Abstract | PURPOSE: EXPERIMENTAL DESIGN: The antitumor activity of KW-0761 against ATLL cell lines was evaluated in vitro using human cells and in mice in vivo. Primary ATLL cells from 23 patients were evaluated for susceptibility to autologous ADCC with KW-0761 by two independent methods. RESULTS:
KW-0761 showed potent antitumor activity against ATLL cell lines both in vitro and in the ATLL mouse model in vivo. In addition, KW-0761 showed potent antitumor activity mediated by highly enhanced ADCC against primary ATLL cells both in vitro and ex vivo in an autologous setting. The degree of KW-0761 ADCC against primary ATLL cells in an autologous setting was mainly determined by the amount of effector natural killer cells present, but not the amount of the target molecule CCR4 on the ATLL cell surface. CONCLUSION:
KW-0761 should be sufficiently active for therapeutic clinical application for ATLL. In addition, combination treatment strategies that augment natural killer cell activity should be promising for amplifying the effect of KW-0761. In the near future, the actual efficacy of KW-0761 will be established in pivotal clinical trials.
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Authors | Toshihiko Ishii, Takashi Ishida, Atae Utsunomiya, Atsushi Inagaki, Hiroki Yano, Hirokazu Komatsu, Shinsuke Iida, Kazunori Imada, Takashi Uchiyama, Shiro Akinaga, Kenya Shitara, Ryuzo Ueda |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 5
Pg. 1520-31
(Mar 01 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20160057
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- CCR4 protein, human
- Receptors, CCR4
- mogamulizumab
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Topics |
- Adult
- Animals
- Antibodies, Monoclonal
(immunology, pharmacology)
- Antibodies, Monoclonal, Humanized
- Antibody-Dependent Cell Cytotoxicity
(drug effects, immunology)
- Antineoplastic Agents
(pharmacology)
- Biosensing Techniques
- Cell Separation
- Flow Cytometry
- Humans
- Immunotherapy
(methods)
- Leukemia-Lymphoma, Adult T-Cell
(drug therapy, immunology)
- Male
- Mice
- Mice, SCID
- Receptors, CCR4
(immunology)
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