| 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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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | CCR4 / 抗体療法 / lymphoma / ADCC / NOGマウス / 成人T細胞白血病リンパ腫(ATL) |
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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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