title: Targeting chemokine receptor CCR4 in adult T-cell leukemia-lymphoma and other T-cell lymphomas.
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 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.
authors.affiliation: Department of Hematology, and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan. ktobinai@ncc.go.jp
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shiro
authors.initials: S
authors.lastname: Akinaga
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D054398:Receptors, CCR4; C549035:mogamulizumab