Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Antitumor effects of cyclophosphamide (CY) and lipopolysaccharide (LPS) were investigated in BCG-treated mice. C3H/He mice and CDF1 mice were injected with BCG and were inoculated subcutaneously with syngeneic mouse hepatoma and mastocytoma P815 respectively. A subsequent injection of LPS caused hemorrhagic necrosis and retarded growth of tumor. When mice were treated with LPS plus suboptimal dose of CY, tumor growth was retarded and survival time was prolonged. The antitumor effects were more remarkable when mice were treated with CY prior to the injection of LPS. Without BCG pretreatment, LPS showed no antitumor activity in mice. Sera from mice treated with BCG plus LPS was cytotoxic for cultured tumor cells. However treatment of mice with CY did not increase the in vitro cytotoxicity. In this experimental condition, CY had no effect on delayed type hypersensitivity when evaluated by the footpad reaction to purified protein derivative (PPD). These results seem to indicate that the antitumor effects of the treatment with CY and LPS in BCG-treated mice are mediated by the reduction of tumor burden by CY and a serum factor induced by LPS.