Prevention of liver metastasis after resection of colorecatal cancer using immunoconjugates composed of anticancer drug and chimeric antibody

抗癌药物与嵌合抗体免疫偶联物预防结直肠癌切除术后肝转移

• 批准号: 08557077
• 负责人: YAMAGUCHI Toshiharu
• 金额: $ 2.88万
• 依托单位: KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557077/
• 关键词: Chimeric antibody; Immunoconjugate; Colon cancer; Liver metastasis; Prevention of recurrence; Anticancer drug; モノクローナル抗体; 抗イディオタイプ抗体; 臨床試験; 化学療法; ミサイル療法; ネオカルチノスタチン; 再発防止

The goal of this study is to develop a new type of targeting chemotherapy using human/mouse chimeric monoclonal antibody and anticancer drug and to apply it for the prevention of hepatic metastasis after curative resection of colorectal cancer. Through the phase I clinical study, maximum tolerance dose of this immunoconjugate could be defined and chirneric immunoconjugate showed less antigenicity compared with immunoconjugate composed of mouse monoclonal antibody. Though, the development of minor reaction of anti-idio type human anti-mouse antibody could not be avoided. The characterization of antigen detected by chimeric antibody is necessary to extend this study, though the characterizations are still in progress. Though the recent change of GCP(good clinical practice) interrupted the permission of clinical trial of this immunoconjugates, application of the phase II clinical study will be authorized near future.

本研究的目的是利用人/鼠嵌合单克隆抗体和抗癌药物开发一种新型靶向化疗，并将其应用于预防结直肠癌根治性切除术后的肝转移。通过I期临床研究，可以确定该免疫偶联物的最大耐受剂量，并且与小鼠单克隆抗体组成的免疫偶联物相比，手性免疫偶联物的抗原性较低。然而，抗独特型人抗小鼠抗体的轻微反应的发生是不可避免的。嵌合抗体检测到的抗原的表征对于扩展这项研究是必要的，尽管表征仍在进行中。虽然最近GCP（良好临床实践）的变化中断了该免疫偶联物的临床试验许可，但II期临床研究的申请将在不久的将来获得批准。

项目成果

山口俊晴: "抗体工学と癌治療:抗癌剤結合抗体" Biotherapy. 10. 114-120 (1996)

Toshiharu Yamaguchi：“抗体工程和癌症治疗：抗癌药物缀合抗体”生物疗法。10. 114-120 (1996)

Otsuji,E.: "End result of simultaneous splenectomy in patients undergoing total gastrectomy for gastric carcinoma." Surgery. 120. 40-44 (1996)

Otsuji,E.：“接受胃癌全胃切除术的患者同时进行脾切除术的最终结果。”

Yamaguchi, t. et al: "Antibody engineering and cancer therapy" Biotherapy. 10. 114-120 (1996)

山口，T。

Kitamura, K., Yamaguchi, T., Okamoto, K., Otsuji, E., Taniguchi, H., Hagiwara, A., Sawai, K., Takahashi, T.: "Clinicopathologic features of synchronous multifocal early gastric cancers" Anticancer Res. 17. 643-646 (1997)

Kitamura, K.、Yamaguchi, T.、Okamoto, K.、Otsuji, E.、Taniguchi, H.、Hagiwara, A.、Sawai, K.、Takahashi, T.：“同步多灶性早期胃癌的临床病理特征”

Yamaguchi, T .et al: "Lymph nodes dissection at hilum of spleen and along the splenic artery" Geka. 58. 1565-1568 (1996)

Yamaguchi, T 等人：“脾门处和沿脾动脉的淋巴结解剖”Geka。