title: 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.
authors.affiliation: Cancer Research UK Centre, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, SO16 6YD, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Remer
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
authors.forename: Martin
authors.initials: M
authors.lastname: Glennie
authors.forename: Peter
authors.initials: P
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D002986:Clinical Trials as Topic; D006031:Glycosylation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000628:therapy*; D015202:Protein Engineering; D054398:Receptors, CCR4 / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C515354:CCR4 protein, human; D054398:Receptors, CCR4; C549035:mogamulizumab
keywords: ADCC; ATL; CCR4; CTCL; FOXP3; PTCL; Treg cell; defucosylated Fc region; glyco-engineering