Cure of experimental human malignant mesothelioma in athymic mice by diphtheria toxin

A single ip or iv dose of 1-3 micrograms of diphtheria toxin consistently cured athymic mice of an advanced stage experimental human malignant mesothelioma. All cancer cells were killed within 18 hours and the profuse ip ascites plus large solid tumor masses associated with this model of neoplastic disease were subsequently eliminated. Treated mice appeared normal in 3 days and lived for greater than 300 days with no signs of recurrence, while control animals did not survive greater than 32 days. The complete tumoricidal effect implies that toxin readily reached, entered, and preferentially killed each human cancer cell. This outcome exemplifies the true therapeutic potential of highly selective, site-directed toxins, and offers a frame of reference for judging the performance of current as well as prospective toxin-based agents.