NO327411B1 - Polynukleotid som koder for en kimaer CD40 ligand. - Google Patents
Polynukleotid som koder for en kimaer CD40 ligand. Download PDFInfo
- Publication number
- NO327411B1 NO327411B1 NO19992756A NO992756A NO327411B1 NO 327411 B1 NO327411 B1 NO 327411B1 NO 19992756 A NO19992756 A NO 19992756A NO 992756 A NO992756 A NO 992756A NO 327411 B1 NO327411 B1 NO 327411B1
- Authority
- NO
- Norway
- Prior art keywords
- ligand
- cells
- gene
- chimeric
- accessory molecule
- Prior art date
Links
- 108010029697 CD40 Ligand Proteins 0.000 title claims description 226
- 102100032937 CD40 ligand Human genes 0.000 title claims description 126
- 108091033319 polynucleotide Proteins 0.000 title claims description 23
- 102000040430 polynucleotide Human genes 0.000 title claims description 23
- 239000002157 polynucleotide Substances 0.000 title claims description 23
- 239000013598 vector Substances 0.000 claims abstract description 167
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 75
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 210000004027 cell Anatomy 0.000 claims description 473
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 156
- 241001529936 Murinae Species 0.000 claims description 105
- 239000002773 nucleotide Substances 0.000 claims description 60
- 125000003729 nucleotide group Chemical group 0.000 claims description 60
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 58
- 230000002068 genetic effect Effects 0.000 claims description 58
- 210000005170 neoplastic cell Anatomy 0.000 claims description 47
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 45
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 claims description 40
- 239000000427 antigen Substances 0.000 claims description 36
- 102000036639 antigens Human genes 0.000 claims description 36
- 108091007433 antigens Proteins 0.000 claims description 36
- 241000701161 unidentified adenovirus Species 0.000 claims description 36
- 208000032839 leukemia Diseases 0.000 claims description 24
- 238000004519 manufacturing process Methods 0.000 claims description 23
- 230000009826 neoplastic cell growth Effects 0.000 claims description 22
- 239000013604 expression vector Substances 0.000 claims description 17
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 14
- 230000003612 virological effect Effects 0.000 claims description 14
- 206010025323 Lymphomas Diseases 0.000 claims description 11
- 208000020816 lung neoplasm Diseases 0.000 claims description 11
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 10
- 210000004962 mammalian cell Anatomy 0.000 claims description 9
- 229920001184 polypeptide Polymers 0.000 claims description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 7
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims description 6
- 230000002163 immunogen Effects 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000003834 intracellular effect Effects 0.000 claims description 3
- 241000702421 Dependoparvovirus Species 0.000 claims description 2
- 101100099884 Homo sapiens CD40 gene Proteins 0.000 claims 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 abstract description 367
- 239000003446 ligand Substances 0.000 abstract description 312
- 241000282414 Homo sapiens Species 0.000 abstract description 98
- 230000000694 effects Effects 0.000 abstract description 29
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 18
- 238000002255 vaccination Methods 0.000 abstract description 17
- 230000036210 malignancy Effects 0.000 abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 5
- 230000002519 immonomodulatory effect Effects 0.000 abstract description 4
- 102000003390 tumor necrosis factor Human genes 0.000 abstract description 4
- 230000006641 stabilisation Effects 0.000 abstract 1
- 238000011105 stabilization Methods 0.000 abstract 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 168
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 152
- 238000000034 method Methods 0.000 description 104
- 238000001415 gene therapy Methods 0.000 description 94
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 88
- 230000014509 gene expression Effects 0.000 description 87
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 74
- 241000699670 Mus sp. Species 0.000 description 62
- 241001465754 Metazoa Species 0.000 description 58
- 210000001744 T-lymphocyte Anatomy 0.000 description 58
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 45
- 101150013553 CD40 gene Proteins 0.000 description 40
