WO2009092087A2 - Selective differentiation, identification, and modulation of human th17 cells - Google Patents

Selective differentiation, identification, and modulation of human th17 cells Download PDF

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Publication number
WO2009092087A2
WO2009092087A2 PCT/US2009/031477 US2009031477W WO2009092087A2 WO 2009092087 A2 WO2009092087 A2 WO 2009092087A2 US 2009031477 W US2009031477 W US 2009031477W WO 2009092087 A2 WO2009092087 A2 WO 2009092087A2
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cell
cells
tgf
podoplanin
bltl
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English (en)
French (fr)
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WO2009092087A3 (en
Inventor
Vijay K. Kuchroo
David E. Anderson
Estelle Bettelli
David Hafler
Mohamed Oukka
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Brigham and Womens Hospital Inc
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Brigham and Womens Hospital Inc
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Priority to EP09702239.6A priority Critical patent/EP2238241B1/en
Priority to JP2010543306A priority patent/JP2011509676A/ja
Priority to US12/863,373 priority patent/US20110245107A1/en
Publication of WO2009092087A2 publication Critical patent/WO2009092087A2/en
Publication of WO2009092087A3 publication Critical patent/WO2009092087A3/en
Anticipated expiration legal-status Critical
Priority to US14/517,116 priority patent/US9732320B2/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
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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
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/15—Transforming growth factor beta (TGF-β)
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    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4728—Details alpha-Glycoproteins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/475—Assays involving growth factors
    • G01N2333/495—Transforming growth factor [TGF]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/54—Interleukins [IL]
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
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    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/06—Gastro-intestinal diseases
    • G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/10—Musculoskeletal or connective tissue disorders
    • G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
    • G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/12—Pulmonary diseases
    • G01N2800/122—Chronic or obstructive airway disorders, e.g. asthma COPD
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/20—Dermatological disorders
    • G01N2800/205—Scaling palpular diseases, e.g. psoriasis, pytiriasis
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    • G01N2800/28—Neurological disorders
    • G01N2800/285—Demyelinating diseases; Multipel sclerosis

Definitions

  • the present invention also relates to the use of antagonists of TGF- ⁇ and IL-21 to inhibit the differentiation of a T cell or T cell population into a TH 17 cell or TH 17 cell population.
  • the present invention also relates to the use of TGF- ⁇ and IL-21 or agonists thereof to increase the expression, activity, secretion or processing of IL- 17 in a T cell or T cell population.
  • the cells enriched for a na ⁇ ve phenotype were uniformly positive for CCR7 expression. These two T cell populations were then stimulated with plate-bound anti-CD3 and soluble anti-CD28 monoclonal antibodies for seven days in serum-free medium containing different combinations of cytokines implicated in CD4 + T cell differentiation. As previously reported, the cytokine interleukin-l ⁇ induced the greatest amount of IL-17A secretion from TCM (Figure Ib). The addition of IL-6 alone had little effect on induction of IL-17A, and when added with IL-l ⁇ had no additive or synergistic effect on IL-17A production. Addition of IL-23 was also able to modestly enhance IL- 17A secretion from TCM.
  • the present invention refines and extends the understanding of the regulation of IL- 17 A secretion from human CD4 + T cells, and defines the conditions required for human TH17 cell differentiation.
  • IL- l ⁇ together with IL-6 or IL-23 can induce IL- 17A secretion, but these cytokines induce IL-17A expression from human memory CD4 + T cells and not from human na ⁇ ve CD4 + T cells.
  • TGF- ⁇ and IL-21 in combination, is required for the differentiation of TH 17 cells from human na ⁇ ve T cells.
  • the TGF- ⁇ agonist can be a TGF- ⁇ polypeptide, a human TGF- ⁇ polypeptide, or an active fragment thereof (e.g., a recombinant human TGF- ⁇ polypeptide or its encoding nucleic acid).
  • the TGF- ⁇ agonist may be a fusion protein comprising an TGF- ⁇ polypeptide, e.g., human TGF- ⁇ polypeptide, or a fragment thereof fused to another polypeptide, e.g., an immunoglobulin polypeptide or a portion thereof (e.g., a Fc region of an immunoglobulin polypeptide); an agonist antibody to the TGF- ⁇ receptor TGF- ⁇ R); or a small molecule agonist.
  • the compounds of the invention may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and cross-linked or amphipathic block copolymers of hydrogels.
  • a drug for example, polylactic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and cross-linked or amphipathic block copolymers of hydrogels.
  • a further embodiment of the present invention provides for a method for modulating the activity of a TH17 cell or TH17 cell population comprising contacting said cell or cell population with an amount of TH 17 activity modulator sufficient to modulate the activity of a TH17 cell or TH17 cell population.
  • the migration activity of TH17 cells may be inhibited by U75-302, an antagonist of the THl7-specific leukotriene B4.
  • the migration activity of TH17 cells may be inhibited by podoplanin.
  • Such THl7-activity-specific modulators may be formulated according to the foregoing discussions for use in vitro and in vivo.
  • expression patterns can be evaluated by northern analysis, PCR, RT-PCR, Taq Man analysis, FRET detection, monitoring one or more molecular beacons, hybridization to an oligonucleotide array, hybridization to a cDNA array, hybridization to a polynucleotide array, hybridization to a liquid microarray, hybridization to a microelectric array, cDNA sequencing, clone hybridization, cDNA fragment fingerprinting, serial analysis of gene expression (SAGE), subtractive hybridization, differential display and/or differential screening.
  • SAGE serial analysis of gene expression
  • RA rheumatoid arthritis
  • the THl7-specific cell surface molecules of the present invention can be used in the diagnosis and monitoring of RA.
  • RA effects about two million patients in the U.S. and is a chronic and debilitating inflammatory arthritis, particularly involving pain and destruction of the joints.
  • RA often goes undiagnosed because patients may have no pain, but the disease is actively destroying the joint.
  • Other patients are known to have RA, and are treated to alleviate symptoms, but the rate of progression of joint destruction is not monitored easily.
  • Drug therapy is available, but the most effective medicines are toxic (e.g., steroids, methotrexate) and should be used with caution.
  • LTB4 may also function as a chemoattractant for T cells.

