Targeting chemokine receptor CCR4 in adult T-cell leukemia-lymphoma and other T-cell lymphomas.

Targeting chemokine receptor CCR4 in adult T-cell leukemia-lymphoma and other T-cell lymphomas.
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DOI:
10.1007/s11899-012-0124-3
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发表时间:
2012-09
影响因子:
2.9
通讯作者:
Akinaga, Shiro
Akinaga, Shiro
中科院分区:
医学3区
文献类型:
--
作者:
Tobinai, Kensei;Takahashi, Takeshi;Akinaga, Shiro

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外周T细胞淋巴瘤(PTCL)是一组难以治疗的淋巴样恶性肿瘤,因为大多数PTCL是难治性的或复发的,因此医学上对新的治疗方式的需求还没有得到满足。CC趋化因子受体4(CCR4)在包括成人T细胞白血病-淋巴瘤(ATL)在内的各种类型的PTCL中均有表达,是预后最差的一种。一项脱糖人源化的抗CCR4单抗MoGamulizumab(KW-0761)的II期研究显示,在以前接受过化疗的CCR4阳性ATL复发患者中,总有效率为50%(13/26),中位无进展生存期为5.2个月。在美国的一项I/II期研究中,Mogamulizumab也显示出对皮肤T细胞淋巴瘤的潜在疗效。还需要进一步的临床前和临床研究,以检验这种新型药物与其他具有不同作用机制的药物联合使用是否对ATL和其他PTCL更有效。
Peripheral T-cell lymphoma (PTCL) is a group of lymphoid malignancy that remains difficult to treat, as most PTCL becomes refractory or relapses, and thus there is an unmet medical need for novel treatment modalities. CC chemokine receptor 4 (CCR4) is expressed in various types of PTCL including adult T-cell leukemia-lymphoma (ATL), which has the worst prognosis among them. A phase II study of a defucosylated, humanized anti-CCR4 monoclonal antibody, mogamulizumab (KW-0761), yielded an overall response rate of 50 % (13/26) and a median progression-free survival of 5.2 months in relapsed patients with CCR4-positive ATL who had been previously treated with chemotherapy. Mogamulizumab also showed potential efficacy for cutaneous T-cell lymphoma in a US phase I/II study. Further preclinical and clinical investigations are needed to examine whether concomitant use of this novel agent with other agents with different mechanisms of action would be more effective for ATL and other PTCLs.
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