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 39
- 238000002347 injection Methods 0.000 description 35
- 239000007924 injection Substances 0.000 description 35
- 206010039073 rheumatoid arthritis Diseases 0.000 description 35
- 230000000735 allogeneic effect Effects 0.000 description 33
- 206010003246 arthritis Diseases 0.000 description 29
- 210000005260 human cell Anatomy 0.000 description 29
- 108020004414 DNA Proteins 0.000 description 27
- 210000000987 immune system Anatomy 0.000 description 27
- 230000001965 increasing effect Effects 0.000 description 27
- 102000008070 Interferon-gamma Human genes 0.000 description 24
- 108010074328 Interferon-gamma Proteins 0.000 description 24
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 23
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 23
- 235000001014 amino acid Nutrition 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 23
- 230000028993 immune response Effects 0.000 description 23
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 22
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 22
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 22
- 230000006870 function Effects 0.000 description 22
- 230000001613 neoplastic effect Effects 0.000 description 22
- 239000013612 plasmid Substances 0.000 description 22
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 21
- 241000700605 Viruses Species 0.000 description 21
- 229960003130 interferon gamma Drugs 0.000 description 20
- 230000003211 malignant effect Effects 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 210000002966 serum Anatomy 0.000 description 17
- 125000003275 alpha amino acid group Chemical group 0.000 description 16
- 108010005774 beta-Galactosidase Proteins 0.000 description 16
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 15
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 15
- 239000012636 effector Substances 0.000 description 15
- 210000004698 lymphocyte Anatomy 0.000 description 15
- 210000004881 tumor cell Anatomy 0.000 description 15
- 238000002474 experimental method Methods 0.000 description 14
- 102100025221 CD70 antigen Human genes 0.000 description 13
- 238000002965 ELISA Methods 0.000 description 13
- 101150064015 FAS gene Proteins 0.000 description 13
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 13
- 208000015181 infectious disease Diseases 0.000 description 13
- 238000002372 labelling Methods 0.000 description 13
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 12
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 12
- 230000006907 apoptotic process Effects 0.000 description 12
- 230000000638 stimulation Effects 0.000 description 12
- 101000868216 Mus musculus CD40 ligand Proteins 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 11
- 101710097160 Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 230000000981 bystander Effects 0.000 description 11
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 210000004988 splenocyte Anatomy 0.000 description 11
- 238000012353 t test Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 229940104230 thymidine Drugs 0.000 description 11
- 102100027207 CD27 antigen Human genes 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 10
- 101100059511 Homo sapiens CD40LG gene Proteins 0.000 description 10
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 10
- 238000000692 Student's t-test Methods 0.000 description 10
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 102000053826 human CD70 Human genes 0.000 description 10
- 210000001503 joint Anatomy 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 238000011725 BALB/c mouse Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 230000008488 polyadenylation Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- 210000002437 synoviocyte Anatomy 0.000 description 8
- 210000004102 animal cell Anatomy 0.000 description 7
- 230000005875 antibody response Effects 0.000 description 7
- 230000001086 cytosolic effect Effects 0.000 description 7
- 238000010790 dilution Methods 0.000 description 7
- 239000012895 dilution Substances 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 210000002950 fibroblast Anatomy 0.000 description 7
- 238000010348 incorporation Methods 0.000 description 7
- 210000001616 monocyte Anatomy 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 6
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 6
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 6
