Papers

Peer-reviewed
Oct, 2015

Phase Ia Study of FoxP3(+) CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients

CLINICAL CANCER RESEARCH
  • Koji Kurose
  • Yoshihiro Ohue
  • Hisashi Wada
  • Shinsuke Iida
  • Takashi Ishida
  • Takashi Kojima
  • Toshihiko Doi
  • Susumu Suzuki
  • Midori Isobe
  • Takeru Funakoshi
  • Kazuhiro Kakimi
  • Hiroyoshi Nishikawa
  • Heiichiro Udono
  • Mikio Oka
  • Ryuzo Ueda
  • Eiichi Nakayama
  • Display all

Volume
21
Number
19
First page
4327
Last page
4336
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1158/1078-0432.CCR-15-0357
Publisher
AMER ASSOC CANCER RESEARCH

Purpose: FoxP3(+) Tregs inhibit immune responses against tumors. KW-0761 is a humanized anti-human CCR4 monoclonal antibody (mAb) that has antibody-dependent cellular cytotoxicity activity. Depletion of CCR4-expressing FoxP3(+) CD4 Tregs by KW-0761 infusion was investigated in solid cancer patients.
Experimental Design: We conducted a phase Ia clinical trial of KW-0761 infusion in 7 lung and 3 esophageal cancer patients. Toxicity, clinical efficacy, changes in lymphocyte subpopulations, including Tregs, and induction of immune responses were analyzed.
Results: The results showed that KW-0761 infusion in a dose range between0.1mg/kg and 1.0mg/kgwas safe andwell tolerated. Nodose-limiting toxicitywas observed. Four of 10 patients showed stable disease during treatment and were long survivors. The monitoring of FoxP3(+) Tregs in the peripheral blood mononuclear cells during treatment indicated efficient depletion of those cells, even at the lowest dose of 0.1 mg/kg used. The reduction in Th 1 CD4 T cells and CD8 T cells was limited, whereas a significant reduction was observed with Th 2 and Th 17 CD4 T cells. Immune responses to cancer/testis (CT) antigens and an autoantibody response to thyroid peroxidase were observed in some patients.
Conclusions: The findings showed Tregs depletion and the possible occurrence of an immune response following KW-0761 infusion. Combined use of KW-0761 to deplete FoxP3(+) Tregs with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, is a promising approach to augment immune responses. (C) 2015 AACR.

Link information
DOI
https://doi.org/10.1158/1078-0432.CCR-15-0357
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000363330500014&DestApp=WOS_CPL
ID information
  • DOI : 10.1158/1078-0432.CCR-15-0357
  • ISSN : 1078-0432
  • eISSN : 1557-3265
  • Web of Science ID : WOS:000363330500014

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