DK2536746T3 - Disulphid-bindingsstabiliserede funktionelt opløselige MHC klasse II heterodimere - Google Patents
Disulphid-bindingsstabiliserede funktionelt opløselige MHC klasse II heterodimere Download PDFInfo
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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Claims (18)
1. Rekombinant MHC klasse II molekyle, som omfatter: (i) hele eller en del af den ekstracellulære del af en MCH klasse II a-kæde; (ii) hele eller en del af den ekstracellulære del af en MCH klasse II β-kæde; hvor (i) og (ii) tilvejebringer et funktionelt peptidbindingsdomæne og hvor (i) og (ii) er forbundet med en disulphidbinding mellem cysteinrester lokaliseret i a2-domænet af α-kæden og p2-domænet af β-kæden, hvor cyste in resterne ikke er til stede i nativ MHC klasse II a2- og β2^0ΓΠ3εηθΓ, og hvor det rekombinante molekyle ikke omfatter et leucin-zipper-motiv.
2. Det rekombinante MHC klasse II molekyle ifølge krav 1, hvor disulphidbindingen er lokaliseret mellem cysteinrester positioneret ved Pro 96a2-Ser 119p2 (rang 1), Ser 95a2 - Ser 121p2 (rang 2) eller Arg 94a2 - Asn 151p2 (rang 3) afen murin I-E isotype eller de ækvivalente positioner i en alternativ MHC klasse II isotype.
3. Det rekombinante MHC klasse II molekyle ifølge krav 1 eller krav 2, yderligere hvor en eller flere af cysteinresterne svarende til positioner 38, 42 eller 106 af referencesekvensen H-2EB*01 (SEQ ID NO:2) eller en eller flere af cystein resterne ved ækvivalente positioner i en alternativ MHC klasse II isotype er fjernet.
4. Rekombinant MHC klasse II molekyle, som omfatter: (i) hele eller en del af den ekstracellulære del af en MCH klasse II a-kæde; (ii) hele eller en del af den ekstracellulære del af en MCH klasse II β-kæde; hvor (i) og (ii) tilvejebringer et funktionelt peptidbindingsdomæne og hvor (i) og (ii) er forbundet med en disulphidbinding mellem cysteinrester lokaliseret i a2-domænet af α-kæden og β2^οηη3θηθί af β-kæden, hvor cystein resterne ikke er til stede i nativ MHC klasse II a2- og β2^οιτΐ06ηθΓ, og hvor det rekombinante molekyle er udtrykt på overfladen af en filamentær phag.
5. Det rekombinante MHC klasse II molekyle ifølge krav 4, hvor disulphidbindingen er lokaliseret mellem cysteinrester positioneret ved Pro 96a2-Ser 119*32 (rang 1), Ser 95a2-Ser 121p2 (rang 2) eller Arg 94a2- Asn 151*32 (rang 3) afen murin I-E isotype eller de ækvivalente positioner i en alternativ MHC klasse II isotype, og/eller hvor en eller flere af cysteinresterne svarende til positioner 38, 42 eller 106 af referencesekvensen H-2EB*01 (SEQ ID NO:2) eller en eller flere af cystein resterne ved ækvivalente positioner i en alternativ MHC klasse II isotype er fjernet.
6. Det rekombinante MHC klasse II molekyle ifølge krav 4 eller krav 5, hvor det rekombinante molekyle er udtrykt som en fusionering til phagoverfladeproteinet gpIII, gpVII, gpVIII eller gpIX.
7. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 3, hvor molekylet er et opløseligt molekyle.
8. Det rekombinante MHC klasse II molekyle ifølge krav 7, hvor (i) eller (ii) af molekylet er fusioneret til en Fc-del af en immunoglobulin.
9. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 8, hvor molekylet er multimerisk.
10. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 9, hvor (i) og (ii) af molekylet er afledt fra muse- eller human MHC klasse II molekyler, fortrinsvis human.
11. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 10, hvor molekylet er fremstillet af en bakterievært.
12. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 11, hvor disulphidbindingen tilvejebringer det eneste middel til stabilisering af MHC klasse II molekylet.
13. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 12, hvor molekylet er i stand til at farve T-celler.
