2009 Fiscal Year Final Research Report
Development of novel cancer immunotherapy using anti-CCR4 mAb combined with immunomodulatory agents
| Project/Area Number |
20790680
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Nagoya City University |
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Principal Investigator |
ISHIDA Takashi Nagoya City University, 大学院・医学研究科, 講師 (80405183)
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| Project Period (FY) |
2008 – 2009
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| Keywords | CCR4 / 抗体療法 / lymphoma / ADCC |
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| Research Abstract |
There is a lack of suitable small animal models to evaluate human ADCC in vivo, because of the species incompatibility between humans and animals or due to nonspecific allogeneic immune reactions. To overcome these problems, we established a human tumor-bearing mouse model, using NOG mice as recipients, in which autologous human immune cells are engrafted and mediate ADCC but in which endogenous murine cells are unable to mediate ADCC. We demonstrate significant antitumor activity in vivo associated with robust ADCC mediated by autologous effector cells from the same patients. The present study is the first to report a mouse model in which a potent antitumor effect of the therapeutic mAb against primary tumor cells is mediated by autologous human immune cells. This approach makes it possible to model the human immune system active in Ab-based cancer immunotherapy including combination treatment in vivo, and thus to perform more appropriate preclinical evaluations of novel therapeutic mAb.
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[Journal Article] Defucosylated anti-CCR4 monoclonal antibody exerts potent ADCC against primary ATLL Cells mediated by autologous human immune cells in NOD/Shi-scid, IL-2Rgamma(null) mice in vivo.2009
Author(s)
Ito A, Ishida T, Utsunomiya A, Sato F, Mori F, Yano H, Inagaki A, Suzuki S, Takino H, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R.
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Journal Title
J Immunol. 183
Pages: 4782-91
Peer Reviewed
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[Journal Article] The Asn505 mutation of c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity.2009
Author(s)
Ding J, Komatsu H, Iida S, Yano H, Kusumoto S, Inagaki A, Mori F, Ri M, Ito A, Wakita A, Ishida T, Nitta M, Ueda R.
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Journal Title
Peer Reviewed
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[Journal Article] Expression of the ULBP ligands for NKG2D by B-NHL cells plays an important role in determining their susceptibility to rituximab-induced ADCC.2009
Author(s)
Inagaki A, Ishida T, Yano H, Ishii T, Kusumoto S, Ito A, Ri M, Mori F, Ding J, Komatsu H, Iida S, Ueda R.
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Journal Title
Int J Cancer. 125
Pages: 212-21
Peer Reviewed
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[Journal Article] Bortezomib-induced apoptosis in mature T-cell lymphoma cells partially depends on upregulation of Noxa and functional repression of Mcl-1.2009
Author(s)
Ri M, Iida S, Ishida T, Ito A, Yano H, Inagaki A, Ding J, Kusumoto S, Komatsu H, Utsunomiya A, Ueda R.
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Journal Title
Cancer Sci. 100
Pages: 341-8
Peer Reviewed
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[Journal Article] Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in the novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model.2009
Author(s)
Ito A, Ishida T, Yano H, Inagaki A, Suzuki S, Sato F, Takino H, Mori F, Ri M, Kusumoto S, Komatsu H, Iida S, Inagaki H, Ueda R.
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Journal Title
Cancer Immunol Immunother. 58
Pages: 1195-206
Peer Reviewed
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[Journal Article] Overexpression of carboxylesterase-2 results in enhanced efficacy of topoisomerase I inhibitor, irinotecan (CPT-11), for multiple myeloma.2008
Author(s)
Yano H, Kayukawa S, Iida S, Nakagawa C, Oguri T, Sanda T, Ding J, Mori F, Ito A, Ri M, Inagaki A, Kusumoto S, Ishida T, Komatsu H, Inagaki H, Suzuki A, Ueda R.
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Journal Title
Cancer Sci. 99
Pages: 2309-14
Peer Reviewed
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