The past, the present and future of the OK-432 therapy for patients with malignant effusions.
The past, the present and future of the OK-432 therapy for patients with malignant effusions.
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OK-432 治疗恶性胸腔积液患者的过去、现在和未来。
作者：
Mitsuo Katano;T. Morisaki
近20年来，我们课题组采用链球菌制剂OK432腹腔注射（OK-432疗法）治疗恶性胸腔积液400余例，并对该疗法的抗肿瘤机制进行了深入研究。前瞻性临床数据表明，OK-432 疗法使约 60% 的病例（有反应者）的积液明显减少，并显着延长了反应良好的患者的生存时间。此外，约 20% 的病例发现原始肿瘤体积明显减少。我们已经证明，OK432 诱导的中性粒细胞、淋巴细胞，可能还有巨噬细胞，可能在腹水肿瘤细胞破坏中发挥重要作用。肿瘤坏死因子α（TNF-α）诱导的白细胞上的CD11b/CD18表达和干扰素-γ（IFN-γ）诱导的肿瘤细胞上的ICAM-1表达可能在白细胞介导的肿瘤破坏中发挥重要作用。研究还表明，OK-432 可诱导多种细胞因子，例如 TNF-α、TNF-β、IFN-α、IFN-γ、白介素-1 (IL-1)、IL-2、IL-6、IL-12、肿瘤生长抑制因子 (TGIF) 以及可能未知的细胞凋亡诱导因子。其中一些细胞因子已被认为代表抗肿瘤活性。这些数据表明，可以在腹膜腔中同时诱导两种抗肿瘤活性途径，即细胞介导的和细胞因子介导的。 OK-432 疗法对于治疗恶性胸腔积液患者可能很有价值。未来的临床和基础研究应有助于 OK-432 疗法的进一步进展。
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.