WO1994011011A1 - Traitement des maladies autoimmunes par induction d'une tolerance des cellules, des tissus et des organes - Google Patents
Traitement des maladies autoimmunes par induction d'une tolerance des cellules, des tissus et des organes Download PDFInfo
- Publication number
- WO1994011011A1 WO1994011011A1 PCT/US1993/010534 US9310534W WO9411011A1 WO 1994011011 A1 WO1994011011 A1 WO 1994011011A1 US 9310534 W US9310534 W US 9310534W WO 9411011 A1 WO9411011 A1 WO 9411011A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cells
- antigens
- dna encodes
- autoimmune disease
- dna
- Prior art date
Links
- 208000023275 Autoimmune disease Diseases 0.000 title claims abstract description 31
- 210000000056 organ Anatomy 0.000 title claims abstract description 20
- 230000001939 inductive effect Effects 0.000 title description 4
- 210000004027 cell Anatomy 0.000 claims abstract description 116
- 239000000427 antigen Substances 0.000 claims abstract description 65
- 102000036639 antigens Human genes 0.000 claims abstract description 65
- 108091007433 antigens Proteins 0.000 claims abstract description 65
- 210000001519 tissue Anatomy 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 26
- 210000004738 parenchymal cell Anatomy 0.000 claims description 18
- 210000002510 keratinocyte Anatomy 0.000 claims description 14
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 claims description 8
- 230000001363 autoimmune Effects 0.000 claims description 8
- 210000000663 muscle cell Anatomy 0.000 claims description 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000003325 follicular Effects 0.000 claims description 5
- 208000000509 infertility Diseases 0.000 claims description 5
- 230000036512 infertility Effects 0.000 claims description 5
- 231100000535 infertility Toxicity 0.000 claims description 5
- 210000002569 neuron Anatomy 0.000 claims description 5
- 230000002611 ovarian Effects 0.000 claims description 5
- 230000002381 testicular Effects 0.000 claims description 5
- 210000001685 thyroid gland Anatomy 0.000 claims description 5
- 208000003807 Graves Disease Diseases 0.000 claims description 4
- 208000015023 Graves' disease Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 18
- 102000004169 proteins and genes Human genes 0.000 abstract description 17
- 108010045634 B7 Antigens Proteins 0.000 abstract description 3
- 230000017274 T cell anergy Effects 0.000 abstract description 3
- 102000005738 B7 Antigens Human genes 0.000 abstract description 2
- 238000002054 transplantation Methods 0.000 abstract description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 18
- 239000013598 vector Substances 0.000 description 11
- 239000013604 expression vector Substances 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 210000000612 antigen-presenting cell Anatomy 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 241000701832 Enterobacteria phage T3 Species 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- 208000001204 Hashimoto Disease Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- -1 Nonidet Chemical compound 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 208000007984 Female Infertility Diseases 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 206010021928 Infertility female Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000713862 Moloney murine sarcoma virus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 101000884281 Rattus norvegicus Signal transducer CD24 Proteins 0.000 description 1
- 102100037968 Ribonuclease inhibitor Human genes 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 241000713896 Spleen necrosis virus Species 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000010841 mRNA extraction Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 108010024226 placental ribonuclease inhibitor Proteins 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
Classifications
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- 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
- A61K39/0005—Vertebrate antigens
- A61K39/001—Preparations to induce tolerance to non-self, e.g. prior to transplantation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Definitions
- This invention relates to the treatment of autoimmune diseases. More particularly, this invention relates to the treatment of autoimmune diseases by administering genetically engineered cells which induce tolerance to a particular protein, cell, or organ.
- autoimmune diseases such as Type I diabetes, Graves or Hashimoto's disease, rheumatoid arthritis, autoimmune male and female infertility, myasthenia gravis, and multiple sclerosis
- proteins in an individual sometimes referred to as "self” proteins
- self proteins proteins
- proteins and the cells which express such proteins are recognized as foreign, which results in the activation of autoimmune pathogenic lymphocytes. Once such lymphocytes are activated, they are continuously produced.
- the T-cells recognize the antigen displayed upon the antigen presenting cell; however, interactions of this T-cell with this antigen does not stimulate clonal expansion, but instead stimulates a long-lasting tolerance to the antigen, known as anergy.
- SUBSTITUTE SHEET encoding a plurality of antigens of a cell, tissue, or organ to which tolerance is to be induced.
- the genetically engineered cells are free of co-stimulatory antigens, such as B7 or heat stable antigen, also known as HSA.
- T-cell anergy leads to a "re-education" of the immune system, resulting in the induction of tolerance to the target cell antigens, whereby the T-cells will not respond when they come in contact with proteins, cells, or organs that contain these antigens.
- a single cDNA library may be obtained for a particular cell, tissue, or organ. This cDNA library may then be used to engineer cells which may be used for the treatment of any and all patients.
- the genetically engineered cells which are free of co-stimulatory antigens such as B7 antigen or HSA are parenchy al cells; i.e., cells which are contained within an organ or a gland.
