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

由化脓性链球菌减毒株制备的抗肿瘤药物OK-432 （5ke）溶于1 ml抑酶蛋白（1000 KIE）中，与80 mg含因子- xiii的纤维蛋白原混合。对100多例结直肠癌患者进行了术前内镜下单次瘤内注射。术后组织病理学检查显示注射部位纤维蛋白网状物形成，注射次日肿瘤间质有明显的炎症细胞浸润；4 ~ 7天后形成含有大量巨细胞的肉芽肿；14天后肿瘤组织大面积破坏。我们分析了一种治疗肝细胞癌（HCC）的新疗法的结果：经动脉免疫栓塞（TIE）与OK-432和纤维蛋白原。在其他治疗无效的19例晚期HCC患者中，14例（74%）在TIE后2至16个月存活。所有患者的血清肿瘤标志物水平均下降，其中6例患者的肿瘤大小明显缩小。所有患者均出现高热。然而，肝功能的恶化似乎可以忽略不计。TIE术后切除标本的组织学检查显示，主要肿瘤细胞巢周围有大量单核细胞浸润和肝内转移。

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.