Curr Hematol Malig Rep (2012) 7:235–240 DOI 10.1007/s11899-012-0124-3 LYMPHOMAS (J ARMITAGE AND P MCLAUGHLIN, SECTION EDITORS) Targeting Chemokine Receptor CCR4 in Adult T-Cell Leukemia-Lymphoma and Other T-Cell Lymphomas Kensei Tobinai & Takeshi Takahashi & Shiro Akinaga Published online: 27 April 2012 # The Author(s) 2012. This article is published with open access at Springerlink.com Abstract 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 chemo- therapy. 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. K. Tobinai (*) Department of Hematology, and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan e-mail: ktobinai@ncc.go.jp T. Takahashi Clinical Development Department, Kyowa Hakko Kirin Co., Ltd, 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo 100-8185, Japan e-mail: takeshi.takahashi@kyowa-kirin.co.jp S. Akinaga Development Division, Kyowa Hakko Kirin Co., Ltd, 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo 100-8185, Japan e-mail: shiro.akinaga@kyowa-kirin.co.jp Keywords Chemokine receptor . CCR4 . Adult T-cell leukemia-lymphoma . ATL . Peripheral T-cell lymphoma . PTCL . Monoclonal antibody . Mogamulizumab . KW-0761 Introduction Peripheral T-cell lymphoma (PTCL) represents a small, heterogeneous group of non-Hodgkin lymphoma (NHL) which is derived from more mature T-cells and natural killer (NK) cells, and accounts for approximately 10 % of NHL cases in Western countries [1, 2] and for approximately 20 %–25 % of those in Japan [3, 4]. PTCL, a collective entity of nearly 20 different subtypes defined according to morphology, immunophenotype, genotype, and clinical fea- tures [5], can be largely classified into the following two groups according to clinical features including the sites of lesions: (1) cutaneous T-cell lymphoma (CTCL), which is the general term for diseases that initially or mainly occur in the skin, and (2) PTCL other than CTCL. Treatment strategies have been separately developed for these two groups [6]. Treatment options are substantially different for B-cell and T-cell lymphomas. Rituximab, an anti-CD20 monoclo- nal antibody, was developed for the treatment of B-cell lymphomas. The introduction of this agent into clinical practice has greatly improved the prognosis of patients with B-cell lymphoma [7]. Recently, bendamustine, which has little cross resistance with other chemotherapeutic agents presumably associated with its unique chemical structure of an alkylating agent and a nucleoside analog, has been developed as effective treatment of relapsed or refractory B-cell lymphoma, considering its lack of cross resistance with other chemotherapeutic agents [8]. However, PTCL remains extremely difficult to treat, because most PTCL sub- types become refractory to even aggressive chemotherapy