Combination cancer therapy with local and systemic injection of biological response modifiers (BRMs) in mice

To evaluate local Shwartzman's phenomenon in the treatment of malignant tumor, mice were given local injections followed by intravenous injections of biological response modifiers (BRMs). An intradermal injection of IL-1β and TNFα followed by an intravenous injection of OK-432 24 hours later induced acute inflammation with hemorrhage and necrosis at the injection site. An intratumoral injection of these cytokines into MH-134 tumor in the back followed by an intravenous injection of OK-432 induced similar hemorrhage and necrosis in the tumor, and repetition of combined injections suppressed tumor growth and prolonged survival in tumor-bearing mice. Intravenous injections of TNFα were also effective as an eliciting agent in this tumor therapy model. These results indicated serial local and systemic combination therapy with BRMs may be a new clinical therapy for patients with malignant tumor.

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