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DEVELOPMENT OF A LUNG CANCER TREATMENT USING ANTI-KL-6/MUC1 MULTI-MONOCLONAL ANTIBODIES

使用抗 KL-6/MUC1 多单克隆抗体开发肺癌治疗方法

基本信息

批准号：
10670548
负责人：
KOHNO Nobuoki
金额：
$ 1.98万
依托单位：
HIROSHIMA UNIVERSITY (2000)Ehime University (1998-1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670548/
关键词：
Lung Cancer KL-6 MUC1 mouse monoclonal antibody CAIMAN human monoclonal antibody chimera antibody antibody supplement therapy Muc1

项目摘要

MUC1 mucin, which is a membrane penetrating glycoprotein expressed on a variety of epithelial malignant cells, has a biological function to inhibit physically cell adhesion because of its length. We have clarified that a mouse monoclonal antibody, KL-6/MUC1 antibody, produced by us induces cell adhesion and suppress cancer cell proliferation. These results suppose that the supplementation of anti-KL-6/MUC1 antibodies might be effective as a new strategy against malignancies.There are some problems in the application of mouse monoclonal antibodies to human being such as immunogenicity, deterioration of reactivity and metabolism. Humanization of mouse monoclonal antibodies, mouse-human chimera and CDR-grafted humanized antibody, have been attempted.Cloning and the gene sequence analysis of cDNA, VH and Vκ genes, of the variable region of the KL-6/MUC1 mouse antibody was performed by the RT-PCR method using Mouse Ig-Primer set (Novagen, USA) after the extraction of RNA from KL-6/MUC1 mouse antibody producing hybridoma. Two different sequences were obtained both in VH and Vκ genes. Each one of the two was from P3/NS1/Ag-4-1 cell which is a parental murine myeloma cell of the hybridoma. The VH and Vκ genes were inserted into an expression vector which has the promotor and constant region arangements of human immunoglobulin. The reactivities of cloned humanized antibodies are examined.

MUC 1粘蛋白是一种在多种上皮恶性细胞上表达的穿膜糖蛋白，由于其长度而具有物理抑制细胞粘附的生物学功能。我们已经阐明了我们生产的小鼠单克隆抗体KL-6/MUC 1抗体诱导细胞粘附并抑制癌细胞增殖。这些结果表明，抗KL-6/MUC 1抗体的补充可能是一种有效的抗肿瘤新策略。从KL-6/MUC 1鼠抗体产生杂交瘤中提取RNA后，用小鼠Ig引物组（Novagen，USA）通过RT-PCR方法克隆KL-6/MUC 1鼠抗体可变区的cDNA（VH和Vκ基因）并进行基因序列分析。在VH和Vκ基因中获得了两种不同的序列。这两种细胞中的每一种均来自P3/NS 1/Ag-4-1细胞，其是杂交瘤的亲本鼠骨髓瘤细胞。将VH和Vκ基因分别插入到含有人免疫球蛋白启动子和恒定区序列的表达载体中。检查克隆的人源化抗体的反应性。