WO1997040182A1 - Gentransfizierte humane dendritische zellen, ihre herstellung und ihre verwendung, bevorzugt als vakzine - Google Patents
Gentransfizierte humane dendritische zellen, ihre herstellung und ihre verwendung, bevorzugt als vakzine Download PDFInfo
- Publication number
- WO1997040182A1 WO1997040182A1 PCT/DE1997/000772 DE9700772W WO9740182A1 WO 1997040182 A1 WO1997040182 A1 WO 1997040182A1 DE 9700772 W DE9700772 W DE 9700772W WO 9740182 A1 WO9740182 A1 WO 9740182A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dendritic cells
- human
- gene
- mucin
- cells
- Prior art date
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 44
- 210000004443 dendritic cell Anatomy 0.000 title claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 34
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 30
- 210000004027 cell Anatomy 0.000 claims abstract description 18
- 238000001890 transfection Methods 0.000 claims abstract description 12
- 229940121672 Glycosylation inhibitor Drugs 0.000 claims abstract description 8
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 claims abstract description 6
- 239000002502 liposome Substances 0.000 claims abstract description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 3
- 238000002360 preparation method Methods 0.000 claims abstract 3
- 108010063954 Mucins Proteins 0.000 claims description 28
- 102000015728 Mucins Human genes 0.000 claims description 28
- 239000013598 vector Substances 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 12
- 239000002299 complementary DNA Substances 0.000 claims description 9
- 241000701022 Cytomegalovirus Species 0.000 claims description 7
- 239000000427 antigen Substances 0.000 claims description 7
- 108091007433 antigens Proteins 0.000 claims description 7
- 102000036639 antigens Human genes 0.000 claims description 7
- 239000002773 nucleotide Substances 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 230000002163 immunogen Effects 0.000 claims description 6
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 4
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- ZUJDLWWYFIZERS-RGDJUOJXSA-N n-[(2r,3r,4r,5r,6r)-4,5-dihydroxy-6-(hydroxymethyl)-2-phenoxyoxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=CC=C1 ZUJDLWWYFIZERS-RGDJUOJXSA-N 0.000 claims description 4
- 210000005259 peripheral blood Anatomy 0.000 claims description 4
- 239000011886 peripheral blood Substances 0.000 claims description 4
- 102000004388 Interleukin-4 Human genes 0.000 claims description 3
- 108090000978 Interleukin-4 Proteins 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 208000024011 parotid gland neoplasm Diseases 0.000 claims description 2
- 238000012637 gene transfection Methods 0.000 claims 3
- 206010017577 Gait disturbance Diseases 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 abstract description 5
- 102100034256 Mucin-1 Human genes 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract 1
- 210000004881 tumor cell Anatomy 0.000 description 16
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 210000003719 b-lymphocyte Anatomy 0.000 description 7
- 210000002865 immune cell Anatomy 0.000 description 7
- 210000000987 immune system Anatomy 0.000 description 7
- 238000012546 transfer Methods 0.000 description 6
- 230000004913 activation Effects 0.000 description 5
- 230000000139 costimulatory effect Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 108020004635 Complementary DNA Proteins 0.000 description 3
- 238000010804 cDNA synthesis Methods 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000003151 transfection method Methods 0.000 description 3
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 2
- 201000008274 breast adenocarcinoma Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 229940076144 interleukin-10 Drugs 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 241000186216 Corynebacterium Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101150114927 MUC1 gene Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001573961 Parotis Species 0.000 description 1
- 241001483952 Peach chlorotic mottle virus Species 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000037455 tumor specific immune response Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 244000000009 viral human pathogen Species 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4727—Mucins, e.g. human intestinal mucin
-
- 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
- A61K39/46—Cellular immunotherapy
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464469—Tumor associated carbohydrates
- A61K39/46447—Mucins, e.g. MUC-1
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Definitions
- the invention relates to gene-transfected human dendritic cells.
- Gene-transfected dendritic cells can be used in basic research as well as in the construction of vaccines, e.g. B. tumor vaccines, find application. An efficient gene transfer to human dendritic cells has not been described so far.
- the invention further relates to a method for producing these cells and their use, preferably as a vaccine.
