Toshihiko Ishii

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PURPOSE Adult T-cell leukemia/lymphoma (ATLL) has a very poor prognosis. We have developed the humanized defucosylated anti-CC chemokine receptor 4 (CCR4) monoclonal antibody KW-0761 as a next generation immunotherapeutic agent. The first aim of the present study was to evaluate whether the antitumor activity of KW-0761 would likely be sufficient for(More)
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs)(More)
Patients with adult T-cell leukemia/lymphoma (ATLL) are in a severely immunocompromised state. Therefore, it is assumed that ATLL cells either express particular cytokines or induce their expression in host immune cells, disrupting the balanced production of cytokines and causing the host's immune system to break down. We examined the levels of serum(More)
Antibody-dependent cellular cytotoxicity (ADCC) is a major antitumor mechanism of action of therapeutic monoclonal antibodies (mAbs). The aim of this study was to identify tumor-associated factors which determine susceptibility to rituximab-induced ADCC. Thirty different CD20+ non-Hodgkin lymphoma cell lines were phenotyped for characteristics such as level(More)
PURPOSE The heat shock protein 90 (Hsp90) plays an important role in chaperoning oncogenic client proteins in multiple myeloma (MM) cells, and several Hsp90 inhibitors have shown antitumor activities both in vitro and in vivo. However the precise mechanism of action of Hsp90 inhibitor in MM has not been fully elucidated. EXPERIMENTAL DESIGN We evaluated(More)
Adult T-cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3, which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL(More)
Hodgkin lymphoma (HL) is characterized by the presence of a small number of tumor cells in a rich background of inflammatory cells, but the contribution of the abundant nontumor cells to HL pathogenesis is poorly understood. We showed that migratory CD4(+) cells induced by HL cells were hyporesponsive to T-cell receptor stimulation and suppressed the(More)
We investigated the clinical significance of a blood eosinophilia in a cohort of 158 consecutive patients with adult T-cell leukemia/lymphoma (ATLL), and multivariate analysis revealed that a blood eosinophilia was an independent and a significant unfavorable prognostic factor. Interestingly, a blood eosinophilia was independent of serum LDH level, which(More)
PURPOSE Sézary syndrome (SS) and Mycosis fungoides (MF) in the advanced stage have dismal prognoses. Because CC chemokine receptor 4 (CCR4) has an important role in the skin-homing capacity of MF/SS cells, we postulated that anti-CCR4 monoclonal antibody (mAb) could represent a novel therapeutic agent against aggressive/refractory MF/SS. EXPERIMENTAL(More)
implications in the leukemogenesis. Leukemia Research, 27, 371–374. Srour, E.F., Brandt, J.E., Briddell, R.A., Leemhuis, T., van Besien, K. & Hoffman, R. (1991) Human CD34+ HLA-DR-bone marrow cells contain progenitor cells capable of self-renewal, multilineage differentiation, and long-term in vitro hematopoiesis. Blood Cells, 17, 287–295.