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Mogamulizumab and the treatment of CCR4-positive T-cell lymphomas.
Immunotherapy 2014; 6(11):1187-206I

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.

Authors+Show Affiliations

Cancer Research UK Centre, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, SO16 6YD, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

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 -