- the glycoprotein mucin encoded by the MUC1 gene, is expressed on the surface of pancreatic, Mamraa, colon, Parotis and ovarian carcinomas as well as on the corresponding healthy cells.
- Muzin encoded by MUC1 consists of two thirds of 20 to 100 "tandem nucleotide repeats".
- a "tandem nucleotide repeat” consists of 60 nucleotides that encode a polypeptide of 20 amino acids (see Fig. 2).
- peptide epitopes are exposed on tumor cells and can be recognized as foreign by the immune system, in particular T cells (these peptide epitopes are "hidden” by healthy carbohydrates on cells and therefore dissolve normal cells no immune response). These mucin epitopes are suitable for stimulating the immune system to protect the body against a tumor.
- Electroporation was used as the transfection method, a method which is not always successful and in which a large number of cells die.
- EBV-immortalized B cells have been used as immune cells and transfected with MUCl vectors and used to stimulate the immune system (described in Jerome KR, N. Domenech, and OJ Finn. 1993. Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells tranfected with polymorphyc epitheal mucin complementary DNA. J. of Immunol. 151: 1654-1662 and in Pecher G. and Finn O. j. 1996. Induction of cellular immunity in chimpanzees to tumor-associated antigen mucin by vaccination with MUC1 cDNA-transfected EBV-immortalized autologous B-cells.
- EBV Epstein-Barr virus
- the aim of the invention is to provide gene-transfected human dendritic cells.
- These cells are also to be genetically engineered to develop a vaccine which specifically stimulates the immune system against tumor cells already present in the body and which is intended to reduce or eliminate the tumor.
- "professional” immune cells for the expression of tumor-associated epitopes are to be used to construct a vaccine.
- Certain "professional” immune cells, in contrast to tumor cells, express the costimulatory ligands necessary for optimal T cell activation, such as CD80 and CD86.
- the essential feature of the manufacturing process is the transfection of the foreign gene into the dendrial cells using liposomes.
- the method according to the invention is efficient, simple to carry out, safe to use and, in comparison to, for example, retroviral gene transfer, inexpensive.
- the vaccine consists of human autologous dendritic cells which are transfected with a partial sequence of the human mucin MUCl gene, which contains several "tandem repeat nucleotide sequences" from the MUCl (FIG. 2), by means of lipofectin using the plasmid, and which are by Treatment with the glycosylation inhibitor phenyl-N-acetyl- ⁇ -D-galactosaminide express tumor-associated epitopes.
- the MUCl transfected cells are treated with the glycosylation inhibitor phenyl-N-acetyl- ⁇ -D-galactosaminide for 24 to 36 hours so that the immunogenic, tumor-associated mucin epitopes are formed.
- the Expression can be checked by a FACS analysis using mucin-epitope-specific antibodies.
- the invention also relates to the vector pCMV / MUCl according to FIG. 1 for transfection of the dendritic cells, which consists of the following essential components:
- CMV cytomegalovirus
- the vaccine according to the invention has the following advantages / innovations compared to previous tumor vaccines:
- the vaccine does not contain tumor cells, but a clearly defined antigen (MUCl).
- Immune cells used to construct the vaccine are dendritic cells.
- dendritic cells do not produce any immunosuppressive substances such as interleukin 10.
- Human dendritic cells are produced from peripheral blood of patients or healthy people using interleukin 4 and granulocyte macrophage colony stimulating factor. This is a simple and easy to practice procedure.
- the transfection method is lipofection. A high gene transfer rate in dendritic cells is achieved. The method is easy to carry out and reproducible.
- PCMV / MUCl according to Fig.l is used as the vector for gene transfer.
- the corresponding mucin cDNA was cloned into the vector under the immediate early promoter of CMV.
- the vector contains no cDNA for resistance to antibiotics or the like. The vector thus fulfills high requirements Safety requirements for human use.
- Another advantage of the vaccine according to the invention is that the recognition of the mucin-peptide epitopes by cytotoxic T cells does not follow the previously known classic way of recognizing short peptide epitopes in connection with the HLA complex.
- the mucin-peptide epitopes are recognized by the T cells without "help" from the HLA complex.
- This peculiarity in the detection of tumor-associated mucin epitopes can be explained by the above-mentioned special "tandem repeat" structure of the molecule and the high density of the antigen on the presenting cell.
