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Antibody therapy for Adult T-cell leukemia–lymphoma

  • Progress in Hematology
  • Memorial PIM: adult T-cell leukemia—from discovery to recent progress
  • Published:
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Abstract

Adult T-cell leukemia–lymphoma (ATL) has a very poor prognosis. Since there currently are limited treatment options for ATL patients, several novel agents are being developed and tested clinically. Antibody therapy against ATL was initially started with interleukin-2 receptor α-subunit, CD25, as a target molecule in the late 1980s, and is currently ongoing. CC chemokine receptor 4 (CCR4) was postulated as a novel molecular target in ATL antibody therapy, and humanized anti-CCR4 mAb (KW-0761), whose Fc region was defucosylated to enhance antibody-dependent cellular cytotoxicity, was developed. A phase I study of KW-0761 in relapsed ATL and peripheral T-cell lymphoma was started in 2006, and a subsequent phase II study was completed in 2010. KW-0761 showed a clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. The prognosis of ATL patients should be improved in the near future with clinical applications of novel treatment strategies, including those involving KW-0761 and other promising antibody therapies targeting CD25 or CD30.

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Acknowledgments

We are grateful to all the members of the CCR4 research group, Drs. Asahi Ito, Fumiko Mori, Ayako masaki, Fumihiko Sato, Toshihiko Ishii, Atsushi Inagaki, Hiroki Yano, Shigeru Kusumoto, Hirokazu Komatsu, and Shinsuke Iida (Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan), Dr. Hiroshi Inagaki and Hisashi Takino (Department of Clinical Pathology, Nagoya City University Graduate School of Medical Sciences), Dr. Atae Utsunomiya (Department of Hematology, Imamura Bun-in Hospital), Dr. Kouji Matsushima (Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan), Drs. Kenya Shitara, Shiro Akinaga, Takeshi Takahashi, Rinpei Niwa, and Nobuo Hanai (Tokyo Research Laboratories, Kyowa Hakko Kirin), for continuing fruitful collaborations over many years. We wish to thank Ms. Chiori Fukuyama for her skillful technical assistance. This work was supported by Grants-in-Aid for General Scientific Research (No. 22689029, T. Ishida and No 22300333, R. Ueda) and Scientific Support Programs for Cancer Research (No. 221S0001, T. Ishida) from the Ministry of Education, Culture, Science, Sports, and Technology, Japan; Grants-in-Aid for National Cancer Center Research and Development Fund (No. 21-6-3, T. Ishida) from the Ministry of Health, Labor, and Welfare, Japan.

Conflict of interest

Takashi Ishida has received honoraria for lectures from Kyowa Hakko Kirin. Nagoya City University Graduate School of Medical Sciences has received research grant support from Kyowa Hakko Kirin for works provided by Takashi Ishida. No other conflict of interest relevant to this article was reported.

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  1. Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan

    Takashi Ishida & Ryuzo Ueda

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Ishida, T., Ueda, R. Antibody therapy for Adult T-cell leukemia–lymphoma. Int J Hematol 94, 443–452 (2011). https://doi.org/10.1007/s12185-011-0941-5

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