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 6
- 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 6
- 230000004913 activation Effects 0.000 description 6
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 230000004663 cell proliferation Effects 0.000 description 6
- 210000000285 follicular dendritic cell Anatomy 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 210000001865 kupffer cell Anatomy 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 108010082808 4-1BB Ligand Proteins 0.000 description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 5
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 5
- 108091008874 T cell receptors Proteins 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 5
- 108700012920 TNF Proteins 0.000 description 5
- -1 TNFβ Proteins 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 5
- 102000005936 beta-Galactosidase Human genes 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 5
- 108010052621 fas Receptor Proteins 0.000 description 5
- 102000018823 fas Receptor Human genes 0.000 description 5
- 230000008105 immune reaction Effects 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 238000010255 intramuscular injection Methods 0.000 description 5
- 239000007927 intramuscular injection Substances 0.000 description 5
- 101150066555 lacZ gene Proteins 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 210000001179 synovial fluid Anatomy 0.000 description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 102000004634 CD30 Ligand Human genes 0.000 description 4
- 108010017987 CD30 Ligand Proteins 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 4
- 101000638240 Mus musculus Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 4
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 4
- 108010025020 Nerve Growth Factor Proteins 0.000 description 4
- 102000015336 Nerve Growth Factor Human genes 0.000 description 4
- 241000714474 Rous sarcoma virus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 210000004207 dermis Anatomy 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 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 4
- 229940044627 gamma-interferon Drugs 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 210000003127 knee Anatomy 0.000 description 4
- 208000037841 lung tumor Diseases 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 210000005087 mononuclear cell Anatomy 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 229940053128 nerve growth factor Drugs 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 102000013415 peroxidase activity proteins Human genes 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000002864 sequence alignment Methods 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000000451 tissue damage Effects 0.000 description 4
- 231100000827 tissue damage Toxicity 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 3
- 208000009386 Experimental Arthritis Diseases 0.000 description 3
- 101100273745 Homo sapiens CD70 gene Proteins 0.000 description 3
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 3
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 3
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 3
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 206010067125 Liver injury Diseases 0.000 description 3
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 229920001222 biopolymer Polymers 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- XVLXYDXJEKLXHN-UHFFFAOYSA-M dioc6 Chemical compound [I-].O1C2=CC=CC=C2[N+](CCCCCC)=C1C=CC=C1N(CCCCCC)C2=CC=CC=C2O1 XVLXYDXJEKLXHN-UHFFFAOYSA-M 0.000 description 3
- 210000003162 effector t lymphocyte Anatomy 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 201000003444 follicular lymphoma Diseases 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 102000057041 human TNF Human genes 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 3
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 3
- 210000001821 langerhans cell Anatomy 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000003362 replicative effect Effects 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 210000001258 synovial membrane Anatomy 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000010370 Adenoviridae Infections Diseases 0.000 description 2
- 206010060931 Adenovirus infection Diseases 0.000 description 2
- 101000738343 Bos taurus CD40 ligand Proteins 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 2
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 2
