IE852191L - Therapeutic agent for treating tumours - Google Patents
Therapeutic agent for treating tumoursInfo
- Publication number
- IE852191L IE852191L IE852191A IE219185A IE852191L IE 852191 L IE852191 L IE 852191L IE 852191 A IE852191 A IE 852191A IE 219185 A IE219185 A IE 219185A IE 852191 L IE852191 L IE 852191L
- Authority
- IE
- Ireland
- Prior art keywords
- therapeutic agent
- treatment
- cells
- nca
- tumor cells
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 16
- 229940124597 therapeutic agent Drugs 0.000 title claims abstract description 16
- 206010028980 Neoplasm Diseases 0.000 title description 9
- 239000000427 antigen Substances 0.000 claims abstract description 15
- 102000036639 antigens Human genes 0.000 claims abstract description 15
- 108091007433 antigens Proteins 0.000 claims abstract description 15
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 8
- 102000005348 Neuraminidase Human genes 0.000 claims abstract description 7
- 108010006232 Neuraminidase Proteins 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 6
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 4
- 230000028993 immune response Effects 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000006641 stabilisation Effects 0.000 claims description 3
- 238000011105 stabilization Methods 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 210000005260 human cell Anatomy 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 28
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000013049 sediment Substances 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- SPJOZZSIXXJYBT-UHFFFAOYSA-N Fenson Chemical compound C1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 SPJOZZSIXXJYBT-UHFFFAOYSA-N 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001844 chromium Chemical class 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- -1 for example Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000001768 subcellular fraction Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
- Window Of Vehicle (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
The process entails either tumour cells which carry antigens which are bound by the monoclonal antibodies described in German Offenlegungsschrift 33 29 184 being dried or stabilised by a chemical treatment, or antigens being isolated from human cells using these monoclonal antibodies, and converted into a therapeutic agent, adding neuraminidase where appropriate.
Description
58658 - 2 - The invention relates to a process for the preparation of a therapeutic agent from tumor cells for the therapy of tumorous diseases, and to a therapeutic agent of this type. 5 It is known, for example from "Mechanisms of Tumor Immunity," Gree et al., eds., John Wiley and Sons, N.Y., 1977, page 196, that attempts have already been made to treat tumorous diseases by inoculation with tumor cells which have been modified by freezing and thawing, freeze-10 drying, pressure or homogenization. Subcellular fractions or cell extracts have also been used for this purpose. However, as yet no vaccine against a tumorous disease has been disclosed.
We have found, surprisingly, that cells, which have 15 been freeze-dried or treated with an aldehyde, from human tumors or from cell aggregates obtained from the latter, which carry the antigens CEA or NCA can be used as a therapeutic agent for the treatment of tumorous diseases. 20 Thus the invention relates to a therapeutic agent for the treatment of a tumorous disease, containing human tumor cells which have been freeze-dried or stabilized by a chemical treatment and which carry the membrane-associated antigens CEA 25 or NCA.
One advantage of a therapeutic agent of this type compared with the use. of unmodified cells is that unmodified cells are not stable, so that they have to be prepared fresh each time. Moreoever, for this reason, they 30 cannot be standardized.
The invention furthermore relates to a process for the preparation of a therapeutic agent for the treatment of a tumorous disease, which comprises the freeze-drying or stabilization, by a chemical treatment, and the processing 35 to a therapeutic agent, neuraminidase being added where appropriate, of human tumor cells which carry the antigens CEA or NCA. - 3 - The possibility of potentiating an immune response by neuraminidase is disclosed in German Offenlegungsschrift 2,620,649.
A therapeutic agent is to be understood to be an 5 agent which may be suitable both as a prophylatic and for the treatment of a manifest disease.
The cells which can be used within the scope of the invention are obtained from tumors by known cell culture processes. Cells which have been obtained from such cul-10 tures by mechanical or enzymatic means and have, where appropriate, been inactivated with mitomycin C, are dried, preferably freeze-dried, or treated with an agent known to those skilled in the art as a stabilizing agent for organic tissue, preferably a nonoaldehyde or dialdehyde having 1 15 to 6 carbon atoms.
The agents which are particularly suitable for chemical stabilization and fixation include, in particular, bifunctional compounds, that is to say those which contain two groups which can react with functional groups 20 on the biological material - 1n other words can "crosslink" it. Examples of these are dialdehydes, in particular aliphatic dialdehydes having 2-8 carbon atoms. However, monoaIkanaIs having 1-4 carbon atoms, such as formaldehyde, which can undergr bifunctional reactions, as well as bi-25 functional imino esters, such as suberimidate, isocyanates or isothiocyanates, are also suitable for this purpose.
