JP5442452B2 - 単純ヘルペスウイルスおよびウイルス複製法 - Google Patents
単純ヘルペスウイルスおよびウイルス複製法 Download PDFInfo
- Publication number
- JP5442452B2 JP5442452B2 JP2009549472A JP2009549472A JP5442452B2 JP 5442452 B2 JP5442452 B2 JP 5442452B2 JP 2009549472 A JP2009549472 A JP 2009549472A JP 2009549472 A JP2009549472 A JP 2009549472A JP 5442452 B2 JP5442452 B2 JP 5442452B2
- Authority
- JP
- Japan
- Prior art keywords
- herpes simplex
- simplex virus
- ing4
- hsv
- cells
- 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.)
- Expired - Fee Related
Links
- 241000700584 Simplexvirus Species 0.000 title claims description 209
- 230000029812 viral genome replication Effects 0.000 title description 10
- 210000004027 cell Anatomy 0.000 claims description 229
- 101001001418 Homo sapiens Inhibitor of growth protein 4 Proteins 0.000 claims description 182
- 102100035677 Inhibitor of growth protein 4 Human genes 0.000 claims description 177
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 106
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 104
- 229920001184 polypeptide Polymers 0.000 claims description 103
- 206010028980 Neoplasm Diseases 0.000 claims description 88
- 150000007523 nucleic acids Chemical group 0.000 claims description 70
- 230000010076 replication Effects 0.000 claims description 56
- 108020004707 nucleic acids Proteins 0.000 claims description 41
- 102000039446 nucleic acids Human genes 0.000 claims description 41
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 24
- 238000000338 in vitro Methods 0.000 claims description 23
- 239000002773 nucleotide Substances 0.000 claims description 23
- 125000003729 nucleotide group Chemical group 0.000 claims description 23
- 210000004881 tumor cell Anatomy 0.000 claims description 22
- 101150027249 RL1 gene Proteins 0.000 claims description 21
- 101150076998 ICP34.5 gene Proteins 0.000 claims description 20
- 101100508081 Human herpesvirus 1 (strain 17) ICP34.5 gene Proteins 0.000 claims description 19
- 231100000501 nonneurotoxic Toxicity 0.000 claims description 17
- 238000001727 in vivo Methods 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000003362 replicative effect Effects 0.000 claims description 6
- 230000003612 virological effect Effects 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 230000000174 oncolytic effect Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 238000013518 transcription Methods 0.000 claims description 5
- 230000035897 transcription Effects 0.000 claims description 5
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 229960005486 vaccine Drugs 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 2
- 208000009889 Herpes Simplex Diseases 0.000 claims 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 74
- 241000700605 Viruses Species 0.000 description 65
- 210000002845 virion Anatomy 0.000 description 60
- 241000699670 Mus sp. Species 0.000 description 40
- 230000014509 gene expression Effects 0.000 description 38
- 108090000623 proteins and genes Proteins 0.000 description 31
- 230000004083 survival effect Effects 0.000 description 29
- 208000015181 infectious disease Diseases 0.000 description 27
- 206010061535 Ovarian neoplasm Diseases 0.000 description 24
- 239000013598 vector Substances 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 239000012634 fragment Substances 0.000 description 16
- 230000012010 growth Effects 0.000 description 15
- 108020004414 DNA Proteins 0.000 description 14
- 206010033128 Ovarian cancer Diseases 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 230000001772 anti-angiogenic effect Effects 0.000 description 14
- 238000009396 hybridization Methods 0.000 description 14
- 230000035772 mutation Effects 0.000 description 14
- 238000007920 subcutaneous administration Methods 0.000 description 14
