2021 Fiscal Year Annual Research Report
Understanding the efficacy of therapeutic antibodies through their interaction with cellular receptors.
| Project/Area Number |
20H03228
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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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| Keywords | Antobody / fc receptor / hinge / structure / immunology / glycosylation / protein expression |
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| Outline of Annual Research Achievements |
In this year we have made progress in several fronts. First, we have advanced the study of the effect of glycosylation in an antibody. In that study we habe been able to verify that CH2 glycosylation had a double effect. First, the tendency to aggregate decreased, and second, the immunogenecity of the protein also decreased in mice. Ths results suggested that aggregation and immunogenicity may be correlated. In this study is was also found that a stabilized from of CH2, by employing disulfide bonds, was also influenced by the gycosylation. The effect of stabilization was significant, since it also decreased the aggregation propensity. Therefore the combination of glycosylation and improvement of the stability could be a strategy to develop immunoglobulins with desired properties.
In a second study, we expanded the concept of a new modality of antibodies by site-directed chemical modification. Previously we demonstrated that these novel antibodies can improve their biological effect , and now we have extended their usefulness. We report that the chemical modification can be employed to keep high efficacy while decreasing polyreactivity, a pernicious effect that restrict the application of engineered antibodies (and others) in therapeutic applications.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The tough working environment at universities in Japan has continued in fiscal year 2021, but we have been able to proceed forward with the project as demonstrated by the two studies published.
However, as in 2020, I was not able to attend international conferences because of the continuous tough medical environment caused by COVID-19.
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| Strategy for Future Research Activity |
In this year we will continue our muti-factorial approach in the four lines we have been working.
(1) Production of samples suitable for structural analysis by X-ray crystallography, and now, even more enthusiastically, by Cryo-EM since our Faculty has recently acquired two state-of-the-art instruments of 200 kev and 300 kev.
(2) Further understand the effect of glycosylation in the properties of antibodies and their interaction with Fc receptors.
(3) Preparation of mutations of the hinge region of IgG1 to evaluate its effect in stability and receptor binding.
(4) Continue the efforts to prapara an assay to study the clustering effect in model membranes.
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