- Autoimmune diseases which may be prevented or treated with the genetically engineered cells of the present invention include, but are not limited to, Type I diabetes (wherein the parenchymal cells are engineered with DNA encoding pancreatic
- the selected cells are then cultured in vitro and treated with Vitamin D, TNF- ⁇ , or gamma-interferon to increase expression of the MHC antigens of the target cells that display the processed target cell proteins. Expression of such antigens may be confirmed with FACS analysis.
- the keratinocytes may then be administered to a patient in an amount effective for preventing the onset of or for treating an autoimmune disease. Such administration may be by intravenous administration or alternatively, the keratinocytes may be administered directly into the thymus. After administration, peripheral blood samples may be obtained and quantitated for changes in antibodies directed against "self" epitopes. Also, spleen and lymph node T-cells may be tested in vitro for auto-reactivity against target cells.
- Example A mRNA extraction from cells to be used in the production of a cDNA library
- RNA is then dissolved in sterile water, heated, and 2X buffer is added. The solution is applied to the column. The eluate is collected, heated, and re-applied to the column. 1ml fractions are then collected, and absorbance of each fraction is read at OD260. PolyA and RNA are eluted with Tris, EDTA and SDS. 3M sodium acetate is then added to the eluted RNA, and RNA is recovered by centrifugation. mRNA
- the engineered cells are expanded such that 10 cells can be injected into the patient daily for 2 weeks. Circulating 1 antibody levels are routinely quantitated in vitro by FITC analysis for activity directed against the cells from which the mRNA was obtained. During this time, peripheral blood leukocytes are obtained from the patient and tested by a mixed leukocyte reaction for their ability to respond to the cell from which the mRNA was obtained.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Microbiology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Cellules ayant subi un traitement génétique par ADN codant plusieurs antigènes d'une cellule, d'un tissu ou d'un organe auquel une tolérance doit être conférée. Ces cellules sont exemptes d'antigènes de co-stimulation, tels que les antigènes B7. Ces cellules induisent une anergie des cellules T à l'égard des protéines codées par l'ADN et peuvent être administrées à un patient pour prévenir l'apparition ou traiter une maladie autoimmune, ou pour conférer une tolérance à un tissu ou à un organe avant qu'il soit transplanté.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6512168A JPH08503135A (ja) | 1992-11-09 | 1993-11-03 | 細胞、組織および器官に耐性を誘導することによる自己免疫疾患の治療 |
| EP94901247A EP0668771A4 (fr) | 1992-11-09 | 1993-11-03 | Traitement des maladies autoimmunes par induction d'une tolerance des cellules, des tissus et des organes. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97377692A | 1992-11-09 | 1992-11-09 | |
| US973,776 | 1992-11-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1994011011A1 true WO1994011011A1 (fr) | 1994-05-26 |
Family
ID=25521214
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1993/010534 WO1994011011A1 (fr) | 1992-11-09 | 1993-11-03 | Traitement des maladies autoimmunes par induction d'une tolerance des cellules, des tissus et des organes |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0668771A4 (fr) |
| JP (1) | JPH08503135A (fr) |
| CA (1) | CA2148835A1 (fr) |
| WO (1) | WO1994011011A1 (fr) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0695347A1 (fr) * | 1993-04-20 | 1996-02-07 | William S. Robinson | Methode et materiel de traitement de patients infectes par des agents infectieux intracellulaires |
| WO1997033975A1 (fr) | 1996-03-12 | 1997-09-18 | Rhone-Poulenc Rorer S.A. | Milieu pour la conservation de materiel biologique |
| US5877021A (en) * | 1995-07-07 | 1999-03-02 | Ribozyme Pharmaceuticals, Inc. | B7-1 targeted ribozymes |
| EP1015034A1 (fr) * | 1996-05-29 | 2000-07-05 | University Of Southern California | Construction et utilisation de genes codant des epitopes pathogeniques pour le traitement de maladies autoimmunes |
-
1993
- 1993-11-03 JP JP6512168A patent/JPH08503135A/ja active Pending
- 1993-11-03 CA CA002148835A patent/CA2148835A1/fr not_active Abandoned
- 1993-11-03 EP EP94901247A patent/EP0668771A4/fr not_active Withdrawn
- 1993-11-03 WO PCT/US1993/010534 patent/WO1994011011A1/fr not_active Application Discontinuation
Non-Patent Citations (5)
| Title |
|---|
| EUROPEAN JOURNAL OF IMMUNOLOGY, Volume 20, issued 1990, V. BAL et al., "Antigen Presentation by Keratinocytes Induces Tolerance in Human T Cells", pages 1893-1897. * |
| INTERNATIONAL IMMUNOLOGY, Volume 4, No. 5, issued 1992, G. SCHONRICH et al., "Distinct Mechanisms of Extrathymic T Cell Tolerance Due to Differential Expression of Self Antigen", pages 581-590. * |
