Development and analysis of cancer-specific monoclonal antibodies for glycoproteins
Project/Area Number |
19K07705
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Tohoku University |
Principal Investigator |
KATO Yukinari 東北大学, 医学系研究科, 教授 (00571811)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | モノクローナル抗体 / がん特異的抗体 / FACS / 免疫染色 / ADCC / CDC / 抗腫瘍効果 / コアフコース欠損抗体 / 抗体 / エピトープ / エピトープマッピング / CasMab法 / 抗体医薬 / がん / がん細胞 / スクリーニング / ハイブリドーマ / クローン / がん特異的 / CasMab / 正常細胞 / フローサイトメトリー / 免疫 / 膜タンパク質 / 糖鎖 / 糖ペプチド / 糖タンパク質 |
Outline of Research at the Start |
モノクローナル抗体は実験的ツールや診断薬としてだけでなく、様々ながん治療に応用されている。一方、がん細胞に特異的な抗体を樹立しなければ、常に正常組織への毒性が懸念される。しかし、がん細胞だけに高発現している分子は限られているため、新規の標的分子を発見するのは困難である。 本課題においては、申請者が開発したがん特異的抗体作製法や糖鎖改変技術を駆使し、種々の糖タンパク質に対するがん特異的抗体を作製し、その有用性の証明および最適化を目指す。
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Outline of Final Research Achievements |
EGFR contributes to tumor malignancy via gene amplification and protein overexpression. Previously, we developed an anti-human EGFR (hEGFR) monoclonal antibody, namely, EMab-134, which detects hEGFR and dog EGFR (dEGFR) with high sensitivity and specificity. In this study, we produced a defucosylated mouse-dog chimeric anti-EGFR monoclonal antibody, namely, E134Bf. In vitro analysis revealed that E134Bf highly exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against a canine osteosarcoma cell line (D-17) and a canine fibroblastic cell line (A-72), both of which express endogenous dEGFR. Moreover, in vivo administration of E134Bf significantly suppressed the development of D-17 and A-72 compared with the control dog IgG in mouse xenografts. These results indicate that E134Bf exerts antitumor effects against dEGFR-expressing canine cancers and could be valuable as part of an antibody treatment regimen for dogs.
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Academic Significance and Societal Importance of the Research Achievements |
EGFRに対する抗体医薬は複数開発されているが、その副作用により患者さんのQOLが良くない。我々が開発したCasMab法は、複数のタンパク質に対してがん特異的抗体の作製に成功してきた。今回、EGFRに対する抗体作製を実施した結果、EMab-134という特異的抗体の作製に成功した。また、イヌ腫瘍のマウス移植片モデルにおいて、EMab-134のイヌ化抗体よる高い抗腫瘍効果が得られた。今後、獣医師と共同で、イヌ腫瘍の治療法の開発および臨床試験を行う。さらに、ヒトEGFR高発現がんに対する治療法への応用へと発展させる。
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] An Anti‐HER2 Monoclonal Antibody H2Mab‐41 Exerts Antitumor Activities in Mouse Xenograft Model using Dog HER2‐overexpressed Cells2021
Author(s)
Tateyama N, Asano T, Ohishi T, Takei J, Hosono H, Nanamiya R, Tanaka T, Sano M, Saito M, Kawada M, Kaneko MK, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 4
Pages: 184-190
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Defucosylated Anti-EGFR Monoclonal Antibody 134-mG2a-f Exerts Antitumor Activities in Mouse Xenograft Models of Dog EGFR-overexpressed Cells2021
Author(s)
Tateyama N, Nanamiya R, Ohishi T, Takei J, Nakamura T, Yanaka M, Hosono H, Saito M, Asano T, Tanaka T, Sano M, Kawada M, Kaneko MK, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 4
Pages: 177-183
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Epitope Mapping of an Anti-Human EGFR Monoclonal Antibody (EMab-51) using the REMAP Method2021
Author(s)
Nanamiya R, Sano M, Asano T, Yanaka M, Nakamura T, Saito M, Tanaka T, Hosono H, Tateyama N, Kaneko MK, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 4
Pages: 149-155
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of a Novel Anti-HER2 Monoclonal Antibody H2Mab-181 for Gastric Cancer2021
Author(s)
Takei J, Asano T, Tanaka T, Sano M, Hosono H, Nanamiya R, Tateyama N, Saito M, Suzuki H, Harada H, Kaneko MK, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 4
Pages: 168-176
DOI
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Peer Reviewed / Open Access
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[Journal Article] Anti-HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma2021
Author(s)
Asano T, Ohishi T, Takei J, Nakamura T, Nanamiya R, Hosono H, Tanaka T, Sano M, Harada H, Kawada M, Kaneko MK, Kato Y.
