AU5795798A - Novel expression vectors containing accessory molecule ligand genes and th eir use for immunomodulation and treatment of malignancies and autoimmu ne disease - Google Patents
Novel expression vectors containing accessory molecule ligand genes and th eir use for immunomodulation and treatment of malignancies and autoimmu ne diseaseInfo
- Publication number
- AU5795798A AU5795798A AU57957/98A AU5795798A AU5795798A AU 5795798 A AU5795798 A AU 5795798A AU 57957/98 A AU57957/98 A AU 57957/98A AU 5795798 A AU5795798 A AU 5795798A AU 5795798 A AU5795798 A AU 5795798A
- Authority
- AU
- Australia
- Prior art keywords
- gene
- ligand
- accessory molecule
- cells
- molecule ligand
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 547
- 239000003446 ligand Substances 0.000 title claims abstract description 493
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 81
- 238000011282 treatment Methods 0.000 title abstract description 32
- 230000036210 malignancy Effects 0.000 title abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 9
- 201000010099 disease Diseases 0.000 title abstract description 7
- 230000002519 immonomodulatory effect Effects 0.000 title abstract description 7
- 239000013604 expression vector Substances 0.000 title description 18
- 239000013598 vector Substances 0.000 claims abstract description 216
- 241000282414 Homo sapiens Species 0.000 claims abstract description 114
- 230000000694 effects Effects 0.000 claims abstract description 25
- 210000004027 cell Anatomy 0.000 claims description 459
- 238000000034 method Methods 0.000 claims description 149
- 108010029697 CD40 Ligand Proteins 0.000 claims description 136
- 238000001415 gene therapy Methods 0.000 claims description 122
- 241001529936 Murinae Species 0.000 claims description 117
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 claims description 90
- 102100032937 CD40 ligand Human genes 0.000 claims description 79
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 claims description 75
- 241001465754 Metazoa Species 0.000 claims description 65
- 230000002068 genetic effect Effects 0.000 claims description 63
- 210000005170 neoplastic cell Anatomy 0.000 claims description 54
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 45
- 210000005260 human cell Anatomy 0.000 claims description 42
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 claims description 41
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 claims description 39
- 239000000427 antigen Substances 0.000 claims description 39
- 102000036639 antigens Human genes 0.000 claims description 39
- 108091007433 antigens Proteins 0.000 claims description 39
- 241000701161 unidentified adenovirus Species 0.000 claims description 36
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 35
- 108020004414 DNA Proteins 0.000 claims description 30
- 230000009826 neoplastic cell growth Effects 0.000 claims description 27
- 230000028993 immune response Effects 0.000 claims description 25
- 230000001613 neoplastic effect Effects 0.000 claims description 24
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims description 22
- 241000700605 Viruses Species 0.000 claims description 20
- 210000004881 tumor cell Anatomy 0.000 claims description 16
- 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 claims description 15
- 101710097160 Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 claims description 15
- 102100025221 CD70 antigen Human genes 0.000 claims description 13
- 230000008488 polyadenylation Effects 0.000 claims description 13
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 10
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 10
- 241000894007 species Species 0.000 claims description 10
- 238000003776 cleavage reaction Methods 0.000 claims description 9
- 108700039691 Genetic Promoter Regions Proteins 0.000 claims description 8
- 210000004102 animal cell Anatomy 0.000 claims description 8
- 230000007017 scission Effects 0.000 claims description 8
- 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 claims description 7
- 230000008105 immune reaction Effects 0.000 claims description 7
- 108010017987 CD30 Ligand Proteins 0.000 claims description 6
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 6
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 6
- 230000002163 immunogen Effects 0.000 claims description 6
- 229940053128 nerve growth factor Drugs 0.000 claims description 6
- 241000894006 Bacteria Species 0.000 claims description 5
- 101100273745 Homo sapiens CD70 gene Proteins 0.000 claims description 5
- 229960005486 vaccine Drugs 0.000 claims description 5
- 241001430294 unidentified retrovirus Species 0.000 claims description 4
- 241000233866 Fungi Species 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 3
- 206010054094 Tumour necrosis Diseases 0.000 claims description 3
- 230000001580 bacterial effect Effects 0.000 claims description 3
- 230000002463 transducing effect Effects 0.000 claims 3
