ANTI-TUMOR IMMUNOTHERAPY WITH A HUMANIZED MONOCLONAL ANTIBODY AGAINST HUMAN PROTO-ONCOGENE PRODUCT

人原癌基因产品人源化单克隆抗体的抗肿瘤免疫治疗

• 批准号: 06671229
• 负责人: TOKUDA Yutaka
• 金额: $ 1.41万
• 依托单位: TOKAI UNIVERSITY
• 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-06671229/
• 关键词: C-erbB-2; Proto-oncogene; Humanized monoclonal antibody; Anti-tumor effect; SCID mice; 癌遺伝子; ヒト型モノクローナル抗体; 癌免疫療法

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 anti-tumor 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 xenograft with rhu4D5 revealed that the recombinant protein had potent anti-tumor activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5.These results indicate that rhu4D5 mmight be better in patients than predicted from preclinical studies. A clinical trial would be warranted.

c-erbB-2 产品被认为是过度表达 c-erbB-2 基因的癌症抗体治疗的独特且有用的靶点。研究了针对 c-erbB-2 基因产物 rhu4D5 胞外结构域的人源化抗体的体外和体内抗肿瘤作用。 Rhu4D5 对 c-erbB-2 过表达 SK-BR-3 细胞系的直接抗增殖活性不如其小鼠对应物 mu4D5 有效。用rhu4D5对携带c-erbB-2过表达4-1ST人胃癌异种移植物的SCID小鼠进行体内处理，结果表明重组蛋白具有有效的抗肿瘤活性。此外，rhu4D5 显着增强了人外周血单核细胞针对 4-1ST 的细胞毒性，但 mu4D5 则没有。这些结果表明，rhu4D5 对患者的作用可能比临床前研究预测的更好。临床试验是有必要的。

项目成果

Noriko Watanabe, et al: "Serum c-erbB-2 in breast cancer patients." Acta Oncologica. 33. 901-904 (1994)

Noriko Watanabe 等人：“乳腺癌患者的血清 c-erbB-2。”

Yasuyuki Ohnishi: "Prolonged survival of mice with human gastric cancer treated with an anti-c-ErbB-2 mono-clonal antibody" British Journal of Cancer. 71. 969-973 (1995)

Yasuyuki Ohnishi：“用抗 c-ErbB-2 单克隆抗体治疗人类胃癌小鼠的存活时间延长”英国癌症杂志。

Yutaka Tokuda, et al: "In vitro and in vivo anti-tumor effects of a humanized mono-clonal antibody against c-erbB-2 product." British Journal of Cancer. (in press).

Yutaka Tokuda 等人：“针对 c-erbB-2 产品的人源化单克隆抗体的体外和体内抗肿瘤作用。”

Noriko Watanabe: "Serum c-erbB-2 in breast cancer patients" Acta Oncologica. 33. 901-904 (1994)

Noriko Watanabe：“乳腺癌患者的血清 c-erbB-2”《肿瘤学报》。

Yutaka Tokuda: "In vitro and in vivo anti-tumor effects of a humanized monoclonal antibody against c-erbB-2 product" British Journal of Cancer. (in press).

Yutaka Tokuda：“针对 c-erbB-2 产品的人源化单克隆抗体的体外和体内抗肿瘤作用”英国癌症杂志。