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Development of novel cancer immunotherapy utilizing hyperacute rejection induced by alpha-gal epitope

Research Project

Project/Area Number 26560447
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionOsaka University

Principal Investigator

Fukase Koichi  大阪大学, 理学(系)研究科(研究院), 教授 (80192722)

Co-Investigator(Kenkyū-buntansha) MANABE Yoshiyuki  大阪大学, 大学院理学研究科, 助教 (00632093)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsがん免疫療法 / 抗体薬物複合体(ADC) / 糖鎖 / 糖鎖合成 / α-gal / がんワクチン / アジュバント / 免疫療法 / α-Gal / グリコシル化
Outline of Final Research Achievements

The α-Gal epitope is composed of trisaccharide structure produced in most mammals, however humans are deficient in that structure. On the other hand, humans produce a large amount of anti-Gal antibodies that specifically interact with the α-Gal epitope. Therefore, if pig organ expressing α-Gal is transplanted to human, the organ is heavily injured by hyper acute rejection. The purpose of this research is the development of the novel cancer therapy utilizing the α-Gal / anti-Gal antibody interaction: hyperacute rejection to tumor cell is induced by the labeling of tumor cell with α-Gal.
First, efficient synthesis of α-Gal epitope was achieved via one-pot glycosylation using imidate glycosyl donor and thioglycoside. Synthesized α-Gal was conjugated with anti-CD20 antibody, which is specifically recognize lymphoma cell. Cytotoxic assay using this antibody drug conjugate is under investigation. We also investigated the utilization of α-Gal as an adjuvant.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (33 results)

All 2016 2015 2014

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results)

  • [Journal Article] Efficient synthesis of the disialylated tetrasaccharide motif in N-glycan via an amide protection strategy.2016

    • Author(s)
      Zhou, J.; Manabe, Y.; Tanaka, K.; Fukase, K.
    • Journal Title

      Chem. Asian. J.

      Volume: 11 Issue: 9 Pages: 1436-1440

    • DOI

      10.1002/asia.201600139

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of the Conjugates of Tumor Antigens with Adjuvants for the Efficient Cancer Immunotherapy.2015

    • Author(s)
      Manabe, Y.; Chang, T-C.; Li, H-S.; Terao, N.; Takamatsu, S.; Tanemura, M.; Miyoshi, E.; Fukase, K.
    • Journal Title

      Peptide Science

      Volume: 2015 Pages: 77-78

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effective Synthesis of Oligosaccharide under Microfluidic Conditions2015

    • Author(s)
      Fukase, K.; Shimoyama, A.; Manabe, Y.
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 73 Issue: 5 Pages: 452-459

    • DOI

      10.5059/yukigoseikyokaishi.73.452

    • NAID

      130005077685

    • ISSN
      0037-9980, 1883-6526
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient Glycosylation Using In(OTf)<sub>3</sub> as a Lewis Acid: Activation of <i>N</i>-Phenyltrifluoroacetimidate or Thioglycosides with Halogenated Reagents or PhIO2014

    • Author(s)
      Salmasan, R. M., Manabe, Y., Kitawaki, Y., Chang, T.-C., Fukase, K.
    • Journal Title

      Chemistry Letters

      Volume: 43 Issue: 6 Pages: 956-958

    • DOI

      10.1246/cl.140167

    • NAID

      130004868149

    • ISSN
      0366-7022, 1348-0715
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Practical and Efficient Method for α-Sialylation with an Azide Sialyl Donor Using a Microreactor.2014

    • Author(s)
      Uchinashi, Y., Tanaka, K., Manabe, Y., Fujimoto, Y., Fukase, K.
    • Journal Title

      Journal of carbohydrate chemistry

      Volume: 33 Issue: 2 Pages: 55-67

    • DOI

      10.1080/07328303.2014.880116

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A cascading reaction sequence involving ligand-directed azaelectrocyclization and autooxidation-induced fluorescence recovery enables visualization of target proteins on the surfaces of live cells.2014

    • Author(s)
      Tanaka, K., Kitadani, M., Tsutsui, A., Pradipta, AR., Imamaki, R., Kitazume, S., Taniguchi, N., Fukase K.
    • Journal Title

      Org Biomol Chem.

