Development of novel cancer immunotherapy utilizing hyperacute rejection induced by alpha-gal epitope
| Project/Area Number |
26560447
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Chemical biology
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| Research Institution | Osaka University |
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Principal Investigator |
Fukase Koichi 大阪大学, 理学(系)研究科(研究院), 教授 (80192722)
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| Co-Investigator(Kenkyū-buntansha) |
MANABE Yoshiyuki 大阪大学, 大学院理学研究科, 助教 (00632093)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| 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)
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| 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 |
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| 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.
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Report
(3 results)
Research Products
(33 results)
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[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.
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Journal Title
Chemistry Letters
Volume: 43
Issue: 6
Pages: 956-958
DOI
NAID
ISSN
0366-7022, 1348-0715
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Org Biomol Chem.
Volume: 12
Issue: 9
Pages: 1412-1418
DOI
Related Report
Peer Reviewed
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