WO1988007379A1 - Microbiological process for obtaining tumour-reducing substances and tumour antibodies in a test glass - Google Patents
Microbiological process for obtaining tumour-reducing substances and tumour antibodies in a test glass Download PDFInfo
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- WO1988007379A1 WO1988007379A1 PCT/DE1988/000142 DE8800142W WO8807379A1 WO 1988007379 A1 WO1988007379 A1 WO 1988007379A1 DE 8800142 W DE8800142 W DE 8800142W WO 8807379 A1 WO8807379 A1 WO 8807379A1
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- Prior art keywords
- tumour
- reducing substances
- antibodies
- tumor
- cells
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
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- 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
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/91—Cell lines ; Processes using cell lines
Definitions
- Microbiological process for obtaining tumor reducing substances and tumor antibodies in a test tube is a process for obtaining tumor reducing substances and tumor antibodies in a test tube.
- the invention relates to a microbiological method with the aid of which it is possible to produce substances with a specific effect for reducing tumors of the human or animal body and specific tumor antibodies outside the organism in a test tube.
- the only thing of interest is the problem of biological or immunotherapy. It can be assumed as certain that the human or animal organism, with the help of its own defense system, would be able to fight its own tumor if its own immune system recognized the tumor as hostile to the body. Since tumor cells arise from the body's own cells, the immune system is either not stimulated at all or only minimally when tumors grow, so that tumor cells can continue to grow, until the organism is ultimately no longer functional.
- the task is to produce substances which, in the subsequent therapeutic application, specifically seek out, kill and degrade tumors and their metastases without damaging the rest of the organism.
- Specified tumor cells for example adenocarcinoma cells
- Specified tumor cells are inactivated, for example by freezing and thawing, and added as a cell suspension with living reticuloendothelial system (RES), preferably bone marrow, from another living being and incubated for a few days at 40 ° C.
- RES reticuloendothelial system
- tumor cells and the bone marrow defense cells do not originate from the same organism, the tumor cells are recognized as foreign to the body and thus trigger defense reactions in the living bone marrow cells, in the course of which specific reactions - eg against adenocarcinoma cells - Tumor reducing substances and specific
- Tumor antibodies are generated. By centrifuging the entire incubate, a tumor antiserum with the specific tumor antibodies is obtained as a clear supernatant. It is now a light, tumor-reducing substance to be introduced either as a dilution of the total incubate or the Turaorantiserum as an injection into the diseased organism.
- the present invention extends solely to the microbiological procedure for the production of these tumor-reducing substances and tumor antibodies and the substance and the antibodies themselves and not to their therapeutic use, the benefits of which are subsequently illustrated in an experimental example for testing the effectiveness. It must be emphasized that the antibodies obtained in this way react purely specifically to the tumor tissue in question and otherwise have no side effects on other body tissues.
- Patent protection is not claimed for therapeutic use, but only for the micro biological production method and the product obtained in this way.
- the commercial benefit is therefore not with the treating doctor, but rather with suitable laboratories, e.g. in the pharmaceutical industry, which are able to produce these specific substances and bring them back to the market (hospitals, doctors, etc.) according to the applicable health regulations .
- Treatment Surgical removal of the primary tumor (approximately hen size) and removal of a hazelnut-sized metastasis.
- Weight loss no signs of any disease. Of the 5 metastases, three are neither visible nor palpable, 2 metastases are no longer visible, but can still be palpated as pea-sized tissue densifications.
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
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- Cell Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Beschreibung description
Mikrobiologisches Verfahren zur Gewinnung von Tumor reduzierenden Substanzen und Tumorantikörpern im Reagenzglas.Microbiological process for obtaining tumor reducing substances and tumor antibodies in a test tube.
Die Erfindung betrifft ein mikrobiologisches Verfahren, mit dessen Hilfe es möglich ist, spezifisch wirkende Substanzen zur Reduzierung von Tumoren des menschlichen oder tierischen Körpers sowie spezifische Tumorantikörper außerhalb des Organismus im Reagenzglas zu erzeugen.The invention relates to a microbiological method with the aid of which it is possible to produce substances with a specific effect for reducing tumors of the human or animal body and specific tumor antibodies outside the organism in a test tube.
Wir unterscheiden in der Tumorbekämpfung neben den chirurgischen grundsätzlich 3 Verfahren:We distinguish between three basic methods of tumor control and surgical:
1. Die Chemotherapie1. Chemotherapy
2. Die Strahlentherapie 3. Die biologische oder Immuntherapie2. Radiation therapy 3. Biological or immunotherapy
Es interessiert in diesem Zusammenhang lediglich die Problematik der biologischen oder Immuntherapie. Es darf als gesichert angenommen werden, daß der menschliche oder tierische Organismus mit Hilfe seines eigenen Abwehrsystems in der Lage wäre, selbst gegen seinen Pumor anzukämpfen, würde das eigene Immunsystem den Tumor als körperfeindlich erkennen. Da Tumorzellen aus körpereigenen Zellen entstehen, wird jedoch das Immunsystem beim Wachstum von Tumoren entweder überhaupt nicht oder nur minimal gereizt, so daß Tumorzellen ihr Wachstum fortsetzen können, bis der Organismus letztendlich nicht mehr funktionsfähig ist.In this context, the only thing of interest is the problem of biological or immunotherapy. It can be assumed as certain that the human or animal organism, with the help of its own defense system, would be able to fight its own tumor if its own immune system recognized the tumor as hostile to the body. Since tumor cells arise from the body's own cells, the immune system is either not stimulated at all or only minimally when tumors grow, so that tumor cells can continue to grow, until the organism is ultimately no longer functional.
Durch verschiedene Mittel, deren bekannteste z.B. Interferon und Interleukin sind, gelang es zwar, das Immunsystem des Organismus enorm zu aktivieren, doch zeigten die erhöhten Abwehrreaktionen nicht nur den Angriff auf Tumorzellen, sondern unspezifisch ebenso auf jedes irgendwie geschädigte Gewebe des Körpers, was enorme, zum Teil lebensbedrohende Polgen für den Gesamtorganismus zur Folge hatte.By various means, the best known of which are e.g. Although interferon and interleukin were able to activate the immune system of the organism enormously, the increased defense reactions showed not only the attack on tumor cells, but unspecifically also on every kind of damaged tissue in the body, which is an enormous and sometimes life-threatening pole for the whole organism resulted in.
Es stellt sich die Aufgabe, Substanzen zu erzeugen, die bei der anschließenden therapeutischen Anwendung spezifisch, ohne den übrigen Organismus zu schädigen, Tumoren und deren Metastasen aufsuchen, abtöten und abbauen.The task is to produce substances which, in the subsequent therapeutic application, specifically seek out, kill and degrade tumors and their metastases without damaging the rest of the organism.
Dies gelingt mit dem erfundenen Verfahren. Spezifizierte Tumorzellen, z.B. Adenokarzinomzellen, werden inaktiviert, z.B. durch Einfrieren und Wiederauftauen, und als Zellaufschwemmung mit lebendem retikuloendothelialem System (RES), am besten Knochenmark, eines anderen Lebewesens versetzt und einige Tage bei 40 Grad C. inkubiert. Da Tumorzellen und die Abwehrzellen des Knochenmarks nicht vom selben Organismus stammen, werden die Tumorzellen als körperfremd erkannt und lösen somit bei den lebenden Knochenmarkszellen Abwehrreaktionen aus, in deren Verlauf spezifische - z.B. gegen Adenokarzinomzelln - Tumor reduzierende Substanezen und spezifischeThis is achieved with the invented method. Specified tumor cells, for example adenocarcinoma cells, are inactivated, for example by freezing and thawing, and added as a cell suspension with living reticuloendothelial system (RES), preferably bone marrow, from another living being and incubated for a few days at 40 ° C. Since tumor cells and the bone marrow defense cells do not originate from the same organism, the tumor cells are recognized as foreign to the body and thus trigger defense reactions in the living bone marrow cells, in the course of which specific reactions - eg against adenocarcinoma cells - Tumor reducing substances and specific
Tumorantikörper erzeugt werden. Durch Zentrifugieren des Gesamtinkubates erhält man als klaren Überstand Tumorantiserem mit den spezifischen Tumorantikörpern. Es ist nun ein leichtes, die Tumor reduzierende Substanz entweder als Verdünnung des Gesamtinkubates oder das Turaorantiserum als Injektion in den erkrankten Organismus einzuführen.Tumor antibodies are generated. By centrifuging the entire incubate, a tumor antiserum with the specific tumor antibodies is obtained as a clear supernatant. It is now a light, tumor-reducing substance to be introduced either as a dilution of the total incubate or the Turaorantiserum as an injection into the diseased organism.
Auf Grund verschiedener Versuche steht außer Zweifel, daß nach Verabreichung dar Tumor reduzierenden Substanz bzw. des Tumorantiserums die Tumoren im Körper sowie die Metastasen selektiv identifieziert und in einem Maße bekämpft werden, wie es mit anderen Therapien nicht möglich ist. Die vorliegende Erfindung erstreckt sich jedoch alleine auf die mikrobiologische Verfahrensweise zur Produktion dieser Tumor reduzierenden Substanzen und Tumorantikörper und die Substanz und die Antikörper selbst und nicht auf deren therapeutische Anwendung, deren Nutzen jedoch anschließend in einem Versuchsbeispiel zum Test der Wirksamkeit verdeutlicht wird. Es muß betont werden, daß die so gewonnenen Abwehrstoffe rein spezifisch auf das betreffende Tumorgegewebe reagieren und ansonsten keine Nebenwirkungen auf anderes Körpergewebe haben.Based on various experiments, there is no doubt that after administration of the tumor-reducing substance or the tumor antiserum, the tumors in the body and the metastases are selectively identified and combated to an extent that is not possible with other therapies. However, the present invention extends solely to the microbiological procedure for the production of these tumor-reducing substances and tumor antibodies and the substance and the antibodies themselves and not to their therapeutic use, the benefits of which are subsequently illustrated in an experimental example for testing the effectiveness. It must be emphasized that the antibodies obtained in this way react purely specifically to the tumor tissue in question and otherwise have no side effects on other body tissues.
Der Patentschutz wird nicht beansprucht für die therapeutische Anwendung, sondern alleine auf die mikro biologische Herstellungsweise und das so gewonnene Produkt. Der gewerbliche Nutzen liegt somit nicht beim therapierendem Arzt, sondern vielmehr bei dazu geeigneten Labors z.B. der pharmazeutischen Industrie, die im Stande sind, diese spezifischen Substanzen herzustellen und sie nach den geltenden gesundheitsbehördlichen Auflagen wieder auf den Markt (Krankenhäuser, Ärzte usw.) zu bringen.Patent protection is not claimed for therapeutic use, but only for the micro biological production method and the product obtained in this way. The commercial benefit is therefore not with the treating doctor, but rather with suitable laboratories, e.g. in the pharmaceutical industry, which are able to produce these specific substances and bring them back to the market (hospitals, doctors, etc.) according to the applicable health regulations .
Ausführungsbeispiel: Patient: 8-jähr. Hund, weiblichDesign example: patient: 8 years. Dog, female
Befund: 7 sichtbare Tumoren im Drüsengewebe beiderFindings: 7 visible tumors in the glandular tissue of both
Milchleisten. Behandlung: Operative Entfernung des Primärtumors (etwa Hühnereigröße) und Entfernung einer haselnußgroßen Metastase.Milk bars. Treatment: Surgical removal of the primary tumor (approximately hen size) and removal of a hazelnut-sized metastasis.
Befund der histologischen Untersuchung: Mitosereiches, partiell infiltrierend wachsendes Adenokarzinom. Prognose: Falls bei der Operation nicht sämtliche Metastasen miterfaßt werden, ist in der Regel die Lebenserwartung auf 6 Monate, höchstens 9 Monate begrenzt. Im vorliegenden Fall wurden 5 im Durchschnitt haselnuß- bis kirschgroße Metastasen nicht operativ entfernt. Der Hund wurde mit oben beschriebenen Produkt in folgender Zusammensetzung behandelt: 5 ml Knochenmark einer Katze + 1 ml NatriumeitratFindings of the histological examination: Mitosis-rich, partially infiltrating growing adenocarcinoma. Prognosis: If not all metastases are recorded during the operation, life expectancy is usually limited to 6 months, at most 9 months. In the present case, 5 metastases the size of hazelnuts to cherries on average were not surgically removed. The dog was treated with the product described above in the following composition: 5 ml of bone marrow from a cat + 1 ml of sodium citrate
3,8%ig + 2 ml inaktivierte Adenokarzinomzellaufschwemmung 4 Tage bei 40 Grad C. inkubiert, anschließend im Verhältnis 1 : 1 mit physiologischer Kochsalzlösung verdünnt und bei Kühlschranktemperatur konserviert. Diese Inkubate wurden nach Verbrauch jeweils in der gleichen Weise neu hergestellt. Der Hund wurde zunächst viermal in wöchentlichem, anschließend viermal in 14-tägigem und weiter in 2-monatigem Abstand mit oben beschriebener Lösung in Form einer 2 ml i.m. Injektion behandelt. Nach 4 bis 6 Wochen zeigte sich eine Reduzierung um etwa 50 Prozent der Metastasengröße. Befund nach 12 Monaten: Der Hund ist lebhaft, absolut revitalisiert, keine3.8% + 2 ml of inactivated adenocarcinoma cell suspension for 4 days at 40 degrees C., then diluted 1: 1 with physiological saline and preserved at refrigerator temperature. These incubates were each newly produced in the same way after consumption. The dog was first four times a week, then four times every 14 days and then every two months with the solution described above in the form of a 2 ml i.m. Injection treated. After 4 to 6 weeks there was a reduction of about 50 percent in the size of the metastases. Findings after 12 months: the dog is lively, absolutely revitalized, none
Gewichtsabnahme, keine Anzeichen irgendeiner Erkrankung. Von den 5 Metastasen sind drei weder sichtbar noch palpierbar, 2 Metastasen nicht mehr sichtbar, jedoch noch als etwa erbsengroße Gewebsverdichtungen palpierbar.Weight loss, no signs of any disease. Of the 5 metastases, three are neither visible nor palpable, 2 metastases are no longer visible, but can still be palpated as pea-sized tissue densifications.
Abschließend sei noch erwähnt, daß sich bei der i.m. Applikation der wie oben beschrieben hergestellten Substanz auch bei wiederholter Anwendung weder eine allergische Reaktion noch irgendeine Störung im Allgemeinbefinden des Patienten einstellt und auch an der Applikationsstelle keine örtliche Entzündung feststellbar ist. Finally, it should be mentioned that the i.m. Application of the substance prepared as described above, even with repeated use, does not cause an allergic reaction or any disturbance in the general condition of the patient, and no local inflammation can be detected at the application site either.
Claims
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3709715.6 | 1987-03-25 | ||
| DE3709715 | 1987-03-25 | ||
| DE19873733001 DE3733001A1 (en) | 1987-03-25 | 1987-09-30 | MICROBIOLOGICAL METHOD FOR OBTAINING SPECIFIC TUMOR REDUCING SUBSTANCES IN TEST TUBE |
| DEP3733001.2 | 1987-09-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1988007379A1 true WO1988007379A1 (en) | 1988-10-06 |
Family
ID=25853867
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/DE1988/000142 Ceased WO1988007379A1 (en) | 1987-03-25 | 1988-03-15 | Microbiological process for obtaining tumour-reducing substances and tumour antibodies in a test glass |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU1424688A (en) |
| DE (1) | DE3733001A1 (en) |
| WO (1) | WO1988007379A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010048880A1 (en) | 2008-10-31 | 2010-05-06 | 北京以岭生物工程有限公司 | The nitropyridinyl ethyleneimine compound, the pharmaceutical composition containing it, the preparation method and use thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1086689A (en) * | 1964-12-01 | 1967-10-11 | Alkliam Chemicals Ltd | Pharmaceutically active extracts of bone marrow |
| EP0003173A1 (en) * | 1978-01-11 | 1979-07-25 | The Massachusetts General Hospital | Process for producing human antibodies and composition containing them |
-
1987
- 1987-09-30 DE DE19873733001 patent/DE3733001A1/en active Granted
-
1988
- 1988-03-15 AU AU14246/88A patent/AU1424688A/en not_active Abandoned
- 1988-03-15 WO PCT/DE1988/000142 patent/WO1988007379A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1086689A (en) * | 1964-12-01 | 1967-10-11 | Alkliam Chemicals Ltd | Pharmaceutically active extracts of bone marrow |
| EP0003173A1 (en) * | 1978-01-11 | 1979-07-25 | The Massachusetts General Hospital | Process for producing human antibodies and composition containing them |
Non-Patent Citations (1)
| Title |
|---|
| Chemical Abstracts, Band 84, Nr. 7, 16. February 1976, (Columbus, Ohio, US), R. Revoltella et al.: "In vitro immune response by murine bone marrow cells stimulated against soluble immune complexes", siehe Seite 316 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010048880A1 (en) | 2008-10-31 | 2010-05-06 | 北京以岭生物工程有限公司 | The nitropyridinyl ethyleneimine compound, the pharmaceutical composition containing it, the preparation method and use thereof |
| US8609851B2 (en) | 2008-10-31 | 2013-12-17 | Beijing Yiling Bioengineering Co., Ltd. | Nitropyridinyl ethyleneimine compound, the pharmaceutical composition containing it, the preparation method and use thereof |
| US8940770B2 (en) | 2008-10-31 | 2015-01-27 | Beijing Yiling Bioengineering Co., Ltd. | Nitropyridinyl ethyleneimine compound, the pharmaceutical composition containing it, the preparation method and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3733001C2 (en) | 1989-03-02 |
| DE3733001A1 (en) | 1988-10-06 |
| AU1424688A (en) | 1988-11-02 |
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