SYNERGISTIC EFFECTS OF HUMANIZED ANTI-c-erbB-2 MONOCLONAL ANTIBODY WITH CHEMOTHERAPEUTIC AGENTS

人源化抗c-erbB-2单克隆抗体与化疗药物的协同作用

• 批准号: 09671253
• 负责人: TOKUDA Yutaka
• 金额: $ 2.05万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671253/
• 关键词: C-erbB-2; Humanized monoclonal antibody; Anticancer drugs; SCID mice

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. A humanized antibody which contained only the antigen-binding loops from a murine monoclonal antibody against the extracellular domain of the c-erbB-2 gene product, human variable region framework residues and IgG1 constant domains was constructed.In vivo anti-tumor effects of the humanized anti-c-erbB-2 monoclonal antibody with CDDP were examined using SCID mice bearing 4-1ST and St-40 of c-erbB-2 positive human gastric cancer xenografis. Anti-tumor effects of the antibody were found to be synergistic with CDDP. The precise underlying mechanism for this synergistic interaction remains unknown, though it is currently being evaluated. Preliminary, platinum contents of the tumors were higher in the mice treated with CDDP and the antibody than those only with CDDP. These synergistic or additive effects were also found in the mice treated with etoposide and MMC in conjunction with the antibody.

c-erbB-2产物被认为是针对过表达c-erbB-2基因的癌症进行抗体治疗的独特而有用的靶点。构建了一种人源化抗体，该抗体仅包含针对c-erbB-2基因产物胞外结构域、人可变区框架残基和IgG1恒定结构域的小鼠单克隆抗体的抗原结合环。用携带c-erbB-2阳性人胃癌异种瘤细胞4-1和St-40的SCID小鼠检测人源化抗c-erbB-2单克隆抗体与CDDP的体内抗肿瘤作用。发现该抗体的抗肿瘤作用与CDDP具有协同作用。这种协同作用的确切潜在机制尚不清楚，尽管目前正在进行评估。初步发现，CDDP联合抗体治疗的小鼠肿瘤中铂的含量高于单纯CDDP治疗的小鼠。这些协同或加性效应也发现在小鼠与依托泊苷和MMC联合抗体。

项目成果

Yutaka Tokuda, et al.: "A novel therapy for breast cancer: a humanized antibody to HER2/neu"Geka. 61. 1281-1284 (1999)

Yutaka Tokuda 等人：“乳腺癌的新疗法：HER2/neu 人源化抗体”Geka。

徳田裕他: "乳癌に対する新しい治療法-抗体治療"外科. 61. 1281-1284 (1999)

Yutaka Tokuda 等：“乳腺癌的新疗法 - 抗体疗法” Surg. 61. 1281-1284 (1999)

Yutaka Tokuda,et al.: "Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in…"British Journal of Cancer. 81. 1419-1425 (1999)

Yutaka Tokuda 等人：“人源化抗 HER2 单克隆抗体的剂量递增和药代动力学研究……”英国癌症杂志 81. 1419-1425 (1999)

Yutaka Tokuda, et al: "Dose escalation and phoarmacokinetic study of a humanized anti-HER2 monoclonal antibody in . . ."British Journal of Cancer. 81. 1419-1425 (1999)

Yutaka Tokuda 等人：“人源化抗 HER2 单克隆抗体的剂量递增和药代动力学研究……”英国癌症杂志。

Yutaka Tokuda, et al.: "Dose escalation and pharmaco-kinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer"British Journal of Cancer. 81. 1419-1425 (1999)

Yutaka Tokuda 等人：“人源化抗 HER2 单克隆抗体在 HER2/neu 过表达转移性乳腺癌患者中的剂量递增和药代动力学研究”英国癌症杂志。