- 108010046080 CD27 Ligand Proteins 0.000 claims 1
- 108700005078 Synthetic Genes Proteins 0.000 claims 1
- 108020005202 Viral DNA Proteins 0.000 claims 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 20
- 238000002255 vaccination Methods 0.000 abstract description 18
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 7
- 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 175
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 158
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 155
- 230000014509 gene expression Effects 0.000 description 87
- 239000002773 nucleotide Substances 0.000 description 62
- 125000003729 nucleotide group Chemical group 0.000 description 62
- 241000699670 Mus sp. Species 0.000 description 61
- 210000003719 b-lymphocyte Anatomy 0.000 description 60
- 210000001744 T-lymphocyte Anatomy 0.000 description 59
- 108020004707 nucleic acids Proteins 0.000 description 46
- 102000039446 nucleic acids Human genes 0.000 description 46
- 150000007523 nucleic acids Chemical class 0.000 description 46
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 44
- 101150013553 CD40 gene Proteins 0.000 description 41
- 230000000735 allogeneic effect Effects 0.000 description 35
- 238000002347 injection Methods 0.000 description 34
- 239000007924 injection Substances 0.000 description 34
- 208000032839 leukemia Diseases 0.000 description 31
- 210000000987 immune system Anatomy 0.000 description 27
- 206010003246 arthritis Diseases 0.000 description 26
- 230000006870 function Effects 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 25
- 150000001413 amino acids Chemical class 0.000 description 25
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 24
- 102000008070 Interferon-gamma Human genes 0.000 description 24
- 108010074328 Interferon-gamma Proteins 0.000 description 24
- 239000013612 plasmid Substances 0.000 description 24
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 23
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 23
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 23
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 22
- 241000699666 Mus <mouse, genus> Species 0.000 description 22
- 229960003130 interferon gamma Drugs 0.000 description 20
- 230000003211 malignant effect Effects 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- 239000012636 effector Substances 0.000 description 15
- 208000015181 infectious disease Diseases 0.000 description 15
- 125000003275 alpha amino acid group Chemical group 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 14
- 238000010790 dilution Methods 0.000 description 14
- 239000012895 dilution Substances 0.000 description 14
- 230000001965 increasing effect Effects 0.000 description 14
- 210000004698 lymphocyte Anatomy 0.000 description 14
- 238000002965 ELISA Methods 0.000 description 13
- 108010005774 beta-Galactosidase Proteins 0.000 description 13
- 230000006907 apoptotic process Effects 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 230000003612 virological effect Effects 0.000 description 12
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 11
- 101150064015 FAS gene Proteins 0.000 description 11
- 101100059511 Homo sapiens CD40LG gene Proteins 0.000 description 11
- 101000868216 Mus musculus CD40 ligand Proteins 0.000 description 11
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 210000004988 splenocyte Anatomy 0.000 description 11
- 238000010186 staining Methods 0.000 description 11
- 230000004936 stimulating effect Effects 0.000 description 11
- 230000000638 stimulation Effects 0.000 description 11
- 238000011725 BALB/c mouse Methods 0.000 description 10
- 102100027207 CD27 antigen Human genes 0.000 description 10
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 10
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 10
- 206010025323 Lymphomas Diseases 0.000 description 10
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 10
- 230000000981 bystander Effects 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000002299 complementary DNA Substances 0.000 description 10
- 210000001503 joint Anatomy 0.000 description 10
- 208000020816 lung neoplasm Diseases 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 238000012353 t test Methods 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 9
- 102000053826 human CD70 Human genes 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 238000000692 Student's t-test Methods 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 210000002437 synoviocyte Anatomy 0.000 description 8
- 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 7
- 230000004913 activation Effects 0.000 description 7
- 230000005875 antibody response Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000001086 cytosolic effect Effects 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 210000002950 fibroblast Anatomy 0.000 description 7
- 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 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000006228 supernatant Substances 0.000 description 7