- 238000003780 insertion Methods 0.000 description 13
- 230000037431 insertion Effects 0.000 description 13
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 12
- 239000007943 implant Substances 0.000 description 12
- 206010006187 Breast cancer Diseases 0.000 description 11
- 238000000540 analysis of variance Methods 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 241000700589 Herpes simplex virus (type 1 / strain 17) Species 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 9
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 230000004614 tumor growth Effects 0.000 description 9
- 238000000692 Student's t-test Methods 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 210000003501 vero cell Anatomy 0.000 description 8
- 201000008274 breast adenocarcinoma Diseases 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 241000700328 Herpes simplex virus (type 1 / strain F) Species 0.000 description 6
- 108010084455 Zeocin Proteins 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 230000037430 deletion Effects 0.000 description 6
- 230000002601 intratumoral effect Effects 0.000 description 6
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 206010018338 Glioma Diseases 0.000 description 5
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 5
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 5
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 230000006801 homologous recombination Effects 0.000 description 5
- 238000002744 homologous recombination Methods 0.000 description 5
- 102000044392 human ING4 Human genes 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 208000032612 Glial tumor Diseases 0.000 description 4
- 238000012404 In vitro experiment Methods 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000003966 growth inhibitor Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 230000009826 neoplastic cell growth Effects 0.000 description 3
- 244000309459 oncolytic virus Species 0.000 description 3
- 210000001428 peripheral nervous system Anatomy 0.000 description 3
- 210000002826 placenta Anatomy 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102100021489 Histone H4-like protein type G Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 2
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 102000004459 Nitroreductase Human genes 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 108020001162 nitroreductase Proteins 0.000 description 2
- 231100001096 no neurotoxicity Toxicity 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 230000005909 tumor killing Effects 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100033552 All trans-polyprenyl-diphosphate synthase PDSS2 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- -1 BC007781 Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 241001550206 Colla Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 101100364969 Dictyostelium discoideum scai gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102100033068 Histone acetyltransferase KAT7 Human genes 0.000 description 1
- 101000872070 Homo sapiens All trans-polyprenyl-diphosphate synthase PDSS2 Proteins 0.000 description 1
- 101000944166 Homo sapiens Histone acetyltransferase KAT7 Proteins 0.000 description 1
- 101100195053 Human herpesvirus 1 (strain 17) RIR1 gene Proteins 0.000 description 1
- 241000701072 Human herpesvirus 2 strain HG52 Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 101150090364 ICP0 gene Proteins 0.000 description 1
- 101150027427 ICP4 gene Proteins 0.000 description 1
- 101150035419 ING4 gene Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000289581 Macropus sp. Species 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100233089 Mus musculus Ing4 gene Proteins 0.000 description 1