- the repeated repetition of the immunogenic peptide-epitope motif leads to an activation of the T cells by "crosslinking" the T cell receptor without the HLA complex having to be present.
- peptide epitopes are exposed on tumor cells that can be recognized as foreign by the immune system.
- the activation of the immune system triggered by this is not sufficient in tumor patients to eliminate the tumor because (due to the lack of expression of CD80 and CD86 on tumor cells) there is no costimulation of T cells.
- the vaccine according to the invention triggers an efficient, tumor-specific immune response, which is based on the activation of mucine epitope-specific, cytotoxic T cells. These T cells lead to downsizing or elimination of the tumor cells.
- dendritic cells are transfected with MUCl (copies of the tandem nucleotide sequence of MUCl cloned into the vector) and, if appropriate, treated with the glycosylation inhibitor phenyl-N-acetyl- ⁇ -D-galactosaminide, these express the tumor-associated epitopes.
- MUCl copies of the tandem nucleotide sequence of MUCl cloned into the vector
- Dendritic cells are isolated from human peripheral blood and cultured. On day 4 of the culture of the dendritic cells, the dendritic cells are transfected. For this a vector is used which contains CMV as a promoter for the foreign gene MUCl. 15 ⁇ l lipofectin (Fig. 3) is used for 750,000 dendritic cells. The successful transfection of the foreign gene MUCl is detected by means of FACS analysis with the monoclonal antibody HMFG-2 against mucin epitopes. After transfection, 12% of the dendritic cells show an expression of mucin epitopes. By using a glycosylation inhibitor (Gl), mucine epitopes can be detected on the surface of 48% of the dendritic cells. This marks the successful gene transfer. Even without using the glycosylation inhibitor, there are already sufficient immunogenic mucin epitopes on the surface.
- Gl glycosylation inhibitor
- Mock (vector without foreign gene) transfected cells express mucin epitopes to a maximum of 2% (see Fig. 4)
- Lymphocytes are obtained from human peripheral blood by Ficoll gradient centrifugation and kept in culture. Dendritic cells are selected by the addition of interleukin 4 and granulocyte-macrophage colony stimulating factor and by adherence to platik. The dendritic cells are transfected with the MUCl vector using liposomes. Mucin expression is checked using Western blot methods and FACS analysis with monoclonal mucin antibodies. Phenyl-N-acetyl- ⁇ -D-galactosarainide (concentration 5 mM) is added to the culture medium of the transfected cells for 36 hours. The expression of the tumor-associated mucin-peptide epitopes generated in this way persists for 72 hours and is checked with monoclonal mucin-peptide antibodies by means of FACS analysis. The vaccine is applied to the patient within these 72 hours.
- the vaccine can be used for therapy in patients with mucin (MUCl) -expressing tumors.
- MUCl mucin
- the treatment of breast, pancreas, ovarian, colon and parotid tumors is preferred.
- This vaccine can also be used in healthy people to prevent a tumor expressing mucine epitopes.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Oncology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP97922844A EP0906444A1 (de) | 1996-04-19 | 1997-04-14 | Gentransfizierte humane dendritische zellen, ihre herstellung und ihre verwendung, bevorzugt als vakzine |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19617846.0 | 1996-04-19 | ||
DE1996117846 DE19617846A1 (de) | 1996-04-19 | 1996-04-19 | Verfahren zur Gentransfektion von humanen dendritischen Zellen |
DE19617837A DE19617837A1 (de) | 1996-04-19 | 1996-04-19 | Dendritische Zellen transfiziert mit Muzin-cDNA als Vakzine gegen humane Tumorerkrankungen |
