JP2012527237A - 免疫介在性疾患における臨床応用のための、抑制機能の高められた制御性t細胞のエクスビボ増加方法 - Google Patents
免疫介在性疾患における臨床応用のための、抑制機能の高められた制御性t細胞のエクスビボ増加方法 Download PDFInfo
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Abstract
Description
SLE患者9人、RA患者7人、喘息患者7人、MS患者10人、及びCD患者7人、並びに自己免疫疾患ではない11人から、各50ccの末梢血サンプル約5〜10個を採取した。
SLE患者9人、RA患者7人、喘息患者7人、MS患者8人、及びCD患者7人、並びに自己免疫疾患ではない25人から、各50ccの末梢血サンプル約5〜10個を採取した。
SLE、RA、喘息、MS、CD、及びUC患者から各50ccの約5〜10個の末梢血サンプルを採取した。前記サンプルのPBMCからCD4+Tregを精製した。精製は、実施例1に記載の通り実施した。
実施例3のTregを、以下の通り標準化された抑制アッセイを用いて2週間目に評価した。抗CD3で刺激する培養では、同じドナー由来のアロジェニックなCD4+CD25+ヒトT細胞(5×104細胞/ウェル)をレスポンダー細胞として用い、1mg/mLの抗CD3(OKT3)及びアロジェニックなヒト樹状細胞(1人のドナー由来、5×103細胞/ウェル)及び段階希釈した増加Tregを、トリプリケートで96ウェルプレートに入れた。アロ抗原で刺激する培養では、1人のドナー由来のCD4+CD25+ヒトTreg細胞(5×104細胞/ウェル)、別のドナー由来の5×103個のヒト樹状細胞、及び段階希釈した増加Tregを、トリプリケートで96ウェルプレートに入れた。
(1) a)全身性エリテマトーデス、多発性硬化症、喘息、関節リウマチ、クローン病、又は潰瘍性大腸炎から選択される免疫介在性疾患の個体からT細胞集団を得ることと;b)前記T細胞集団からCD4+CD25+Tregの亜集団を単離及び精製することと;c)前記亜集団のTreg細胞を増加させることとを含む方法であって、前記増加されたTreg細胞が、前記個体から新たに精製された増加されていないTregの集団に比べて高い抑制活性を示す、方法。
(2) 前記増加が、約100〜1,000倍である、実施態様1に記載の方法。
(3) 前記増加が、約3週間にわたって行われた、実施態様1に記載の方法。
(4) 免疫介在性疾患の個体を治療する方法であって、a)全身性エリテマトーデス、多発性硬化症、喘息、関節リウマチ、クローン病、又は潰瘍性大腸炎から選択される免疫介在性疾患の個体からT細胞集団を得ることと;b)前記T細胞集団からCD4+CD25+Tregの亜集団を単離及び精製することと;c)前記亜集団のTreg細胞を増加させることと;d)前記免疫介在性疾患の治療が施されるヒトにCD4+CD25+制御性T細胞の一部を投与することとを含む、方法。
(5) 前記免疫介在性疾患が、全身性エリテマトーデスである、実施態様4に記載の方法。
(6) 前記免疫介在性疾患が、多発性硬化症である、実施態様4に記載の方法。
(7) 前記免疫介在性疾患が喘息、関節リウマチである、実施態様4に記載の方法。
(8) 前記免疫介在性疾患が、関節リウマチである、実施態様4に記載の方法。
(9) 前記免疫介在性疾患が、クローン病である、実施態様4に記載の方法。
(10) 前記免疫介在性疾患が、潰瘍性大腸炎である、実施態様4に記載の方法。
Claims (10)
- a)全身性エリテマトーデス、多発性硬化症、喘息、関節リウマチ、クローン病、又は潰瘍性大腸炎から選択される免疫介在性疾患の個体からT細胞集団を得ることと;b)前記T細胞集団からCD4+CD25+Tregの亜集団を単離及び精製することと;c)前記亜集団のTreg細胞を増加させることとを含む方法であって、前記増加されたTreg細胞が、前記個体から新たに精製された増加されていないTregの集団に比べて高い抑制活性を示す、方法。
- 前記増加が、約100〜1,000倍である、請求項1に記載の方法。
- 前記増加が、約3週間にわたって行われた、請求項1に記載の方法。
- 免疫介在性疾患の個体を治療する方法であって、a)全身性エリテマトーデス、多発性硬化症、喘息、関節リウマチ、クローン病、又は潰瘍性大腸炎から選択される免疫介在性疾患の個体からT細胞集団を得ることと;b)前記T細胞集団からCD4+CD25+Tregの亜集団を単離及び精製することと;c)前記亜集団のTreg細胞を増加させることと;d)前記免疫介在性疾患の治療が施されるヒトにCD4+CD25+制御性T細胞の一部を投与することとを含む、方法。
- 前記免疫介在性疾患が、全身性エリテマトーデスである、請求項4に記載の方法。
- 前記免疫介在性疾患が、多発性硬化症である、請求項4に記載の方法。
- 前記免疫介在性疾患が喘息、関節リウマチである、請求項4に記載の方法。
- 前記免疫介在性疾患が、関節リウマチである、請求項4に記載の方法。
- 前記免疫介在性疾患が、クローン病である、請求項4に記載の方法。
- 前記免疫介在性疾患が、潰瘍性大腸炎である、請求項4に記載の方法。
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US20130273089A1 (en) * | 2011-11-03 | 2013-10-17 | Tolera Therapeutics, Inc. | Antibody and methods for selective inhibition of t-cell responses |
PL236046B1 (pl) | 2015-12-17 | 2020-11-30 | Gdanski Univ Medyczny | Sposób namnażania in vitro limfocytów T regulatorowych CD4+ FoxP3+ |
US11384336B2 (en) | 2016-12-07 | 2022-07-12 | East Carolina University | Compositions and methods for in vitro cultivation and/or expansion of regulatory T cells |
CN107519207A (zh) * | 2017-08-31 | 2017-12-29 | 广东颜值科技有限公司 | 一种免疫抑制细胞制剂及其制备方法和应用 |
WO2019166658A1 (en) * | 2018-03-01 | 2019-09-06 | Fundación Para La Investigación Biomédica Del Hospital Gregorio Marañón | Method for obtaining regulatory t cells derived from thymic tissue and use of said cells as cell immunotherapy in immune system disorders |
WO2020157129A1 (en) * | 2019-01-30 | 2020-08-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Optimisation of the scurfy model for in vivo testing of innovative treatments of autoimmunity |
EP3985106A1 (en) | 2020-10-16 | 2022-04-20 | Uniwersytet Gdanski | Conditioned regulatory t cell population with enhanced therapeutic potential, method for obtaining of regulatory t cell population and the medical use of regulatory t cell population |
EP3985105A1 (en) | 2020-10-16 | 2022-04-20 | Uniwersytet Gdanski | Conditioned regulatory t cell population tregs with enhanced therapeutic potential, method for obtaining of conditioned tregs and the medical use of the tregs population |
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WO2010135255A1 (en) | 2010-11-25 |
US20100291117A1 (en) | 2010-11-18 |
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EP2446022A1 (en) | 2012-05-02 |
US20240191193A1 (en) | 2024-06-13 |
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