Yamana H, Kakegawa T, Tanaka T, Higaki K, Fujii T, Tou U
First Dept. of Surgery, Kurume University School of Medicine.
Gan To Kagaku Ryoho. 1994 May;21(6):755-60.
We produced two types of murine monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitative diagnosis and optimum therapy. The isotypes of KYSM-1 and KIS-1 were IgM and IgG1, respectively. Immunohistochemical staining demonstrated that both antibodies strongly reacted with human carcinoma cell lines of the esophagus, lung and oral cavity. Fluorescence activated cell sorter analysis demonstrated that each antigen of KYSM-1 and KIS-1 exposed to cellular membrane of squamous carcinoma cells and molecular weights of these antigens detected by KYSM-1 and KIS-1 were 60 kDa and 90 kDa, respectively, in non-reduced condition. These 2 monoclonal antibodies were labeled with 125I by the Iodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus. Regarding in vivo accumulation of 125I-labeled antibodies, however, KIS-1 alone showed significantly high values in the tumor at 5 and 7 days after the injection. From this result, KIS-1 was labeled with 131I and injected into the tumor-bearing mice with a dose of 200 microCi. Moderately effective results were found in the tumor by 14 days after the injection. Furthermore, KIS-1 was also conjugated to peplomycin (PEP). In in vitro and in vivo effects of targeting chemotherapy, the conjugates killed human squamous carcinoma cells and tumor-implanted nude mice. These results suggest that the 131I-labeled KIS-1 and/or KIS-1-PEP conjugate may provide a targeting therapy in patients with squamous cell carcinoma of the esophagus.
我们制备了两种针对人食管鳞状细胞癌的鼠单克隆抗体KYSM-1和KIS-1,用于定量诊断和优化治疗。KYSM-1和KIS-1的免疫球蛋白类型分别为IgM和IgG1。免疫组织化学染色显示,这两种抗体均与人食管癌、肺癌和口腔癌细胞系强烈反应。荧光激活细胞分选分析表明,KYSM-1和KIS-1的每种抗原均暴露于鳞状癌细胞的细胞膜,在非还原条件下,KYSM-1和KIS-1检测到的这些抗原的分子量分别为60 kDa和90 kDa。这两种单克隆抗体通过碘甘法用125I标记,并将每种抗体注射到患有人类食管鳞状细胞癌的裸鼠体内。然而,关于125I标记抗体的体内蓄积情况,仅KIS-1在注射后5天和7天在肿瘤中的值显著较高。基于此结果,KIS-1用131I标记,并以200微居里的剂量注射到荷瘤小鼠体内。注射后14天在肿瘤中发现了中等程度的有效结果。此外,KIS-1还与培普利霉素(PEP)偶联。在靶向化疗的体外和体内效应中,偶联物杀死了人鳞状癌细胞和肿瘤植入的裸鼠。这些结果表明,131I标记的KIS-1和/或KIS-1-PEP偶联物可能为食管鳞状细胞癌患者提供靶向治疗。