Protein Engineering for Construction of Bio-interfaces

2008 Fiscal Year Final Research Report

• Project/Area Number: 16106011
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Biofunction/Bioprocess
• Research Institution: Tohoku University
• Principal Investigator: KUMAGAI Izumi Tohoku University, 大学院・工学研究科, 教授 (10161689)
• Co-Investigator(Kenkyū-buntansha): UMETSU Mitsuo 東北大学, 大学院・工学研究科, 准教授 (70333846) ; ASANO Ryutaro 東北大学, 大学院・工学研究科, 助教 (80323103)
• Co-Investigator(Renkei-kenkyūsha): TSUMOTO Kouhei 東京大学, 大学院・新領域創成科学研究科, 准教授 (90271866)
• Project Period (FY): 2004 – 2008
• Keywords: バイオインターフェイス / ペプチド移植 / マテリアル認識抗体 / 酸化亜鉛認識抗体 / 金表面特異的抗体 / 高機能性非天然型抗体 / 無作為変異導入 / ファージ提示法

Research Abstract

本研究では、医薬開発、ナノ材料への応用の著しい加速を可能にする技術基盤の構築を目的に、特に生体免疫系では特異的抗原性が発現し難い、細胞表面抗原、工学材料表面に焦点を絞り、特異的抗体分子の人工選択とその機能評価を進めた。結果、新たに取得した抗体の人工組換えや精密機能解析に基づき、医用への展開が期待できる複数の非天然型抗体分子の構築や、蛋白質間、あるいは蛋白質と工学材料間のバイオインターフェイスとして機能する抗体分子の構築に成功した。

Research Products

• [Journal Article] 次世代抗体医薬の分子設計 (2009)
  • Author(s): 熊谷泉, 浅野竜太郎
  • Journal Title: ケミカルエンジニヤリング 54 Pages: 65-71
• [Journal Article] Diabody-based recombinant formats of humanized IgG-like bispecific antibody with effective retargeting of lymphocytes to tumor cells (2008)
  • Author(s): Asano R., Kawaguchi H., Watanabe Y., Nakanishi T., Umetsu M., Hayashi H., Katayose Y., Unno M., Kudo T., Kumagai I.
  • Journal Title: J. Immunother. 31 Pages: 752-761
  • Peer Reviewed
• [Journal Article] Preferential heterodimerization of a bispecific diabody based on a humanized anti-EGFR antibody 528 (2008)
  • Author(s): Asano R. Sone Y., Ikoma K. Hayashi H., Nakanishi T., Umetsu M., Katayose Y., Unno M., Kudo T., Kumagai I.
  • Journal Title: Protein Eng. Des. Sel. 10 Pages: 597-603
  • Peer Reviewed
• [Journal Article] Grafting of material-binding function into antibodies Functionalization by peptide grafting (2008)
  • Author(s): Hattori T., Umetsu M., Nakanishi T., Tsumoto K., Ohara S., Abe H., Naito M.,Asano R., Adschiri T., Kumagai I.
  • Journal Title: Biochem. Biophys. Res. Commun. 365 Pages: 751-757
  • Peer Reviewed
• [Journal Article] Thermodynamic consequences of mutations in Vernier zone residues of a humanized anti-human epidermal growth factor receptor (EGFR) murine antibody, 528 (2008)
  • Author(s): Makabe K., Nakanishi T., Tsumoto K., Tanaka Y., Kondo H., Umetsu M., Sone Y., Asano R., Kumagai I.
  • Journal Title: J. Biol. Chem. 283 Pages: 1156-1166
  • Peer Reviewed
• [Journal Article] Critical Contribution of VH-VL Interaction to Reshaping of an Antibody : The case of humanization of anti-lysozyme antibody, HyHEL-10 (2008)
  • Author(s): Nakanishi T., Tsumoto K., Yokota A., Kondo H., Kumagai I.
  • Journal Title: Protein Sci. 17 Pages: 261-270
  • Peer Reviewed
• [Journal Article] Critical contribution of aromatic rings to specific recognition of polyether rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49 (2008)
  • Author(s): Tsumoto K., Yokota A., Tanaka Y., Ui M., Tsumuraya T., Fujii I., Kumagai I., Nagumo Y., Oguri H., Inoue M., Hirama M.
