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
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- 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
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- Prior art keywords
- cells
- antigens
- dna encodes
- autoimmune disease
- dna
- Prior art date
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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
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- 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
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- 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.
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- 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)
- Reproductive Health (AREA)
- Urology & Nephrology (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 EP EP94901247A patent/EP0668771A4/fr not_active Withdrawn
- 1993-11-03 WO PCT/US1993/010534 patent/WO1994011011A1/fr not_active Application Discontinuation
- 1993-11-03 CA CA002148835A patent/CA2148835A1/fr not_active Abandoned
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 |
|---|---|
| EP0668771A1 (fr) | 1995-08-30 |
| EP0668771A4 (fr) | 1998-04-01 |
| JPH08503135A (ja) | 1996-04-09 |
| CA2148835A1 (fr) | 1994-05-26 |
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