DE19617837.1 | 1996-04-19 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1997040182A1 true WO1997040182A1 (de) | 1997-10-30 |
WO1997040182B1 WO1997040182B1 (de) | 1997-12-18 |
Family
ID=26025378
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DE1997/000772 WO1997040182A1 (de) | 1996-04-19 | 1997-04-14 | Gentransfizierte humane dendritische zellen, ihre herstellung und ihre verwendung, bevorzugt als vakzine |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP0906444A1 (de) |
WO (1) | WO1997040182A1 (de) |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0925059A1 (de) * | 1996-09-11 | 1999-06-30 | Albany Medical College | Protein-lipid vesikel sowie diese enthaltender autogener impfstoff |
WO1999045098A2 (en) * | 1998-03-06 | 1999-09-10 | Bruggen Pierre B V D | Delivery or proteins into eukaryotic cells with recombinant yersinia |
WO2001024832A2 (de) * | 1999-09-27 | 2001-04-12 | Gabriele Pecher | Pharmazeutische zusammensetzung zur behandlung und prophylaxe von humanen tumoren, die das tumorantigen muzin und/oder das carcinoembryonale antigen (cea) exprimieren und ihre verwendung |
US6440735B1 (en) | 1998-03-31 | 2002-08-27 | Geron Corporation | Dendritic cell vaccine containing telomerase reverse transcriptase for the treament of cancer |
WO2005017130A3 (en) * | 2003-08-18 | 2005-06-23 | Glycotope Gmbh | Tumour cell lines nm-f9 (dsm acc2606) and nm-d4 (dsm acc2605), uses thereof |
US7118738B2 (en) | 1997-02-24 | 2006-10-10 | Therion Biologics Corporation | Recombinant pox virus for immunization against MUC1 tumor-associated antigen |
US7402307B2 (en) | 1998-03-31 | 2008-07-22 | Geron Corporation | Method for identifying and killing cancer cells |
US7595192B2 (en) | 2002-08-16 | 2009-09-29 | Glycotype Gmbh | Process for the production of temperature-induced tumor cell lysates for use as immunogenic compounds |
US8592165B2 (en) | 2006-11-10 | 2013-11-26 | Glycotope Gmbh | Carbohydrate specific cellular immunity inducing microorganisms and fractions thereof |
US9051356B2 (en) | 2006-09-10 | 2015-06-09 | Glycotope Gmbh | Use of human cells of myeloid leukaemia origin for expression of antibodies |
US9700610B2 (en) | 2011-08-22 | 2017-07-11 | Glycotope Gmbh | Microorganisms carrying a tumor antigen |
US11872289B2 (en) | 2018-05-18 | 2024-01-16 | Daiichi Sankyo Co., Ltd. | Anti-MUC1 antibody-drug conjugate |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997003703A1 (en) * | 1995-07-21 | 1997-02-06 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Adeno-associated viral liposomes and their use in transfecting dendritic cells to stimulate specific immunity |
-
1997
- 1997-04-14 EP EP97922844A patent/EP0906444A1/de not_active Withdrawn
- 1997-04-14 WO PCT/DE1997/000772 patent/WO1997040182A1/de not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997003703A1 (en) * | 1995-07-21 | 1997-02-06 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Adeno-associated viral liposomes and their use in transfecting dendritic cells to stimulate specific immunity |
Non-Patent Citations (9)
Title |
---|
ARTHUR J. ET AL.: "A comparison of gene transfer methods in human dendritic cells", CANCER GENE THERAPY, vol. 2, no. 4, 1995, pages 312, XP002039139 * |
BARRATT-BOYES S. ET AL.: "Studies in a chimpanzee model of dendritic cell-based cancer vaccines", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, vol. 37, March 1996 (1996-03-01), pages 444, XP002039146 * |
BARRATT-BOYES S. ET AL.: "Use of dendritic cells to augment the immune response to tumor-associated mucin in two animal models", JOURNAL OF CELLULAR BIOCHEMISTRY, vol. Sup. 21a, 1995, pages 18, XP002039147 * |
FINN,O.: "Mucin-based cancer vaccines", CANCER BIOTHERAPY, vol. 10, no. 1, 1995, pages 82, XP002039140 * |