14. Det rekombinante MHC klasse II molekyle ifølge et hvilket som helst af kravene 1 til 13, hvor molekylet yderligere omfatter et peptid bundet til peptidbindingsdomænet.
15. Fremgangsmåde til fremstilling af et rekombinant MHC klasse II molekyle, som omfatter: (i) hele eller en del af den ekstracellulære del af en MCH klasse II a-kæde; (ii) hele eller en del af den ekstracellulære del af en MCH klasse II P kæde; hvor (i) og (ii) tilvejebringer et funktionelt peptidbindingsdomæne og hvor (i) og (ii) er forbundet med en disulphidbinding mellem cysteinrester lokaliseret i a2-domænet af α-kæden og p2-domænet af β-kæden, hvor cysteinresterne ikke er til stede i nativ MHC klasse II a2- og β2^0ΓΠ3Ξη6Γ, fremgangsmåden omfattende at udtrykke det rekombinante molekyle i en prokaryotisk vært.
16. Fremgangsmåde til identificering af antigen-peptidepitoper som kan genkendes af T-celler, hvor fremgangsmåden omfatter trinnene at bringe et rekombinant MHC klasse II molekyle ifølge krav 14 i kontakt med en T-cellereceptor og detektere binding af det rekombinante MHC klasse II molekyle til T-cellereceptoren.
17. Fremgangsmåde til detektering af antigen-specifikke T-celler i en prøve, hvor fremgangsmåden omfatter trinnene at bringe et rekombinant MHC klasse II molekyle ifølge krav 14 i kontakt med prøven og detektere binding af det rekombinante MHC klasse II molekyle til T-cellerne.
18. Fremgangsmåden ifølge krav 17, hvor fremgangsmåden anvendes til at detektere tilstedeværelsen af sygdomsspecifikke T-celler i en prøve og til at diagnosticere tilstedeværelsen eller fraværet på sygdom.
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| PCT/GB2011/050325 WO2011101681A2 (en) | 2010-02-18 | 2011-02-18 | Disulphide bond-stabilized functional soluble mhc class ii heterodimers |
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| GB201309469D0 (en) | 2013-05-28 | 2013-07-10 | Imcyse Sa | Detection of CD4+ T lymphocytes |
| DK3167065T3 (da) * | 2014-07-09 | 2020-07-06 | Lupin Ltd | Dobbelt cistronisk bakterielt ekspressionssystem |
| WO2017004252A1 (en) | 2015-06-30 | 2017-01-05 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Redirected cells with mhc chimeric receptors and methods of use in immunotherapy |
| MA45489A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés de culture de cellules, kits et appareil associés |
| US10294454B2 (en) | 2016-08-24 | 2019-05-21 | General Electric Company | Methods and kits for cell activation |
| KR102646495B1 (ko) * | 2016-11-09 | 2024-03-12 | 유티아이 리미티드 파트너쉽 | 재조합 pMHC II형 분자 |
| NZ758485A (en) | 2017-04-27 | 2024-02-23 | Juno Therapeutics Gmbh | Oligomeric particle reagents and methods of use thereof |
| DE102018122546B3 (de) | 2018-09-14 | 2019-12-05 | Immatics Biotechnologies Gmbh | Verfahren zum Hochdurchsatz-Peptid-MHC-Affinitätsscreening für TCR-Liganden |
| WO2020064915A1 (en) * | 2018-09-28 | 2020-04-02 | Danmarks Tekniske Universitet | High throughput epitope identification and t cell receptor specificity determination using loadable detection molecules |
| TW202043256A (zh) | 2019-01-10 | 2020-12-01 | 美商健生生物科技公司 | 前列腺新抗原及其用途 |
| EP3719033A1 (en) * | 2019-04-02 | 2020-10-07 | imusyn GmbH & Co. KG | Stabilized mhc i |
| WO2021035049A1 (en) * | 2019-08-21 | 2021-02-25 | Uti Limited Partnership | Improved recombinant pmhc molecules |