It is also possible for so-called tanning agents such as, for example, tannic acid and its derivatives, or chromium salts, to be used as agents which can stabilize 30 biological material. SulfosaIicy I ic acid is also suitable. _ 4 - In general, the cells are in the form of cell aggregates or single cells.
Examples of antigens are CEA (carcino-embyronic antigen; J.exp. Med. <1965) 122, *67) NCA (non-5 specific crossreacting antigen; J. Immun. (1973) III/ 1926) which can be isolated from the tumor cells by immunoadsorp-tion chromatography. For this purpose, the monoclonal antibodies described in Table I of German Offenlegungs-schrift 3,416,774 are covalently bound as purified pro-10 teins, to CN8r-activated sepharose 48, and the antigens (CEA, NCA) recognised by these monoclonal antibodies, are isolated from DE-TA colon carcinoma cell extracts. A suitable process is described in the Pharmacia book "Affinity Chromatography, Principles and Methods", 12-18 (1979), 15 summarized on page 15.
Quality control of a material which is to be used as a vaccine is carried out by, for fxample, typing with monoclonal antibodies, or by fractionation of the total cellular proteins using SDS-polyacrylamide gel electro-20 phoresis or isoelectric focusing (1st dimension) combined with SDS-polyacrylam1de gel electrophoresis (2nd dimension) followed by staining of the gel (silver stain).
The antigenic material 1s preferably administered i ntraderma lly, preferably by the checkerboard vaccination 25 method (Cancer Immunol, and Immunother. 6,47-58 (1979), in particular page 48) in combination with an adjuvant, in particular neuraminidase (German Of f enlegungsschri ft 2,620,649) .
A vaccine of this type is preferably used for certain stages of colon carcinoma (Duke C) and for other tumors which carry antigens or epitopes which are present in the 5 vaccine. Other tumors of this type are solid tumors, for example carcinomas of the pancreas, of the stomach, of the breast and of the lungs. The vaccine can be administered parenterally or orally. The antigens can be administered dissolved or suspended in physiological saline, preferably 10 i nt ra d er ma 11 y in PBS.
Two tests were carried out to assess the stability of the antigenic composition of the vaccine: a) the Terasaki IIF Assay (indirect immunofluorescence using tumor cells which grow in the wells of the Terasaki 15 microtiter plate) with monoclonal antibodies of various specificities. It is pcssible by means of this test to measure the expression of membrane antigens on intact tumor cells, against which a number of moncclonal antibodies are available (Cancer Detection and Prevention The examples which follow illustrate the invention. 30 Example 1 The carcinoma cell line BW X was cultivated in a cell culture in plastic bottles, growing as a monolayer in RPMI-1640 medium (Moore, G.E., Gerner, R.E., Franklin, H.A., Culture of normal human leukocytes, J.A.M.A. 199, 519-524 35 (1967)) with 10% fetal calf serum. The adherent cells growing in confluent cultures were separated mechanically or using trypsin which was dissolved in RPMI-1640 medium containing no fetal calf serum, the collagenase was inactivated by addition of fetal calf serum dissolved in RPMI-1640, and then the cells were detached from the tissue culture bottles and washed 3 times in phosphate-buffered saline CPBS) at 37°C.
About 107 cells, the major part of which as in 5 the form of aggregates, were incubated at 37°C for 1 hour in 1 ml of PBS which contained 100 pg of mitomycin C.
Then the cells thus inactivated were washed 3 times with PBS and a) washed 3 times in 0.18 molar ammonium bicarbonate buffer 10 which had been adjusted to pH 7.4 with acetic acid. A cell sediment corresponding to 10^ cells was taken up in 100 jjI of the same ammonium bicarbonate buffer and frozen at -70°C. The frozen material was then freeze-dried and stored in a small glass bottle, which was closed air-tight, 15 in a refrigerator at +4°C. The cell material thus treated can, after having been taken up in PBS, be used for vaccination of patients.