- 101100364971 Mus musculus Scai gene Proteins 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 101150000187 PTGS2 gene Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 1
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000021995 interleukin-8 production Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 101710130522 mRNA export factor Proteins 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000009020 malignant peripheral nerve sheath tumor Diseases 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 206010061311 nervous system neoplasm Diseases 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000029974 neurofibrosarcoma Diseases 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000005257 nucleotidylation Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/245—Herpetoviridae, e.g. herpes simplex virus
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/869—Herpesviral vectors
- C12N15/8695—Herpes simplex virus-based vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/13—Tumour cells, irrespective of tissue of origin
-
- 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
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
- C12N2710/16641—Use of virus, viral particle or viral elements as a vector
- C12N2710/16643—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- 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
- C12N2799/028—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a herpesvirus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0703066.1 | 2007-02-16 | ||
| GB0703066A GB0703066D0 (en) | 2007-02-16 | 2007-02-16 | Viruses |
| US91686207P | 2007-05-09 | 2007-05-09 | |
| US60/916,862 | 2007-05-09 | ||
| PCT/GB2008/000527 WO2008099189A2 (en) | 2007-02-16 | 2008-02-15 | Herpes simplex viruses and methods of viral replication |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010518816A JP2010518816A (ja) | 2010-06-03 |
| JP2010518816A5 JP2010518816A5 (enExample) | 2011-04-07 |
| JP5442452B2 true JP5442452B2 (ja) | 2014-03-12 |
Family
ID=39271813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009549472A Expired - Fee Related JP5442452B2 (ja) | 2007-02-16 | 2008-02-15 | 単純ヘルペスウイルスおよびウイルス複製法 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US8163292B2 (enExample) |
| EP (1) | EP2114420B1 (enExample) |
| JP (1) | JP5442452B2 (enExample) |
| GB (1) | GB2446721B (enExample) |
| WO (1) | WO2008099189A2 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9415320D0 (en) | 1994-07-29 | 1994-09-21 | Medical Res Council | Cancer treatment |
| US7897146B2 (en) | 2003-11-17 | 2011-03-01 | Crusade Laboratories Limited | Treatment using herpes simplex virus |
| WO2005049846A2 (en) | 2003-11-17 | 2005-06-02 | Crusade Laboratories Limited | Mutant herpes simplex virus and use thereof in the treatment of squamous cell cancer |
| JP5442452B2 (ja) * | 2007-02-16 | 2014-03-12 | ウイルツ・バイオロジクス・リミテッド | 単純ヘルペスウイルスおよびウイルス複製法 |
| EP2764119A2 (en) | 2011-10-05 | 2014-08-13 | Genelux Corporation | Method for detecting replication or colonization of a biological therapeutic |
| US20140087362A1 (en) | 2012-03-16 | 2014-03-27 | Aladar A. Szalay | Methods for assessing effectiveness and monitoring oncolytic virus treatment |
| WO2013158265A1 (en) | 2012-04-20 | 2013-10-24 | Genelux Corporation | Imaging methods for oncolytic virus therapy |
| EP2662117A1 (en) * | 2012-05-11 | 2013-11-13 | Virttu Biologics Limited | Herpes Simplex Virus for the treatment of liver cancer |
| US20140140959A1 (en) | 2012-10-05 | 2014-05-22 | Aladar A. Szalay | Energy Absorbing-Based Diagnostic and Therapeutic Methods Employing Nucleic Acid Molecules Encoding Chromophore-Producing Enzymes |
| US10238700B2 (en) | 2014-01-02 | 2019-03-26 | Genelux Corporation | Oncolytic virus adjunct therapy with agents that increase virus infectivity |