  • Journal Title: J. Biol. Chem. 283 Pages: 12259-12266
  • Peer Reviewed
• [Journal Article] Nanoparticles withfor biopolymer - Bioassisted room-temperature selective multistacking of inorganic particles on biopolymer film - (2008)
  • Author(s): Umetsu M., Hattori T., Kikuchi S., Muto I., Nakanishi T., Watanabe H., Kumagai I.
  • Journal Title: J. Mater. Res. 23 Pages: 3241-3246
  • Peer Reviewed
• [Journal Article] Human Anti-gold Antibodies : BIOFUNCTIONALIZATGOLD NANOPARTICLES AND SURFACES WITH ANTI-GOLD ANTIBODIES. (2008)
  • Author(s): Watanabe H., Nakanishi T., Umetsu M., Kumagai I.
  • Journal Title: J. Biol. Chem., 283 Pages: 36031-36038
  • Peer Reviewed
• [Journal Article] リンパ球とがん細胞を認識するヒト型化二重特異性抗体 (2008)
  • Author(s): 熊谷泉, 浅野竜太郎
  • Journal Title: Drug Delivery System 23 Pages: 518-525
• [Journal Article] Highly effective recombinant format of a humanized IgG-like bispecific antibody for cancer immunotherapy with retargeting of lymphocytes to tumor cells (2007)
  • Author(s): Asano R., Watanabe Y., Kawaguchi H., Fukazawa H., Nakanishi T., Umetsu M., Hayashi H., Katayose Y., Unno M., Kudo T., Kumagai I.
  • Journal Title: J. Biol. Chem. 282 Pages: 27659-27665
  • Peer Reviewed
• [Journal Article] Structural consequences of mutaof a protein antigen-antibody complex. The case of HyHEL-10-HEL (2007)
  • Author(s): Shiroishi M., Tsumoto K., Tanaka Y., Yokota A., Nakanishi T., Kondo H., Kumagai I.
  • Journal Title: J. Biol. Chem. 282 Pages: 6783-6791
  • Peer Reviewed
• [Journal Article] A Human antibody fragment with high affinity for biodegradable polymer film (2007)
  • Author(s): Watanabe H., Tsumoto K., Taguchi S., Yamashita K., Doi Y., Nishimiya Y., Kondo H., Umetsu M., Kumagai I.
  • Journal Title: Bioconjug. Chem. 18 Pages: 645-651
  • Peer Reviewed
• [Journal Article] 抗体ライブラリー技術の現状と今後の展望 (2007)
  • Author(s): 中西猛, 熊谷泉
  • Journal Title: 細胞工学 26 Pages: 254-257
• [Journal Article] Humanization of the bispecific epidermal growth or receptor x CD3 diabody and its efficacy as a potential clinical reagent, (2006)
  • Author(s): Asano R., Sone Y., Makabe K., Tsumoto K., Hayashi H., Katayose Y., Unno M., Kudo T., Kumagai I.
  • Journal Title: Clin. Cancer Res. 12 Pages: 4036-4042
  • Peer Reviewed
• [Journal Article] Efficient leIg-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer (2006)
  • Author(s): Shiroishi M., Kuroki K., Ose T., Rasubala L., Shiratori I., Arase H., Tsumoto K., Kumagai I., Kohda D., Maenaka K.
  • Journal Title: J. Biol. Chem. 281 Pages: 10439-10447
  • Peer Reviewed
• [Journal Article] Structural basis for reon of the nonclassical MHC molecule HLA-G by the leukocyte Ig-like receptor B2 (LILRB2/LIR2/ILT4/CD85d) (2006)
  • Author(s): Shiroishi M., Kuroki K., Rasubala L., Tsumoto K., Kumagai I., Kurimoto E., Kato K., Kohda D., Maenaka K.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 16412-16417
  • Peer Reviewed
• [Journal Article] Entropically driven MHC class I recognition by human inhibitory receptor leukocyte Ig-like receptor B1 (LILRB1/ILT2/CD85j) (2006)
  • Author(s): Shiroishi M., Kuroki K., Tsumoto K., Yokota A., Sasaki T., Amano K., Shimojima T., Shirakihara Y., Rasubala L., van der MerKohda D., Maenaka K.