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 2
- 101000764535 Homo sapiens Lymphotoxin-alpha Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000638255 Homo sapiens Tumor necrosis factor ligand superfamily member 8 Proteins 0.000 description 2
- 108700001097 Insect Genes Proteins 0.000 description 2
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 2
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 108700005443 Microbial Genes Proteins 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 101000638260 Rattus norvegicus Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 101800000859 Tumor necrosis factor ligand superfamily member 6, soluble form Proteins 0.000 description 2
- 102400000084 Tumor necrosis factor ligand superfamily member 6, soluble form Human genes 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000000240 adjuvant effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 210000003423 ankle Anatomy 0.000 description 2
- 230000000719 anti-leukaemic effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000003618 borate buffered saline Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 238000010805 cDNA synthesis kit Methods 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 102000055229 human IL4 Human genes 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000009546 lung large cell carcinoma Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 235000020030 perry Nutrition 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000036647 reaction Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- KHOITXIGCFIULA-UHFFFAOYSA-N Alophen Chemical compound C1=CC(OC(=O)C)=CC=C1C(C=1N=CC=CC=1)C1=CC=C(OC(C)=O)C=C1 KHOITXIGCFIULA-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000597784 Bos taurus Tumor necrosis factor Proteins 0.000 description 1
- 101150088890 CD70 gene Proteins 0.000 description 1
- 101100378877 Caenorhabditis elegans allo-1 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108010039471 Fas Ligand Protein Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 1
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 1
- 101000599940 Homo sapiens Interferon gamma Proteins 0.000 description 1
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- 101000830565 Homo sapiens Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 1
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100025390 Integrin beta-2 Human genes 0.000 description 1
- 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- 108010031801 Lipopolysaccharide Receptors Proteins 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 102100026238 Lymphotoxin-alpha Human genes 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 101000638253 Mus musculus Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 101100290374 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) mcd-4 gene Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 206010036700 Primary immunodeficiency syndromes Diseases 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010068348 X-linked lymphoproliferative syndrome Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000006154 adenylylation Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 230000036732 histological change Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 102000043557 human IFNG Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000001911 interdigitating cell Anatomy 0.000 description 1
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- 210000003041 ligament Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 208000018555 lymphatic system disease Diseases 0.000 description 1
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 1
- 230000001589 lymphoproliferative effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011536 re-plating Methods 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 108020001568 subdomains Proteins 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 210000000457 tarsus Anatomy 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/48—Nerve growth factor [NGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/525—Tumour necrosis factor [TNF]
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/525—Tumour necrosis factor [TNF]
- C07K14/5255—Lymphotoxin [LT]
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3214596P | 1996-12-09 | 1996-12-09 | |
| US08/982,272 US7070771B1 (en) | 1996-12-09 | 1997-12-01 | Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells |
| PCT/US1997/022740 WO1998026061A2 (fr) | 1996-12-09 | 1997-12-08 | Nouveaux vecteurs d'expression contenant des genes de ligands de molecules accessoires et leur emploi a des fins d'immunomodulation et de traitement des tumeurs malignes et des maladies autoimmunes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO992756D0 NO992756D0 (no) | 1999-06-07 |
| NO992756L NO992756L (no) | 1999-08-09 |
| NO327411B1 true NO327411B1 (no) | 2009-06-22 |
Family
ID=26708033
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19992756A NO327411B1 (no) | 1996-12-09 | 1999-06-07 | Polynukleotid som koder for en kimaer CD40 ligand. |
| NO20074906A NO331434B1 (no) | 1996-12-09 | 2007-09-27 | Kimaert nukleinsyremolekyl, rekombinant ekspresjonsvektor og vertcelle |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20074906A NO331434B1 (no) | 1996-12-09 | 2007-09-27 | Kimaert nukleinsyremolekyl, rekombinant ekspresjonsvektor og vertcelle |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US7070771B1 (fr) |
| EP (4) | EP2287309A1 (fr) |
| JP (1) | JP4015201B2 (fr) |
| CN (1) | CN1221662C (fr) |
| AT (2) | ATE547524T1 (fr) |
| AU (1) | AU5795798A (fr) |
| BR (1) | BR9714004A (fr) |
| CA (2) | CA2274498C (fr) |
| DE (1) | DE69739220D1 (fr) |
| DK (1) | DK0948614T3 (fr) |
| ES (1) | ES2321246T3 (fr) |
| IL (3) | IL130247A0 (fr) |
| NO (2) | NO327411B1 (fr) |
| NZ (1) | NZ336092A (fr) |
| PT (1) | PT948614E (fr) |
| WO (1) | WO1998026061A2 (fr) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7070771B1 (en) * | 1996-12-09 | 2006-07-04 | Regents Of The University Of California | Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells |
| WO2000063395A1 (fr) * | 1999-04-16 | 2000-10-26 | F. Hoffmann-La Roche Ag | Acides nucleiques codant pour des polypeptides chimeres cd40/cd40l, leurs procedes de production et leurs utilisations |
| GB9917180D0 (en) * | 1999-07-23 | 1999-09-22 | Univ Sheffield | Cell surface receptor |
| GB0025307D0 (en) * | 2000-10-16 | 2000-11-29 | Celltech Chiroscience Ltd | Biological products |
| AU2002221780A1 (en) * | 2000-10-31 | 2002-05-15 | F.Hoffmann-La Roche Ag | Nucleic acids encoding cd40/cd40l chimeric polypeptides, methods for their production and uses thereof |
| US7786282B2 (en) * | 2001-12-06 | 2010-08-31 | The Regents Of The University Of California | Nucleic acid molecules encoding TNF-α ligand polypeptides having a CD154 domain |
| US20050214311A1 (en) * | 2002-02-25 | 2005-09-29 | Screaton Gavin R | Novel complexes for inducing an immune response |
| US7495090B2 (en) * | 2002-05-23 | 2009-02-24 | The Regents Of The University Of California | Nucleic acids encoding chimeric CD154 polypeptides |
| US20130266551A1 (en) | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
| US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
| US20080044393A1 (en) * | 2004-07-16 | 2008-02-21 | White Robert L | Retinal dystrophin transgene and methods of use thereof |
| WO2008109825A2 (fr) * | 2007-03-08 | 2008-09-12 | Mayo Foundation For Medical Education And Research | Induction de mort de cellule tumorale par voie immunitaire |
| US20100050276A1 (en) * | 2008-08-22 | 2010-02-25 | Brown University | Transgenic non-human animal models of apoptosis-mediated conditions |
| DK2788021T3 (en) | 2011-12-09 | 2017-04-10 | Bavarian Nordic As | POXVIRUS VECTOR FOR EXPRESSION OF BACTERIAL ANTIGENES CONNECTED TO TETANANOX INFRAGMENT C |
| BR112015008612A2 (pt) * | 2012-10-17 | 2017-09-26 | Vascular Biogenics Ltd | métodos de tratamento utilizando adenovirus |
| CN106574241A (zh) * | 2014-03-27 | 2017-04-19 | 密执安大学评议会 | 癌症免疫疗法组合物和方法 |
| AU2015259877B2 (en) | 2014-05-15 | 2021-02-25 | National University Of Singapore | Modified natural killer cells and uses thereof |
| CN105567679B (zh) * | 2014-10-10 | 2019-07-05 | 深圳市北科生物科技有限公司 | 可分泌型trail蛋白构建物和表达载体 |
| US20180244750A1 (en) | 2015-11-02 | 2018-08-30 | Memgen, Llc | Methods for treatment of cancer |
| US11298420B2 (en) | 2016-12-21 | 2022-04-12 | Memgen, Llc | Armed oncolytic viruses |
| KR102660336B1 (ko) | 2017-03-27 | 2024-04-26 | 내셔널 유니버시티 오브 싱가포르 | 절단된 nkg2d 키메라 수용체 및 자연 살해 세포 면역요법에서의 그의 용도 |
| WO2018191369A1 (fr) | 2017-04-12 | 2018-10-18 | Memgen, Llc | Procédés d'activation immunitaire de récepteur de type cd40 et toll |
| AU2019219454A1 (en) | 2018-02-09 | 2020-08-27 | National University Of Singapore | Activating chimeric receptors and uses thereof in natural killer cell immunotherapy |
| CN112055717B (zh) | 2018-04-02 | 2024-04-26 | 新加坡国立大学 | 用在免疫细胞中表达的膜结合抗细胞因子非信号传导粘合剂中和人细胞因子 |