| JP6625627B2 (ja) | 2014-10-14 | 2019-12-25 | ハロザイム インコーポレイテッド | アデノシンデアミナーゼ−２（ａｄａ２）、その変異体の組成物およびそれを使用する方法 |
| CA3019199A1 (en) | 2016-04-15 | 2017-10-19 | Alpine Immune Sciences, Inc. | Icos ligand variant immunomodulatory proteins and uses thereof |
| AU2017248830B2 (en) | 2016-04-15 | 2023-03-09 | Alpine Immune Sciences, Inc. | CD80 variant immunomodulatory proteins and uses thereof |
| US11834490B2 (en) | 2016-07-28 | 2023-12-05 | Alpine Immune Sciences, Inc. | CD112 variant immunomodulatory proteins and uses thereof |
| EP3491013A1 (en) | 2016-07-28 | 2019-06-05 | Alpine Immune Sciences, Inc. | Cd155 variant immunomodulatory proteins and uses thereof |
| US11471488B2 (en) | 2016-07-28 | 2022-10-18 | Alpine Immune Sciences, Inc. | CD155 variant immunomodulatory proteins and uses thereof |
| AU2017345764A1 (en) | 2016-10-20 | 2019-05-02 | Alpine Immune Sciences, Inc. | Secretable variant immunomodulatory proteins and engineered cell therapy |
| CA3052473A1 (en) | 2017-02-09 | 2018-08-16 | Indapta Therapeutics, Inc. | Engineered natural killer (nk) cells and compositions and methods thereof |
| IL320149A (en) | 2017-03-16 | 2025-06-01 | Alpine Immune Sciences Inc | Pd-l1 variant immunomodulatory proteins and uses thereof |
| CA3053812A1 (en) | 2017-03-16 | 2018-09-20 | Alpine Immune Sciences, Inc. | Pd-l2 variant immunomodulatory proteins and uses thereof |
| IL319966A (en) | 2017-03-16 | 2025-05-01 | Alpine Immune Sciences Inc | CD80 Variant Immune Modulator Proteins and Uses Thereof |
| TW202500579A (zh) | 2017-10-18 | 2025-01-01 | 美商艾爾潘免疫科學有限公司 | 變異型icos 配位體免疫調節蛋白及相關組合物及方法 |
| US12297253B2 (en) | 2018-01-03 | 2025-05-13 | Alpine Immune Sciences, Inc. | Multi-domain immunomodulatory proteins and methods of use thereof |
| US11505782B2 (en) | 2018-06-04 | 2022-11-22 | Calidi Biotherapeutics, Inc. | Cell-based vehicles for potentiation of viral therapy |
| ES2966045T3 (es) | 2018-06-04 | 2024-04-18 | Calidi Biotherapeutics Inc | Vehículos basados en células para la potenciación de la terapia viral |
| WO2019241758A1 (en) | 2018-06-15 | 2019-12-19 | Alpine Immune Sciences, Inc. | Pd-1 variant immunomodulatory proteins and uses thereof |
| US11242528B2 (en) | 2018-08-28 | 2022-02-08 | Actym Therapeutics, Inc. | Engineered immunostimulatory bacterial strains and uses thereof |
| CA3116192C (en) | 2018-11-06 | 2025-09-23 | Calidi Biotherapeutics (Nevada), Inc. | IMPROVED SYSTEMS FOR CELL-MEDIATED ONCOLYTIC VIRAL THERAPY |
| EP3884041A2 (en) | 2018-11-21 | 2021-09-29 | Indapta Therapeutics, Inc. | Methods for expansion of natural killer (nk) cell subset and related compositions and methods |
| WO2020113141A2 (en) | 2018-11-30 | 2020-06-04 | Alpine Immune Sciences, Inc. | Cd86 variant immunomodulatory proteins and uses thereof |
| US12024709B2 (en) | 2019-02-27 | 2024-07-02 | Actym Therapeutics, Inc. | Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment |
| MX2021010273A (es) | 2019-02-27 | 2021-09-23 | Actym Therapeutics Inc | Bacterias inmunoestimuladoras modificadas para colonizar tumores, celulas inmunitarias residentes de tumor y el microentorno tumoral. |
| US20230118087A1 (en) * | 2019-09-03 | 2023-04-20 | Krystal Biotech, Inc. | Compositions and methods for the treatment of congenital ichthyoses |
| JP2023523429A (ja) | 2020-04-22 | 2023-06-05 | インダプタ セラピューティクス インコーポレイテッド | ナチュラルキラー（ｎｋ）細胞組成物およびそれを生成させるための方法 |
| WO2022147481A1 (en) | 2020-12-30 | 2022-07-07 | Ansun Biopharma Inc. | Combination therapy of an oncolytic virus delivering a foreign antigen and an engineered immune cell expressing a chimeric receptor targeting the foreign antigen |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000023589A2 (en) * | 1998-10-20 | 2000-04-27 | Incyte Pharmaceuticals, Inc. | Proliferation and apoptosis related proteins |
