DE2024458A1 - Tumour antigen - modified and potentiated by irradiation - Google Patents
Tumour antigen - modified and potentiated by irradiationInfo
- Publication number
- DE2024458A1 DE2024458A1 DE19702024458 DE2024458A DE2024458A1 DE 2024458 A1 DE2024458 A1 DE 2024458A1 DE 19702024458 DE19702024458 DE 19702024458 DE 2024458 A DE2024458 A DE 2024458A DE 2024458 A1 DE2024458 A1 DE 2024458A1
- Authority
- DE
- Germany
- Prior art keywords
- cell
- tumor
- culture
- modified
- potentiated
- 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.)
- Pending
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 40
- 239000000427 antigen Substances 0.000 title claims abstract description 17
- 102000036639 antigens Human genes 0.000 title claims abstract description 17
- 108091007433 antigens Proteins 0.000 title claims abstract description 17
- 238000004113 cell culture Methods 0.000 claims abstract description 9
- 239000013049 sediment Substances 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 3
- 230000011278 mitosis Effects 0.000 claims abstract description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000035935 pregnancy Effects 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 230000000394 mitotic effect Effects 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 abstract description 2
- 206010057248 Cell death Diseases 0.000 abstract description 2
- 206010027476 Metastases Diseases 0.000 abstract description 2
- 230000009089 cytolysis Effects 0.000 abstract description 2
- 230000001678 irradiating effect Effects 0.000 abstract 1
- 238000010254 subcutaneous injection Methods 0.000 abstract 1
- 230000036266 weeks of gestation Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 8
- 230000001900 immune effect Effects 0.000 description 8
- 230000007123 defense Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 241000700605 Viruses Species 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000012406 Carcinoembryonic Antigen Human genes 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000004614 tumor growth Effects 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
- A61K39/0011—Cancer antigens
-
- 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
- A61K2039/5152—Tumor cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
Verfahren zur Herstellung eines abgewandelten und potenzierten Tumorantigens zur Krebsbekämpfung Zum näheren Verständnis der Erfindung seien zunächst die folgenden Überlegungen vorangestellt.Process for the production of a modified and potentiated tumor antigen for combating cancer For a more detailed understanding of the invention, let the following be the first First considerations.
Durch die Existenz tumorspezifischer Antigene, deren Nachweis vielseitig erbracht wurde, ist es möglich, eine tumorspezifische immunologische Therapie anzuwenden.Due to the existence of tumor-specific antigens, the detection of which is versatile it is possible to apply tumor-specific immunological therapy.
Neoplastische Zellen verfügen im Gegensatz zu normalen Zellen über spezifische antigene Determinanten, die als tumorspezifische Transplantantionsantigens (TSTA) bezeichnet werden.Unlike normal cells, neoplastic cells have specific antigenic determinants acting as tumor-specific transplant antigen (TSTA).
Tumoren, die während der fetalen Entwicklung bereits genetisch determiniert sind, induzieren eine immunologische Toleranz, so daß der Organismus nicht in der Trage ist, tumorspezifische Antigene immunologisch zu beantworten.Tumors that are already genetically determined during fetal development are, induce an immunological tolerance, so that the organism is not in the It is difficult to immunologically answer tumor-specific antigens.
Chemisch oder physikalisch induzierte Tumoren besitzen individuelle Antigen-Determinanten mit verschieden stark ausgeprägter Immunogenität, die für Jeden einzelnen Tumor spezifisch sind.Chemically or physically induced tumors have individual ones Antigen determinants with different degrees of immunogenicity that are responsible for Each individual tumor are specific.
Virusinduzierte Tumoren dagegen besitzen alle das gleiche tumorspezifische Transpiantationsantigen (TSTA), so sie vom gleichen Virus erzeugt worden sind.Virus-induced tumors, on the other hand, all have the same tumor-specific one Transplant antigen (TSTA), if they have been produced by the same virus.
