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Mogamulizumab and the treatment of CCR4-positive T-cell lymphomas.

Abstract

Glyco-engineering has been developed to enhance the pharmacological properties of monoclonal antibodies (mAbs) resulting in superior immune effector function. Mogamulizumab is the first approved glyco-engineered therapeutic antibody and first approved mAb to target the CC chemokine receptor 4 (CCR4). CCR4 is principally expressed on Tregs and helper T cells (Th) where it functions to induce homing of these leukocytes to sites of inflammation. Tregs play an essential role in maintaining immune balance; however, in malignancy, Tregs impair host antitumor immunity and provide a favorable environment for tumors to grow. CCR4 is highly expressed by aggressive peripheral T-cell lymphomas (PTCLs), particularly adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphomas (CTCLs). Mogamulizumab is a humanized anti-CCR4 mAb with a defucosylated Fc region that enhances antibody-dependent cellular cytotoxicity (ADCC). In addition, mogamulizumab depletes CCR4(+) Tregs, potentially evoking antitumor immune responses by autologous effector cells. This ability is highly pertinent as subsets of malignant T cells are believed to function as CD4(+) Tregs, overexpressing CCR4. Clinical trials with mogamulizumab have demonstrated clinical efficacy and tolerability for the treatment of relapsed/refractory aggressive T-cell lymphomas, previously associated with very poor outcomes.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Cancer Research UK Centre, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, SO16 6YD, UK.

    , ,

    Source

    Immunotherapy 6:11 2014 pg 1187-206

    MeSH

    Adult
    Animals
    Antibodies, Monoclonal, Humanized
    Antibody-Dependent Cell Cytotoxicity
    Clinical Trials as Topic
    Glycosylation
    Humans
    Immunotherapy
    Lymphoma, T-Cell
    Protein Engineering
    Receptors, CCR4
    T-Lymphocytes, Regulatory

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    25496334

    Citation

    Remer, Marcus, et al. "Mogamulizumab and the Treatment of CCR4-positive T-cell Lymphomas." Immunotherapy, vol. 6, no. 11, 2014, pp. 1187-206.
    Remer M, Al-Shamkhani A, Glennie M, et al. Mogamulizumab and the treatment of CCR4-positive T-cell lymphomas. Immunotherapy. 2014;6(11):1187-206.
    Remer, M., Al-Shamkhani, A., Glennie, M., & Johnson, P. (2014). Mogamulizumab and the treatment of CCR4-positive T-cell lymphomas. Immunotherapy, 6(11), pp. 1187-206. doi:10.2217/imt.14.94.
    Remer M, et al. Mogamulizumab and the Treatment of CCR4-positive T-cell Lymphomas. Immunotherapy. 2014;6(11):1187-206. PubMed PMID: 25496334.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mogamulizumab and the treatment of CCR4-positive T-cell lymphomas. AU - Remer,Marcus, AU - Al-Shamkhani,Aymen, AU - Glennie,Martin, AU - Johnson,Peter, PY - 2014/12/16/entrez PY - 2014/12/17/pubmed PY - 2015/8/1/medline KW - ADCC KW - ATL KW - CCR4 KW - CTCL KW - FOXP3 KW - PTCL KW - Treg cell KW - defucosylated Fc region KW - glyco-engineering SP - 1187 EP - 206 JF - Immunotherapy JO - Immunotherapy VL - 6 IS - 11 N2 - Glyco-engineering has been developed to enhance the pharmacological properties of monoclonal antibodies (mAbs) resulting in superior immune effector function. Mogamulizumab is the first approved glyco-engineered therapeutic antibody and first approved mAb to target the CC chemokine receptor 4 (CCR4). CCR4 is principally expressed on Tregs and helper T cells (Th) where it functions to induce homing of these leukocytes to sites of inflammation. Tregs play an essential role in maintaining immune balance; however, in malignancy, Tregs impair host antitumor immunity and provide a favorable environment for tumors to grow. CCR4 is highly expressed by aggressive peripheral T-cell lymphomas (PTCLs), particularly adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphomas (CTCLs). Mogamulizumab is a humanized anti-CCR4 mAb with a defucosylated Fc region that enhances antibody-dependent cellular cytotoxicity (ADCC). In addition, mogamulizumab depletes CCR4(+) Tregs, potentially evoking antitumor immune responses by autologous effector cells. This ability is highly pertinent as subsets of malignant T cells are believed to function as CD4(+) Tregs, overexpressing CCR4. Clinical trials with mogamulizumab have demonstrated clinical efficacy and tolerability for the treatment of relapsed/refractory aggressive T-cell lymphomas, previously associated with very poor outcomes. SN - 1750-7448 UR - https://www.unboundmedicine.com/medline/citation/25496334/Mogamulizumab_and_the_treatment_of_CCR4_positive_T_cell_lymphomas_ L2 - http://www.futuremedicine.com/doi/full/10.2217/imt.14.94?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -