WO2003030965A2 - Artificial lymph node - Google Patents
Artificial lymph node Download PDFInfo
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- 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
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- Prior art keywords
- antigen
- lymph node
- module
- artificial lymph
- cell
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- 210000001165 lymph node Anatomy 0.000 title claims abstract description 17
- 210000004027 cell Anatomy 0.000 claims abstract description 20
- 239000000427 antigen Substances 0.000 claims abstract description 16
- 102000036639 antigens Human genes 0.000 claims abstract description 12
- 108091007433 antigens Proteins 0.000 claims abstract description 12
- 210000004443 dendritic cell Anatomy 0.000 claims description 19
- 210000002865 immune cell Anatomy 0.000 claims description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 3
- 210000001124 body fluid Anatomy 0.000 claims 1
- 239000010839 body fluid Substances 0.000 claims 1
- 230000009918 complex formation Effects 0.000 claims 1
- 230000003612 virological effect Effects 0.000 abstract description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 244000052769 pathogen Species 0.000 abstract description 3
- 230000024932 T cell mediated immunity Effects 0.000 abstract description 2
- 208000035143 Bacterial infection Diseases 0.000 abstract 1
- 208000036142 Viral infection Diseases 0.000 abstract 1
- 208000022362 bacterial infectious disease Diseases 0.000 abstract 1
- 230000002950 deficient Effects 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000012636 effector Substances 0.000 description 8
- 230000028993 immune response Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 241000941423 Grom virus Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 201000009053 Neurodermatitis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004049 embossing Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
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- 230000002163 immunogen Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
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- 239000012528 membrane Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
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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
-
- 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.
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- 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
Description
Künstlicher Lymphknoten Artificial lymph node
Gebiet der ErfindungField of the Invention
Die vorliegende Erfindung betrifft einen künstlichen Lymphknote und ein Verfahren zum Aktivieren von Immunzellen.The present invention relates to an artificial lymph node and a method for activating immune cells.
Hintergrund der ErfindungBackground of the Invention
Es existiert derzeit keine ausreichend funktionierende Therapie gegen virale chronische Infektionserkrankungen. Die Chro- nizität basiert auf der persistierenden Präsenz des viralen Antigens im Gewebe und der unzureichenden Immunantwort dagegen. Virale Erkrankungen werden zumeist mit Chemotherapeutika therapiert . Dies hat häufig .Resistenzbildung der Viren und starke Nebenwirkungen zur Folge. Bisherige Experimente mit der ex vivo Stimulation von Effektorzellen mittels dendritischer Zellen (DC) z.B. bei Tumorerkrankungen waren nur bedingt erfolgreich. Vermutlich ist die ex vivo- Stimulation der Effektorzellen und die anschließende Rückfuhr in den Patienten zu störanfällig und zu schwach, um klinisch relevante Veränderungen zu induzieren. Darüber hinaus werden bei den derzeitig angewandten Methoden die Gedächtniszellen isoliert r die in sehr geringer Menge im Blut vorkommen. Die ex vivo Expansion dieser Zellen ist dabei ein weiterer störanfälliger Schritt.There is currently no functioning therapy against viral chronic infectious diseases. Chronicity is based on the persistent presence of the viral antigen in the tissue and the inadequate immune response against it. Viral diseases are mostly treated with chemotherapy drugs. This often results in virus resistance and strong side effects. Previous experiments with the ex vivo stimulation of effector cells using dendritic cells (DC), for example in the case of tumor diseases, have met with only limited success. The ex vivo stimulation of the effector cells and the subsequent return to the patient are presumably too susceptible to interference and too weak to induce clinically relevant changes. In addition, the memory cells r isolated in the current methods are found in very small quantities in the blood. The ex vivo expansion of these cells is another step prone to failure.
Der Erfindung zugrunde liegende AufgabeObject of the invention
Ziel der vorliegenden Erfindung ist es, ein Modul bereitzustellen, das geeignet ist, Immunzellen zu aktivieren. Außerdem soll ein Verfahren unter Einsatz des Moduls zur Verfügung gestellt werden.The aim of the present invention is to provide a module which is suitable for activating immune cells. In addition, a method using the module is to be made available.
Gegenstand der ErfindungSubject of the invention
Die der vorliegenden Erfindung zugrunde liegende Aufgabe wird durch den künstlichen Lymphknoten nach Anspruch 1 gelöst. Dieser künstliche Lymphknoten besteht aus einem Modul mit einer Einlaß- und Auslaßöffnung, wobei in dem Modul auf einem Träger ein Komplex aus Antigen-präsentierender Zelle, MHC und Antigen immobilisiert ist. Das erfindungsgemäße Modul kann bei Patienten bzw. klinischen Situationen mit mangelnder zellulärer Immunantwort z.B. gegen virale oder bakterielle Infektionserreger oder Tumorantigene eingesetzt werden.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.
Das erfindungsgemäße Modul kann beispielsweise in denThe module according to the invention can, for example, in the
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Blutstrom des Patienten eingesetzt werden. Eine bevorzugte Ausführungsform besteht darin, daß das Modul mit autologen dentritischen Zellen plus MHC-Antigen-Komplex (beispielsweise Tetramere) mit spezifischen immunrelevanten Peptiden zum transienten Einbringen in den Patienten-Blutstrom über einen Shaldon-Katheter eingesetzt wird. Dadurch binden zirkulierende Peptid-spezifische T-Zellen an die Tetramere im Modul und gelangen so in Kontakt mit den DC. Die Effektorzellen mit nur unzureichender spezifischer Funktion werden stimuliert und verlassen als hoch aktive Zellen das Modul. CD4- und CD8-Gedächtniszellen, die zuvor Kontakt mit dem natürlichen Peptid hatten, binden ebenfalls an die Tetramere und/oder an die DC. Auch diese bereits geprägten Zellen werden stark aktiviert. Weiterhin binden ungeprägte (naive) T-Zellen an die DC und werden gegen das präsentierte Peptid geprüft. Durch die ko-stimulatorischen Faktoren im Modul (z.B. DC-Adhäsionsmoleküle, Zytokine etc.) kommt es zur Aktivierung dieser Zellen, die zurück in den Blutkreislauf gelangen, um dort bzw. nach Extravasation im erkrankten Gewebe mittels spezifischer Effektormechanismen das Pathogen zu eliminieren. Die Induktion einer humoralen Immunreaktion kann sich anschließen (T-Zell vermittelte B-Zellaktivierung) .Blood flow of the patient are used. A preferred embodiment is that 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. As a result, 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. Furthermore, unprinted (naive) 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, which 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).
Die Vorteile der Erfindung gegenüber den herkömmlichen Verfahren sind, daß die Erfindung die de novo Induktion bzw. Verstärkung einer hoch spezifischen Immunantwort gegen das Pathogen erlaubt .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.
Durch die Kombination der Peptid-präsentierenden DC mit den MHC/Peptid-Konstrukten können bereits geprägte Immunzellen spezifisch in ihrer Immunantwort verstärkt werden. Die in niedriger Frequenz im Blut enthaltenen Zellen müssen nicht aufwendig isoliert und ex vivo expandiert werden, da die Zellen über 'den Blutstrom automatisch in den Filter gelangen. Nur diejenigen Zellen, die bereits Kontakt mit dem Peptid hatten, binden an die MHC-Antigen-Komplexe (mit Peptid beladene Tetramere, Bimere bzw. Trimere) und werden mit Hilfe der Ko-Stimulation durch die benachbarten DC ausreichend aktiviert. Nach ihrer Aktivierung gehen die Effektorzellen direkt in den Blutkreislauf und in die betroffenen Gewebe. Ähnlich ist es bei der Prägung naiver Zellen, die primär nicht mit den MHC-Antigen-Komplexen, jedoch mit den Antigen- tragenden DC interagieren und geprägt werden. Durch die physiologische Umgebung im Blutstrom ist gewährleistet, daß alle notwendigen Faktoren für eine Ausreifung zu hochaktiven Effektorzellen vorhanden sind. Somit umfaßt der Ausdruck "Aktivierung" in der vorliegenden Erfindung sowohl die Erhöhung der Aktivität bereits aktivierter Immunzellen als auch die 'Prägung noch ungeprägter Immunzellen.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. It is similar with the imprinting of naive cells, which do not primarily interact and are imprinted with the MHC-antigen complexes, but with the antigen-bearing DC. The physiological environment in the bloodstream ensures that all the necessary factors for maturation into highly active effector cells are available. Thus, the term "activation" in the present invention includes both increasing the activity of already activated immune cells as well as the 'embossing yet unembossed immune cells.
Ein weiterer Vorteil des erfindungsgemäßen Lymphknotens ist die hohe erreichbare Dichte der DC im Modul. Ein zusätzlicher Vorteil ist, daß im Gegensatz zur ex vivo- Stimulation der Effektorzellen keine große Menge an Effektorzellen für die Rückgabe in den Patienten angereichert werden muß. Defekte, die eine Ansiedlung der DC in den natürlichen Lymphknoten des Patienten verhindern, können mit Hilfe des erfindungsgmäßen Lymphknotens umgangen werden.Another advantage of the 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.