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 6
- 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
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 6
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 6
- 230000005867 T cell response Effects 0.000 description 6
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 6
- 230000003416 augmentation 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
- 230000003053 immunization Effects 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- 238000010348 incorporation Methods 0.000 description 6
- 210000001911 interdigitating cell Anatomy 0.000 description 6
- 210000001865 kupffer cell Anatomy 0.000 description 6
- 210000001821 langerhans cell Anatomy 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 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 5
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 description 5
- 108091008874 T cell receptors Proteins 0.000 description 5
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 102000005936 beta-Galactosidase Human genes 0.000 description 5
- 201000010902 chronic myelomonocytic leukemia Diseases 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
- 230000006698 induction Effects 0.000 description 5
- 238000010255 intramuscular injection Methods 0.000 description 5
- 239000007927 intramuscular injection Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 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 5
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 210000001179 synovial fluid Anatomy 0.000 description 5
- 229940104230 thymidine Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 108010002350 Interleukin-2 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
- 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
- -1 TNFα Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 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 4
- 210000000481 breast Anatomy 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 238000003501 co-culture 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
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000037841 lung tumor Diseases 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 210000005087 mononuclear cell Anatomy 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002829 reductive effect Effects 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
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 108010082808 4-1BB Ligand Proteins 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
- 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
- 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
- 241000701024 Human betaherpesvirus 5 Species 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
- 206010033128 Ovarian cancer Diseases 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
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000012228 culture supernatant Substances 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
- 239000007850 fluorescent dye Substances 0.000 description 3
- 201000003444 follicular lymphoma Diseases 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000002962 histologic effect Effects 0.000 description 3
- 230000036039 immunity 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
- 210000004072 lung Anatomy 0.000 description 3
- 238000013507 mapping Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229960004857 mitomycin Drugs 0.000 description 3
- 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 102000013415 peroxidase activity proteins Human genes 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 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
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000013207 serial dilution Methods 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 210000001258 synovial membrane Anatomy 0.000 description 3
- 208000037816 tissue injury Diseases 0.000 description 3
- 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
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000000503 Collagen Type II Human genes 0.000 description 2
- 108010041390 Collagen Type II Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 102100033215 DNA nucleotidylexotransferase Human genes 0.000 description 2
- 108010008286 DNA nucleotidylexotransferase Proteins 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
- 238000012286 ELISA Assay Methods 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 108010093031 Galactosidases Proteins 0.000 description 2
- 102000002464 Galactosidases Human genes 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 2
- 241000282412 Homo 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
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- 101000638255 Homo sapiens Tumor necrosis factor ligand superfamily member 8 Proteins 0.000 description 2
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 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