| NATURE, Volume 336, issued 01 December 1988, J. MARKMANN et al., "Antigen Presenting Function of Class II MHC Expressing Pancreatic Beta Cells", pages 476-479. * |
| NATURE, Volume 342, issued 30 November 1989, L.C. BURKLY et al., "T-Cell Tolerance by Clonal Anergy in Transgenic Mice with Nonlymphoid Expression of MHC Class II I-E", pages 564-566. * |
| See also references of EP0668771A4 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0695347A1 (fr) * | 1993-04-20 | 1996-02-07 | William S. Robinson | Methode et materiel de traitement de patients infectes par des agents infectieux intracellulaires |
| EP0695347A4 (fr) * | 1993-04-20 | 1997-01-02 | William S Robinson | Methode et materiel de traitement de patients infectes par des agents infectieux intracellulaires |
| US5738852A (en) * | 1993-04-20 | 1998-04-14 | Solis Therapeutics, Inc. | Methods of enhancing antigen-specific T cell responses |
| US5877021A (en) * | 1995-07-07 | 1999-03-02 | Ribozyme Pharmaceuticals, Inc. | B7-1 targeted ribozymes |
| US6194150B1 (en) | 1995-07-07 | 2001-02-27 | Ribozyme Pharmaceuticals, Inc. | Nucleic acid based inhibition of CD40 |
| WO1997033975A1 (fr) | 1996-03-12 | 1997-09-18 | Rhone-Poulenc Rorer S.A. | Milieu pour la conservation de materiel biologique |
| EP1015034A1 (fr) * | 1996-05-29 | 2000-07-05 | University Of Southern California | Construction et utilisation de genes codant des epitopes pathogeniques pour le traitement de maladies autoimmunes |
| EP1015034A4 (fr) * | 1996-05-29 | 2004-12-01 | Univ Southern California | Construction et utilisation de genes codant des epitopes pathogeniques pour le traitement de maladies autoimmunes |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0668771A4 (fr) | 1998-04-01 |
| JPH08503135A (ja) | 1996-04-09 |
| CA2148835A1 (fr) | 1994-05-26 |
| EP0668771A1 (fr) | 1995-08-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5939400A (en) | DNA vaccination for induction of suppressive T cell response | |
| Mason et al. | Mechanisms of allograft rejection: the roles of cytotoxic T‐cells and delayed‐type hypersensitivity | |
| Vanderlugt et al. | Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis | |
| Green et al. | The role of Fas ligand in immune privilege | |
| McCoy et al. | The role of CTLA‐4 in the regulation of T cell immune responses | |
| DE69834330T2 (de) | Verwendung von mhc klasse ii liganden als adjuvantien zur impfung und von lag-3 zur krebstherapie | |
| Apasov et al. | Cell-mediated cytotoxicity: contact and secreted factors | |
| US8551494B2 (en) | Methods of immune modulation with death receptor-induced apoptosis | |
| EP1919943A2 (fr) | Oligopeptides associes au complexe d'histocompatibilite principale (mhc) de classe i, associes au melanome et leurs utilisations | |
| CN100558745C (zh) | 同种排斥反应的特异性抑制 | |
| EP1299522B1 (fr) | Alteration des membranes cellulaires | |
| EP1702622A1 (fr) | Proteine BTNL2 soluble pour l'inhibition de maladies inflammatoires | |
| EP0941329A1 (fr) | Procede de prevention de rejet de greffon dans une transplantation et de production d'une cellule hote universelle de therapie genique a partir du gene d'activation des lymphocytes (lag-3) | |
| Grønevik et al. | DNA transfection of mononuclear cells in muscle tissue | |
| EP1484397B1 (fr) | ADN correspondant à un peptide dérivé de l'antigène MUC-1 destiné à déclencher une réaction immunitaire contre des cellules tumorales | |
| DE69720065T2 (de) | Therapeutische anwendungen von antigenen oder epitopen assoziert mit unvollständiger zellulärer peptidprozesierung , z.b.: exprimiert in rma-s zellen transfiziert mit b7-1 gen | |
| Kelley et al. | Renal tubular epithelial and T cell interactions in autoimmune renal disease. | |
| EP0668771A1 (fr) | Traitement des maladies autoimmunes par induction d'une tolerance des cellules, des tissus et des organes | |
| WO1992006117A1 (fr) | Inhibition de reponses immunes indesirees | |
| JP2003527435A (ja) | 免疫療法におけるｍｉａの使用 | |
| CA2158932A1 (fr) | Methodes de suppression de la reponse auto-immunitaire | |
| Wu et al. | Targeting antigen-specific T cells by genetically engineered antigen presenting cells: a strategy for specific immunotherapy of autoimmune disease | |
| JP2003513619A (ja) | 自己免疫疾患および免疫病因を含む疾患を治療するための遺伝子導入ベクター | |
| Steinaa et al. | Linked foreign T-cell help activates self-reactive CTL and inhibits tumor growth | |
| EP1250055B1 (fr) | Modulation immunitaire avec apoptose induite par recepteur de mort cellulaire |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA JP |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| WWE | Wipo information: entry into national phase |
Ref document number: 2148835 Country of ref document: CA |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1994901247 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1994901247 Country of ref document: EP |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1994901247 Country of ref document: EP |