EFFECT OF BIOLOGICAL RESPONSE MODIFIERS ON GROWTH AND CELL-PROLIFERATION OF HUMAN TUMOR XENOGRAFTS IN NUDE-MICE

The effect of biological response modifiers on macroscopic tumor growt h and on tumor cell proliferation of a human renal cell carcinoma and a squamous cell carcinoma (hypopharynx) in nude mice has been studied. Tumor necrosis factor alpha (TNF-alpha) and interferon alpha (IFN-alp ha) as well as granulocyte-macrophage colony-stimulating factor (GM-CS F) were applied either alone or in combination, and TNF-alpha was also combined with etoposide (ETP). TNF-alpha and IFN-alpha alone or in co mbination did not substantially affect the course of tumor growth, how ever, they did influence the pattern of tumor growth. There was also o nly a marginal effect on tumor cell proliferation. However, IFN-alpha protects the animals from tumor growth associated weight loss. ETP and ETP plus TNF-alpha leads to a deceleration of tumor growth, a decreas e of the labeling index and to a significant decrease of the animal we ight which indicates that the first two effects may be partly due to t he toxicity of the treatment. GM-CSF modifies cell proliferation in a dose-dependent manner, i.e. stimulation at low doses and tendency to i nhibition at higher doses. Although there is no substantial direct ant ineoplastic effect of the agents studied, the results make clear that indirect effects of therapeutic agents due to therapy induced cachexia should always be regarded. It is interesting that IFN-alpha has a pro tective effect against cachexia.