Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody

Sci Rep. 2016 Jun 2:6:27150. doi: 10.1038/srep27150.


Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory diseases. Because anti-HTLV-1 immune responses are critical for suppressing infected cells, enhancing cellular immunity is beneficial for the treatment of HTLV-1-associated diseases. Using simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaques, we analyzed the immune responses to viral antigens and the dynamics of virus-infected cells. The chemokine receptor CCR4 is expressed on STLV-1 infected cells, and administration of humanized monoclonal antibody to CCR4, mogamulizumab, dramatically decreased the number of STLV-1-infected cells in vivo. Concurrently, mogamulizumab treatment enhanced STLV-1 specific CD4(+) and CD8(+) T cell responses by simultaneously targeting CCR4(+) effector regulatory T (Treg) cells and infected cells. Mogamulizumab promoted the phagocytosis of CCR4(+) infected cells by macrophages, which likely enhanced antigen presentation. Vaccination with recombinant vaccinia virus (rVV) expressing viral antigens suppressed the proviral load and the number of Tax-expressing cells. Enhanced T-cell responses were also observed in some ATL patients who were treated with mogamulizumab. This study shows that mogamulizumab works not only by killing CCR4(+) infected cells directly, but also by enhancing T cell responses by increasing the phagocytosis of infected cells by antigen-presenting cells and suppressing CCR4(+) effector Treg cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antigens, Viral / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Deltaretrovirus Infections / drug therapy*
  • Deltaretrovirus Infections / virology
  • Human T-lymphotropic virus 1 / drug effects*
  • Human T-lymphotropic virus 1 / immunology
  • Humans
  • Macaca / immunology
  • Macaca / virology
  • Mice
  • Receptors, CCR4 / metabolism*
  • Simian T-lymphotropic virus 1 / drug effects*
  • Simian T-lymphotropic virus 1 / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Viral Load / drug effects


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