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Journal Title
Oncol. Rep
Volume: 46
Issue: 2
Pages: 173-173
DOI
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Peer Reviewed / Open Access
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[Journal Article] Ferret Podoplanin is Detected by PMab-241 in Immunohistochemistry2021
Author(s)
Nanamiya R, Takei J, Asano T, Sano M, Tanaka T, Hosono H, Harada H, Sakai Y, Mizuno T, Suzuki H, Kaneko MK, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 3
Pages: 134-140
DOI
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Peer Reviewed
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[Journal Article] Development of Monoclonal Antibody PMab-269 Against California Sea Lion Podoplanin2021
Author(s)
Tanaka T, Asano T, Sano M, Takei J, Hosono H, Nanamiya R, Nakamura T, Yanaka M, Harada H, Fukui M, Suzuki H, Uchida K, Nakagawa T, Kato Y, Kaneko MK.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 3
Pages: 124-133
DOI
Related Report
Peer Reviewed
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[Journal Article] An anti-TROP2 monoclonal antibody TrMab-6 exerts antitumor activity in breast cancer mouse xenograft models2021
Author(s)
Tanaka T, Ohishi T, Asano T, Takei J, Nanamiya R, Hosono H, Sano M, Harada H, Kawada M, Kaneko MK, Kato Y.
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Journal Title
Oncol Rep
Volume: 46
Issue: 1
Pages: 132-132
DOI
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Peer Reviewed / Open Access
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[Journal Article] Development of Anti-Human T-Cell Immunoreceptor with Ig and ITIM Domains (TIGIT) Monoclonal Antibodies for Flow Cytometry2021
Author(s)
Takei J, Asano T, Nanamiya R, Nakamura T, Yanaka M, Hosono H, Tanaka T, Sano M, Kaneko MK, Harada H, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 40
Issue: 2
Pages: 71-75
DOI
Related Report
Peer Reviewed
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[Journal Article] The Anti-EpCAM monoclonal antibody (EpMab-16) exerts anti-tumor activity against oral squamous cell carcinomas2020
Author(s)
Kaneko MK, Ohishi T, Takei J, Sano M, Nakamura T, Hosono H, Yanaka M, Asano T, Sayama Y, Harada H, Kawada M, Kato Y
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Journal Title
Oncol Rep
Volume: 44
Issue: 6
Pages: 2517-2526
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Development of Core-fucose Deficient Humanized and Chimeric Anti-Human Podoplanin Antibodies2020
Author(s)
Kaneko MK, Ohishi T, Nakamura T, Inoue H, Takei J, Sano M, Asano T, Sayama Y, Hosono H, Suzuki H, Kawada M, Kato Y.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother
Volume: 39
Issue: 5
Pages: 167-174
DOI
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Peer Reviewed / Open Access
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[Journal Article] A defucosylated anti-CD44 monoclonal antibody 5-mG2a-f exerts antitumor effects in mouse xenograft models of oral squamous cell carcinoma2020
Author(s)
Takei J, Kaneko MK, Ohishi T, Hosono H, Nakamura T, Yanaka M, Sano M, Asano T, Sayama Y, Kawada M, Harada H, Kato Y
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Journal Title
Oncol Rep.
Volume: 44
Pages: 1949-1960
DOI
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Peer Reviewed / Open Access
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[Journal Article] The anti-EGFR monoclonal antibody 134-mG2a exerts antitumor effects in mouse xenograft models of oral squamous cell carcinoma2020
Author(s)
Hosono H, Takei J, Ohishi T, Sano M, Asano T, Sayama Y, Nakamura T, Yanaka M, Kawada M, Harada H, Kaneko MK, Kato Y
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Journal Title
Int J Mol Med
Volume: 46
Pages: 1443-1452
DOI
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[Journal Article] Characterization of anti-goat podoplanin monoclonal antibody PMab-235 using immunohistochemistry against goat tissues2019
Author(s)
Takei J, Itai S, Harada H, Furusawa Y, Miwa T, Fukui M, Nakamura T, Sano M, Sayama Y, Yanaka M, Handa S, Hisamatsu K, Nakamura Y, Yamada S, Kaneko MK, Kato Y
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 38
Issue: 5
Pages: 213-219
DOI
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Peer Reviewed
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[Journal Article] PMab-235: a monoclonal antibody for immunohistochemical analysis against goat podoplanin2019
Author(s)
Furusawa Y, Yamada S, Nakamura T, Sano M, Sayama Y, Itai S, Takei J, Harada H, Fukui M, Kaneko MK, Kato Y
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Journal Title
Heliyon
Volume: 5
Issue: 7
Pages: e02063-e02063
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[Journal Article] Anti-bovine podoplanin monoclonal antibody PMab-44 detects goat podoplanin in immunohistochemistry2019
Author(s)
Yamada S, Kaneko MK, Furusawa Y, Itai S, Sano M, Nakamura T, Yanaka M, Handa S, Hisamatsu K, Nakamura Y, Koyanagi M, Fukui M, Harada H, Kato Y
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 38
Issue: 2
Pages: 96-99
DOI
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Peer Reviewed
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[Journal Article] PMab-210: A Monoclonal Antibody Against Pig Podoplanin2019
Author(s)
Furusawa Y, Yamada S, Itai S, Sano M, Nakamura T, Yanaka M, Fukui M, Harada H, Mizuno T, Sakai Y, Takasu M, Kaneko MK, Kato Y*.
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Journal Title
Monoclon. Antib. Immunodiagn. Immunother.
Volume: 38
Issue: 1
Pages: 30-36
DOI
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Peer Reviewed
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