Selective toxicity of diphtheria toxin for malignant cells

Purified diphtheria toxin is shown to inhibit protein synthesis in Ehrlich-Lettré ascites carcinoma cells in vitro. Protein synthesis in Ehrlich-Lettré cells is at least 10,000 times more sensitive to toxin than protein synthesis in normal mouse spleen or thymus cells. This sensitivity correlates with the observation that Ehrlich-Lettré tumors regress in mice injected with diphtheria toxin but not diphtheria toxoid. Using the criterion of inhibition of protein synthesis in vitro, we show that other mouse malignancies (lymphoma and myeloma) are also more sensitive to diphtheria toxin than normal spleen or thymus. Metastatic human breast carcinoma cells from two individuals, cells from two melanoma nodules removed at different times from a third patient, and cells from melanoma nodules from three additional individuals are shown to be more sensitive to diphtheria toxin than some normal human cells. The toxin sensitivity of protein synthesis in some of the malignant cells tested was so much greater than that of normal cells, that we have proposed that diphtheria toxin should be studied further since it might prove a useful anti-cancer agent in patients whose tumors are first shown to be highly sensitive to toxin in vitro.