| EP3844186A4 (fr) | 2018-08-29 | 2022-08-17 | National University of Singapore | Procédé permettant de stimuler de manière spécifique la survie et l'expansion de cellules immunitaires génétiquement modifiées |
| US12590148B2 (en) | 2018-11-26 | 2026-03-31 | Nkarta, Inc. | Methods for the simultaneous expansion of multiple immune cell types, related compositions and uses of same in cancer immunotherapy |
| AU2020232691B2 (en) | 2019-03-05 | 2023-06-29 | Nkarta, Inc. | CD19-directed chimeric antigen receptors and uses thereof in immunotherapy |
| CN112725379B (zh) * | 2021-01-27 | 2024-08-13 | 上海南方模式生物科技股份有限公司 | 人源化cd40基因改造动物模型的构建方法及应用 |
| US11585330B1 (en) * | 2021-09-29 | 2023-02-21 | Halliburton Energy Services, Inc. | Flow control for geothermal well |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3750056T2 (de) | 1986-06-20 | 1995-04-06 | Dainippon Pharmaceutical Co | Polypeptid-Mutanten des menschlichen TNF und für diese Mutanten codierende DNS. |
| JPH082315B2 (ja) | 1987-05-29 | 1996-01-17 | 財団法人相模中央化学研究所 | リンホトキシンを含む融合蛋白質 |
| ATE148992T1 (de) | 1989-08-16 | 1997-03-15 | Chiron Corp | Zusammensetzungen zur hemmung der bildung von proteinhormon und deren verwendungen |
| US5519119A (en) | 1990-09-21 | 1996-05-21 | Ishihara Sangyo Kaisha Ltd. | Muteins of TNF pharmaceutical compositions and a method of making |
| CA2055168A1 (fr) | 1990-11-21 | 1992-05-22 | Walter Fiers | Muteines de tnf |
| AU661360B2 (en) | 1991-10-25 | 1995-07-20 | Immunex Corporation | Novel cytokine |
| NZ251820A (en) | 1992-03-30 | 1996-07-26 | Immunex Corp | Fusion proteins with tnf-r (tumour necrosis factor-receptor) peptide linked to another tnf-r or an il-1r (interleukin-1-receptor) peptide |
| CZ283533B6 (cs) | 1992-04-02 | 1998-04-15 | F. Hoffmann-La Roche Ag | TNF - muteiny a způsob jejich výroby |
| DE69334070T2 (de) | 1992-05-26 | 2007-01-04 | Immunex Corp., Thousand Oaks | Neue zytokine die cd30 binden |
| AU5098493A (en) | 1992-08-21 | 1994-03-15 | Schering Corporation | Cd40 ligand, anti cd40 antibodies, and soluble cd40 |
| EP0656947A1 (fr) | 1992-08-21 | 1995-06-14 | Schering Corporation | Interleukine-13 humaine |
| US5540926A (en) | 1992-09-04 | 1996-07-30 | Bristol-Myers Squibb Company | Soluble and its use in B cell stimulation |
| US5573924A (en) | 1992-09-08 | 1996-11-12 | Immunex Corporation | CD27 ligand |
| US5565321A (en) | 1993-01-22 | 1996-10-15 | Immunex Corporation | Detection of mutations in a CD40 ligand gene |
| ATE256180T1 (de) | 1993-01-22 | 2003-12-15 | Immunex Corp | Detektion und behandlung von mutationen in einem gen für einen cd40-liganden |
| US5830463A (en) | 1993-07-07 | 1998-11-03 | University Technology Corporation | Yeast-based delivery vehicles |
| US5861310A (en) * | 1993-11-03 | 1999-01-19 | Dana-Farber Cancer Institute | Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor |
| JPH08127594A (ja) | 1993-11-10 | 1996-05-21 | Mochida Pharmaceut Co Ltd | Ｆａｓ抗原に結合する新規蛋白質およびそれをコードするＤＮＡ |
| AU1059095A (en) * | 1993-11-24 | 1995-06-13 | Australian National University, The | Treatment of viral disease with cd40l peptide |
| EP0751781B1 (fr) | 1993-12-23 | 2004-05-26 | Immunex Corporation | Utilisation d'anticorps monoclonaux ou de ligands oligomeriques solubles pour la preparation d'un medicament pour le traitement de maladies neoplasiques |
| JPH09508009A (ja) | 1994-01-07 | 1997-08-19 | イミュネックス・コーポレーション | Ｆａｓ抗原を結合するリガンド |
| ES2251719T3 (es) | 1994-04-28 | 2006-05-01 | Boehringer Ingelheim Pharmaceuticals Inc. | Metodos para la proliferacion y diferenciacion de celulas b y su empleo. |
| US5606023A (en) | 1994-05-24 | 1997-02-25 | Thomas Jefferson University | Mutant tumor necrosis factor proteins |
| US5759536A (en) | 1994-05-27 | 1998-06-02 | University Technology Corporation | Use of fas ligand to supress T-lymphocyte-mediated immune responses |
| JPH09508140A (ja) | 1994-07-22 | 1997-08-19 | エフ・ホフマン−ラ ロシュ アーゲー | キメラｔｎｆ結合タンパク質を含有する医薬組成物 |
| GB9425060D0 (en) | 1994-12-13 | 1995-02-08 | Univ Birmingham | Carcinoma treatment |
| US5888764A (en) * | 1995-01-20 | 1999-03-30 | Uab Research Foundation | Human fas gene promoter region |
| US6017527A (en) * | 1996-07-10 | 2000-01-25 | Immunex Corporation | Activated dendritic cells and methods for their activation |
| US6544523B1 (en) | 1996-11-13 | 2003-04-08 | Chiron Corporation | Mutant forms of Fas ligand and uses thereof |