JEROME K. ET AL.: "Expression of tumor-associated epitopes on Epstein-Barr Virus-immortalized B-cells and Burkitt's Lymphomas transfected with epithelial mucin complementary DNA", CANCER RESEARCH, vol. 52, no. 21, 1 November 1992 (1992-11-01), pages 5985 - 5990, XP002039143 * |
JEROME K. ET AL.: "Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA", THE JOURNAL OF IMMUNOLOGY, vol. 151, no. 3, 1 August 1993 (1993-08-01), pages 1654 - 1662, XP002039145 * |
PECHER G. AND FINN O.: "Induction of cellular immunity in chimpanzees to human tumor-associated antigen mucin by vaccination with MUC-1 cDNA-transfected Epstein-Barr virus-immortalized autologous B cells", PNAS, U.S.A., vol. 93, no. 4, 20 February 1996 (1996-02-20), pages 1699 - 1704, XP002039144 * |
PECHER G. ET AL.: "MUC1-gene transfer into antigen presenting cells for immunotherapy of pancreatic cancer", ONKOLOGIE, vol. 18, no. Sup.2, 1995, pages 176, XP002039141 * |
SPAHN G. ET AL.: "MUC1 gene transfer into human dendritic cells", PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, vol. 37, March 1996 (1996-03-01), pages 486 - 487, XP002039142 * |
Cited By (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0925059A4 (de) * | 1996-09-11 | 2002-03-27 | Albany Medical College | Protein-lipid vesikel sowie diese enthaltender autogener impfstoff |
EP0925059A1 (de) * | 1996-09-11 | 1999-06-30 | Albany Medical College | Protein-lipid vesikel sowie diese enthaltender autogener impfstoff |
US7118738B2 (en) | 1997-02-24 | 2006-10-10 | Therion Biologics Corporation | Recombinant pox virus for immunization against MUC1 tumor-associated antigen |
WO1999045098A2 (en) * | 1998-03-06 | 1999-09-10 | Bruggen Pierre B V D | Delivery or proteins into eukaryotic cells with recombinant yersinia |
WO1999045098A3 (en) * | 1998-03-06 | 1999-12-23 | Bruggen Pierre B V D | Delivery or proteins into eukaryotic cells with recombinant yersinia |
US6602506B1 (en) | 1998-03-06 | 2003-08-05 | Ludwig Institute For Cancer Research | Delivery of proteins into eukaryotic cells with recombinant Yersinia |
US7824849B2 (en) | 1998-03-31 | 2010-11-02 | Geron Corporation | Cellular telomerase vaccine and its use for treating cancer |
US6440735B1 (en) | 1998-03-31 | 2002-08-27 | Geron Corporation | Dendritic cell vaccine containing telomerase reverse transcriptase for the treament of cancer |
US7402307B2 (en) | 1998-03-31 | 2008-07-22 | Geron Corporation | Method for identifying and killing cancer cells |
WO2001024832A3 (de) * | 1999-09-27 | 2002-04-18 | Gabriele Pecher | Pharmazeutische zusammensetzung zur behandlung und prophylaxe von humanen tumoren, die das tumorantigen muzin und/oder das carcinoembryonale antigen (cea) exprimieren und ihre verwendung |
WO2001024832A2 (de) * | 1999-09-27 | 2001-04-12 | Gabriele Pecher | Pharmazeutische zusammensetzung zur behandlung und prophylaxe von humanen tumoren, die das tumorantigen muzin und/oder das carcinoembryonale antigen (cea) exprimieren und ihre verwendung |
US7595192B2 (en) | 2002-08-16 | 2009-09-29 | Glycotype Gmbh | Process for the production of temperature-induced tumor cell lysates for use as immunogenic compounds |
WO2005017130A3 (en) * | 2003-08-18 | 2005-06-23 | Glycotope Gmbh | Tumour cell lines nm-f9 (dsm acc2606) and nm-d4 (dsm acc2605), uses thereof |
US8017388B2 (en) | 2003-08-18 | 2011-09-13 | Glycotope Gmbh | Tumour cell lines and uses thereof |
US8283161B2 (en) | 2003-08-18 | 2012-10-09 | Glycotope Gmbh | Tumour cell lines and uses thereof |
US9051356B2 (en) | 2006-09-10 | 2015-06-09 | Glycotope Gmbh | Use of human cells of myeloid leukaemia origin for expression of antibodies |
US10280230B2 (en) | 2006-09-10 | 2019-05-07 | Glycotope Gmbh | Use of human cells of myeloid leukemia origin for expression of antibodies |
