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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.

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  • Authors+Show Affiliations

    ,

    Department of Hematology, and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan. ktobinai@ncc.go.jp

    ,

    Source

    MeSH

    Antibodies, Monoclonal, Humanized
    Antineoplastic Agents
    Humans
    Leukemia-Lymphoma, Adult T-Cell
    Lymphoma, T-Cell
    Molecular Targeted Therapy
    Prognosis
    Receptors, CCR4

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    22538464

    Citation

    Tobinai, Kensei, et al. "Targeting Chemokine Receptor CCR4 in Adult T-cell Leukemia-lymphoma and Other T-cell Lymphomas." Current Hematologic Malignancy Reports, vol. 7, no. 3, 2012, pp. 235-40.
    Tobinai K, Takahashi T, Akinaga S. Targeting chemokine receptor CCR4 in adult T-cell leukemia-lymphoma and other T-cell lymphomas. Curr Hematol Malig Rep. 2012;7(3):235-40.
    Tobinai, K., Takahashi, T., & Akinaga, S. (2012). Targeting chemokine receptor CCR4 in adult T-cell leukemia-lymphoma and other T-cell lymphomas. Current Hematologic Malignancy Reports, 7(3), pp. 235-40. doi:10.1007/s11899-012-0124-3.
    Tobinai K, Takahashi T, Akinaga S. Targeting Chemokine Receptor CCR4 in Adult T-cell Leukemia-lymphoma and Other T-cell Lymphomas. Curr Hematol Malig Rep. 2012;7(3):235-40. PubMed PMID: 22538464.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Targeting chemokine receptor CCR4 in adult T-cell leukemia-lymphoma and other T-cell lymphomas. AU - Tobinai,Kensei, AU - Takahashi,Takeshi, AU - Akinaga,Shiro, PY - 2012/4/28/entrez PY - 2012/4/28/pubmed PY - 2012/12/19/medline SP - 235 EP - 40 JF - Current hematologic malignancy reports JO - Curr Hematol Malig Rep VL - 7 IS - 3 N2 - 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. SN - 1558-822X UR - https://www.unboundmedicine.com/medline/citation/22538464/Targeting_chemokine_receptor_CCR4_in_adult_T_cell_leukemia_lymphoma_and_other_T_cell_lymphomas_ L2 - https://dx.doi.org/10.1007/s11899-012-0124-3 DB - PRIME DP - Unbound Medicine ER -