Synergistic therapeutic effect of combination therapy with OK-432 and interferon-alpha or -gamma on Meth-A ascites tumor in BALB/c mice.

A synergistic therapeutic effect on Meth-A ascites tumor was obtained in BALB/c mice by the simultaneous i.p. injection of OK-432 and interferon alpha A/D (IFN-alpha). BALB/c mice that were cured of their Meth-A tumors showed significant tumor-specific rechallenge resistance. Combined therapeutic effect was significantly weaker in nude mice than in haired mice. The stimulation of host T-cell immunity was indicated to be crucially important for obtaining cured mice. Natural killer activity of peritoneal exudate cells was enhanced and peaked on day 1 with IFN-alpha, on day 3 with OK-432, and was sustained for up to 5 days with combination therapy. Macrophage activity assayed by in vivo resistance to the challenge of Listeria monocytogenes was stronger in order of OK-432 greater than OK-432 + IFN-alpha greater than IFN-alpha. Cytotoxic T-lymphocyte activity induced by immunization with the allogeneic tumor was enhanced most strongly by OK-432 plus IFN-alpha treatment. Each of the agents had tumor inhibitory activity on the growth of Meth-A cells in vitro, and there was a slight additive effect when two agents were used together. These findings suggest that the synergistic therapeutic effect of OK-432 plus IFN-alpha treatment on Meth-A ascites tumor was partly due to the direct antitumor activity of these two agents, but was also due in part to the beneficial antitumor immune responses that were induced. A similar synergism on Meth-A tumor was also observed by OK-432 plus interferon gamma treatment. However, this combination therapy was not effective on MH-134 ascites tumor in C3H mice.