The scientific clinical study of antibody therapy

抗体疗法的科学临床研究

• 批准号: 17016065
• 负责人: UEDA Ryuzo
• 金额: $ 133.82万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17016065/
• 关键词: 抗体療法; CCR4; ADCC; 成人T細胞白血病リンパ腫(ATL); ケモカイン; CD10; 抗体リモデリング; CCD4

CCR4 is a chemokine receptor selectively expressed on Treg and Th2 cells. Because we previously found that CCR4 is expressed on certain types of T-cell leukemia/lymphoma, we postulated that this molecule might represent a novel molecular target for immunotherapy against refractory T-cell leukemia/lymphoma. Accordingly, we have developed a next-generation anti-CCR4 mAb, the Fc region of which is defucosylated, resulting in highly enhanced ADCC. Based on our laboratory work on CCR4, and as an outcome of the success of this translational research, we have completed phase I & II clinical trials of anti-CCR4 mAb in patients with CCR4-positive T-cell leukemia/lymphoma in Japan, and are in the process of preparing an application to the regulatory authority for approval.

CCR4是一种在Treg和Th2细胞上选择性表达的趋化因子受体。因为我们之前发现 CCR4 在某些类型的 T 细胞白血病/淋巴瘤上表达，所以我们推测该分子可能代表针对难治性 T 细胞白血病/淋巴瘤免疫治疗的新分子靶点。因此，我们开发了下一代抗 CCR4 mAb，其 Fc 区被去岩藻糖基化，从而导致 ADCC 高度增强。基于我们对 CCR4 的实验室工作，并且作为这项转化研究成功的成果，我们已在日本完成了针对 CCR4 阳性 T 细胞白血病/淋巴瘤患者的抗 CCR4 mAb 的 I 期和 II 期临床试验，并且正在准备向监管机构提交批准申请。

项目成果

The Asn505 mutation of c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity.

c-MPL 基因的 Asn505 突变会导致家族性原发性血小板增多症，由于强氨基酸极性，会诱导 c-Mpl 蛋白自主同二聚化。

• 发表时间: 2009
• 期刊: Blood 114
• 作者: Ding J;Komatsu H;Iida S;Yano H;Kusumoto S;Inagaki A;Mori F;Ri M;Ito A;Wakita A;Ishida T;Nitta M;Ueda R
• 通讯作者: Ueda R

Defucosylated humanized anti-CCR4 monoclonal antibody KW-0761 as a novel immunotherapeutic agent for adult T-cell leukemia/lymphoma (ATLL).

去岩藻糖基化人源化抗 CCR4 单克隆抗体 KW-0761 作为成人 T 细胞白血病/淋巴瘤 (ATLL) 的新型免疫治疗剂。

• 发表时间: 2010
• 期刊: Clin Cancer Res. 16
• 作者: Ishii T;Ishida T;Utsunomiya A;Inagaki A;Yano H;Komatsu H;Iida S;Imada K;Uchiyama T;Akinaga S;Shitara K;Ueda R
• 通讯作者: Ueda R

Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor.

新型 IkappaB 激酶抑制剂抑制多发性骨髓瘤细胞的生长。

• 发表时间: 2005
• 期刊: Clin Cancer Res. 11(5)
• 作者: Sanda;T.;Ueda;R.;et al.
• 通讯作者: et al.

Detection of the API2-MALT1 fusion transcripts in cytological speciments of patients with pulmonary mucosa-associated lymphoid tissue lymphoma.

肺粘膜相关淋巴组织淋巴瘤患者细胞学标本中 API2-MALT1 融合转录本的检测。

• 发表时间: 2005
• 期刊: Int J Hematol. 82(1)
• 作者: Inagaki;H.;Ueda;R.;et al.
• 通讯作者: et al.

Regulatory T-cell function of adult T-cell leukemia/lymphoma cells

• DOI: 10.1002/ijc.22536
• 发表时间: 2007-05-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Yano, Hiroki;Ishida, Takashi;Ueda, Ryuzo
• 通讯作者: Ueda, Ryuzo