Alternatively b) incubated with 0.1% glutaraIdehyde in PBS at +4°C for 20 5 minutes, the excess glutaraIdehyde being removed by washing 3 times with PBS, and then incubated with 2% BSA (Bovine Serum Albumin) at +4°C for 5 minutes and washed 3 times in PBS. The cells thus treated can be stored at +4°C and used for the vaccination of patients. 25 Or c) incubated in formalin according to Lilly (Benno Romeis (1968), page 65, section 266, Oldenburg Verlag, Munich) at 25°C overnight, shaking occasionally. The cells (about 108) were centrifuged with decantation of the supernatant 30 (10 minutes at 800 x g), and the cell sediment was suspended in 7 ml of double-distilled water (= 1st wash). This washing process was repeated 4 times at intervals of 1 hour. The cell sediment was then washed 3 times, at intervals of 1 hour, in 7 ml of 70% ethanol each time. The cell sedi-35 ment was then washed 3 times, at intervals of 30 minutes, in 7 ml of 80% ethanol each time. The cell sediment was then washed 3 times, at intervals of 30 minutes, in 7 ml of 96% ethanol each time. The cell sediment was then washed 3 times, at intervals of 30 minutes, in 7 ml of 99% ethanol each time. The cell sediment was then washed 3 times, at intervals of 30 minutes, in 7 ml of sterile PBS each time, and was stored sterile at 4°C. The cells thus treated can be stored at 4°C and used for the vaccination of patients. - 8 -
Claims (6)
1. A therapeutic agent for the treatment of a tumorous disease, containing human tumor cells which have been freeze-dried or stabilized by a chemical 5 treatment and which carry the membrane-associated antigens CEA or NCA.
2. A therapeutic agent as claimed in claim 1, which contains an adjuvant which potentiates the immune response, preferably neuraminidase. 10
3. A process for the preparation of a therapeutic agent for the treatment of a tumorous disease, which comprises the freeze-drying or stabilization by a chemical treatment, and, the processing to a therapeutic agent, of human tumor cells which carry the membrane-15 associated antigens CEA or NCA.
4. The process as claimed in claim 3, wherein an adjuvant which potentiates the immune response, preferably neuraminidase, is additionally added to the therapeutic agent. 20
5. The use of human tumor cells which carry the membrane-associated antigens CEA or NCA, where appropriate in combination with an adjuvant which potentiates the immune response, preferably neuraminidase, for the preparation of a therapeutic 25 agent for the treatment of tumorous diseases.
6. A therapeutic agent as claimed in claim 1, substantially as hereinbefore described and exemplified. F. R. KELLY & CO., AGENTS FOR THE APPLICANTS
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843432714 DE3432714A1 (en) | 1984-09-06 | 1984-09-06 | TUMOR THERAPEUTICS AND METHOD FOR THE PRODUCTION THEREOF |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE852191L true IE852191L (en) | 1986-03-06 |
| IE58638B1 IE58638B1 (en) | 1993-10-20 |
Family
ID=6244749
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE219185A IE58638B1 (en) | 1984-09-06 | 1985-09-05 | A tumor therapeutic agent and a process for its preparation |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0173951B1 (en) |
| JP (1) | JPS6168427A (en) |
| AT (1) | ATE64531T1 (en) |
| CA (1) | CA1277600C (en) |
| DE (2) | DE3432714A1 (en) |
| DK (1) | DK172253B1 (en) |
| ES (1) | ES8704082A1 (en) |
| FI (1) | FI88360C (en) |
| GR (1) | GR852149B (en) |
| IE (1) | IE58638B1 (en) |
| IL (1) | IL76289A (en) |
| PT (1) | PT81093B (en) |
| ZA (1) | ZA856807B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3806565A1 (en) * | 1988-03-01 | 1989-09-14 | Deutsches Krebsforsch | VIRUS-MODIFIED TUMOR VACCINES FOR THE IMMUNOTHERAPY OF TUMOR METAL KEYS |
| AT398900B (en) * | 1991-02-12 | 1995-02-27 | Pekar Rudolf Dr | Vaccine for immunotherapy |
| US7070782B1 (en) | 1992-11-05 | 2006-07-04 | Sloan-Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
| US7105159B1 (en) | 1992-11-05 | 2006-09-12 | Sloan-Kettering Institute For Cancer Research | Antibodies to prostate-specific membrane antigen |
