| Project/Area Number |
17K07299
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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 |
Structural biochemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
Kaneko Mika 東北大学, 医学系研究科, 准教授 (00323163)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | CasMab / 抗体創薬 / PODXL / 腫瘍特異的 / 糖鎖 |
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| Outline of Final Research Achievements |
Podocalyxin (PODXL), a CD34-related sialomucin, is expressed not only in many tumors but also in normal cells such as epithelial cells and endothelial cells; therefore, PODXL could not be a target of antibody therapy. We recently established cancer-specific anti-PODXL mAb (ex.clone: PcMab-6), which could target only cancer cells although PODXL is highly expressed in both cancer and normal cells. PcMab-6 reacted with PODXL-expressing many cancer cell lines whereas it did not bind to vascular endothelial cells (VECs) in flow cytometry. Furthermore, PcMab-6 reacted only with PODXL-expressing cancer cells, not with VECs in breast and oral cancer tissues using immunohistochemistry. We have further constructed chPcMab-6, a mouse-human chimeric mAb from the PcMab-6, which also responds with only podocalyxin-expressing cancer cells. chPcMab-6 has ADCC activity in vitro and anti-tumor effect in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、モノクローナル抗体をキメラ抗原受容体T細胞（CART）療法や二重特異的抗体によるT細胞やNK細胞誘導療法（BiTEなど）と組み合わせる治療法の開発が盛んである。これら新しい免疫療法における副作用（毒性）は、これまでの治療法に比べ、影響が甚大であることが懸念されており、いかに特異性の高い抗体を樹立するかが重要な課題となっている。本研究課題においても検討したCasMab法は、非常に高いがん特異性抗体を作製できることが特徴であり、社会的に意義ある成果であると考えられる。
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