Auqmetation of antitumor immunity by a mixture of OK-432 and fibrinogen

OK-432（5 KE）是一种由化脓性链球菌减毒菌株制成的抗肿瘤药物，溶于1 ml抑肽酶（1, 000 KIE）中，与80 mg含凝血因子XIII的纤维蛋白原混合，在100多例大肠癌患者术前内镜下瘤内注射。术后组织病理学检查显示注射部位形成纤维蛋白网，注射后第2天肿瘤间质中有明显的炎性细胞浸润; 4 ~ 7天形成含有许多巨细胞的肉芽肿; 14天后肿瘤组织广泛破坏。我们分析了一种新的治疗肝细胞癌（HCC）的方法：OK-432和纤维蛋白原经动脉免疫栓塞（TIE）的结果。在19例其他治疗无效的晚期肝癌患者中，14例（74%）在TIE后2 ~ 16个月存活，所有患者血清肿瘤标志物水平均下降，6例患者肿瘤体积明显缩小，所有患者均出现高热。然而，肝功能恶化似乎可以忽略不计。TIE后切除标本的组织学检查显示主肿瘤和肝内转移瘤的肿瘤细胞巢周围有大量单核细胞浸润。

OK-432 (5 KE), an antineoplastic agent prepared form an attenuated strain of Streptococcus pyogenes, was dissolved in 1 ml of aprotinin (1,000 KIE) and mixed with 80 mg of fibrinogen containing factor-XIII.A single intratumoral injection of the mixture was administered preoperatively under endoscopy in more than 100 patients with colorectal carcinoma. Postoperative histopathological examinations revealed the formation of fibrin mesh at the site of injection and marked infiltration of inflammatory cells into the tumor stroma on the day following injecton ; the formation of granulomas containing many giant cells after 4 to 7 days ; and extensive destruction of tumor tissue after 14 days. We analyzed the results of a new therapy for hepatocellular carcinoma (HCC) : transarterial immuno-embolization (TIE) with OK-432 and fibrinogen. Of 19 patients with advanced HCC in which other treatments were ineffective, 14 (74%) were surviving at 2 to 16 months after TIE.Serum levels of the tumor markers decreased in all patients and a marked reduction of tumor size was observed in 6 patients after TIE.High fever was observed in all patients. However, deterioration of liver function seemed to be negligible. Histological examination of resected specimens following TIE showed massive infiltration of mononuclear cells around tumor cell nests of the main tumor and intrahepatic metastases.