Development and characterization of a cancer-specific monoclonal antibody (CasMab) against podoplanin

• Project/Area Number: 26440019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Tohoku University
• Principal Investigator: Kaneko Mika 東北大学, 医学系研究科, 准教授 (00323163)
• Co-Investigator(Renkei-kenkyūsha): KUNITA Akiko 東京大学, 大学院医学系研究科, 助教 (50608768)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: CasMab / PDPN / 腫瘍型糖鎖構造 / 糖転移酵素遺伝子 / 抗体医薬開発 / 糖転移酵素関連遺伝子 / 糖鎖

Outline of Final Research Achievements

Podoplanin (PDPN) is a platelet aggregation-inducing mucin-like sialoglycoprotein that is highly expressed in many cancers and normal tissues. PDPN has also been reported to be a marker to enrich tumor-initiating cells. Recently, we established the platform to produce a cancer-specific mAb (CasMab) by combining glycobiology and cell engineering technologies. In this study, we also established glycan-deficient CHO-S and HEK-293T cell lines, using the CRISPR/Cas or TALEN. We investigate several novel cancer-specific anti-PDPN or anti-glycopeptide mAbs. Antitumor activity of chimeric anti-human PDPN antibodies were validated. The CasMab-producing platform could lead to establishment of the side effect-reducing mAbs.

Research Products

• [Journal Article] Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study. (2018)
  • Author(s): Zhang, R., Liu, T-Y, Senju, S., Haruta, M., Hirosawa, N., Suzuki, M., Tatsumi, M., Ueda, N., Maki, H., Nakatsuka, R., Matsuoka, Y., Sasaki, Y., Tsuzuki, S., Nakanishi, H., Araki, R., Abe, M., Akatsuka, Y., Sakamoto, Y., Sonoda, Y., Nishimura, Y., Kuzushima, K. and Uemura, Y.
  • Journal Title: Cancer Immunology Research Volume: in press Pages: 1-12
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity. (2017)
  • Author(s): Kaneko MK, Yamada S, Nakamura T, Abe S, Nishioka Y, Kunita A, Fukayama M,Fujii Y, Ogasawara S, Kato Y.
  • Journal Title: Cancer Medicine Volume: - Pages: 768-777
  • DOI: 10.1002/cam4.1049
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity. (2017)
  • Author(s): Kato Y, Kunita A, Fukayama M, Abe S, Nishioka Y, Uchida H, Tahara H, Yamada S,Yanaka M, Nakamura T, Saidoh N, Yoshida K, Fujii Y, Honma R, Takagi M, Ogasawara S, Murata T, Kaneko MK.
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: 36(1) Pages: 20-24
  • DOI: 10.1089/mab.2016.0045
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Chimeric Anti-Human Podoplanin Antibody NZ-12 of Lambda Light Chain Exerts Higher Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity Compared with NZ-8 of Kappa Light Chain (2017)
  • Author(s): Kaneko MK, Abe S, Ogasawara S, Fujii Y, Yamada S, Murata T, Uchida H, Tahara H, Nishioka Y, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunothe Volume: 36(1) Pages: 25-29
  • DOI: 10.1089/mab.2016.0047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 3)Kaneko MK**, Nakamura T**, Honma R, Ogasawara S**, Fujii Y**, Abe S**, Takagi M, Harada H**, Suzuki H**, Nishioka Y**, Kato Y**: Development and characterization of anti-glycopeptide monoclonal antibodies against human podoplanin, using glycan-deficient cell lines generated by CRISPR/Cas9 and TALEN. (2017)
  • Author(s): Kaneko MK, Nakamura T, Honma R, Ogasawara S, Fujii Y, Abe S, Takagi M, Harada H, Suzuki H, Nishioka Y, Kato Y.
