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Fundamental Studies on New Effective Diagnosis and Treatment for Esophageal Carcinomas by using Monoclonal Antibody and its Fragment.

单克隆抗体及其片段新型有效诊治食管癌的基础研究。

基本信息

批准号：
04807096
负责人：
IRIE Hitoshi
金额：
$ 1.28万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04807096/
关键词：
Esophageal carcinoma Monoclonal antibody F[ab']2 Fab Biodistribution Tumor imaging F(ab′)_2フラグメント F(ab)'2 Fab

项目摘要

We had produced two types of monoclonal antibodies, KYSM-1 and KIS-1, against human squamous cell carcinoma of the esophagus for quantitaive diagnosis and optimum therapy. The isotype of KYSM-1 and KIS-1 were IgM and IgG1, respectively. These two antibodies were treated by papain to get their fragment. KYSM-1 fragment F[ab']2u and KIS-1 fragment F[ab']2 and Fab were obtained.Reactivities of these fragments were analyzed by ELISR.Reactivities of all fragments were reduced after the treatment, -28% in KYSM-1 f[ab']2u, -22% in KIS-1 F[ab']2 and -60% in KIS-1 Fab. These monoclonal antibodies and their fragments were lebeled with ^<125>I or ^<131>I by the lodogen method, and each antibody was injected into nude mice with human squamous cell carcinoma of the esophagus [KE-1]. Regarding in vivo accumulation of ^<125>I - or ^<131>I - labeled antibodies, however, ^<125>I - labeled KIS-1 F[ab']2 alone showed significantly high values in the tumor at 3 days after the injection. While, ^<125>I - labeled intact KIS-1 also showed significantly high values in the tumor by 7 days. From these results, Intact KIS-1 and KIS-1 F[ab'] 2 were labeled with ^<131>I and each or both of them were injected into the tumor-bearing nude mice with a total dose of 250uCI.The most significant inhibition of the tumor growth was noted in the mixed administration of intact and fragment KIS-1.These results suggest that the mixed administration of ^<131>I - labeled intact KIS-1 and KIS-1 F[ab']2 may provide a quantitative tumor imaging and a targeting therapy in patients with esophageal carcinoma.

制备了两种抗人食管鳞状细胞癌的单克隆抗体KYSM-1和kiss -1，用于定量诊断和优化治疗。KYSM-1和kiss -1的同型分别为IgM和IgG1。这两种抗体经木瓜蛋白酶处理后得到它们的片段。获得KYSM-1片段F[ab']2u和kiss -1片段F[ab']2和Fab。用elisa分析这些片段的反应性。治疗后，所有片段的反应性均降低，KYSM-1 f[ab']2u -28%, kiss -1 f[ab']2 -22%, kiss -1 Fab -60%。用lodogen法将这些单克隆抗体及其片段标记为^<125>I或^<131>I，并分别注射到人食管鳞状细胞癌裸鼠体内[KE-1]。然而，对于^<125 >i -或^<131 >i -标记抗体的体内积累，在注射后3天，单独使用^<125 >i -标记的kiss -1 F[ab']2在肿瘤中显示出显著的高值。而^<125 bb0 I -标记的完整的kiss -1在肿瘤中7天也显示出显著的高值。根据这些结果，将完整的kiss -1和kiss -1 F[ab'] 2标记为^<131>I，分别或同时以总剂量250uCI注射到荷瘤裸鼠体内。对肿瘤生长最显著的抑制是在完整的和片段的kiss -1混合给药中发现的。这些结果表明，混合使用^<131>I标记的完整的kiss -1和kiss -1 F[ab']2可能为食管癌患者提供定量肿瘤成像和靶向治疗。