Intratumoral tumor necrosis factor induction in tumor-bearing mice by exogenous/endogenous tumor necrosis factor therapy as compared with systemic administration of various biologic response modifiers.

Abstract

The relationship between the induction of tumor necrosis factor (TNF) (as an indicator of inflammatory reaction) in tumor tissues and its antitumor effect was investigated in tumor-bearing mice by using nine biologic response modifiers (BRMs) and by exogenous/endogenous TNF therapy following a previously reported protocol. Close correlation between the induction of TNF-rich inflammation in tumor tissues and the antitumor effect of BRM were observed. The results of this study suggest that the conditions necessary for exerting antitumor effects of biologic response modifiers may be the induction of TNF (50 to 200 U/g) at the tumor lesions at an early stage after BRM administration and maintenance of the detectable amount of TNF (approximately 10 U/g) for more than 6 hours. Tumor necrosis factor should also be induced in the liver and spleen so that its activity can be maintained in the tumor lesions.