      Volume: 12 Issue: 9 Pages: 1412-1418

    • DOI

      10.1039/c3ob42267d

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Kinetically controlled Fischer glycosylation using acidic silica-gel under fluidic conditions2016

    • Author(s)
      eiji Masui, Yoshiyuki Manabe, Atsushi Shimoyama, Takahide Fukuyama, Ilhyong Ryu, Koichi Fukase
    • Organizer
      PACIFICHEM2015
    • Place of Presentation
      Hawaii
    • Year and Date
      2016-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Novel Approach in Cancer Immunotherapy: Using Synthetic α-gal Epitope to Increase the Immunogenicity of Tumor Antigens2016

    • Author(s)
      HaoSheng Li, Yoshiyuki Manabe, Kento Tokunaga, Naoko Terao, Shinji Takamatsu, Masahiro Tanemura, Eiji Miyoshi, Koichi Fukase
    • Organizer
      PACIFICHEM2015
    • Place of Presentation
      Hawaii
    • Year and Date
      2016-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖鎖抗原 α-gal エピトープの効率合成と新規がん療法への適用2016

    • Author(s)
      徳永健斗、真鍋良幸、樺山一哉、深瀬浩一
    • Organizer
      日本化学会第96回春季年会
    • Place of Presentation
      京都
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] インフルエンザ感染阻害剤開発を目指した糖鎖クラスターの合成研究2016

    • Author(s)
      市川浩章、真鍋良幸、深瀬浩一
    • Organizer
      日本化学会第96回春季年会
    • Place of Presentation
      京都
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 水素結合ネットワークの形成阻害による反応性向上を鍵としたABO式血液型糖鎖の合成研究2016

    • Author(s)
      筒井正斗・真鍋良幸・深瀬浩一
    • Organizer
      日本化学会第96回春季年会
    • Place of Presentation
      京都
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] 機能集積中分子の創製を目指して:反応集積による合成的アプローチ2016

    • Author(s)
      深瀬浩一
    • Organizer
      生命分子機能研究会セミナー2016「生命分子・ペプチド科学に基づく創薬:医療への貢献」
    • Place of Presentation
      滋賀
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Development of New Generation Cancer Vaccines: Conjugation of Antigens with Adjuvants2016

    • Author(s)
      Yoshiyuki Manabe, HaoSheng Li, Kento Tokunaga, Naoko Terao, Shinji Takamatsu, Masahiro Tanemura, Eiji Miyoshi, Koichi Fukase
    • Organizer
      The 8th Takeda Science Foundation Symposium on PharmaScience
    • Place of Presentation
      Osaka
    • Year and Date
      2016-01-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 中分子戦略と医理連携2016

    • Author(s)
      深瀬浩一
    • Organizer
      日本化学会フロンティア生命化学研究会
    • Place of Presentation
      長崎
    • Year and Date
      2016-01-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] SYNTHESIS OF THE CONJUGATES OF TUMOR ANTIGENS WITH ADJUVANTS FOR THE EFFICIENT CANCER IMMUNOTHERAPY2015

    • Author(s)
      Yoshiyuki Manabe, Tsung-Che Chang, HaoSheng Li, Naoko Terao, Shinji Takamatsu, Masahiro Tanemura, Eiji Miyoshi, Koichi Fukase
    • Organizer
      第52回ペプチド討論会
    • Place of Presentation
      神奈川
    • Year and Date
      2015-11-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Fully synthetic self-adjuvanting antitumor vaccine candidate consisting of N-modified TriSTn antigen combined with lipopeptide and T-helper-cell-epitope2015

    • Author(s)
      CHANG, Tsung-che; MANABE, Yoshiyuki; FUJIMOTO, Yukari; FUKASE, Koichi
    • Organizer
      the 13th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-13)
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of Novel Tumor Vaccine Using Synthetic α-Gal as an Adjuvant2015

    • Author(s)
      Yoshiyuki Manabe, HaoSheng Li, Kento Tokunaga, Naoko Terao, Shinji Takamatsu, Masahiro Tanemura, Eiji Miyoshi, Koichi Fukase
    • Organizer
      the 13th International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC-13)
    • Place of Presentation
      Kyoto
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アミド基のイミド保護による反応性向上を鍵としたABO式血液型糖鎖の合成研究2015

    • Author(s)
      筒井正斗・真鍋良幸・深瀬浩一
    • Organizer
      第5回CSJ化学フェスタ2015
    • Place of Presentation
      東京
    • Year and Date
      2015-10-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] α-galエピトープをアジュバントとして利用する革新的がんワクチン療法の開発2015

    • Author(s)
      真鍋良幸,李 昊晟,寺尾尚子,高松真二,種村匡弘,三善英知,深瀬浩一
    • Organizer
      第9回バイオ関連化学シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2015-09-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Synthetic and biofunctional studies of glycoconjugates toward immunoregulation2015