  • Journal Title: Cancer Medicine Volume: 6(2) Pages: 382-396
  • DOI: 10.1002/cam4.954
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Podoplanin Expression in Canine Melanoma (2016)
  • Author(s): Ogasawara S, Honma R, Kaneko MK, Fujii Y, Kagawa Y, Konnai S, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 35(6) Pages: 304-306
  • DOI: 10.1089/mab.2016.0040
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MAP Tag: A Novel Tagging System for Protein Purification and Detection. (2016)
  • Author(s): Fujii Y, Kaneko MK, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 35(6) Pages: 293-299
  • DOI: 10.1089/mab.2016.0039
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PMab-38 Recognizes Canine Podoplanin of Squamous Cell Carcinomas. (2016)
  • Author(s): Kaneko MK, Honma R, Ogasawara S, Fujii Y, Nakamura T, Saidoh N, Takagi M, Kagawa Y, Konnai S, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: 35(5) Pages: 263-266
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] LpMab-19 Recognizes Sialylated O-Glycan on Thr76 of Human Podoplanin. (2016)
  • Author(s): Ogasawara S, Kaneko MK, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother Volume: 35(5) Pages: 245-253
  • Peer Reviewed
• [Journal Article] Specific Detection of Dog Podoplanin Expressed in Renal Glomerulus by a Novel Monoclonal Antibody PMab-38 in Immunohistochemistry (2016)
  • Author(s): Honma R, Kaneko MK, Ogasawara S, Fujii Y, Konnai S, Takagi M, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 35(4) Pages: 212-216
  • DOI: 10.1089/mab.2016.0022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Establishment of Mouse Monoclonal Antibody LpMab-13 Against Human Podoplanin. (2016)
  • Author(s): Ogasawara S, Kaneko MK, Honma R, Oki H, Fujii Y, Takagi M, Suzuki H, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 35(3) Pages: 155-162
  • DOI: 10.1089/mab.2016.0006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model. (2016)
  • Author(s): Abe S, Kato KM, Tsuchihashi Y, Izumi T, Ogasawara S, Okada N, Sato C, Tobiume M, Otsuka K, Miyamoto L, Tsuchiya K, Kawazoe K, Kato Y, Nishioka Y.
  • Journal Title: Cancer Sci. Volume: 107(9) Pages: 1198-1205
  • DOI: 10.1111/cas.12985
  • NAID: 120006535008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PMab-44 Detects Bovine Podoplanin in Immunohistochemistry. (2016)
  • Author(s): Honma R, Ogasawara S, Kaneko MK, Fujii Y, Oki H, Nakamura T, Takagi M, Konnai S, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 35(4) Pages: 186-190
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] LpMab-12 Established by CasMab Technology Specifically Detects Sialylated O-Glycan on Thr52 of Platelet Aggregation-Stimulating Domain of Human Podoplanin. (2016)
  • Author(s): Kato Y, Ogasawara S, Oki H, Goichberg P, Honma R, Fujii Y, Kaneko MK.
  • Journal Title: PLoS One. Volume: 11(3)
  • DOI: 10.1371/journal.pone.0152912
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Characterization of monoclonal antibody LpMab-3 recognizing sialylated glycopeptide of podoplanin. (2015)
  • Author(s): Oki H, Ogasawara S, Kaneko MK, Takagi M, Yamauchi M, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 34(1) Pages: 44-50
  • DOI: 10.1089/mab.2014.0087
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. (2015)
  • Author(s): Ochoa-Alvarez JA, Krishnan H, Pastorino JG, Nevel E, Kephart D, Lee JJ, Retzbach EP, Shen Y, Fatahzadeh M, Baredes S, Kalyoussef E, Honma M, Adelson ME, Kaneko MK, Kato Y, Young MA, Deluca-Rapone L, Shienbaum AJ, Yin K, Jensen LD, Goldberg GS.
