| Project/Area Number |
15K06876
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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 |
Tumor therapeutics
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐久間 裕司 札幌医科大学, 医学部, 准教授 (10364514)
西井 ゆかり 札幌医科大学, 医学部, 研究員 (10619505)
内田 宏昭 東京大学, 医科学研究所, 講師 (20401250)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | EGFR阻害薬耐性細胞株 / ADC型抗体薬 / モノクローナル抗体 / 抗体スクリーニング / 内在化 / EGFR阻害薬耐性 / 抗体結合型トキシンタンパク質 / DT3C |
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| Outline of Final Research Achievements |
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.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 187 MoAb clones were obtained which performed immunotoxin cytocydal on EGFR-mutant lung adenocarcinomas.Our method provide an excellent way to obtain promising superior mAbs for antibodies drug conjugation(ADC) therapy.In this study, we established adc candidate antibodies such as CD98hc, CD155, CD224, ACE2, EGFR, ICAM1.We intend to advance these antibodies to clinical applications in the future.
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