Daß es trotz der körpereigenen immunologischen Abwehr zur Tumorenstehung kommen kann, hat neben der immunologischen Toleranz und der Immunosupression verschiedene Ursachen: Das spezifische Transplantationsantigen der Tumorzelle ist lediglich ein schwaches Immunogen. Werden gegen das tumorspezifische Antigen bevorzugt h u m o r a 1 e Antikörper gebildet, so kommt es zu einer spezifischen Bindung zwischen TSTA und humoralen Antikörpern und dadurch zu einer Maskierung tumorspezifischer Transplantationsantigene.That it leads to tumors in spite of the body's own immunological defense can come, has different in addition to immunological tolerance and immunosuppression Causes: The specific transplant antigen of the tumor cell is only a weak immunogen. Are preferred against the tumor-specific antigen h u m o r a 1 e antibodies are formed, there is a specific binding between TSTA and humoral antibodies and thereby masking tumor-specific Transplant antigens.
Neuere Untersuchungen haben nun ergeben, daB die immunologische Tumorabwehr hauptsächlich durch spezifisch sensibilisierte Lymphocyten repräsentiert wird, also Ausdruck einer z e i 1-v e r m i t t e 1 n d e n Immunität ist.More recent studies have now shown that the immunological defense against tumors is mainly represented by specifically sensitized lymphocytes, i.e. Expression of a z e i 1-v e r m i t t e 1 n d e n immunity.
Sind nun die antigenen Leterminanten des TSTA durch bumorale Antikörper bereits maskiert, ehe es zur Ausbildung der zellvermittelnden Immunität kommt, kann es sogar zu einer Verstärkung des Tumorwachstums kommen (Enhancement Phänomen).Are now the antigenic leterminants of the TSTA by bumoral antibodies masked before cell-mediating immunity can develop there is even an increase in tumor growth (enhancement phenomenon).
Ist der Stimulus der tumorspezifischen Antigene nur ungenügend, so kommt es zu keiner genügenden Ausbildung einer immunologischen Abwehrfunktion und besonders bei metastasierenden Carcinomen wird eine Verminderung des immunologischen Reaktion vermögens vom verzögerten Typ (Tunerkulnreaktion) gefunden.If the stimulus of the tumor-specific antigens is insufficient, so there is insufficient development of an immunological defense function and especially in the case of metastatic carcinomas there is a reduction in the immunological Delayed type reaction (tunerkuln reaction) found.
Aufgabe der Erfindung ist es deshalb, mit Hilfe gewonnenen Tumormaterials und dessen Abwandlung eine Stimulierung und Potenzierung des schwachen tumorspezifischen A n t i g e n s zu erreichen, um dadurch die Ausbildung einer zellvermittelnden Immunität zu erzielen. Dazu kann man wie folgt vorgehen: Monolayertumorzellkulturen werden durch Trypsinierung des operativ gewonnenen Tumormaterials angelegt in Eagle mit foetalem Kälberserum und nach gänzlichem Auswachsen der Zellkulturen mit 200 r mitosegeschädigt und das mehrmals gewaschene Zellsediment in eine injizierbare Form gebrachte Dieses Zellsediment in histopathalogisch und blutgruppengleiche Tumorkranke injiziert, erzielte cytolytische Erfolge, ohne jegliche zusätzliche Therapie aufgrund der sicherlich sorhandenen genetischen Differenz.The object of the invention is therefore to use tumor material obtained with the aid and its modification a stimulation and potentiation of the weak tumor-specific A n t i g e n s to achieve thereby the formation of a cell mediating To achieve immunity. To do this, you can proceed as follows: Monolayer tumor cell cultures are created in Eagle by trypsinating the surgically obtained tumor material with fetal calf serum and after the cell cultures have fully grown out with 200 r mitosis-damaged and the cell sediment washed several times in an injectable Formed This cell sediment in histopathology and blood group of the same Injected into tumor patients, achieved cytolytic successes without any additional results Therapy based on the genetic difference that is certainly present.