| US7070771B1 (en) * | 1996-12-09 | 2006-07-04 | Regents Of The University Of California | Methods of expressing chimeric mouse and human CD40 ligand in human CD40+ cells |
| US6016832A (en) * | 1997-04-16 | 2000-01-25 | Woodward Governor Company | Valve for controlling gas mass flow |
| CA2304130C (fr) | 1997-09-17 | 2008-10-28 | Mochida Pharmaceutical Co., Ltd. | Nouveau derive du ligand fas |
| US7786282B2 (en) * | 2001-12-06 | 2010-08-31 | The Regents Of The University Of California | Nucleic acid molecules encoding TNF-α ligand polypeptides having a CD154 domain |
| US7495090B2 (en) * | 2002-05-23 | 2009-02-24 | The Regents Of The University Of California | Nucleic acids encoding chimeric CD154 polypeptides |
| GB2392158B (en) * | 2002-08-21 | 2005-02-16 | Proimmune Ltd | Chimeric MHC protein and oligomer thereof |
-
1997
- 1997-12-01 US US08/982,272 patent/US7070771B1/en not_active Expired - Fee Related
- 1997-12-08 EP EP10184082A patent/EP2287309A1/fr not_active Withdrawn
- 1997-12-08 EP EP97954089A patent/EP0948614B1/fr not_active Expired - Lifetime
- 1997-12-08 WO PCT/US1997/022740 patent/WO1998026061A2/fr not_active Ceased
- 1997-12-08 PT PT97954089T patent/PT948614E/pt unknown
- 1997-12-08 NZ NZ336092A patent/NZ336092A/en not_active IP Right Cessation
- 1997-12-08 IL IL13024797A patent/IL130247A0/xx active IP Right Grant
- 1997-12-08 BR BR9714004-0A patent/BR9714004A/pt not_active IP Right Cessation
- 1997-12-08 AT AT09164341T patent/ATE547524T1/de active
- 1997-12-08 AT AT97954089T patent/ATE420956T1/de not_active IP Right Cessation
- 1997-12-08 EP EP09164341A patent/EP2145958B1/fr not_active Expired - Lifetime
- 1997-12-08 CA CA2274498A patent/CA2274498C/fr not_active Expired - Fee Related
- 1997-12-08 AU AU57957/98A patent/AU5795798A/en not_active Abandoned
- 1997-12-08 JP JP52695698A patent/JP4015201B2/ja not_active Expired - Fee Related
- 1997-12-08 EP EP06125424A patent/EP1806360A3/fr not_active Ceased
- 1997-12-08 CA CA2707726A patent/CA2707726C/fr not_active Expired - Fee Related
- 1997-12-08 DE DE69739220T patent/DE69739220D1/de not_active Expired - Lifetime
- 1997-12-08 ES ES97954089T patent/ES2321246T3/es not_active Expired - Lifetime
- 1997-12-08 CN CNB971816743A patent/CN1221662C/zh not_active Expired - Fee Related
- 1997-12-08 DK DK97954089T patent/DK0948614T3/da active
-
1999
- 1999-06-02 IL IL130247A patent/IL130247A/en not_active IP Right Cessation
- 1999-06-07 NO NO19992756A patent/NO327411B1/no not_active IP Right Cessation
-
2004
- 2004-12-17 US US11/015,117 patent/US7524944B2/en not_active Expired - Fee Related
-
2006
- 2006-09-26 IL IL178306A patent/IL178306A0/en not_active IP Right Cessation
-
2007
- 2007-09-27 NO NO20074906A patent/NO331434B1/no not_active IP Right Cessation
-
2009
- 2009-02-13 US US12/371,188 patent/US7906638B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7906638B2 (en) | Chimeric nucleic acids encoding polypeptides comprising CD70 and Fas ligand domains | |
| US20220233670A1 (en) | Induced activation in dendritic cells | |
| KR100689739B1 (ko) | 단백질 및 펩티드 항원의 면역원성을 증강시키는 Ｆｃ융합 단백질 | |
| CN100482283C (zh) | 新型嵌合cd154 | |
| KR102754876B1 (ko) | 재조합 mva 및 항체의 정맥내 투여에 의한 암 치료를 위한 병용 요법 | |
| JPH09503911A (ja) | ヒトｈ４−１ｂｂ受容体 | |
| WO1998026061A9 (fr) | Nouveaux vecteurs d'expression contenant des genes de ligands de molecules accessoires et leur emploi a des fins d'immunomodulation et de traitement des tumeurs malignes et des maladies autoimmunes | |
| Bot et al. | Immune response of neonates elicited by somatic transgene vaccination with naked DNA | |
| WO2019101062A9 (fr) | Vaccin recombiné et son application | |
| KR20060003903A (ko) | 사람 암배아 항원을 암호화하는 합성 유전자 및 이의 용도 | |
| Wu et al. | Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer | |
| JP2026506591A (ja) | 天然タンパク質ｔｓｈを抗原結合部位とした、ｔｓｈｒを標的とするｃａｒ－ｔ細胞の構築 | |
| HK1154886A (en) | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease | |
| HK1105209A (en) | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease | |
| HK1140230A (en) | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease | |
| AU781104B2 (en) | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease | |
| CN101260152A (zh) | 负调节Osteoprotegerin配体活性的方法 | |
| Class et al. | Patent application title: INDUCED ACTIVATION IN DENDRITIC CELLS Inventors: David Spencer (Houston, TX, US) David Spencer (Houston, TX, US) Brent Hanks (Houston, TX, US) Kevin Slawin (Houston, TX, US) | |
| CN114302739A (zh) | 用于治疗多形性胶质母细胞瘤的免疫治疗组合物 | |
| MXPA99005326A (en) | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |