Targeting Chemokine Receptor CCR4 in Adult T-Cell Leukemia-Lymphoma and Other T-Cell Lymphomas

Department of Hematology, and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
Current Hematologic Malignancy Reports (Impact Factor: 2.2). 04/2012; 7(3):235-40. DOI: 10.1007/s11899-012-0124-3
Source: PubMed


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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    • "The CC-chemokine receptor 4 (CCR4) is also highly expressed on tumor cells of T-cell derived variants of non-Hodgkin’s lymphoma (NHL), such as adult T-cell leukemia/lymphoma (ATLL) [13], [14], cutaneous T-cell lymphoma (CTCL) [15], [16], and other kinds of malignancies belonging to the heterogeneous group of peripheral T-cell lymphoma (PTCL) [17]. In Western countries, PTCL accounts for 15–20% of aggressive lymphomas and 5–10% of all NHL [18]. "
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