  • Journal Title: Oncotarget. Volume: 6(11) Pages: 9045-9060
  • DOI: 10.18632/oncotarget.3515
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Anti-podoplanin Monoclonal Antibody LpMab-7 Detects Metastatic Lesions of Osteosarcoma. (2015)
  • Author(s): Kaneko MK, Oki H, Ogasawara S, Takagi M, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 34(3) Pages: 154-61
  • DOI: 10.1089/mab.2014.0091
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characterization of Monoclonal Antibody LpMab-7 Recognizing Non-PLAG Domain of Podoplanin. (2015)
  • Author(s): Oki H, Kaneko MK, Ogasawara S, Tsujimoto Y, Liu X, Sugawara M, Takakubo Y, Takagi M, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 34(3) Pages: 174-180
  • DOI: 10.1089/mab.2014.0090
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Monoclonal Antibody LpMab-9 Recognizes O-glycosylated N-Terminus of Human Podoplanin. (2015)
  • Author(s): Kaneko MK, Oki H, Hozumi Y, Liu X, Ogasawara S, Takagi M, Goto K, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 34(5) Pages: 310-317
  • DOI: 10.1089/mab.2015.0022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of Monoclonal Antibody LpMab-10 Recognizing Non-glycosylated PLAG1/2 Domain Including Thr34 of Human Podoplanin. (2015)
  • Author(s): Ogasawara S, Oki H, Kaneko MK, Hozumi Y, Liu X, Honma R, Fujii Y, Nakamura T, Goto K, Takagi M, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 34(5) Pages: 318-326
  • DOI: 10.1089/mab.2015.0018
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of Sensitive Monoclonal Antibody PMab-2 Against Rat Podoplanin. (2015)
  • Author(s): Oki H, Honma R, Ogasawara S, Fujii Y, Liu X, Takagi M, Kaneko MK, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 34(6) Pages: 396-403
  • DOI: 10.1089/mab.2015.0041
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity. (2015)
  • Author(s): Kato Y, Kunita A, Abe S, Ogasawara S, Fujii Y, Oki H, Fukayama M, Nishioka Y, Kaneko MK.
  • Journal Title: Oncotarget Volume: 6(34) Pages: 36003-18
  • DOI: 10.18632/oncotarget.5339
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Establishment of Novel Monoclonal Antibody PMab-32 Against Rabbit Podoplanin. (2015)
  • Author(s): Honma R, Fujii Y, Ogasawara S, Oki H, Liu X, Nakamura T, Kaneko MK, Takagi M, Kato Y.
  • Journal Title: Monoclon Antib Immunodiagn Immunother. Volume: 35(1) Pages: 41-47
  • DOI: 10.1089/mab.2015.0066
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A platform of C-type lectin-like receptor CLEC-2 for binding O-glycosylated podoplanin and nonglycosylated rhodocytin. (2015)
  • Author(s): Nagae M, Morita-Matsumoto K, Kato M, Kaneko MK, Kato Y, Yamaguchi Y.
  • Journal Title: Structure. Volume: 22 Pages: 1711-1721
  • DOI: 10.1016/j.str.2014.09.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A cancer-specific monoclonal antibody recognizes the aberrantly glycosylated podoplanin. (2014)
  • Author(s): Kato Y, Kaneko MK.
  • Journal Title: Sci Rep. Volume: 4:5924 Pages: 1-9
  • DOI: 10.1038/srep05924
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity (2016)