US8592165B2 (en) | 2006-11-10 | 2013-11-26 | Glycotope Gmbh | Carbohydrate specific cellular immunity inducing microorganisms and fractions thereof |
US9494587B2 (en) | 2006-11-10 | 2016-11-15 | Glycotope Gmbh | Microorganisms or fractions thereof capable of activating cellular immunity against carbohydrates |
US9700610B2 (en) | 2011-08-22 | 2017-07-11 | Glycotope Gmbh | Microorganisms carrying a tumor antigen |
US11872289B2 (en) | 2018-05-18 | 2024-01-16 | Daiichi Sankyo Co., Ltd. | Anti-MUC1 antibody-drug conjugate |
Also Published As
Publication number | Publication date |
---|---|
EP0906444A1 (de) | 1999-04-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE69114299T3 (de) | Verfahren und zusammensetzungen für gentherapie und stärkung des immunsystems. | |
DE69937294T2 (de) | Von cyclophilin b abstammende tumorantigen-peptide | |
DE19541450C2 (de) | Genkonstrukt und dessen Verwendung | |
DE69731756T2 (de) | Melanomzellinien, welche immundominante melanomantigene teilen und verfahren zu deren anwendung | |
DE69533334T2 (de) | Impfstoff zum Auflösen einer Immunreaktion auf ein tumorspezifisches Antigen | |
DE69834022T2 (de) | Fusionproteine für intra- und interzelluläre transport und deren verwendungen | |
DE60038011T2 (de) | Verbesserung der immunantwort als anwendung in impfstoff und gentherapie | |
DE69435075T2 (de) | Immunogene chimäre umfassend nucleinsäuresequenzen, die signalsequenzpeptide des endoplasmatischen reticulums und mindestens ein anderes peptid codieren, deren verwendung in impfstoffen und zur behandlung von krankheiten | |
DE60038503T2 (de) | AKTIVIERUNG DES IMMUNSYSTEMS DURCH EINEN ANTIGEN UND EINEN NF-kappaB AUSLÖSER | |
DE102005041616B4 (de) | Melanom-assoziierte MHC Klasse I assoziierte Oligopeptide und für diese kodierende Polynukleotide und deren Verwendungen | |
DE60133287T2 (de) | Tumorantigen | |
WO1997026910A2 (de) | Tumorimpfstoff für die immuntherapie von malignen tumoren | |
EP1615662A1 (de) | Transfektion von blutzellen mit mrna zur immunstimulation und gentherapie | |
DE69921981T2 (de) | ZUSAMMENSETZUNG AUS MUTIERTERN PEPTIDEN, DERIVATE DES hsp70 UND IHRE VERWENDUNG IN DER IMMUNTHERAPIE VON KREBS | |
DE102004026135A1 (de) | An MHC-Moleküle bindende Tumor-assoziierte Peptide | |
WO1997040182A1 (de) | Gentransfizierte humane dendritische zellen, ihre herstellung und ihre verwendung, bevorzugt als vakzine | |
EP1699480B1 (de) | Allogenes tumortherapeutikum | |
DE69931482T2 (de) | Isolierte peptide die aminosäuresequenzen von ny-eso-1 entsprechen und an mhc-klasse i und mhc klasse ii moleküle binden, und deren verwendungen | |
DE60128070T2 (de) | Impfstoff spezifisch gegen nierentumore, gerichtet gegen das antigen g-250 des nierentumors | |
WO2000018806A1 (de) | Bispezifische und trispezifische antikörper, die spezifisch mit induzierbaren oberflächenantigenen als operationelle zielstrukturen reagieren | |
EP1171587B1 (de) | Peptid aus antigen muc-1 zur auslösung einer immunreaktion gegen tumorzellen | |
WO1997040182B1 (de) | Gentransfizierte humane dendritische zellen, ihre herstellung und ihre verwendung, bevorzugt als vakzine | |
EP1308167A1 (de) | Antigenpräsentierende Vesikel | |
DE10208653A1 (de) | Mikroorganismus als Träger von Nukleotidsequenzen kodierend für Zellantigene zur Behandlung von Tumoren | |
DE19516673A1 (de) | Vakzine gegen Tumorerkrankungen |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 1997922844 Country of ref document: EP |
|
NENP | Non-entry into the national phase |
Ref country code: JP Ref document number: 97537584 Format of ref document f/p: F |
|
WWP | Wipo information: published in national office |
Ref document number: 1997922844 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1997922844 Country of ref document: EP |