Journal
ONCOLOGY
Volume 89, Issue -, Pages 16-21Publisher
KARGER
DOI: 10.1159/000431059
Keywords
CCR4; Anti-CCR4 antibody; Mogamulizumab; Adult T-cell leukemia; Regulatory T cells; Antibody-dependent cellular cytotoxicity; Potelligent technology; Tumor immunotherapy; Regulatory T-cell depletion
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Funding
- Chugai Pharmaceutical Co., Ltd.
- Kyowa Kirin Co., Ltd.
- Medical & Biological Laboratories Co., Ltd.
- Rikaken Co., Ltd.
- Bristol-Myers KK (Japan)
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Mogamulizumab (KW-0761) is a humanized anti-CCR4 monoclonal antibody with a defucosylated Fc region (Potelligent (R) Technology), which markedly enhances antibody-dependent cellular cytotoxicity by increasing its binding affinity to the Fcy receptor expressed on effector cells. It is an effective agent for patients with CCR4-positive adult T-cell leukemia and peripheral T-cell lymphoma, for which no standard therapy exists, and it has an acceptable toxicity profile. In addition, because CCR4 is expressed on CD45RA-FOXP3(high)CD4(+) effector regulatory T (Treg) cells, it is an even more attractive target, because Treg cells involved in the tumor escape from host immunity in the tumor microenvironment. Based on this concept, we conducted a clinical study of mogamulizumab for the treatment of CCR4-negative advanced or recurrent solid cancer, with the aim of depleting effector Treg cells and thus boosting anticancer immune responses. In this study, mogamulizumab infusion at doses ranging from 0.1 to 1.0 mg/kg was safe and well tolerated. Four of 10 patients showed stable disease during treatment and showed long-term survival. Mogamulizumab efficiently depleted effector Treg cells even at the lowest dose of 0.1 mg/kg, and an augmentation or induction of specific immune responses to cancer/testis antigens was observed in some patients. In the near future, a novel immunotherapy targeting Treg cells with mogamulizumab will be offered to patients with different types of cancer. (C) 2015 S. Karger AG, Basel
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