| 研究実績の概要 |
The aim of this year's research was to improve the tolerogenic nanoparticle(tNP) for inducing immune tolerance and preventing allergic reactions.
1. Through research on the preparation of the tNP, size control, and dissolution experiments, we successfully determined the basic properties of the tNP in this year.
2. Regarding the interaction between tNP and cells, through co-culture observations with BMDCs, we confirmed that the tNP can be phagocytosed by BMDCs and can change the differentiation direction of BMDCs. Additionally, we confirmed that the tNP has certain T cell stimulation capability, which are crucial for establishing immune tolerance.
3. In terms of animal experiments, we conducted safety evaluation and confirmed the safety of the tNP without causing anaphylaxis. Subsequently, we applied the tNP in prevention experiments on OVA allergy model mice. The experimental results showed that the tNP can effectively prevent allergic reactions. This means that the tNP we developed can become a new type of allergy treatment.
The significance of this research lies in inducing immune tolerance through tNP preparation to prevent allergic reactions without affecting normal immune responses. Compared to traditional allergy treatment methods, tNP has the advantages of being easy to prepare and quick to take effect, which can greatly improve the convenience of patient treatment and quality of life. Overall, the research results of this year provide a new idea and method for immune tolerance research and allergy treatment, with potential application value in clinical treatment.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
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理由
The research on tNP has progressed as follows:
1.Basic properties of tNP: Methods for production, purification, and storage of tNP have been determined. The tNP size has been controlled to be 200 nm or less by adjusting the agitation intensity, dispersion strength, and addition of crosslinking agents during the preparation process. It has been reported that nanoparticles around 200 nm have been shown to accumulate at inflammatory sites and be easily taken up by cells. The release property is important to generate tolerance signal, so the tNP release profile was adjusted to ideally prolonged release behavior.
2.Reaction between tNP and cells: Co-culture of tNP with bone marrow-derived dendritic cells (BMDCs) was conducted to observe the uptake of tNP by cells, changes in DC markers, and determine DC differentiation direction. Then co-culture of tNP with BMDCs and T cells was performed to evaluate the T cell stimulating ability of tNP based on the level of IL-2 produced by T cells.
3.Animal experiments: To confirm the safety of tNP, tNP were administered to a mouse model sensitized with OVA to investigate whether anaphylaxis was induced by measuring the body temperature change. For allergy therapy assay, a plan was made to use tNP in the OVA allergy model mouse to investigate the preventive effects of tNP. These developments have demonstrated the progress in the basic properties of tNP, cell reactions, and safety confirmation in animal experiments. It is important to conduct more detailed experiments in the future and confirm therapeutic effects.
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| 今後の研究の推進方策 |
The strategies for advancing future research are as follows:
1.We will confirm the effectiveness of tNP in animal experiments and verify their efficacy as the therapeutic strategy. Then the tNP will be incorporated immunomodulator such as rapamycin and evaluate the allergy treatment effect compare to tNP without drug by subcutaneous. The drug expected to be more effectively to treat allergy disease with significantly increased anti inflammation cytokine production and tolerance type T cells generation.
2.The anti-drug antibody(ADA) will be evaluated to verify the safety and potential impairment on therapy efficacy of tNP. The mice will be applied for tNP weekly by subcutaneous injection and collect serum after 1 month to measure the IgG and IgM towards tNP. Also, the reactivity between anti OVA IgE antibody and tNP will be done to verify the safety of tNP. If there are any safety concerns, to improve the tNP to ensure their safety.
3.As next step, after we achieve the positive result. We aim to clarify the effective allergy treatment mechanisms of tNP by investigating changes in cellular reactions and immune responses in vivo by measuring the cytokine, the cell phenotype change. And clarify the biodistribution by cell kind measurement of the tNP in vivo.
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