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WO2003030965A2 - Noeud lymphatique artificiel - Google Patents

Noeud lymphatique artificiel Download PDF

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Publication number
WO2003030965A2
WO2003030965A2 PCT/DE2002/003465 DE0203465W WO03030965A2 WO 2003030965 A2 WO2003030965 A2 WO 2003030965A2 DE 0203465 W DE0203465 W DE 0203465W WO 03030965 A2 WO03030965 A2 WO 03030965A2
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
lymph node
module
artificial lymph
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DE2002/003465
Other languages
German (de)
English (en)
Other versions
WO2003030965A3 (fr
Inventor
Martin Scholz
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to DE10294532T priority Critical patent/DE10294532D2/de
Priority to AU2002349265A priority patent/AU2002349265A1/en
Publication of WO2003030965A2 publication Critical patent/WO2003030965A2/fr
Anticipated expiration legal-status Critical
Publication of WO2003030965A3 publication Critical patent/WO2003030965A3/fr
Ceased legal-status Critical Current

Links

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • 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
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • 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
    • A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/20—Pathogenic agents
    • A61M2202/203—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/20—Pathogenic agents
    • A61M2202/206—Viruses

Definitions

  • the present invention relates to an artificial lymph node and a method for activating immune cells.
  • the aim of the present invention is to provide a module which is suitable for activating immune cells.
  • a method using the module is to be made available.
  • the object underlying the present invention is achieved by the artificial lymph node according to claim 1.
  • This artificial lymph node consists of a module with an inlet and outlet opening, a complex of antigen-presenting cell, MHC and antigen being immobilized in the module on a support.
  • the module according to the invention can be used in patients or clinical situations with a poor cellular immune response, for example against viral or bacterial pathogens or tumor antigens.
  • the module according to the invention can, for example, in the
  • the module with autologous dendritic cells plus MHC-antigen complex (for example tetramers) with specific immune-relevant peptides is used for transient introduction into the patient's blood stream via a Shaldon catheter.
  • MHC-antigen complex for example tetramers
  • circulating peptide-specific T cells bind to the tetramers in the module and thus come into contact with the DC.
  • the effector cells with insufficient specific function are stimulated and leave the module as highly active cells.
  • CD4 and CD8 memory cells that have previously been in contact with the natural peptide also bind to the tetramers and / or to the DC. These already imprinted cells are also strongly activated.
  • T cells bind to the DC and are tested against the presented peptide.
  • the co-stimulatory factors in the module e.g. DC adhesion molecules, cytokines etc.
  • activate these cells return to the bloodstream in order to eliminate the pathogen there or after extravasation in the diseased tissue using specific effector mechanisms.
  • the induction of a humoral immune response can follow (T cell mediated B cell activation).
  • the advantages of the invention over the conventional methods are that the invention allows the de novo induction or enhancement of a highly specific immune response against the pathogen.
  • peptide-presenting DC By combining the peptide-presenting DC with the MHC / peptide constructs, already imprinted immune cells can be specifically strengthened in their immune response.
  • the in low frequency in the blood cells contained need not consuming isolated and expanded ex vivo, since the cell will automatically pass via 'the blood stream into the filter. Only those cells that have already been in contact with the peptide bind to the MHC-antigen complexes (tetramers, bimers or trimers loaded with peptide) and are sufficiently activated with the help of the co-stimulation by the neighboring DC. After their activation, the effector cells go directly into the bloodstream and into the affected tissues.
  • activation in the present invention includes both increasing the activity of already activated immune cells as well as the 'embossing yet unembossed immune cells.
  • lymph node according to the invention is the high achievable density of the DC in the module.
  • An additional advantage is that, in contrast to the ex vivo stimulation of the effector cells, no large amount of effector cells has to be enriched for the return in the patient. Defects that prevent DC from settling in the patient's natural lymph nodes can be avoided with the aid of the lymph node according to the invention.
  • the artificial lymph node according to the invention can also be used to induce tolerance in patients with pathologically increased immune reactions to natural antigens (allergies) or the body's own structures (autoimmune diseases). Examples include:
  • the artificial lymph node according to the invention preferably consists of a housing with a diameter of 10 cm, for example.
  • the diameter of the inflow and outflow connections is adapted to the hose connections of the catheter connections.
  • a carrier for example a three-dimensionally folded polyester membrane with a modified surface, for the application of MHC antigen
  • DC dentritic cells
  • the pretreatment of the DC includes the immunological maturation of the DC in various ways. In this way, a peptide-specific immune response, but also the tolerance to individual peptides can be induced as desired.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Public Health (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • Wood Science & Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Anesthesiology (AREA)
  • Cardiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

