Discovery
The theory of an anti-tumoral response of the immune system in vivo was recognized by the physician William B. Coley. In 1968, Dr. Gale A Granger from the University of California, Irvine, reported a cytotoxic factor produced by lymphocytes and named it lymphotoxin (LT). Credit for this discovery is shared by Dr. Nancy H. Ruddle from Yale University, who reported the same activity in a series of back-to-back articles published in the same month. Subsequently in 1975 Dr. Lloyd J. Old from Memorial Sloan-Kettering Cancer Center, New York, reported another cytotoxic factor produced by macrophages, and named it tumor necrosis factor (TNF). Both factors were described based on their ability to kill mouse fibrosarcoma L-929 cells.
When the cDNAs encoding LT and TNF were cloned in 1984, they were revealed to be similar. The binding of TNF to its receptor and its displacement by LT confirmed the functional homology between the two factors. The sequential and functional homology of TNF and LT led to the renaming of TNF as TNFα and LT as TNFβ. In 1985, Bruce A. Beutler and Anthony Cerami discovered that a hormone that induces cachexia and previously-named cachectin was actually TNF. These investigators then identified TNF as a mediator of lethal endotoxin poisoning. Kevin J. Tracey and Cerami discovered the key mediator role of TNF in lethal septic shock, and identified the therapeutic effects of monoclonal anti-TNF antibodies.
Read more about this topic: Tumor Necrosis Factor-alpha
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