Studies for clinical application of missile therapy for cancer.

癌症导弹治疗的临床应用研究。

• 批准号: 02454318
• 负责人: TAKAHASHI Toshio
• 金额: $ 3.97万
• 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 General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454318/
• 关键词: Missile Therapy; Monoclonal Antibody; Chimeric Antibody; Colon Cancer; HAMA; モノクロ-ナル抗体; 抗癌剤; 膵癌; ポリエチレングリコ-ル; 癌化学療法; ネオカルチノスタチン

Monoclonal antibody-drug conjugate,A7-NCS,was applied for 80 patients with colorectal and pancreatic cancer, including metastasis of liver, lung and peritoneum. Fifty-four patients with colon cancer, fifteen patients with postoperative liver metastasis of colorectal cancer and one patient with advanced pancreatic cancer ware given A-NCS intra-arterially. Two patients with postoperative lung metastasis of colon cancer were injected intra-venously and one patient with postoperative peritoneal metastasis of colon cancer was given it intraperitoneally. Three patients with liver metastasis showed evidence of tumor reduction on CT scan and three claimed pain relief. Postoperative survival of the patients with distant metastasis exhibited slightly higher survival rate in the patients with A7-NCS, as compared with the patients without A7-NCS. There was no serious adverse effect in the patients given A7-NCS.Human anti-body(HAMA)was detected in all patients given the conjugate. Repeated injections of A7-NCS for several consecutive days following the first injection brought about the same A pattern as the first injection. Chimeric monoclonal antibody A7 and its conjugate chimeric A7-NCS were successfully produced.

应用单抗-药物结合物A7-NCS治疗80例结直肠癌和胰腺癌，包括肝、肺和腹膜转移。对54例结肠癌患者、15例结直肠癌术后肝转移患者和1例晚期胰腺癌患者进行A-NCS动脉内化疗。2例结肠癌术后肺转移患者静脉注射，1例结肠癌术后腹膜转移患者腹腔注射。3例肝转移患者CT扫描显示肿瘤缩小，3例疼痛缓解。A7-NCS患者术后有远处转移患者的生存率略高于无A7-NCS患者。服用A7-NCS的患者没有严重的不良反应，所有服用该结合物的患者都检测到了人类抗体(HAMA)。在第一次注射后连续几天重复注射A7-NCS可产生与第一次注射相同的A型。成功制备了嵌合单抗A7及其偶联的嵌合A7-NCS。

项目成果

山口 俊晴: "腫瘍マーカーと免疫療法" Modern Physician. 12. 1055-1058 (1992)

山口俊晴：《肿瘤标志物与免疫治疗》《现代医师》12. 1055-1058 (1992)。

Noguchi,A.: "Enhanced tumor localization of monoclonal anti-body by treatment with Kininase Inhibitor." Jpn.J.Cancer Res.83. 240-243 (1992)

Noguchi,A.：“通过激肽酶抑制剂治疗增强单克隆抗体的肿瘤定位。”

Noguchi,A.: "Preparation and properties of the immuno-conjugate composed of anti-human colon cancer monoclonal antibody and MMC-dextran conjugate." Bioconjugate Chemistry. 3. 132-137 (1992)

Noguchi,A.：“由抗人结肠癌单克隆抗体和 MMC-葡聚糖缀合物组成的免疫缀合物的制备和特性。”

Kitamura,K,Takahashi,T, K,Noguchi,A.et al.: "Pharmacokinetics analysis of monoclonal antibody A7ーneocarzinostatin conjugate administered to nude mice." Tohoku J exp.Med. 164. 203-211 (1991)

Kitamura,K,Takahashi,T,K,Noguchi,A.et al.：“给予裸鼠的单克隆抗体 A7-新制癌菌素缀合物的药代动力学分析。Tohoku J exp.Med 164. 203-211 (1991)

Otsuji, E., Yamaguchi, T., Yamaguchi, M., Koyama, K., Imanishi, J., Yamaoka, N., Takahashi, T.: "Expression of cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines." Surgery Today Jpn J surg. 22. 351-256 (1992)

Otsuji, E.、Yamaguchi, T.、Yamaguchi, M.、Koyama, K.、Imanishi, J.、Yamaoka, N.、Takahashi, T.：“胰腺癌中单克隆抗体 A7 检测到的细胞表面抗原的表达