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

International Journal of Hematology

, Volume 94, Issue 5, pp 443-452

First online:

Antibody therapy for Adult T-cell leukemia–lymphoma

  • Takashi IshidaAffiliated withDepartment of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences Email author 
  • , Ryuzo UedaAffiliated withDepartment of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences

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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.

Keywords

CCR4 CD25 ADCC KW-0761