DK2201100T3 - Forbedring af t-cellestimulerende evne for humane antigenpræsenterende celler og anvendelse heraf i vaccination - Google Patents
Forbedring af t-cellestimulerende evne for humane antigenpræsenterende celler og anvendelse heraf i vaccination Download PDFInfo
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- DK2201100T3 DK2201100T3 DK08804137.1T DK08804137T DK2201100T3 DK 2201100 T3 DK2201100 T3 DK 2201100T3 DK 08804137 T DK08804137 T DK 08804137T DK 2201100 T3 DK2201100 T3 DK 2201100T3
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Claims (14)
1. Fremgangsmåde in vitro til forbedring af de immunstimulerende egenskaber for humane antigenpræsenterende celler, hvilken fremgangsmåde omfatter samtidig introduktion af mindst to forskellige mRNA- eller DNA-molekyler, der koder for funktionelle immunstimulerende proteiner i de antigenpræsenterende celler, kendetegnet ved, at mindst CD40L og caTLR4 er introduceret blandt de funktionelle proteiner, og hvor eventuelt ydermere CD70 er introduceret.
2. Fremgangsmåde in vitro til fremstilling af et immunterapimiddel, hvilken fremgangsmåde omfatter følgende trin: a) modificering in vitro af en pool af antigenpræsenterende celler ved at introducere mRNA- eller DNA-molekyler i de antigenpræsenterende celler, der koder for det immunstimulerende antigen CD40L og caTLR4 og eventuelt ydermere CD70, b) modificering in vitro af poolen af antigenpræsenterende celler fra trin a) ved at introducere et målspecifikt antigen i de antigenpræsenterende celler, således at de præsenterer målspecifikke antigenafledte epitoper.
3. Fremgangsmåde ifølge et hvilket som helst af kravene 1-2, hvor de antigenpræsenterende celler er udvalgt fra gruppen bestående af dendritiske celler (DC), B-celler, der er isoleret fra eller genereret af blod fra et individ, dendritiske cellelinjer eller B-cellelinjer.
4. Fremgangsmåde ifølge et hvilket som helst af kravene 1-3, hvor det målspecifikke antigen er et tumor-, bakterie-, virus- eller svampeantigen.
5. Vaccine omfattende et immunterapimiddel, der omfatter antigenpræsenterende celler, der er modificeret in vitro ved: a) introduktion af mRNA- eller DNA-molekyler i de antigenpræsenterende celler, der koder for mindst det immunstimulerende antigen CD40L og caTLR4, og eventuelt ydermere CD70, hvilke antigenpræsenterende celler derved udtrykker de immunstimulerende antigener, og b) introduktion i de antigenpræsenterende celler af et målspecifikt antigen, hvilke antigenpræsenterende celler derved præsenterer det målspecifikke antigen, hvilken vaccine endvidere omfatter et eller flere farmaceutisk acceptable adjuvanser.
6. Præparat af antigenpræsenterende celler til anvendelse i udløsning af et immunrespons hos en patient med behov derfor, kendetegnet ved, at mindst to forskellige mRNA- eller DNA-molekyler, der koder for funktionelle immunstimulerende proteiner, hvor iblandt der mindst er CD40L og caTLR4, og eventuelt ydermere CD70, introduceret i de antigenpræsenterende celler.
7. Vaccine ifølge krav 5 til anvendelse i udløsning af et immunrespons hos en patient med behov derfor.
8. Fremgangsmåde in vitro til at screene for nye målspecifikke epitoper, der kan anvendes til vaccination af patienter, hvilken fremgangsmåde omfatter følgende trin: a) stimulering in vitro af T-celler fra raske donorer eller patienter, der tidligere er vaccineret eller ikke vaccineret, med en antimålvaccine, med antigenpræsenterende celler, hvori der er mindst to forskellige mRNA- eller DNA-molekyler, der koder for funktionelle immunstimulerende proteiner, introduceret, hvor iblandt der mindst er CD40L og caTLR4, og eventuelt ydermere CD70, hvilke antigenpræsenterende celler derved udtrykker de immunstimulerende proteiner; b) identifikation af T-celler, der er specifikke for det anvendte målantigen; og c) identifikation af den målantigenafledte epitop, for hvilken T-cellen er specifik.
9. Sammensætning omfattende en kombination af mindst to forskellige mRNA- eller DNA-molekyler, der koder for: a) et funktionelt immunstimulerende protein CD40L og caTLR4, og eventuelt ydermere b) et funktionelt immunstimulerende protein CD70.
10. Sammensætning ifølge krav 9, hvor de to eller flere mRNA- eller DNA-molekyler, der koder for immunstimulerende proteiner, er dele af et enkelt mRNA- eller DNA-molekyle, hvor det enkelte single mRNA- eller DNA-molekyle er i stand til at udtrykke de to eller flere proteiner samtidigt, eller hvor de to eller flere mRNA- eller DNA-molekyler, der koder for immunstimulerende proteiner, er adskilt i det enkelte mRNA- eller DNA-molekyle ved et internt ribosomalt indgangssted (IRES) eller en selvkløvende 2a peptidkodende sekvens.
11. Fremgangsmåde in vitro til at følge effekterne af behandlingen med en anti-målvaccine hos en patient, hvilken fremgangsmåde omfatter påvisning og analyse af immunresponset over for det målspecifikke antigen udløst i en hudbiopsi for hypersensitivitet af forsinket type eller en perifer blodprøve fra individet, der tidligere har fået injiceret vaccinen ifølge krav 5 eller sammensætningen ifølge et hvilket som helst af kravene 9-10.