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PCT/US2009/031477 2008-01-18 2009-01-21 Selective differentiation, identification, and modulation of human th17 cells Ceased WO2009092087A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP09702239.6A EP2238241B1 (en) 2008-01-18 2009-01-21 Selective differentiation, identification, and modulation of human th17 cells
JP2010543306A JP2011509676A (ja) 2008-01-18 2009-01-21 ヒトＴｈ１７細胞の選択的分化、同定および調節
US12/863,373 US20110245107A1 (en) 2008-01-18 2009-01-21 Selective differentiation, identification, amd modulation of human th17 cells
US14/517,116 US9732320B2 (en) 2008-01-18 2014-10-17 Selective differentiation, identification, and modulation of human TH17 cells

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US654108P 2008-01-18 2008-01-18
US61/006,541 2008-01-18
US3182408P 2008-02-27 2008-02-27
US61/031,824 2008-02-27

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US14/517,116 Division US9732320B2 (en) 2008-01-18 2014-10-17 Selective differentiation, identification, and modulation of human TH17 cells

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WO2009092087A3 WO2009092087A3 (en) 2009-10-15

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WO2011014775A1 (en) * 2009-07-31 2011-02-03 The Brigham And Women's Hospital, Inc. Modulation of sgk1 expression in th17 cells to modulate th17-mediated immune responses
JP2011122937A (ja) * 2009-12-10 2011-06-23 Sharp Corp 生体内に蓄積した粒子の分析方法
FR2960882A1 (fr) * 2010-06-04 2011-12-09 Hospices Civils Lyon Co-culture de cellules mononucleees et de cellules mesenchymateuses pour l'obtention de cellules productrices d'il-17
CN102482667A (zh) * 2009-07-29 2012-05-30 希森美康株式会社 人的产生il-17的辅助性t细胞的检测用标记物及试剂、以及人的产生il-17的辅助性t细胞的检测方法
EP2578232A4 (en) * 2010-06-02 2013-11-20 Dainippon Sumitomo Pharma Co TREATMENT FOR AUTOIMMUN DISEASES AND ALLERGIC DISEASES
WO2017069958A3 (en) * 2015-10-09 2017-09-21 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
US10822587B2 (en) 2013-02-27 2020-11-03 The Broad Institute, Inc. T cell balance gene expression, compositions of matters and methods of use thereof

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US10189899B2 (en) * 2013-07-23 2019-01-29 Biocon Limited Use of a CD6 binding partner and method based thereon
CN105658672A (zh) 2013-08-22 2016-06-08 阿塞勒隆制药公司 TGF-β受体II型变体及其用途
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US12226449B2 (en) * 2018-11-15 2025-02-18 The University Of Toledo Materials and methods for the prevention of rheumatoid arthritis
WO2021168376A1 (en) * 2020-02-20 2021-08-26 Kite Pharma, Inc. Chimeric antigen receptor t cell therapy
WO2022040504A2 (en) * 2020-08-21 2022-02-24 Georgetown University Stem cell-like memory t cells and uses thereof

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