2013 Fiscal Year Final Research Report
Generation of immunotoxins with super-targeting mAb in the acute myelocytic leukemia
| 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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| 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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Research Products
(12 results)
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[Journal Article] Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV2013
Author(s)
Wang PY, Currier MA, Hansford L, Kaplan D, Chiocca EA, Uchida H, Goins WF, Cohen JB, Glorioso JC, van Kuppevelt TH, Mo X, Cripe TP
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Journal Title
Gene Ther
Volume: 20(7)
Pages: 761-769
Peer Reviewed
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[Journal Article] Effective treatment of an orthotopic xenograft model of human glioblastoma using an EGFR-retargeted oncolytic herpes simplex virus2013
Author(s)
Uchida H, Marzulli M, Nakano K, Goins WF, Chan J, Hong CH, Mazzacurati L, Yoo JY, Haseley A, Nakashima H, Baek H, Kwon H, Kumagai I, Kuroki M, Kaur B, Chiocca EA, Grandi P, Cohen JB, Glorioso JC
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Journal Title
Mol Ther
Volume: 21(3)
Pages: 561-569
Peer Reviewed
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