The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-cell leukemia/lymphoma

Takashi Ishida, Shinsuke Iida, Yoshiki Akatsuka, Toshihiko Ishii, Mikinori Miyazaki, Hirokazu Komatsu, Hiroshi Inagaki, Noriko Okada, Teizo Fujita, Kenya Shitara, Shiro Akinaga, Toshitada Takahashi, Atae Utsunomiya, Ryuzo Ueda

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)


Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCM4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.

Original languageEnglish
Pages (from-to)7529-7539
Number of pages11
JournalClinical Cancer Research
Issue number22
Publication statusPublished - 15-12-2004

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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