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Targeted radio-immuno-chemotherapy against liver metastases of gastric cancer using radio-labeled chimeric monoclonal antibody and chimeric antibody-drug conjugates.

使用放射性标记的嵌合单克隆抗体和嵌合抗体-药物缀合物对胃癌肝转移进行靶向放射免疫化疗。

基本信息

批准号：
15591426
负责人：
OKAMOTO Kazuma
金额：
$ 1.98万
依托单位：
Kyoto Prefectural University of Medicine, Graduate School of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

1)Preparation of radio-labeled chimeric monoclonal antibodyChimeric monoclonal antibody chA7 was labeled with 131-I, and purified.2)In vitro antitumor effects of 131-I labeled chA7In vitro antitumor effects of 131-I labeled chA7 against human gastric cancer cell lines were investigated. The effects showed greater than that of chA7 alone.3)Production of murine liver metastases model using human gastric cancer cell linesA murine liver metastases model of gastric cancer was tried to produce using human gastric cancer cell lines, such as MKN1, MKN45 and KATOIII, injected into subserosa of spleen. A suitable model was not succeeded to produce.4)Acute toxicity of 131-I labeled chA7 for miceAcute toxicity of 131-I labeled chA7 for mice was checked. No severe toxicity was noted under 55.5MBq/a mouse of 131-I chA7.5)Biodistribution of 131-I chA7 in mice bearing liver metastases of gastric cancerBiodistribution of 131-I chA7 in mice bearing liver metastases of gastric cancer was not investigated because murine liver metastases model could not be made. So biodistribution of 131-I chA7 in mice bearing subcutaneous gastric cancer tumor. 131-I chA7 accumulated most in the tumor 2 hour after injection.6)In vivo tumoricidal effects of 131-I chA7 against gastric cancerNude mice bearing human gastric cancer tumor were received 7.4MBq/ a mouse or 14.8MBq/ a mouse of 131-I chA7 2 weeks after tumor inoculation. No significnant effect was noted in both group.

1)放射性标记嵌合单克隆抗体chA 7的制备用131-I标记嵌合单克隆抗体chA 7，并纯化。2）131-I标记chA 7的体外抗肿瘤作用研究131-I标记chA 7对人胃癌细胞株的体外抗肿瘤作用。3）使用人胃癌细胞系的小鼠肝转移模型的产生尝试使用人胃癌细胞系如MKN 1、MKN 45和KATO III，注射到脾浆膜下来产生胃癌的小鼠肝转移模型。4）131-I标记chA 7对小鼠的急性毒性试验131-I标记chA 7对小鼠的急性毒性试验。5）131-IchA 7在胃癌肝转移小鼠体内的生物分布131-IchA 7在胃癌肝转移小鼠体内的生物分布由于无法建立小鼠肝转移模型，故未进行研究。因此，131-I chA 7在皮下胃癌荷瘤小鼠中的生物分布。131-IchA 7体内抗肿瘤作用荷人胃癌裸鼠接种肿瘤2周后，分别给予7.4MBq/只和14.8MBq/只131-IchA 7。两组均无显著性差异。