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 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
- 108010076504 Protein Sorting Signals Proteins 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
- 238000013459 approach Methods 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 230000015572 biosynthetic process 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
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229920001436 collagen Polymers 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
- 230000002950 deficient Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 102000055229 human IL4 Human genes 0.000 description 2
- 102000057041 human TNF Human genes 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 210000004201 immune sera Anatomy 0.000 description 2
- 229940042743 immune sera Drugs 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 150000002540 isothiocyanates Chemical class 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 201000009546 lung large cell carcinoma Diseases 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 235000020030 perry Nutrition 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000036647 reaction Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000035939 shock Effects 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
- 230000008961 swelling Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 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 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-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
- 238000010600 3H thymidine incorporation assay Methods 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
- 101100401100 Caenorhabditis elegans mes-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 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
- 241000699800 Cricetinae Species 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 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
- 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
- 101100207070 Homo sapiens TNFSF8 gene Proteins 0.000 description 1
- 101000830565 Homo sapiens Tumor necrosis factor ligand superfamily member 10 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 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
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- 108010052285 Membrane Proteins 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
- 101100207071 Mus musculus Tnfsf8 gene Proteins 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
- 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
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 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
- 238000012288 TUNEL assay Methods 0.000 description 1
- 239000007983 Tris buffer Substances 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
- 230000001154 acute effect Effects 0.000 description 1
- 230000002730 additional 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
- 210000003423 ankle Anatomy 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 230000003190 augmentative effect 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
- 244000309464 bull Species 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 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
- 230000002860 competitive effect Effects 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 230000000139 costimulatory effect Effects 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
- 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
- 239000010432 diamond Substances 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 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 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
- 230000002708 enhancing effect Effects 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
- 238000013213 extrapolation Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 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 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
- 102000043557 human IFNG Human genes 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
- 230000037451 immune surveillance Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001771 impaired 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
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 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
- 210000000629 knee joint Anatomy 0.000 description 1
- 238000002372 labelling Methods 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
- 210000003141 lower extremity Anatomy 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
- 201000001268 lymphoproliferative syndrome Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 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
- 229930182817 methionine Natural products 0.000 description 1
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 1
- 229960002455 methoxyflurane Drugs 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
- 238000012544 monitoring process 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
