Mogamulizumab, a humanized mAb against C-C chemokine receptor 4 for the potential treatment of T-cell lymphomas and asthma

Curr Opin Mol Ther. 2010 Dec;12(6):770-9.

Abstract

Mogamulizumab (KW-0761; AMG-761), under development by Kyowa Hakko Kirin and Amgen, is a defucosylated humanized IgG1 mAb against C-C chemokine receptor 4 (CCR4) for the potential intravenous treatment of T-cell lymphomas and asthma. Chemokines and their receptors are signaling molecules constitutively responsible for lymphocyte and neutrophil chemotaxis, which can also be involved in pathogenic mechanisms of various diseases. In particular, CCR4 has been demonstrated to play a major role in adult T-cell leukemia/lymphoma (ATL), in which it is a marker of poor prognosis. Consequently, CCR4 blockade might have therapeutic potential in treating ATL, a disease that is most often aggressive in course, and for which existing therapies are not always effective. Mogamulizumab reduced tumor load via enhanced antibody-dependent cell cytotoxicity in preclinical studies and demonstrated promising efficacy in early clinical trials in patients with ATL. In addition, CCR4 also has a role in maintaining T-helper cell type 2 airways inflammation in asthma, and Amgen have acquired the rights to develop mogamulizumab for this indication and other non-oncology indications; however, at the time of publication, no data were available from Amgen's investigations. This is a review on the potential use of mogamulizumab for the treatment of T-cell lymphomas and asthma, with specific emphasis on the treatment of ATL.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Asthma / drug therapy*
  • Asthma / immunology
  • Clinical Trials as Topic
  • Humans
  • Lymphoma, T-Cell / drug therapy*
  • Lymphoma, T-Cell / immunology
  • Receptors, CCR4 / immunology*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Receptors, CCR4
  • mogamulizumab