The past, the present and future of the OK-432 therapy for patients with malignant effusions.

For the past 20 years, our group has treated over 400 cases of malignant effusion by the intraperitoneal injection of streptococcal preparation OK432 (OK-432 therapy) and has investigated extensively the antitumor mechanisms of this therapy. Prospective clinical data has demonstrated that the OK-432 therapy induced a definite reduction of the effusions in around 60% (responders) of cases and significantly prolonged the survival time in patients who responded well. In addition, a definite reduction of original tumor mass volume was found in around 20% of cases. We have shown that OK432-induced neutrophils, lymphocytes, and probably macrophages may play an important role in tumor cell destruction in ascites. Tumor necrosis factor alpha (TNF-alpha)-induced CD11b/CD18 expression on leukocytes and interferon-gamma (IFN-gamma)-induced ICAM-1 expression on tumor cells may play an important role in leukocyte-mediated tumor destruction. It has also been shown that OK-432 induces various cytokines, such as TNF-alpha, TNF-beta, IFN-alpha IFN-gamma, interleukin-1 (IL-1), IL-2, IL-6, IL-12, tumor growth inhibitory factor(s) (TGIF), and possibly unknown apoptosis-inducing factor(s). Some of these cytokines have been adduced as representing the antitumor activity. These data suggest that two pathways of antitumor activity, i.e., cell-mediated and cytokine-mediated, can be induced simultaneously in the peritoneal cavity. OK-432 therapy may be valuable in the management of patients with malignant effusions. Future clinical and basic research should contribute to further progress in OK-432 therapy.