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical 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
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000000424 optical density measurement Methods 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000037361 pathway Effects 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
- 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
- 238000012342 propidium iodide staining Methods 0.000 description 1
- 235000019419 proteases Nutrition 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
- 230000009467 reduction Effects 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
- 210000003705 ribosome Anatomy 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
- 238000001370 static light scattering Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003860 storage 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
- 230000008093 supporting effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 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
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 230000005030 transcription termination 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
- 230000001131 transforming effect 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
- 239000013603 viral vector Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 210000000707 wrist Anatomy 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU24608/02A AU781104B2 (en) | 1996-12-09 | 2002-03-15 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3214596P | 1996-12-09 | 1996-12-09 | |
| US60032145 | 1996-12-09 | ||
| US08982272 | 1997-12-01 | ||
| 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 (en) | 1996-12-09 | 1997-12-08 | Expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU24608/02A Division AU781104B2 (en) | 1996-12-09 | 2002-03-15 | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU5795798A true AU5795798A (en) | 1998-07-03 |
Family
ID=26708033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU57957/98A Abandoned AU5795798A (en) | 1996-12-09 | 1997-12-08 | Novel expression vectors containing accessory molecule ligand genes and th eir use for immunomodulation and treatment of malignancies and autoimmu ne disease |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US7070771B1 (enExample) |
| EP (4) | EP0948614B1 (enExample) |
| JP (1) | JP4015201B2 (enExample) |
| CN (1) | CN1221662C (enExample) |
| AT (2) | ATE420956T1 (enExample) |
| AU (1) | AU5795798A (enExample) |
| BR (1) | BR9714004A (enExample) |
| CA (2) | CA2274498C (enExample) |
| DE (1) | DE69739220D1 (enExample) |
| DK (1) | DK0948614T3 (enExample) |
| ES (1) | ES2321246T3 (enExample) |
| IL (3) | IL130247A0 (enExample) |
| NO (2) | NO327411B1 (enExample) |
| NZ (1) | NZ336092A (enExample) |
| PT (1) | PT948614E (enExample) |
| WO (1) | WO1998026061A2 (enExample) |
Families Citing this family (28)
| 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 (en) * | 1999-04-16 | 2000-10-26 | F. Hoffmann-La Roche Ag | Nucleic acids encoding cd40/cd40l chimeric polypeptides, methods for their production and uses thereof |
| 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 |
| 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 |
| US20130266551A1 (en) | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
| US20080044393A1 (en) * | 2004-07-16 | 2008-02-21 | White Robert L | Retinal dystrophin transgene and methods of use thereof |
| WO2008109825A2 (en) * | 2007-03-08 | 2008-09-12 | Mayo Foundation For Medical Education And Research | Inducing immune-mediated tumor cell death |
| US20100050276A1 (en) * | 2008-08-22 | 2010-02-25 | Brown University | Transgenic non-human animal models of apoptosis-mediated conditions |
| EP2788021B1 (en) | 2011-12-09 | 2017-01-18 | Bavarian Nordic A/S | Poxvirus vector for the expression of bacterial antigens linked to tetanus toxin fragment c |
| SI2908865T1 (sl) * | 2012-10-17 | 2019-02-28 | Vascular Biogenics Ltd. | Adenovirus, ki izraža Fas himero in uporaba le-tega v postopkih zdravljenja raka |
| WO2015148879A1 (en) * | 2014-03-27 | 2015-10-01 | The Regents Of The University Of Michigan | Cancer immunotherapy compositions and methods |
| EP3805371A1 (en) | 2014-05-15 | 2021-04-14 | 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 |
| WO2017079297A1 (en) | 2015-11-02 | 2017-05-11 | Memgen Llc | Methods for treatment of cancer |
| US11298420B2 (en) | 2016-12-21 | 2022-04-12 | Memgen, Llc | Armed oncolytic viruses |
| IL269553B2 (en) | 2017-03-27 | 2025-10-01 | Nat Univ Singapore | Truncated NKG2D chimeric receptors and their uses in immunotherapy with natural killer cells |
| WO2018191369A1 (en) | 2017-04-12 | 2018-10-18 | Memgen, Llc | Methods of cd40 and toll like receptor immune activation |
| US12258381B2 (en) | 2018-02-09 | 2025-03-25 | 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 (en) | 2018-08-29 | 2022-08-17 | National University of Singapore | METHOD OF SPECIFIC STIMULATION OF SURVIVAL AND EXPANSION OF GENETICALLY MODIFIED IMMUNE CELLS |