Der erfindungsgemäße künstliche Lymphknoten kann darüber hinaus zur Toleranzinduktion bei Patienten mit pathologisch erhöhten Immunreaktionen gegenüber natürlichen Antigenen (Allergien) oder körpereigenen Strukturen (Autoimmunerkrankungen) eingesetzt werden. Als Beispiele seien genannt :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:
- Patienten mit chronischer Hepatitis B Erkrankung- Patients with chronic hepatitis B disease
- Asthma, Neurodermitis, Heuschnupfen- asthma, neurodermatitis, hay fever
- Multiple Sklerose. Der erfindungsgemäße künstliche Lymphknoten besteht vorzugsweise aus einem Gehäuse mit z.B. 10 cm Durchmesser. Die Einström- und Ausströmstutzen sind in ihrem Durchmesser angepaßt an die Schlauchverbindungen der Katheter-Anschlüsse. Im Innern des Moduls befindet sich ein Träger, beispielsweise eine dreidimensional gefaltete Polyestermembran mit modifizierter Oberfläche, zur Aufbringung von MHC-Antigen-- Multiple sclerosis. 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. Inside the module is a carrier, for example a three-dimensionally folded polyester membrane with a modified surface, for the application of MHC antigen
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Komplexen (Bimere, Trimere, Tetramere) mit immunrelevanten (immunogenen) Peptiden, isoliert aus z.B. Viren-, Bakterienoder Tumorzellpräparationen. Vorzugsweise werden auf den Träger dentritische Zellen (DC) des Patienten (autologe Zellen) aufgetragen, die zuvor ex vivo mit den entsprechenden Peptiden und/oder mit z.B. Viruspräparationen behandelt wurden. Die Vorbehandlung der DC schließt die inmmunologische Ausreifung der DC in verschiedenen Weisen ein. So kann eine Peptid-spezifische Immunantwort, aber auch die Toleranz gegenüber einzelnen Peptiden nach Wunsch induziert werden. Complexes (bimers, trimers, tetramers) with immune-relevant (immunogenic) peptides isolated from e.g. Virus, bacterial or tumor cell preparations. Preferably dentritic cells (DC) of the patient (autologous cells) are applied to the carrier, which previously ex vivo with the corresponding peptides and / or with e.g. Virus preparations were treated. 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.
Claims
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10294532T DE10294532D2 (en) | 2001-09-27 | 2002-09-16 | Artificial lymph node |
| 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 (en) | 2003-04-17 |
| WO2003030965A3 WO2003030965A3 (en) | 2004-04-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DE2002/003465 WO2003030965A2 (en) | 2001-09-27 | 2002-09-16 | Artificial lymph node |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2002349265A1 (en) |
| DE (1) | DE10294532D2 (en) |
| WO (1) | WO2003030965A2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1571204A1 (en) | 2004-03-04 | 2005-09-07 | LeukoCare GmbH | Leukocyte stimulation matrix |
| WO2007069755A1 (en) * | 2005-12-12 | 2007-06-21 | Riken | Method for production of antigen-specific hybridoma using artificial lymph node with good efficiency |
| CN101001954B (en) * | 2004-05-27 | 2013-01-30 | 西尔斯公司 | Nucleotide sequences and their encoded polypeptides for changing plant characteristics |
| EP2969149A4 (en) * | 2013-03-14 | 2016-12-21 | Brian J Leberthon | METHOD AND DEVICE FOR TREATING CANCER |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993020185A1 (en) * | 1992-04-01 | 1993-10-14 | Steinman Ralph M | 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 |
| CN1180079C (en) * | 1998-11-12 | 2004-12-15 | 基质细胞有限责任公司 | Generation of lymphoid tissue-specific cells from hematopoietic progenitors in a three-dimensional device |
-
2002
- 2002-09-16 WO PCT/DE2002/003465 patent/WO2003030965A2/en not_active Application Discontinuation
- 2002-09-16 AU AU2002349265A patent/AU2002349265A1/en not_active Abandoned
- 2002-09-16 DE DE10294532T patent/DE10294532D2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1571204A1 (en) | 2004-03-04 | 2005-09-07 | LeukoCare GmbH | Leukocyte stimulation matrix |
| WO2005085420A3 (en) * | 2004-03-04 | 2005-11-17 | Leukocare Gmbh | Leukocyte stimulation matrix |
| CN101001954B (en) * | 2004-05-27 | 2013-01-30 | 西尔斯公司 | Nucleotide sequences and their encoded polypeptides for changing plant characteristics |
| WO2007069755A1 (en) * | 2005-12-12 | 2007-06-21 | Riken | Method for production of antigen-specific hybridoma using artificial lymph node with good efficiency |
| EP2969149A4 (en) * | 2013-03-14 | 2016-12-21 | Brian J Leberthon | METHOD AND DEVICE FOR TREATING CANCER |
Also Published As
| Publication number | Publication date |
|---|---|
| DE10294532D2 (en) | 2004-08-26 |
| WO2003030965A3 (en) | 2004-04-01 |
| AU2002349265A1 (en) | 2003-04-22 |
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