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Development of radiolabeled humanized monoclonal antibodies for therapy using gene technology.

利用基因技术开发用于治疗的放射性标记人源化单克隆抗体。

基本信息

批准号：
09557067
负责人：
ENDO Keigo
金额：
$ 7.36万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

This research project was performed to investigate the radiolabeled humanized monoclonal antibodies developed by gene technology.Monoclonal antibodies are expected to bind to the tumor expressing the corresponding antigens. For this purpose murine monoclonal antibodies are used for the diagnostic imagings and the therapy of cancers. However, antibodies derived from mice may cause allergic reactions, when administered to patients, due to the species difference. In order to decrease the immunogenecity of murine monoclonal antibodies, humanized antibodies are produced by using the gene technology. In the present study, ィイD1131ィエD1I-labeled murine monoclonal antibodies reactive with CD20 B cell antigen were investigated in the animals and confirmed to accumulate in the transplanted tumor. After getting the permission from the ethical committee of our institute ィイD1131ィエD1I-labeled antibody against CD20 antigen was safely administered to patients with non-Hodgkin lymphoma. Further studies remains to be in vestigated.ィイD1131ィエD1I-labeled monoclonal antibody named A33 was humanized and administered to gastric cancer patients (Co-investigator Junichi Sakamoto, M.D. of Aichi Prefectural Hospital and Hiroyuki Kuwano, M.D. of Gunma University Hospital). This antibody accumulated to cancer tissue with tumor to blood ratios of about 2 and tumor to normal tissue ratio of about 4.For the therapy of various diseases, new radionuclides have been investigated such as rhenium-186 and yttrium-90, which are expected to have favorable characteristics for clinical use.

本研究旨在研究利用基因技术开发的放射性标记人源化单抗，该单抗有望与表达相应抗原的肿瘤结合。为此，鼠源性单抗被用于癌症的诊断成像和治疗。然而，由于物种的差异，来自小鼠的抗体在给患者使用时可能会引起过敏反应。为了降低鼠源性单抗的免疫原性，利用基因工程技术制备了人源化抗体。在本研究中，ィイD1131ィエD1I标记的小鼠与CD20B细胞抗原反应的单抗在动物体内进行了研究，并证实在移植瘤中积累。经本所伦理委员会批准，ィイD1131ィエD1I标记抗体可安全用于非霍奇金淋巴瘤患者。进一步的研究还有待调查。将ィイD1131ィエD1I标记的单抗A33人源化，应用于胃癌患者(共同研究员，爱知县医院医学博士坂本纯一和群马大学医院医学博士久野博之)。这种抗体聚集在肿瘤组织中，肿瘤与血液的比例约为2，肿瘤与正常组织的比例约为4。在各种疾病的治疗中，人们已经研究出了新的放射性核素，如Re-186和Y-90，它们有望具有良好的临床应用特性。