12. Præparat af antigenpræsenterende celler ifølge krav 6 eller fremgangsmåde ifølge krav 8 eller 11, hvor patienten lider af en sygdom eller lidelse, der er udvalgt fra gruppen af: forekomst af tumor, cancer, forekomst af melanom, bakterie-, virus- eller svampeinfektion, HIV-infektion eller hepatitisinfektion.
13. Fremgangsmåde til amplifikation ex-vivo af en pool af T-celler fra en patient, hvilken fremgangsmåde omfatter; a) at bringe T-celler opnået fra en patient, der var vaccineret før isolationen, eller som ikke er vaccineret, i kontakt med et immunterapimiddel omfattende antigenpræsenterende celler, hvori der mindst er introduceret to forskellige mRNA- eller DNA-molekyler, der koder for funktionelle immunstimulerende proteiner, hvor iblandt der mindst er CD40L og caTLR4, og eventuelt ydermere CD70, hvilke antigenpræsenterende celler derved udtrykker de immunstimulerende proteiner; og hvori et målspecifikt antigen er introduceret, hvilke antigenpræsenterende celler derved præsenterer målspecifikke antigenafledte epitoper, og b) identifikation, isolering og ekspansion af T-celler ex vivo, der er specifikke for antigenet præsenteret af de antigenpræsenterende celler, som de har været i kontakt med.
14. Pool af T-celler til anvendelse i en anordning til adoptiv T-celleoverførsel hos en patient, kendetegnet ved, at poolen af T-celler består af T-celler, der er opnået fra patienten, der er stimuleret ex vivo med immunterapimidlet omfattende antigenpræsenterende celler, hvor mindst to forskellige mRNA-eller DNA-molekyler, der koder for funktionelle immunstimulerende proteiner, hvor iblandt der mindst er CD40L og caTLR4, og eventuelt ydermere CD70, introduceret i de antigenpræsenterende celler; hvor et målspecifikt antigen er introduceret i de antigenpræsenterende celler, hvorved der præsenteres målspecifikke antigenafledte epitoper; der er ekspanderet ex vivo, og der er specifikke for antigenet præsenteret af de antigenpræsenterende celler, som de har været i kontakt med.
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| PCT/EP2008/062174 WO2009034172A1 (en) | 2007-09-14 | 2008-09-12 | Enhancing the t-cells stimulatory capacity of human antigen presenting cells and their use in vaccination |
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| US9408909B2 (en) | 2007-09-14 | 2016-08-09 | Vrije Universiteit Brussel | Enhancing the T-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and its use in vaccination |
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| WO2010102278A1 (en) * | 2009-03-06 | 2010-09-10 | President And Fellows Of Harvard College | Methods and compositions for the generation and maintenance of regulatory t cells |
| EP2494038B1 (en) * | 2009-10-27 | 2019-06-26 | Immunicum AB | Method for proliferation of antigen-specific t cells |
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| US20150290306A1 (en) * | 2012-10-29 | 2015-10-15 | David E. Anderson | Compositions and methods for diagnosis and treatment of malignant gliomas |
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| JP2019519516A (ja) | 2016-05-18 | 2019-07-11 | モデルナティーエックス， インコーポレイテッド | がんの治療のためのｍＲＮＡ併用療法 |
| SI3458083T1 (sl) | 2016-05-18 | 2023-03-31 | Modernatx, Inc. | Polinukleotidi, ki kodirajo interlevkin-12 (IL12) in njihova uporaba |
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| US11422127B2 (en) * | 2016-12-07 | 2022-08-23 | Albany Medical College | Ex vivo antigen and adjuvant pulsed peripheral blood mononuclear cells as a screening platform for candidate novel vaccines and candidate antigens |
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| US20210388390A1 (en) * | 2018-10-04 | 2021-12-16 | Sqz Biotechnologies Company | Intracellular delivery of biomolecules to enhance antigen presenting cell function |
| US20210386843A1 (en) * | 2019-01-04 | 2021-12-16 | Etherna Immunotherapies Nv | mRNA Vaccine |
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| US6969609B1 (en) * | 1998-12-09 | 2005-11-29 | The United States Of America As Represented By The Department Of Health And Human Serivces | Recombinant vector expressing multiple costimulatory molecules and uses thereof |
| EP1651755B1 (en) * | 2003-08-04 | 2010-10-13 | IMBA-Institut für Molekulare Biotechnologie GmbH | Method for immunotherapy of tumors |
| WO2005118788A2 (en) * | 2004-05-27 | 2005-12-15 | The Trustees Of The University Of Pennsylvania | Novel artificial antigen presenting cells and uses therefor |
| WO2006042177A2 (en) * | 2004-10-07 | 2006-04-20 | Argos Therapeutics, Inc. | Mature dendritic cell compositions and methods for culturing same |
| EP1806395A1 (en) * | 2006-01-06 | 2007-07-11 | Stichting Sanquin Bloedvoorziening | Maturation of dendritic cells |
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| PL2201100T3 (pl) | 2016-10-31 |
| US20100215674A1 (en) | 2010-08-26 |
| ES2573458T3 (es) | 2016-06-08 |
| HUE029164T2 (hu) | 2017-02-28 |
| PT2201100E (pt) | 2016-06-03 |
| US8476419B2 (en) | 2013-07-02 |
| WO2009034172A1 (en) | 2009-03-19 |
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