Um das e i g e n e Tumormaterial und damit das e i g e n e Tumorantigen zu verändern, da nicht immer geeignetes Austauschtumorgewebe zur Verfügung steht, wird gemäß weiterer Erfindung vorgeschlagen, die Tumorzellkulturen, nachdem sie zu 3/4 ausgewachsen sind, mit Zellkulturen aus menschlichen Feten früher, d.h. etwa der 1. - 124 Schwangerschaftswochen zu überschichten und nach gänzlichem Auswachsen der Kulturen, dies ist meist nach 4 Tagen, in der vorher beschriebenen Weise das Zellsediment zu bereiten. Nur die ersten vier Subkulturen des fetalen Gewebes werden dazu verwendet. Diese überschichteten Gewebekulturen werden 4000 - 8000 r röntgen-oder kobaltbestrahlt um die Mitosefähigkeit der Zellen gänzlich zu unterbinden. Trotz ausgedehnter Metastasen und ausgesprochener Erebsskachexie können mit dem gewaschenem Zellsediment dieser Kulturen eine deutliche Cytolyse der Tumoren erzielt werden.About your own tumor material and thus your own tumor antigen to change, since suitable exchange tumor tissue is not always available, is proposed according to a further invention, the tumor cell cultures after they are 3/4 grown, with cell cultures from human fetuses earlier, i.e. about the 1st - 124 weeks of pregnancy to be layered and after it has completely grown out of the cultures, this is usually after 4 days, in the manner described above Prepare cell sediment. Only the first four subcultures of the fetal tissue will be used for this. These layered tissue cultures are x-rayed or 4000 - 8000 r Cobalt irradiated to completely prevent the cells from being able to mitosis. Despite extensive metastases and pronounced erection cachexia can with the washed Cell sediment of these cultures a significant cytolysis of the tumors can be achieved.
Die Patienten bekommen in der Regel innerhalb vom 8 - 10 Tagen viermal je 2 - 3 Mild. Zeilen s.c. injiziert, um durch die wiederholte Antigengabe einen möglichen Boostereffekt zu erzielen. Dieses so bereitete Zellsediment in blutgruppengleiche Patienten injiziert mit histopathalogisch gleichen Tumoren erzielte einen starken Stimulus über das immunologische System und es kommt auch hier zur Lyse der Tumoren.The patients usually receive four times within 8-10 days 2 - 3 mild each. Lines s.c. injected to give a possible booster effect. This so prepared cell sediment in blood group matches Injected patients with histopathologically identical tumors scored a strong Stimulus via the immunological system and here, too, the tumors are lysed.
Die Potenzierung des Tumorantigens mag verursacht sein durch das carcinoembryonale Antigen des embryonalen menschlichen Gewebes, 2 PatentansprücheThe potentiation of the tumor antigen may be caused by the carcinoembryonic Antigen of embryonic human tissue, 2 claims
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19702024458 DE2024458A1 (en) | 1970-05-20 | 1970-05-20 | Tumour antigen - modified and potentiated by irradiation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19702024458 DE2024458A1 (en) | 1970-05-20 | 1970-05-20 | Tumour antigen - modified and potentiated by irradiation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2024458A1 true DE2024458A1 (en) | 1971-12-02 |
Family
ID=5771500
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19702024458 Pending DE2024458A1 (en) | 1970-05-20 | 1970-05-20 | Tumour antigen - modified and potentiated by irradiation |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2024458A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2314076A1 (en) * | 1972-11-09 | 1974-05-22 | Hoffmann La Roche | METHOD FOR MANUFACTURING CARCINOEMBRYONIC ANTIGEN |
| EP0019167A3 (en) * | 1979-05-10 | 1981-09-09 | Hans Dr. Limburg | Medicinal preparation for the treatment of carcinoma and process for preparing it |
| WO1998025645A1 (en) * | 1996-12-12 | 1998-06-18 | Karolinska Innovation Ab | Therapeutic applications of antigens or epitopes associated with impaired cellular peptide processing, e.g. expressed on rma-s cells transfected with a b7-1 gene |
-
1970
- 1970-05-20 DE DE19702024458 patent/DE2024458A1/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2314076A1 (en) * | 1972-11-09 | 1974-05-22 | Hoffmann La Roche | METHOD FOR MANUFACTURING CARCINOEMBRYONIC ANTIGEN |
| EP0019167A3 (en) * | 1979-05-10 | 1981-09-09 | Hans Dr. Limburg | Medicinal preparation for the treatment of carcinoma and process for preparing it |
| WO1998025645A1 (en) * | 1996-12-12 | 1998-06-18 | Karolinska Innovation Ab | Therapeutic applications of antigens or epitopes associated with impaired cellular peptide processing, e.g. expressed on rma-s cells transfected with a b7-1 gene |
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