  • Journal Title: J. Mol. Biol. 355 Pages: 237-248
  • Peer Reviewed
• [Journal Article] 抗 EGF レセプター・抗 CD3二重特異性抗体の抗腫瘍作用 (2006)
  • Author(s): 熊谷泉, 林洋毅, 浅野竜太郎
  • Journal Title: 臨床免疫 45 Pages: 497-502
• [Journal Article] Tumor-directed lymphocyte-activating cytokines : refolding-based preparation of recombinant human interleukin-12 and an antibody variable domain-fused protein by additive-intoduced stepwise dialysis (2005)
  • Author(s): Makabe K., Asano R., Ito T., Tsumoto K., Kudo T., Kumagai I.
  • Journal Title: Biochem. Biophys. Res. Commun. 328 Pages: 98-105
  • Peer Reviewed
• [Journal Article] Glorioso J.C., Herpes simplex virus targeting to the EGF receptor by a gD-specific soluble bridging molecule (2005)
  • Author(s): Nakano K., Asano R., Tsumoto K., Kwon H., Goins W.F., Kumagai I., Cohen J.B.
  • Journal Title: Mol. Ther. 11 Pages: 617-626
  • Peer Reviewed
• [Journal Article] Bioassisted room-temperature immobilization and mineralization of zinc oxide -The structural ordering of ZnO nanoparticles into a flower-type morphorogy (2005)
  • Author(s): Umetsu M., Mizuta M., Tsumoto K., Ohara S., Takami S., Watanabe H., Kumagai I., Adschiri T.
  • Journal Title: Adv. Mater. 17 Pages: 2571-2575
  • Peer Reviewed
• [Journal Article] Nondenaturing solubilization of beta2 microglobulin from inclusion bodies by L-arginine (2005)
  • Author(s): Umetsu M., Tsumoto K., Nitta S., Adschiri T., Ejima D., Arakawa T., Kumagai I.
  • Journal Title: Biochem. Biophys. Res. Commun. 328 Pages: 189-197
  • Peer Reviewed
• [Journal Article] A highly effectivbispecific diabody for cancer immunotherapy : cure of xenografted tumors by bispecific diabody and T-LAK cells (2004)
  • Author(s): Hayashi H., Asano R., Tsumoto K., Katayose Y., Suzuki M., Unno M., Kodama H., Takemura S., Yoshida H., Makabe K., Imai K., Matsuno S., Kumagai I., Kudo T.
  • Journal Title: Cancer Immunol. Immunother. 53 Pages: 497-509
  • Peer Reviewed
• [Journal Article] Phage-display selection of antibodies to the left end of CTX3C using synthetic fragments, (2004)
  • Author(s): Nagumo Y., Oguri H., Tsumoto K., Shindo Y., Hirama M., Tsumuraya T., Fujii I., Tomioka Y., Mizugaki M., Kumagai I.
  • Journal Title: J. Immunol. Meth. 289 Pages: 137-146
  • Peer Reviewed
• [Journal Article] Fucose depletion from human IgG1 oligosaccharide enhancbinding enthalpy and association rate between IgG1 and FcγRIIIa (2004)
  • Author(s): Okazaki A., Shoji-Hosaka E., Nakamura K., Wakitani M., Uchida K., Kakita S., Tsumoto K., Kumagai I., Shitara K.
  • Journal Title: J. Mol. Biol. 336 Pages: 1239-1249
  • Peer Reviewed
• [Journal Article] Pathway to insoluble aggregates on the refolding of a single-chain Fv antibody: morphological changes of aggregated protein onrefolding (2004)
  • Author(s): Umetsu M., Ashish K., Tsumoto K., Kumagai I.
