Mogamulizumab是一种针对C-C趋化因子受体4的人源化单抗,可用于治疗t细胞淋巴瘤和哮喘。

Sabina A Antoniu
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摘要

Mogamulizumab (kw - 0761;AMG-761)是一种去聚焦的人源化IgG1单抗,靶向C-C趋化因子受体4 (CCR4),可能用于静脉注射治疗t细胞淋巴瘤和哮喘。趋化因子及其受体是构成淋巴细胞和中性粒细胞趋化的信号分子,也参与多种疾病的发病机制。特别是,CCR4已被证明在成人t细胞白血病/淋巴瘤(ATL)中发挥重要作用,它是预后不良的标志。因此,CCR4阻断可能在治疗ATL方面具有治疗潜力,ATL是一种病程中最具侵袭性的疾病,现有的治疗方法并不总是有效。Mogamulizumab在临床前研究中通过增强抗体依赖性细胞毒性来降低肿瘤负荷,并在ATL患者的早期临床试验中显示出有希望的疗效。此外,CCR4还在维持哮喘患者的t辅助细胞2型气道炎症中发挥作用,安进已获得针对该适应症和其他非肿瘤学适应症开发mogamulizumab的权利;然而,在本文发表时,安进公司的调查没有数据。这是一篇关于mogamulizumab治疗t细胞淋巴瘤和哮喘的潜在应用的综述,特别强调ATL的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mogamulizumab, a humanized mAb against C-C chemokine receptor 4 for the potential treatment of T-cell lymphomas and asthma.

Mogamulizumab (KW-0761; AMG-761), under development by Kyowa Hakko Kirin and Amgen, is a defucosylated humanized IgG1 mAb against C-C chemokine receptor 4 (CCR4) for the potential intravenous treatment of T-cell lymphomas and asthma. Chemokines and their receptors are signaling molecules constitutively responsible for lymphocyte and neutrophil chemotaxis, which can also be involved in pathogenic mechanisms of various diseases. In particular, CCR4 has been demonstrated to play a major role in adult T-cell leukemia/lymphoma (ATL), in which it is a marker of poor prognosis. Consequently, CCR4 blockade might have therapeutic potential in treating ATL, a disease that is most often aggressive in course, and for which existing therapies are not always effective. Mogamulizumab reduced tumor load via enhanced antibody-dependent cell cytotoxicity in preclinical studies and demonstrated promising efficacy in early clinical trials in patients with ATL. In addition, CCR4 also has a role in maintaining T-helper cell type 2 airways inflammation in asthma, and Amgen have acquired the rights to develop mogamulizumab for this indication and other non-oncology indications; however, at the time of publication, no data were available from Amgen's investigations. This is a review on the potential use of mogamulizumab for the treatment of T-cell lymphomas and asthma, with specific emphasis on the treatment of ATL.

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Current Opinion in Molecular Therapeutics
Current Opinion in Molecular Therapeutics 医学-生物工程与应用微生物
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