| CN1183250C (zh) * | 2000-12-01 | 2005-01-05 | 卫健生物科技有限公司 | 高效表达肿瘤血管生成抑制因子的肿瘤细胞内特异性增殖的病毒及其构建方法 |
| GB0317511D0 (en) * | 2003-07-25 | 2003-08-27 | Biovex Ltd | Viral vectors |
| GB0326798D0 (en) | 2003-11-17 | 2003-12-24 | Crusade Lab Ltd | Methods for generating mutant virus |
| WO2005049846A2 (en) * | 2003-11-17 | 2005-06-02 | Crusade Laboratories Limited | Mutant herpes simplex virus and use thereof in the treatment of squamous cell cancer |
| CN1714871A (zh) * | 2004-06-29 | 2006-01-04 | 上海人类基因组研究中心 | 人类ing4基因作为化疗药物增敏剂的用途 |
| JP5442452B2 (ja) * | 2007-02-16 | 2014-03-12 | ウイルツ・バイオロジクス・リミテッド | 単純ヘルペスウイルスおよびウイルス複製法 |
| CN101058809B (zh) * | 2007-04-02 | 2010-09-08 | 苏州大学 | 人源化改造的鼠ing4基因及其腺病毒表达载体在制备治疗肺癌的药物中的应用 |
-
2008
- 2008-02-15 JP JP2009549472A patent/JP5442452B2/ja not_active Expired - Fee Related
- 2008-02-15 US US12/527,380 patent/US8163292B2/en not_active Expired - Fee Related
- 2008-02-15 GB GB0802868A patent/GB2446721B/en not_active Expired - Fee Related
- 2008-02-15 EP EP08709418.1A patent/EP2114420B1/en not_active Not-in-force
- 2008-02-15 WO PCT/GB2008/000527 patent/WO2008099189A2/en not_active Ceased
-
2012
- 2012-03-12 US US13/417,708 patent/US8969063B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US8163292B2 (en) | 2012-04-24 |
| WO2008099189A3 (en) | 2009-01-15 |
| JP2010518816A (ja) | 2010-06-03 |
| EP2114420B1 (en) | 2016-01-27 |
| GB2446721A (en) | 2008-08-20 |
| WO2008099189A2 (en) | 2008-08-21 |
| US20100092515A1 (en) | 2010-04-15 |
| GB2446721B (en) | 2009-03-25 |
| US20120237999A1 (en) | 2012-09-20 |
| GB0802868D0 (en) | 2008-03-26 |
| US8969063B2 (en) | 2015-03-03 |
| EP2114420A2 (en) | 2009-11-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5442452B2 (ja) | 単純ヘルペスウイルスおよびウイルス複製法 | |
| JP7522088B2 (ja) | 単純ヘルペス１型および他の関連するヘルペスウイルスのｒｎａガイド除去 | |
| JP5284780B2 (ja) | 癌の治療のための単純ヘルペスウイルス２型変異体の使用 | |
| JP6375273B2 (ja) | 腫瘍選択的ｅ１ａおよびｅ１ｂ変異体 | |
| JP2024026075A (ja) | 改変ワクシニアベクター | |
| EP3291841B1 (en) | Oncolytic hsv1 vector and methods of use | |
| MXPA02002142A (es) | Promotor especifico de la celula y/o especifico del tumor, que re-selecciona como objetivo la expresion del gen gamma 35.5 de herpes. | |
| WO2020106566A1 (en) | Regulatable fusogenic oncolytic herpes simplex virus type 1 virus and methods of use | |
| JP2022531976A (ja) | 弱毒化黄熱ウイルス及びがんの処置のためのその使用 | |
| JP2024508088A (ja) | 全身送達及び抗腫瘍活性の向上のための腫瘍溶解性ウイルス | |
| CN116144607A (zh) | 一种溶瘤病毒及其应用 | |
| Saha et al. | Viral oncolysis of glioblastoma | |
| WO2022235905A2 (en) | Method of delivery of fusogenic oncolytic virus and therapeutic molecules | |
| HK40063431A (en) | Oncolytic hsv1 vector and methods of use | |
| TW202102677A (zh) | 經修飾腺病毒及含有其之醫藥 | |
| CN116782917A (zh) | 用于全身递送的溶瘤病毒及增强的抗肿瘤活性 | |
| Ad | 593. Recombinant Measles Viruses Encoding Suicide Genes for Oncolytic Therapy | |
| HK1251177B (en) | Oncolytic hsv1 vector and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110215 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110215 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120131 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121102 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130201 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130201 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130502 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130801 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130823 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131029 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131119 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131218 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5442452 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |