Understanding the efficacy of therapeutic antibodies through their interaction with cellular receptors.
| Project/Area Number |
20H03228
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 43040:Biophysics-related
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| Research Institution | Kyushu University |
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Principal Investigator |
CAAVEIRO Jose 九州大学, 薬学研究院, 教授 (00536732)
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| Co-Investigator(Kenkyū-buntansha) |
高橋 大輔 九州大学, 薬学研究院, 講師 (70791523)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | Antibody / Fc receptor / hinge / structure / immunology / glycosylation / bnAbs / HIV-1 / antibody / fc receptor / Antobody / protein expression / Mechanism / Molecular interactios / molecular interactions / mechanism |
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| Outline of Research at the Start |
Therapeutic antibodies are improving human healthcare.
To improve their efficacy and safety we need to understand how they work in a more precise manner.
The binding of antibodies to Fc receptors starts a strong cellular response.
We aim to understand how that happens at the molecular level.
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| Outline of Final Research Achievements |
We advanced the understanding of the interaction between antibodies of the IgG family and their cellular receptors at the molecular level. We have described the less-than expected effect of mutations in the middle hinge region to the strength of the interaction with receptors (the middle hinge is where the disulfide bond is located). However, residues in close proximity to the binding interface had a profound effect. Our studies support the engineering of antibodies in the hinge region without major effect in the potency of Abs.
Additionally, we made an important contribution to improve the potency of Abs. This process was patented and consist on (i) the introduction of a CYS residue in a strategic location and (2) chemical modification of the CYS residue by a yodo acetamide molecule of specific atomic structure. Using this approach we have improved the potency of anti-HIV-1 Abs by more than 500-fold.
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| Academic Significance and Societal Importance of the Research Achievements |
From a scientific point, we have advanced the basic knowledge of the interaction between antibodies and their cellular receptors. From a social point of view, the technology discovered herein improves the potency of antibodies and might save the lives of people suffering from infectious diseases.
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Report
(4 results)
Research Products
(8 results)