    • Author(s)
      Fukase, K.
    • Organizer
      18th European Carbohydrate Symposium (Eurocarb18)
    • Place of Presentation
      Russia
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 効率的がんワクチン療法を指向した免疫調節法の開発2015

    • Author(s)
      中川翔、下山敦史、相羽俊彦、藤本ゆかり、深瀬浩一
    • Organizer
      第2回FCCAグライコサイエンス若手フォーラム2015
    • Place of Presentation
      東京
    • Year and Date
      2015-07-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Synthetic and biofunctional studies of microbial and animal glycans toward immunoregulation2015

    • Author(s)
      Fukase, K.
    • Organizer
      CIC Biogune
    • Place of Presentation
      Spain
    • Year and Date
      2015-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synthetic α-gal Epitope as a Novel Vaccine Adjuvant in Cancer Immunotherapy2015

    • Author(s)
      李昊晟、真鍋良幸、徳永健斗、寺尾尚子、高松真二、種村匡弘、三善英知、深瀬浩一
    • Organizer
      日本ケミカルバイオロジー学会第10回年会
    • Place of Presentation
      宮城
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 免疫調節分子を利用した効率的がんワクチン療法の開発2015

    • Author(s)
      真鍋良幸
    • Organizer
      東海大学医学会講演会
    • Place of Presentation
      神奈川
    • Year and Date
      2015-05-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Novel Tumor Immunotherapy: Studies on Synthetic α-gal as a Vaccine Adjuvant2015

    • Author(s)
      李昊晟、真鍋良幸、徳永健斗、寺尾尚子、高松真二、種村匡弘、三善英知、深瀬浩一
    • Organizer
      第16回 関西グライコサイエンスフォーラム
    • Place of Presentation
      大阪
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Synthetic study of glycoconjugates toward immunoregulation2015

    • Author(s)
      Fukase, K.
    • Organizer
      2015 Glyco Retreat
    • Place of Presentation
      Taiwan
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Full Synthetic Self-Adjuvanting N-modified sTn Antigen BasedAnticancer Vaccine2015

    • Author(s)
      CHANG Tsung-che, MANABE Yoshiyuki, FUJIMOTO Yukari, FUKASE Koichi
    • Organizer
      日本化学会第95回春季年会
    • Place of Presentation
      千葉
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of Novel Tumor Immunotherapy Using Synthetic α-Gal as An Ajuvant2015

    • Author(s)
      李昊晟、真鍋良幸、徳永健斗、野中祐二、寺尾尚子、高松真二、種村匡弘、三善英知、深瀬浩一
    • Organizer
      日本化学会第95回春季年会
    • Place of Presentation
      千葉
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Research-status Report
  • [Presentation] An Efficient Synthesis of α-Gal epitope2014

    • Author(s)
      Kento Tokunaga, Yoshiyuki Manabe and Koichi Fukase
    • Organizer
      The Ninth International Symposium on Integrated Synthesis(ISIS9)
    • Place of Presentation
      Hyogo, Japan
    • Year and Date
      2014-11-14 – 2014-11-15
    • Related Report
      2014 Research-status Report
  • [Presentation] alpha-Galエピトープの効率合成法の開発 - One-potグリコシル化とマイクロフロー系への適用 -2014

    • Author(s)
      徳永健斗、真鍋良幸、深瀬浩一
    • Organizer
      第4回CSJ化学フェスタ2014
    • Place of Presentation
      東京
    • Year and Date
      2014-10-14 – 2014-10-16
    • Related Report
      2014 Research-status Report
  • [Presentation] Fully Synthetic Self-Adjuvanting N-modified sTn Antigen Based Anticancer Vaccine2014

    • Author(s)
      張宗哲、林俊成、真鍋良幸、藤本ゆかり、深瀬浩一
    • Organizer
      第8回バイオ関連化学シンポジウム
    • Place of Presentation
      岡山
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] In(III)を用いた温和なグリコシル化法の開発2014

    • Author(s)
      北脇夕莉子, 真鍋良幸, Regina M. Salmasan, Tsung-Che Chang, 深瀬浩一
    • Organizer
      第34回有機合成若手セミナー
    • Place of Presentation
      大阪
    • Year and Date
      2014-08-05
    • Related Report
      2014 Research-status Report
  • [Presentation] 徳永健斗、真鍋良幸、深瀬浩一2014

    • Author(s)
      新規がん免疫療法を目指したα-Galエピトープの効率合成
    • Organizer
      第34回有機合成若手セミナー
    • Place of Presentation
      大阪
    • Year and Date
      2014-08-05
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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