Development of Magnetite Conjugated to Monoclonal Antibodies for Cancer Diagnosis and Therapy

用于癌症诊断和治疗的磁铁矿缀合单克隆抗体的开发

• 批准号: 07557088
• 负责人: TAKAHASHI Toshio
• 金额: $ 10.94万
• 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557088/
• 关键词: monoclonal antibody; intraoperative diagnosis; colonic cancer; chimeric antibody; 転移; 磁性体; 簡中診断; ハイブリッド; 磁気検出

Recently, aggressive lymph node dissection in conjunction with resection of main tumor for visceral malignancy has been reported to result in substantial improvements in survival. However, normal organs or lymph nodes without cancer involvment are resected simultaneously with cancerous tissues. It is difficult to differenciate cancerous tissues from normal tissues with CT scan ot MRI.We have developed monoclonal antibody (Mab) A7 against human colon cancer. MAbA7 has been reported to react with 88% of human colonic carcinomas tested. Recently, we also developed human/mouse chimeric Fab fragments of MabA7 (ChA7Fab) using recombinant DNA techniques. In this study, ChA7Fab was labeled with ^<131>I and administered to nude mice bearing human colon cancer. Radioactivities in the small tumors were measured using portable gamma detecting probe (GDP) two days after injection. Radioactivities in the small tumors were able to detected by GDP.In contrast, radioactivity of normal tissue was not detected. If these ideas could be applied to the human with colon cancer, cancerous tissues could be easily differenciated from normal tissues intraoperatively, because GDP is small device and can be used intraoperatively. Furthermore, if magnetite are used insted of ^<131>I and the device which measure the accumulation of mignetite, we will not be exposed to radioactivity.

最近，有报道称，积极淋巴结清扫结合主要肿瘤切除治疗内脏恶性肿瘤可显著提高生存率。然而，没有癌症累及的正常器官或淋巴结与癌组织同时切除。CT扫描或MRI扫描很难将癌变组织与正常组织区分开来。我们已研制出抗人结肠癌单克隆抗体A7。据报道，MAbA7与88%的人类结肠癌发生反应。最近，我们还利用重组DNA技术开发了MabA7的人/小鼠嵌合Fab片段（ChA7Fab）。在本研究中，ChA7Fab被标记为^<131>I，并给予患有人结肠癌的裸鼠。注射后2天，用便携式伽马探测探针（GDP）测量小肿瘤的放射性。小肿瘤的放射性可以通过GDP检测到。正常组织未检测到放射性。如果这些想法可以应用于结肠癌患者，术中可以很容易地区分癌组织和正常组织，因为GDP是一个小的装置，可以在术中使用。此外，如果用磁铁矿代替^<131>I和测量磁铁矿积累的装置，我们将不会暴露在放射性中。

项目成果

山口俊晴他: "大腸癌-診断と治療の最近の進歩-診断.モノクローナル抗体による大腸癌の診断" 消化器病セミナー61. 65-76 (1995)

Toshiharu Yamaguchi 等人：“结肠癌 - 诊断和治疗的最新进展 - 诊断。使用单克隆抗体诊断结直肠癌”胃肠病学研讨会 61. 65-76 (1995)

Otsuji E 他: "Biodistribution of murine and chimeric Fab fragments of the monoclonal antibody A7 in human pancreatic cancer" Pancreas. 10 (3). 265-273 (1995)

Otsuji E 等人：“单克隆抗体 A7 的鼠类和嵌合 Fab 片段在人胰腺癌中的生物分布”10 (3) (1995)。

C.Sakakura et al: "Inhibition of colon cancer cell proliferation by antisense oligonucleo-tides targeting the mesenger.RNA of the Ki-ras gene" Anti-cancer Drugs. 6. 553-561 (1995)

C.Sakakura 等人：“通过针对 Ki-ras 基因的信使 RNA 的反义寡核苷酸抑制结肠癌细胞增殖”抗癌药物。

T.Imanishi et al: "1st Int.Gastric cancer congress" Intraperitoneal cisplatin microspheres for the treatment of malignant ascites induced by gastric cancer., 4 (1995)

T.Imanishi 等：“第一届国际胃癌大会”腹腔内顺铂微球治疗胃癌引起的恶性腹水。，4 (1995)

A.Hagiwara et al: "1st Int.Gastric cancer congress" Endoscopic injetion of methotrexate bound to activated carbon particles for the treatment of gastric cancer,a pilot study., 4 (1995)

A.Hagiwara 等人：“第一届国际胃癌大会”内窥镜注射甲氨蝶呤与活性炭颗粒结合用于治疗胃癌，一项初步研究。，4 (1995)