TUMOR NECROSIS FACTOR (TNF) is the most recent biologic response modifier to reach clinical trials in cancer therapy. Yet it is the direct descendant of one of the earliest attempts to provoke an antitumor immune response.
The rationale for therapy with TNF—a protein secreted by macrophages challenged by bacterial endotoxins—dates to the late 1800s, when physicians noticed that cancer patients who had spontaneous tumor regression often also had bacterial infections. In 1893, a New York city physician, William Coley, MD, began to treat cancer patients with a cocktail of bacterial products, which came to be known as Coley's toxins. The patients usually developed high fevers, and, in some, tumors regressed.
In 1934, the American Medical Association labeled Coley's toxins as the only known systemic treatment for cancer. But Coley's toxins proved to be less reliable in achieving remissions than did radiation and chemotherapy, and in the 1960s the treatment was