La présente invention concerne un noeud lymphatique artificiel, constitué d'un module pourvu d'un orifice d'entrée et d'un orifice de sortie. Dans ce module, un complexe qui est constitué d'une cellule présentant l'antigène, du MHC et de l'antigène sont immobilisés sur un support. Le module selon l'invention peut être utilisé chez des patients (cas cliniques) présentant une réponse immunitaire cellulaire défaillante vis-à-vis, par exemple, d'agents infectieux viraux ou bactériens ou d'antigènes tumoraux.
PCT/DE2002/003465 2001-09-27 2002-09-16 Noeud lymphatique artificiel Ceased WO2003030965A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE10294532T DE10294532D2 (de) 2001-09-27 2002-09-16 Künstlicher Lymphknoten
AU2002349265A AU2002349265A1 (en) 2001-09-27 2002-09-16 Artificial lymph node

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10147639 2001-09-27
DE10147639.6 2001-09-27

Publications (2)

Publication Number Publication Date
WO2003030965A2 true WO2003030965A2 (fr) 2003-04-17
WO2003030965A3 WO2003030965A3 (fr) 2004-04-01

Family

ID=7700471

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE2002/003465 Ceased WO2003030965A2 (fr) 2001-09-27 2002-09-16 Noeud lymphatique artificiel

Country Status (3)

Country Link
AU (1) AU2002349265A1 (fr)
DE (1) DE10294532D2 (fr)
WO (1) WO2003030965A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1571204A1 (fr) 2004-03-04 2005-09-07 LeukoCare GmbH Matrice de stimulation de leucocytes
WO2007069755A1 (fr) * 2005-12-12 2007-06-21 Riken Procédé pour la production avec un bon rendement d'un hybridome spécifique à un antigène en utilisant un ganglion lymphatique artificiel
CN101001954B (zh) * 2004-05-27 2013-01-30 西尔斯公司 用于改变植物特征的核苷酸序列及其编码的多肽
EP2969149A4 (fr) * 2013-03-14 2016-12-21 Brian J Leberthon Procédé et dispositif pour traiter le cancer

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU687733B2 (en) * 1992-04-01 1998-03-05 Rockefeller University, The Method for in vitro proliferation of dendritic cell precursors and their use to produce immunogens
US6121044A (en) * 1995-07-12 2000-09-19 Dendreon Corporation Potent antigen presenting cell composition
JP2002529073A (ja) * 1998-11-12 2002-09-10 セル サイエンス セラピューティックス インコーポレーテッド 三次元装置における造血前駆細胞からのリンパ様組織特異的細胞の生成

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1571204A1 (fr) 2004-03-04 2005-09-07 LeukoCare GmbH Matrice de stimulation de leucocytes
WO2005085420A3 (fr) * 2004-03-04 2005-11-17 Leukocare Gmbh Matrice de stimulation des leucocytes
CN101001954B (zh) * 2004-05-27 2013-01-30 西尔斯公司 用于改变植物特征的核苷酸序列及其编码的多肽
WO2007069755A1 (fr) * 2005-12-12 2007-06-21 Riken Procédé pour la production avec un bon rendement d'un hybridome spécifique à un antigène en utilisant un ganglion lymphatique artificiel
EP2969149A4 (fr) * 2013-03-14 2016-12-21 Brian J Leberthon Procédé et dispositif pour traiter le cancer

Also Published As

Publication number Publication date
WO2003030965A3 (fr) 2004-04-01
AU2002349265A1 (en) 2003-04-22
DE10294532D2 (de) 2004-08-26

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