PA binding site;
• wherein the LF polypeptide binds to cleaved PA and is translocated into a tumor associated endothelial cell, thereby inhibiting tumor angiogenesis.