| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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