DK2817620T3 - System til immunterapi rettet mod tumorformering og -progression - Google Patents

System til immunterapi rettet mod tumorformering og -progression Download PDF

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DK2817620T3
DK2817620T3 DK13709633.5T DK13709633T DK2817620T3 DK 2817620 T3 DK2817620 T3 DK 2817620T3 DK 13709633 T DK13709633 T DK 13709633T DK 2817620 T3 DK2817620 T3 DK 2817620T3
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tumor
cancer
population
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Nancy L Parenteau
Joseph C Laning
Janet H Young
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Verik Bio Inc
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
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    • C07K—PEPTIDES
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
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    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0693—Tumour cells; Cancer cells
    • C12N5/0695—Stem cells; Progenitor cells; Precursor cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
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    • C12N2501/01—Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
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Claims (15)

1. Fremgangsmåde til identificering af regenereringsdygtige (C-RC)-populationer af cancerceller hos et individ, omfattende (a) at dyrke en tumorprøve opnået fra et individ under betingelser, der inducerer en stressreaktion i differentierende og differentierede celler, men tillader C-RC-celler at formere sig, og som aktiverer en regenerativ reaktion; (b) at isolere den dominerende, aktivt ekspanderende, hurtigst delende population af celler fra trin (a); og (c) at dyrke cellerne til 60 til 95 % konfluens til opnåelse af en population på 51 % til 100 % C-RC, hvor celledyrkningsbetingelserne er udvalgt fra gruppen bestående af: (i) serumfrit, defineret celledyrkningsmedium, der inducerer apoptose og/eller nekrose af de differentierende og differentierede celler, (ii) medium indeholdende cAMP-forøgende midler og (iii) medium udformet til at inhibere eller bryde celle-celle-adhæsion.
2. Fremgangsmåde ifølge krav 1, hvor mediet, der inducerer apoptose og/eller nekrose af cellerne, omfatter et middel udvalgt fra gruppen bestående af tumornekrosefaktor-alfa (TNF-α), interleukin 1-beta og interferongamma (IFN-y).
3. Fremgangsmåde ifølge krav 1, hvor mediet udformet til at inhibere eller bryde celle-celle-adhæsion omfatter et middel udvalgt fra gruppen bestående af nitrogenoxid, hydrokolloid, dextran og mindre end ca. 1 mM calcium.
4. Fremgangsmåde ifølge krav 1, hvor den dyrkede tumorprøve er et tumor-eksplantat, idet fremgangsmåden yderligere omfatter at bekræfte C-RC-cellernes tumorformerende potentiale.
5. Fremgangsmåde ifølge krav 1, yderligere omfattende at dyrke de isolerede celler fra trin (a), hvor 80 % til 100 % af cellerne opnået fra trin (c) er C-RC-celler udvalgt fra gruppen bestående af VSEC-, SDEC- og SCEC-celler.
6. Fremgangsmåde til identificering af C-RC-celle-specifikke T-celler, omfattende at blande C-RC-celler isoleret i henhold til fremgangsmåden ifølge krav 1 med isolerede CD8+ T-celler fra normale donorer eller cancerdonorer, og at isolere T-celler, der reagerer med de behandlede C-RC-celler, hvor de reaktive T-celler omfatter T-celle-receptorer (TCR), der er rettet mod et C-RC-specifikt antigen.
7. Fremgangsmåde ifølge krav 6, omfattende (et) yderligere trin udvalgt fra gruppen bestående af; (i) at behandle C-RC-cellerne med en interferon-gamma-agonist til øgning af ekspression af HLA-peptid-komplekser; (ii) at tilsætte en in v/Yro-aktiveringsprotokol, der selekterer for CD8+ T-celler, der er reaktive over for passende præsenteret peptidantigen i forbindelse med patientrelevante HLA-molekyler; (iii) at isolere det C-RC-specifikke antigen; (iv) at isolere og sekventere det C-RC-specifikke antigen; (v) at isolere det C-RC-specifikke antigen og fremstille antistoffer eller molekylære sonder til det C-RC-specifikke antigen; (vi) at isolere det C-RC-specifikke antigen, at fordøje det C-RC-specifikke antigen til fremstilling af en flerhed af peptider og præsentere et eller flere af peptiderne for CD8+ T-celler og udvælge T-celler, der er reaktive over for det ene eller de flere af peptiderne; og (vii) at klone T-celle-receptorerne fra de reaktive T-celler til fremstilling af et klonet TCR-konstrukt.
8. Fremgangsmåde ifølge krav 7, omfattende at sammenligne det C-RC-specifikke antigen, eller antistoffer eller sonder dertil, med antigen fra ikke-tumorceller eller celler af forskellige typer af tumorer.
9. Fremgangsmåde ifølge krav 7, yderligere omfattende at transducere en population af T-celler med det klonede TCR-konstrukt og at teste de transdu-cerede T-celler for deres evne til at binde og reagere på eksprimeret HLA-begrænset peptidkompleks.
10. Isoleret tumor-C-RC-cellepopulation fremstillet ved fremgangsmåden ifølge krav 1.
11. Isoleret tumorantigen, der kan opnås ved fremgangsmåden ifølge krav 7.
12. Klonet TCR, der kan opnås ved fremgangsmåden ifølge krav 7.
13. T-celler til anvendelse ved behandling af cancer hos en patient, hvor T-cellerne er transduceret med en ekspressionsvektor, der koder for T-celle-receptorer, der er reaktive over for det ene eller de flere antigener, der er identificeret eller opnået ved at analysere en cancerbiopsi fra patienten til bestemmelse af forekomsten af et eller flere antigener identificeret under anvendelse af fremgangsmåden ifølge krav 9, hvor T-cellerne er opnået fra patienten eller fra en donor, inden transduktion.
14. T-celler til anvendelse ifølge krav 13, hvor patienten er identificeret som værende positiv for et eller flere antigener med tilsvarende HLA klasse I-begrænsning.
15. T-celler til anvendelse ifølge krav 13, hvor T-cellerne er transduceret til at eksprimere cytokin eller adjuvans til at øge T-celle-responset.
DK13709633.5T 2012-02-22 2013-02-22 System til immunterapi rettet mod tumorformering og -progression DK2817620T3 (da)

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PCT/US2013/027445 WO2013126785A1 (en) 2012-02-22 2013-02-22 A system for immunotherapy targeting tumor propagation and progression

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CA3116369A1 (en) 2014-12-03 2016-06-09 Verik Bio, Inc. Identification, selection and use of high curative potential t cell epitopes
GB201501175D0 (en) * 2015-01-23 2015-03-11 Univ Oslo Hf A universal T-cell for personalised medicine
US10767164B2 (en) 2017-03-30 2020-09-08 The Research Foundation For The State University Of New York Microenvironments for self-assembly of islet organoids from stem cells differentiation
WO2020191105A2 (en) * 2019-03-19 2020-09-24 Kyuson Yun Methods and systems for evaluation of cell samples
CN112649614A (zh) * 2020-12-09 2021-04-13 中国医学科学院肿瘤医院 Cd8+肿瘤浸润淋巴细胞作为标志物在食管小细胞癌预后判断中的应用

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US6436704B1 (en) 2000-04-10 2002-08-20 Raven Biotechnologies, Inc. Human pancreatic epithelial progenitor cells and methods of isolation and use thereof
US6984522B2 (en) * 2000-08-03 2006-01-10 Regents Of The University Of Michigan Isolation and use of solid tumor stem cells
CN1820069A (zh) 2003-06-03 2006-08-16 器官恢复体系股份有限公司 祖细胞的选择和增殖
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EP2817620B1 (en) 2016-06-01
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