| Project/Area Number |
23501309
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HAMADA Hirofumi 東京薬科大学, 生命科学部, 教授 (00189614)
HIRAI Sachie 札幌医科大学, 医学部, 助手 (20218754)
UCHIDA Hiroaki 東京薬科大学, 生命科学部, 准教授 (20401250)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | AML / 標的治療 / イミュノトキシン / モノクローナル抗体 / DT3C / ADC |
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| Research Abstract |
We generated a recombinant fusion protein DT3C, which contained the catalytic and translocation domain of the truncated diphtheria toxin (DT) as well as the three IgG-binding C domains of streptococcal protein G (3C). Fc of MoAb binds with DT3C, resulting in a MoAb-DT3C complex (two DT3C molecules conjugated with one IgG molecule). The MoAb-DT3C complex binds with the surface Ag, being followed by internalization and translocation into the cytoplasm, leads to the cytocydal effect by protein synthesis inhibition of DT. By using these, we developed a unique screening system to establish cancer-targetable antigens/antibodies sets. In total 224 MoAb clones were obtained which performed immunotoxin cytocydal on leukemic cells. Our method provide an excellent way to obtain promising superior mAbs for antibodies drug conjugation(ADC) therapy.
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