  • Journal Title: Chem. Lett. (Jpn.) 33 Pages: 1600-1601
  • Peer Reviewed
• [Presentation] 次世代抗体創薬のバイオ工学を目指して (2008)
  • Author(s): 熊谷泉
  • Organizer: 第11回シンポジウム ゲノム創薬フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2008-11-07
• [Presentation] Efficacy of Humanized IgG-like Bispecific Antibody Formats in Cancer Immunotherapy (2007)
  • Author(s): Ryutaro Asano
  • Organizer: Antibodies -Europe
  • Place of Presentation: Wien
  • Year and Date: 2007-11-07
• [Presentation] Bottom-up Creation for Antibody with High Affinity for Inorganic Materials (2007)
  • Author(s): Mitsuo Umetsu,
  • Organizer: 2007 MRS Spring Meeting
  • Place of Presentation: San Francisco
  • Year and Date: 2007-04-12
• [Presentation] アカデミアからの蛋白質製造の技術移管と効率的プロセス開発 (2007)
  • Author(s): 熊谷泉
  • Organizer: 第5回トランスレーショナルリサーチ研修会
  • Place of Presentation: 神戸
  • Year and Date: 2007-03-02
• [Presentation] 抗体分子からバイオインターフェイスへの展開 (2006)
  • Author(s): 熊谷泉
  • Organizer: Bio Japan 2006
  • Place of Presentation: 大阪
  • Year and Date: 2006-09-15
• [Presentation] Fabrication of antibody with affinity for inorganic materials by CDR-grafting techniques (2006)
  • Author(s): Mitsuo Umetsu
  • Organizer: Antibody Engineering Conference
  • Place of Presentation: 鹿児島
  • Year and Date: 2006-06-16
• [Book] がん免疫療法への応用研究を目指した抗体-diabody-とシーズ (2009)
  • Author(s): 浅野竜太郎, 熊谷泉
  • Total Pages: 151-161
  • Publisher: シーエムシー出版
• [Book] 抗体ドメインの積み木細工による高機能化と医用への展開, 抗体医薬の最前線 (2007)
  • Author(s): 熊谷泉, 浅野竜太郎, 中西猛
  • Total Pages: 3-13
  • Publisher: シーエムシー出版
• [Remarks]
  • URL: http://www.che.tohoku.ac.jp/~kuma/
• [Patent(Industrial Property Rights)] 組換え型ポリペプチドの製造方法 (2008)
  • Inventor(s): 熊谷泉, 浅野竜太郎, 中西猛, 梅津光央
  • Industrial Property Rights Holder: 国立大学法人東北大学
  • Industrial Property Number: 特許, 特願2008-126612号
  • Filing Date: 2008-05-14
• [Patent(Industrial Property Rights)] 酸化亜鉛結合性タンパク質及びその用途 (2008)
  • Inventor(s): 梅津光央, 熊谷泉, 浅野竜太郎, 中西猛
  • Industrial Property Rights Holder: 国立大学法人東北大学
  • Industrial Property Number: 特許, PCT/JP2008/52917
  • Filing Date: 2008-02-14
  • Overseas
• [Patent(Industrial Property Rights)] 高機能性二重特異性抗体 (2006)
  • Inventor(s): 熊谷 泉, 浅野竜太郎
  • Industrial Property Rights Holder: 国立大学法人東北大学
  • Industrial Property Number: 特許,PCT/JP2006/320571
  • Filing Date: 2006-10-16
  • Overseas
• [Patent(Industrial Property Rights)] 新規なダイアボディ型二重特異性抗体 (2006)
  • Inventor(s): 熊谷泉, 工藤俊雄, 津本浩平, 浅野竜太郎
  • Industrial Property Rights Holder: 東北テクノアーチ
  • Industrial Property Number: 特許,特許登録3803790号
  • Filing Date: 2006-05-19
• [Patent(Industrial Property Rights)] 金結合性タンパク質及びその用途 (2005)
  • Inventor(s): 塩塚秀則, 今村剛士, 熊谷泉
  • Industrial Property Rights Holder: キャノン株式会社
  • Industrial Property Number: 特許,特願2005-105155
  • Filing Date: 2005-03-31