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Development of tumor-imaging and -therapy on small cell lung cancer by chimera antibody.

利用嵌合抗体开发小细胞肺癌的肿瘤成像和治疗。

基本信息

批准号：
01870040
负责人：
OKABE Tetsuro
金额：
$ 17.73万
依托单位：
Univ. of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01870040/
关键词：
small cell lung cancer monoclonal antibody chimera antibody antigen cDNA radioisotope scintigraphy radiation therapy 画像診断肺癌

项目摘要

Small cell lung cancer (SCLC) represents 20% of all lung cancers. Accurate staging is critical for making therapeutic decisions. Clinical staging currently involves chest X ray and CT, CT head and abdomen, bone scan, and bone marrow examinations. More than 100 patients with newly diagnosed SCLC have been imaged 14-17 hours after administration of 15-30 mCi Tc-199m labaled TFS-2 Fab. Interium analysis shows that TFS-2 imaging alone detects about 80% of all organs involved with SCLC and identifies 85% of patients with extensive disease with a positive predicted value of 95%. No other diagnostic test approached this sensitivity and accuracy. TFS-2 imaging alone is virtually as good as the entire standard battery of tests in staging SCLC. TFS-2 imaging also upstaged from limited to extensive disease 15% of patients staged as limited by standard methods.Administration of 300muCi ^<131>I-labeled TFS-2 inhibited the growth of SCLC xenografts in nude mice. The therapeutic effect was dose-dependent and complete disappearcnce of the tumor was observed in animals treated with 500muCi of ^<131>I TFS-2.7 patients with lung cancers were given intravenously with ^<131>I-TFS-2. Although tumor imaging was obtained in all the patients, tumor regression was not observed. Rhenium 186 (beta-emitter) labeled TFS-2 also failed in SCLC therapy. This failure appears to be overcome by increasing the radiation dose, using another monoclonal antibodies to the same antigen as carriers of the therapeutic radionuclide.Development of the new monoclonal antibodies to the same antigen is ongoing.

小细胞肺癌（SCLC）占所有肺癌的20%。准确的分期对于做出治疗决定至关重要。临床分期目前包括胸部X线和CT、头部和腹部CT、骨扫描和骨髓检查。超过100例新诊断的SCLC患者在给予15-30 mCi Tc-199 m标记的TFS-2 Fab后14-17小时成像。内部分析表明，TFS-2成像单独检测约80%的所有涉及SCLC的器官，并确定85%的广泛疾病患者，阳性预测值为95%。没有其他诊断测试接近这种灵敏度和准确性。在SCLC分期中，单独的TFS-2成像几乎与整个标准测试组一样好。TFS-2成像也使15%的患者从局限性病变升级到广泛性病变，标准方法将其分期为局限性病变<131>。用500 μ Ci的~（131）I-TFS-2处理动物，观察到肿瘤完全消失<131>。7例肺癌患者静脉注射~<131>（131）I-TFS-2。虽然在所有患者中获得了肿瘤成像，但未观察到肿瘤消退。铼186（β-发射体）标记的TFS-2在SCLC治疗中也失败了。这种失败似乎可以通过增加辐射剂量来克服，使用针对相同抗原的另一种单克隆抗体作为治疗性放射性核素的载体。