| WO1994009820A1 (en) * | 1992-11-05 | 1994-05-11 | Sloan-Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
| US6953668B1 (en) | 1992-11-05 | 2005-10-11 | Sloan-Kettering Institute For Cancer Research | Prostate-specific membrane antigen |
| US6569432B1 (en) | 1995-02-24 | 2003-05-27 | Sloan-Kettering Institute For Cancer Research | Prostate-specific membrane antigen and uses thereof |
| JP2001526522A (en) | 1995-02-24 | 2001-12-18 | スローン−ケタリング・インスティテュート・フォー・キャンサー・リサーチ | Prostate specific membrane antigen and uses thereof |
| DE19506483A1 (en) * | 1995-02-24 | 1996-08-29 | Jens Dr Dr Atzpodien | Antitumour vaccines |
| US20050215472A1 (en) | 2001-10-23 | 2005-09-29 | Psma Development Company, Llc | PSMA formulations and uses thereof |
| ES2559002T3 (en) | 2001-10-23 | 2016-02-10 | Psma Development Company, L.L.C. | Antibodies against PSMA |
| CN1315536C (en) * | 2002-09-13 | 2007-05-16 | 李进 | Novel vaccine of tumor antigen, its preparation method and vaccine composition |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4152410A (en) * | 1975-09-03 | 1979-05-01 | Eisai Co., Ltd. | Diagnosis reagent for neoplasm and method for diagnosis of neoplasm |
| DE2643215A1 (en) * | 1976-09-25 | 1978-04-06 | Bayer Ag | CANCEROSTATICALLY EFFECTIVE PREPARATIONS FROM TUMOR CELLS AND A METHOD FOR THEIR PRODUCTION |
| ZA776822B (en) * | 1976-11-24 | 1979-06-27 | D Mccollester | Vaccine and method for immunotherapy of neoplastic disease |
| DE2918927A1 (en) * | 1979-05-10 | 1980-11-20 | Hans Prof Dr Limburg | MEDICINAL PRODUCT FOR TREATING CARCINOMAS AND METHOD FOR THE PRODUCTION THEREOF |
| US4446122A (en) * | 1979-12-28 | 1984-05-01 | Research Corporation | Purified human prostate antigen |
| US4468457A (en) * | 1981-06-01 | 1984-08-28 | David M. Goldenberg | Method for producing a CSAp tryptic peptide and anti-CSAp antibodies |
| DE3416774A1 (en) * | 1984-05-07 | 1985-11-14 | Behringwerke Ag, 3550 Marburg | MONOCLONAL ANTIBODIES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
| DE3329184A1 (en) * | 1983-08-12 | 1985-02-21 | Behringwerke Ag, 3550 Marburg | MONOCLONAL ANTIBODIES WITH SPECIFICITY FOR MEMBRANE-ASSOCIATED ANTIGENS |
-
1984
- 1984-09-06 DE DE19843432714 patent/DE3432714A1/en not_active Withdrawn
-
1985
- 1985-08-27 DE DE8585110757T patent/DE3583265D1/en not_active Expired - Lifetime
- 1985-08-27 EP EP85110757A patent/EP0173951B1/en not_active Expired - Lifetime
- 1985-08-27 AT AT85110757T patent/ATE64531T1/en not_active IP Right Cessation
- 1985-09-03 DK DK402485A patent/DK172253B1/en not_active IP Right Cessation
- 1985-09-04 IL IL76289A patent/IL76289A/en not_active IP Right Cessation
- 1985-09-04 GR GR852149A patent/GR852149B/el unknown
- 1985-09-04 FI FI853389A patent/FI88360C/en not_active IP Right Cessation
- 1985-09-04 ES ES546701A patent/ES8704082A1/en not_active Expired
- 1985-09-05 IE IE219185A patent/IE58638B1/en not_active IP Right Cessation
- 1985-09-05 ZA ZA856807A patent/ZA856807B/en unknown
- 1985-09-05 JP JP60195000A patent/JPS6168427A/en active Pending
- 1985-09-05 CA CA000490026A patent/CA1277600C/en not_active Expired - Lifetime
- 1985-09-05 PT PT81093A patent/PT81093B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IE58638B1 (en) | 1993-10-20 |
| FI853389L (en) | 1986-03-07 |
| FI88360B (en) | 1993-01-29 |
| GR852149B (en) | 1986-01-03 |
| DE3583265D1 (en) | 1991-07-25 |
| FI88360C (en) | 1993-05-10 |
| FI853389A0 (en) | 1985-09-04 |
| ES8704082A1 (en) | 1987-03-16 |
| DK402485A (en) | 1986-03-07 |
| JPS6168427A (en) | 1986-04-08 |
| CA1277600C (en) | 1990-12-11 |
| ZA856807B (en) | 1986-04-30 |
| ES546701A0 (en) | 1987-03-16 |
| DE3432714A1 (en) | 1986-04-24 |
| DK172253B1 (en) | 1998-02-09 |
| ATE64531T1 (en) | 1991-07-15 |
| DK402485D0 (en) | 1985-09-03 |
| EP0173951A3 (en) | 1988-06-08 |
| PT81093B (en) | 1988-07-01 |
| IL76289A (en) | 1992-01-15 |
| EP0173951A2 (en) | 1986-03-12 |
| EP0173951B1 (en) | 1991-06-19 |
| PT81093A (en) | 1985-10-01 |
| IL76289A0 (en) | 1986-01-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |