Tumour necrosis factor as an anticancer agent

Abstract

WHEN the human gene encoding tumour necrosis factor (TNF) was cloned in 1984 [ 11, there was excitement at the prospect of large amounts of purified recombinant material for clinical cancer trials. This factor was potentially an important advance in cancer treatment. The historical background [2] and preclinical studies with partially purified material [3] gave grounds for cautious optimism. Manda et al. [4] reported on the antitumour effect of TNF and S-fluorouracil in the murine Meth A sarcoma model, and highlighted the importance of tumour blood supply to the antitumour effect of TNF. This adds to the large body of data now available in animal models on the antitumour efficacy of TNF as a single agent, or in combination with other cytokines and cytotoxic drugs. However, the promising results in animal models have not, as yet, been reflected in clinical trial data. Six years after the TNF gene was cloned there is little evidence for antitumour activity of this agent in man, although most of the completed studies are phase I trials [5]. An understanding of the history of TNF and the advances made since the gene was cloned provides some explanation for the disappointing results obtained in clinical cancer trials. Such information may indicate ways in which the undoubted power of this cytokine could be effectively used singly or in combination with other antitumour agents. In addition, there is now evidence that endogenous TNF production may be inextricably bound with growth and metastasis of some tumours, and that neutralization of TNF activity may be of potential therapeutic benefit.