| KR20210137085A (ko) | 2019-03-05 | 2021-11-17 | 엔카르타, 인크. | Cd19 유도된 키메라 항원 수용체 및 면역 요법에서 이의 용도 |
| 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 |
|---|---|---|---|---|
| EP0251037B1 (en) | 1986-06-20 | 1994-06-15 | Dainippon Pharmaceutical Co., Ltd. | Novel human TNF polypeptide mutants and DNAs encoding said mutants |
| EP0317641B1 (en) | 1987-05-29 | 1993-03-17 | Sagami Chemical Research Center | Fused protein containing lymphotoxin |
| WO1991002540A1 (en) | 1989-08-16 | 1991-03-07 | Cetus Corporation | Compositions for the inhibition of protein hormone formation and uses thereof |
| US5519119A (en) | 1990-09-21 | 1996-05-21 | Ishihara Sangyo Kaisha Ltd. | Muteins of TNF pharmaceutical compositions and a method of making |
| CA2055168A1 (en) | 1990-11-21 | 1992-05-22 | Walter Fiers | Tnf-muteins |
| WO1993008207A1 (en) | 1991-10-25 | 1993-04-29 | Immunex Corporation | Novel cytokine |
| DE69333027T2 (de) | 1992-03-30 | 2004-05-06 | Immunex Corp., Seattle | Fusionsprotein , das zwei rezeptoren des tumornekrose-faktors enthält |
| CZ283533B6 (cs) | 1992-04-02 | 1998-04-15 | F. Hoffmann-La Roche Ag | TNF - muteiny a způsob jejich výroby |
| DK0615451T3 (da) | 1992-05-26 | 2006-04-24 | Immunex Corp | Hidtil ukendt cytokin der binder til CD30 |
| EP0656947A1 (en) | 1992-08-21 | 1995-06-14 | Schering Corporation | Human interleukin-13 |
| WO1994004570A1 (en) | 1992-08-21 | 1994-03-03 | Schering Corporation | Cd40 ligand, anti cd40 antibodies, and soluble cd40 |
| 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 |
| DE69433399T2 (de) | 1993-01-22 | 2004-10-14 | Immunex Corp., Seattle | Detektion und behandlung von mutationen in einem gen für einen cd40-liganden |
| JP4242447B2 (ja) | 1993-01-22 | 2009-03-25 | イミュネックス・コーポレーション | Ｃｄ４０リガンド遺伝子の突然変異の検出および治療 |
| 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 |
| DE69433820T2 (de) | 1993-12-23 | 2005-06-23 | Immunex Corp., Seattle | Verwendung von löslichen oligomerischen cd40 liganden oder monoklonalen antikörpern zur herstellung eines arzneimitells zur vorbeugung oder behandlung von neoplastischen krankheiten |
| WO1995018819A1 (en) | 1994-01-07 | 1995-07-13 | Immunex Corporation | Ligand that binds fas antigen |
| MX9605088A (es) | 1994-04-28 | 1997-08-30 | Boehringer Ingelheim Pharma | Metodos para proliferar y diferenciar celulas b y sus usos. |
| 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 |
| DE69841548D1 (de) | 1997-09-17 | 2010-04-22 | Mochida Pharm Co Ltd | Fas-liganden derivate |
| 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 EP97954089A patent/EP0948614B1/en not_active Expired - Lifetime
- 1997-12-08 ES ES97954089T patent/ES2321246T3/es not_active Expired - Lifetime
- 1997-12-08 JP JP52695698A patent/JP4015201B2/ja not_active Expired - Fee Related
- 1997-12-08 CA CA2274498A patent/CA2274498C/en not_active Expired - Fee Related
- 1997-12-08 BR BR9714004-0A patent/BR9714004A/pt not_active IP Right Cessation
- 1997-12-08 AU AU57957/98A patent/AU5795798A/en not_active Abandoned
- 1997-12-08 DK DK97954089T patent/DK0948614T3/da active
- 1997-12-08 NZ NZ336092A patent/NZ336092A/en not_active IP Right Cessation
- 1997-12-08 WO PCT/US1997/022740 patent/WO1998026061A2/en not_active Ceased
- 1997-12-08 IL IL13024797A patent/IL130247A0/xx active IP Right Grant
- 1997-12-08 EP EP09164341A patent/EP2145958B1/en not_active Expired - Lifetime
- 1997-12-08 EP EP06125424A patent/EP1806360A3/en not_active Ceased
- 1997-12-08 DE DE69739220T patent/DE69739220D1/de not_active Expired - Lifetime
- 1997-12-08 EP EP10184082A patent/EP2287309A1/en not_active Withdrawn
- 1997-12-08 CN CNB971816743A patent/CN1221662C/zh not_active Expired - Fee Related
- 1997-12-08 AT AT97954089T patent/ATE420956T1/de not_active IP Right Cessation
- 1997-12-08 PT PT97954089T patent/PT948614E/pt unknown
- 1997-12-08 AT AT09164341T patent/ATE547524T1/de active
- 1997-12-08 CA CA2707726A patent/CA2707726C/en not_active Expired - Fee Related
-
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 |
|---|---|---|
| AU5795798A (en) | Novel expression vectors containing accessory molecule ligand genes and th eir use for immunomodulation and treatment of malignancies and autoimmu ne disease | |
| WO1998026061A9 (en) | Expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease | |
| CA2486918C (en) | Novel chimeric cd154 | |
| ES2341631T3 (es) | Receptor humano h4-1bb. | |
| US7964712B2 (en) | Chimeric nucleic acids encoding polypeptides comprising TNF alpha, CD70 and FAS ligand domains | |
| AU781104B2 (en) | Novel expression vectors containing accessory molecule ligand genes and their use for immunomodulation and treatment of malignancies and autoimmune disease | |
| US20030082157A1 (en) | Receptor and related products and methods | |
| MXPA99005326A (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 | |
| 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 | |
| HK1076711B (en) | Chimeric cd154 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |