Local immunotherapy with rhTNF-alpha mutein induces strong antitumor activity without overt toxicity--a review.

Tumor necrosis factor (TNF-alpha) is a cytokine possessing antitumor and immunomodulatory properties. The studies reviewed in the present paper evaluate the effect of intratumor or intraperitoneal (i.t./i.p.) injections of human recombinant TNF-alpha (rhTNF-alpha) and its derivatives (muteins V and VI) on the course of experimental tumors. The aim of local cytokine administration was to avoid or reduce the induction of undesired systemic symptoms. Although total remissions were not observed in the studies, morphological analysis of lung tissue, accepted as the toxicity index of the cytokines, showed that rhTNF-alpha produced the least side effects. Mutein V selectively binds to p55R receptor and at the same time exhibits high antitumor activity. These results confirm the usefulness of studies on the structurally altered rhTNF-alpha derivatives, produced by means of genetic engineering techniques, which bind selectively to different cellular receptors of TNF-alpha and show similar or stronger antitumor activity compared with a native molecule, without inducing undesired symptoms.