Development of specific targeting against myebma cells by an internalizing antibody
| Project/Area Number |
18591067
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
OZAKI Shuji The University of Tokushima, University Medical and Dental Hospital, lecturer (90314872)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Hematolopical malignancies / Multiple myeloma / Monoclonal antibody / Molecular targeting therapy / Immunotoxin / Internalization |
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| Research Abstract |
Multiple myeloma is still an incurable disease and new therapeutic strategies are needed. In this study, we focused on HM1.24/BST2 (CD317) that is specifically overexpressed on myeloma cells, and evaluated the potential of a new monoclonal antibody(b-76-8)against this antigen. This antibody had an internalizing activity after binding to myeloma cells by receptor-mediated endocytosis, and 80% of the antibody localized to trans-Golgi network within 60 minutes. Next, we conjugated maytansine (DM1) toxin to b-76-8, and evaluated the potential of this immunoconjugate both in vitro and hi vivo. b-76-8-DM1 significantly inhibited cell cycle and induced apoptosis in myeloma cells compared with b-76-8 or DM1 alone. Moreover, b-76-8-DM1 significantly inhibited myeloma growth in human myeloma xenograft models compared with b-76-8 or DM1 alone. These therapeutic activity was specifically observed against myeloma cells. These results suggest that b-76-8 can deliver the conjugates specifically into myeloma cells, and that HM1.24/BST2 (CD317) is a novel target molecule for therapeutic strategies in multiple myeloma.
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Report
(3 results)
Research Products
(34 results)