  • Author(s): Yukinari Kato, Satoshi Ogasawara, Yuki Fujii, Mika K. Kaneko
  • Organizer: AACR annual meeting 2016
  • Place of Presentation: ニューオリンズ（アメリカ）
  • Int'l Joint Research
• [Presentation] CasMab法により樹立したLpMab-12抗体はポドプラニンの活性中心の糖鎖構造を認識する (2016)
  • Author(s): 金子美華、小笠原諭、藤井勇樹、加藤幸成
  • Organizer: 第８９回日本生化学会大会
  • Place of Presentation: 仙台国際センター（仙台市）
• [Presentation] The chimeric antibody NZ-12 or CAR T cells targeting human podoplanin possesses antitumor activity against orthotopic xenograft models (2016)
  • Author(s): Yukinari Kato, Satoshi Shiina, Atsushi Natsume, Shinji Abe, Yasuhiko Nishioka, Satoshi Ogasawara, Mika K. Kaneko
  • Organizer: AACR, Tumor Immunology and Immunotherapy
  • Place of Presentation: ボストン（アメリカ）
  • Int'l Joint Research
• [Presentation] 新規抗ポドプラニンキメラ抗体による抗腫瘍効果の検討 (2015)
  • Author(s): 国田朱子、小笠原諭、金子美華、加藤幸成
  • Organizer: 第88回日本生化学会大会（BMB2015）
  • Place of Presentation: 神戸ポートピアホテル（神戸市）
  • Year and Date: 2015-12-03
• [Presentation] CasMab法を用いた血小板凝集因子ポドプラニンの糖鎖付加部位解析 (2015)
  • Author(s): 藤井 勇樹、大木 弘治、小笠原 諭、金子 美華、加藤 幸成
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 新規抗ポドプラニン抗体の樹立と骨肉腫におけるポドプラニン発現の検討 (2015)
  • Author(s): 大木 弘治、劉 興、金子 美華、小笠原 諭、加藤 幸成
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] ポドプラニン発現とIDH変異による悪性神経膠腫の予後解析 (2015)
  • Author(s): 高野 晋吾、石川 栄一、松田 真秀、金子 美華、加藤 幸成
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-10
• [Presentation] 新規ヒトキメラ型抗ポドプラニン抗体NZ-12の悪性胸膜中皮腫に対する抗腫瘍効果 (2015)
  • Author(s): 阿部 真治、加藤 幸成、金子 美華、大塚 憲司、 後東 久嗣、埴淵 昌毅、西岡 安彦
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-09
• [Presentation] 新規抗ポドプラニン抗体の樹立と骨肉腫におけるポドプラニン発現の検討 (2015)
  • Author(s): 大木弘治、金子美華、小笠原諭、辻本雄太、劉 興、菅原正登、高窪祐弥、土屋登嗣、高木理彰、加藤幸成
  • Organizer: 第48回日本整形外科学会 骨・軟部腫瘍学術集会
  • Place of Presentation: JRホテルクレメント高松（高松市）
  • Year and Date: 2015-07-09
• [Presentation] 血小板凝集因子受容体 CLEC-2 のリガンド認識機構の結晶学的研究 (2014)
  • Author(s): 長江雅倫・森田加奈・加藤雅樹・金子美華・加藤幸成・山口芳樹
  • Organizer: 平成２６年度日本結晶学会年会
  • Place of Presentation: 東京大学農学部（東京都)
  • Year and Date: 2014-11-01 – 2014-11-03
• [Presentation] ポドプラニンに対するがん特異的抗体（CasMab）の開発 (2014)
  • Author(s): 小笠原諭、金子美華、加藤幸成
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都市）
  • Year and Date: 2014-10-18
• [Presentation] 新規アフィニティータグ「PA tag」のループへの挿入による効果的な利用法 (2014)
  • Author(s): 藤井 勇樹、 金子 美華、 北郷 悠、 加藤 幸成、 高木 淳一
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都市）
  • Year and Date: 2014-10-16
• [Presentation] Development of a cancer-specific monoclonal antibody (CasMab) specific for cancer-type podoplanin (2014)
  • Author(s): Yukinari Kato, Mika Kato Kaneko, Satoshi Ogasawara, Yasuhiko Nishioka
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2014-09-27
• [Presentation] 骨肉腫に対する高感度抗ポドプラニン抗体の樹立 (2014)
  • Author(s): 大木弘治 、金子美華 、小笠原 諭 、辻本雄太 、劉 興 、菅原正登 、高窪祐弥 、土屋登嗣、高木理彰 、加藤幸成
  • Organizer: 第34回日本分子腫瘍マーカー研究会
  • Place of Presentation: パシフィコ横浜(横浜市）
  • Year and Date: 2014-09-24
• [Remarks] 東北大学 抗体創薬研究分野
  • URL: http://www.med-tohoku-antibody.com
• [Remarks] 東北大学大学院医学系研究科・加藤研究室
  • URL: http://www.med-tohoku-antibody.com/
• [Remarks] 東北大学大学院医学系研究科地域イノベーション分野ホームページ
  • URL: http://www.med-tohoku-antibody.com/index.htm