[Basic and clinical evaluation of anti-CCR4 mAb in cancer immunotherapy]

Nihon Rinsho. 2017 Feb;75(2):209-215.
[Article in Japanese]

Abstract

CCR4 is one of the receptors for chemokines and is expressed on Th2, Th17, skin-homing T cells and regulatory T cells (Tregs). Activated Tregs highly express CCR4 and are induced into tumor environment by M2 macrophages-producing CCL22. Tregs show strong suppres- sive functions in cancer immunity, resulting in tumor progression. On the other hand, moga- mulizumab is a humanized anti-human CCR4 monoclonal antibody with a defucosylated Fe region which markedly enhances ADCC activity, and the antibody has been shown to effi- ciently deplete CCR4-positive cells. Therefore, a phase Ia clinical study of mogamulizumab was conducted in the treatment of solid cancers. Mogamulizumab almost depeleted activated Tregs in peripheral blood, and then re-activated CTL function with low grade of adverse events. However, no clinical responses were observed in ten patients. A phase lb study is now on-going, and further clinical studies may be needed in combination with other anti- tumor drugs.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Humans
  • Immunotherapy*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, CCR4 / immunology*

Substances

  • Antibodies, Monoclonal
  • CCR4 protein, human
  • Receptors, CCR4