Development and characterization of a cancer-specific monoclonal antibody against a tumor-associated sialoglycoprotein.
| 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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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Anti-podocalyxin antibody exerts antitumor effects via antibody-dependent cellular cytotoxicity in mouse xenograft models of oral squamous cell carcinoma.2018
Author(s)
Itai S, Ohishi T, Kaneko MK, Yamada S, Abe S, Nakamura T, Yanaka M, Chang YW, Ohba SI, Nishioka Y, Kawada M, Harada H, Kato Y
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Journal Title
Oncotarget.
Volume: Vol.9, No. 32
Issue: 32
Pages: 22480-22497
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Podocalyxin is crucial for the growth of oral squamous cell carcinoma cell line HSC-2.2018
Author(s)
Itai S, Yamada S, Kaneko MK, Sano M, Nakamura T, Yanaka M, Handa S, Hisamatsu K, Nakamura Y, Furusawa Y, Fukui M, Ohishi T, Kawada M, Harada H, Kato Y.
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Journal Title
Biochem Biophys Rep.
Volume: 15
Pages: 93-96
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Antipodocalyxin Antibody chPcMab-47 Exerts Antitumor Activity in Mouse Xenograft Models of Colorectal Adenocarcinomas.2017
Author(s)
Kaneko MK, Kunita A, Yamada S, Nakamura T, Yanaka M, Saidoh N, Chang YW, Handa S, Ogasawara S, Ohishi T, Abe S, Itai S, Harada H, Kawada M, Nishioka Y, Fukayama M, Kato Y.
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Journal Title
Monoclon Antib Immunodiagn Immunother.
Volume: 36(4)
Issue: 4
Pages: 157-162
DOI
Related Report
Peer Reviewed
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