| US20210155670A1 (en) * | 2019-09-13 | 2021-05-27 | The Regents Of The University Of California | Systems and methods for the preparation of peptide-mhc-i complexes with native glycan modifications |
| WO2021113297A1 (en) * | 2019-12-02 | 2021-06-10 | Regeneron Pharmaceuticals, Inc. | Peptide-mhc ii protein constructs and uses thereof |
| TW202144388A (zh) | 2020-02-14 | 2021-12-01 | 美商健生生物科技公司 | 在卵巢癌中表現之新抗原及其用途 |
| TW202144389A (zh) | 2020-02-14 | 2021-12-01 | 美商健生生物科技公司 | 在多發性骨髓瘤中表現之新抗原及其用途 |
| DE102020109447A1 (de) | 2020-04-03 | 2021-10-07 | Jacobs University Bremen Ggmbh | Synthetisches mhc-klasse-ii-protein |
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| WO1990010457A1 (en) | 1989-03-14 | 1990-09-20 | New York University | Method of treating hiv infections using immunotoxins |
| CA2263195A1 (en) * | 1996-08-16 | 1998-02-19 | President And Fellows Of Harvard College | Soluble monovalent and multivalent mhc class ii fusion proteins, and uses therefor |
| AU741130B2 (en) * | 1997-09-16 | 2001-11-22 | Oregon Health Sciences University | Recombinant MHC molecules useful for manipulation of antigen-specific T-cells |
| NZ507887A (en) * | 1998-05-19 | 2002-12-20 | Avidex Ltd | Soluble T cell receptor |
| RU2303264C2 (ru) * | 2001-02-19 | 2007-07-20 | Мерк Патент Гмбх | Способ идентификации эпитопов т-клеток и его применение для получения молекул со сниженной иммуногенностью |
| GB2392158B (en) * | 2002-08-21 | 2005-02-16 | Proimmune Ltd | Chimeric MHC protein and oligomer thereof |
| EP1675607B1 (en) * | 2003-09-05 | 2015-10-21 | Oregon Health & Science University | Monomeric recombinant mhc molecules useful for manipulation of antigen-specific t cells |
| JP2008537736A (ja) * | 2005-03-18 | 2008-09-25 | オレゴン ヘルス アンド サイエンス ユニバーシティ | 抗原特異的ｔ細胞の操作に有用な組換えｍｈｃ分子 |
| EP2476437B1 (en) * | 2006-08-11 | 2018-11-28 | Life Sciences Research Partners VZW | Immunogenic peptides and their use in immune disorders |
| EP2097789B1 (en) * | 2006-12-01 | 2012-08-01 | Carl Zeiss SMT GmbH | Optical system with an exchangeable, manipulable correction arrangement for reducing image aberrations |
| KR101597840B1 (ko) | 2007-08-20 | 2016-02-25 | 넥스테라 에이에스 | ｐⅦ 파아지 디스플레이 |
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| US9056920B2 (en) | 2015-06-16 |
| WO2011101681A2 (en) | 2011-08-25 |
| GB201002730D0 (en) | 2010-04-07 |
| US8828379B2 (en) | 2014-09-09 |
| AU2011217027A1 (en) | 2012-09-06 |
| SI2536746T1 (sl) | 2016-09-30 |
| KR101647176B1 (ko) | 2016-08-09 |
| JP5537675B2 (ja) | 2014-07-02 |
| US20130171668A1 (en) | 2013-07-04 |
| ES2572388T3 (es) | 2016-05-31 |
| CA2789492C (en) | 2017-04-18 |
| RU2012138302A (ru) | 2014-03-27 |
| EP2536746B1 (en) | 2016-04-20 |
| US20140349315A1 (en) | 2014-11-27 |
| RS54744B1 (sr) | 2016-10-31 |
| WO2011101681A3 (en) | 2011-12-08 |
| PL2536746T3 (pl) | 2016-08-31 |
| KR20130009782A (ko) | 2013-01-23 |
| HRP20160475T1 (hr) | 2016-06-03 |
| JP2013519721A (ja) | 2013-05-30 |
| CN102947330A (zh) | 2013-02-27 |
| RU2604813C2 (ru) | 2016-12-10 |
| EP2536746A2 (en) | 2012-12-26 |
| CY1117697T1 (el) | 2017-05-17 |
| CN102947330B (zh) | 2015-09-16 |
| HUE027952T2 (en) | 2016-11-28 |
| AU2011217027B2 (en) | 2015-02-05 |
| CA2789492A1 (en) | 2011-08-25 |
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