In vivo experimeted model for anticancer therapy using murine and humanized monoclonal antibodies

使用鼠和人源化单克隆抗体进行抗癌治疗的体内实验模型

• 批准号: 06680838
• 负责人: SHIMAMURA Kazuo
• 金额: $ 1.47万
• 依托单位: Tokai University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06680838/
• 关键词: c-erbB-2; SCID mice; anti-tumor effect; humanized monoclonal antibody; SCID mouse; human gastric carcinoma; monoclonal antibody; immunotherapy

The c-erbB-2 product is thought to be an unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo antitumor effects of a humanized antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2 overexpressing SK-BR-3 cell line. In vivo treatment of SCID mice carrying the c-erbB-2 overexpressing 4-1ST human gastric carcinoma xanograft anti-tumor activity. Furthemore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was signnificantly augmented with rhu4D5, but not with mu4D5.These results indicate that rhu4D5 might be better in patients than predicted from preclinical studies.Injection of 4-1ST cells into the tail vein resulted in death of the mice within 80 days. Threatment of animals with rhu4D5 prolonged murine survival time slightly but not the level with mu4D5.

C-erb B-2产物被认为是一种独特且有用的靶点，可用于过表达c-erb B-2基因的癌症的抗体治疗。检测了针对c-erbB-2基因产物胞外区的人源化抗体rhu4D5的体内外抗肿瘤作用。Rhu4D5对高表达c-erbB-2的SK-BR-3细胞株的直接抗增殖作用弱于其相应的小鼠模型mu4D5。体内治疗携带c-erbB-2高表达人胃癌第4-1号人胃癌移植瘤活性的SCID小鼠。此外，rhu4D5可显著增强人外周血单个核细胞对4-1细胞的杀伤活性，而mu4D5对其杀伤作用不明显。结果表明，rhu4D5对患者的杀伤作用可能比临床前研究预测的要好。动物受到rhu4D5的威胁后，小鼠的存活时间略有延长，但不能达到mu4D5的水平。

项目成果

Ohnishi, Y., Shimanura, K., et al.: "Prolonged survival of mice with human gastric cancer treated with an anti-c-erbB-2 monoclonal antibody" Br.J.Cancer. 71. 969-973 (1995)

Ohnishi, Y.、Shimanura, K. 等人：“用抗 c-erbB-2 单克隆抗体治疗的人胃癌小鼠的存活时间延长”Br.J.Cancer。

Tokuda, Y., Shimamura, K., et al.: "In vivo and invitro antitumor effect of a humanized monoclonal antibody a against c-erbB-2 product" Br.J.Cancer. (in press).

Tokuda, Y.、Shimamura, K. 等人：“人源化单克隆抗体 a 针对 c-erbB-2 产品的体内和体外抗肿瘤作用”Br.J.Cancer。

Ohishi, Y. Shimamura, K, et al: "Prolonged survival of mice with human gastric cancer treated with an antic-erbb-2 monoclonal antibody" Br. J. Cancer. 71. 969-973 (1995)

Ohishi, Y. Shimamura, K 等人：“用抗 erbb-2 单克隆抗体治疗的人胃癌小鼠的存活时间延长” Br。

Tokuda Y.,Shimamura K.,et al: "In vivo and in vitro antitumor effect of a humanized monoclonal antibody against c-erbB-2 product" Br.J.Cancer. (in press).

Tokuda Y.、Shimamura K.等人：“针对 c-erbB-2 产品的人源化单克隆抗体的体内和体外抗肿瘤作用”Br.J.Cancer。

Ohishi Y.,Shimamura K.,et al: "Prolonged survival of mice with human qastric cancer treated with an anti-c-erbB-2 monoclonal antibody" Br.J.Cancer. 71. 969-973 (1995)

Ohishi Y.、Shimamura K. 等人：“用抗 c-erbB-2 单克隆抗体治疗的人类胃癌小鼠的存活时间延长”Br.J.Cancer。