[Induction of tumor necrosis factor (TNF) in tumor-bearing mice]

Tumor necrosis factor (TNF) can be induced in BALB/c mice bearing syngeneic tumor RL male 1 lymphoma or Meth A fibrosarcoma, by initial injection of either Corynebacterium parvum or BCG, in combination with a second injection of endotoxin (LPS) almost 10 days later. Either treatment resulted in hemorrhagic necrosis and complete regression of tumors in mice. The term, "endogenous induction of TNF therapy" was proposed for this trial. Although the TNF of tumor-bearing mice was identical to that of normal mice in molecular weight (about 40,000 daltons) and isoelectric point (4.4), and differed from IFN, the in vivo effect of endogenous TNF was much more remarkable than in mice receiving passive TNF administration. The mice bearing RL male 1 lymphoma cured after endogenous induction of TNF, rejected rechallenge of the same tumor cells but not Meth-A tumor cells. Splenocytes obtained from these cured mice were also found to be inhibitory in Winn's neutralization assay. The data indicate that tumor-specific immunity can be induced in mice receiving endogenous induction of TNF.