JP2011520993A - 間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 - Google Patents
間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 Download PDFInfo
- Publication number
- JP2011520993A JP2011520993A JP2011510787A JP2011510787A JP2011520993A JP 2011520993 A JP2011520993 A JP 2011520993A JP 2011510787 A JP2011510787 A JP 2011510787A JP 2011510787 A JP2011510787 A JP 2011510787A JP 2011520993 A JP2011520993 A JP 2011520993A
- Authority
- JP
- Japan
- Prior art keywords
- reovirus
- virus
- administered
- subject
- agent
- 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.)
- Pending
Links
- 244000309459 oncolytic virus Species 0.000 title claims abstract description 82
- 238000012384 transportation and delivery Methods 0.000 title abstract description 15
- 230000033228 biological regulation Effects 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 115
- 230000002062 proliferating effect Effects 0.000 claims abstract description 43
- 230000008728 vascular permeability Effects 0.000 claims abstract description 30
- 241000702263 Reovirus sp. Species 0.000 claims description 139
- 239000003795 chemical substances by application Substances 0.000 claims description 101
- 241000700605 Viruses Species 0.000 claims description 75
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- 108010002350 Interleukin-2 Proteins 0.000 claims description 40
- 102000000588 Interleukin-2 Human genes 0.000 claims description 40
- 108090000695 Cytokines Proteins 0.000 claims description 36
- 208000035475 disorder Diseases 0.000 claims description 36
- 230000035772 mutation Effects 0.000 claims description 36
- 102000004127 Cytokines Human genes 0.000 claims description 35
- 230000000770 proinflammatory effect Effects 0.000 claims description 33
- 241000282414 Homo sapiens Species 0.000 claims description 17
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 16
- 229930012538 Paclitaxel Natural products 0.000 claims description 14
- 229960001592 paclitaxel Drugs 0.000 claims description 14
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 14
- 229960004562 carboplatin Drugs 0.000 claims description 12
- 241000700618 Vaccinia virus Species 0.000 claims description 9
- 150000003058 platinum compounds Chemical class 0.000 claims description 9
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 8
- 229940123237 Taxane Drugs 0.000 claims description 8
- 229910001424 calcium ion Inorganic materials 0.000 claims description 8
- 230000007423 decrease Effects 0.000 claims description 8
- 238000012217 deletion Methods 0.000 claims description 8
- 230000037430 deletion Effects 0.000 claims description 8
- 230000037396 body weight Effects 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 241000710960 Sindbis virus Species 0.000 claims description 6
- 210000003722 extracellular fluid Anatomy 0.000 claims description 6
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 6
- 102000000589 Interleukin-1 Human genes 0.000 claims description 5
- 108010002352 Interleukin-1 Proteins 0.000 claims description 5
- 238000002428 photodynamic therapy Methods 0.000 claims description 5
- 241000711404 Avian avulavirus 1 Species 0.000 claims description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 4
- MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 claims description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 4
- 241000711975 Vesicular stomatitis virus Species 0.000 claims description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 4
- 108010093008 Kinins Proteins 0.000 claims description 3
- 102000002397 Kinins Human genes 0.000 claims description 3
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims description 3
- 101800004538 Bradykinin Proteins 0.000 claims description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 claims description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 claims description 2
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 claims description 2
- 208000007514 Herpes zoster Diseases 0.000 claims description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 2
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 claims description 2
- 241000712079 Measles morbillivirus Species 0.000 claims description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000006 Nitroglycerin Substances 0.000 claims description 2
- 102000001253 Protein Kinase Human genes 0.000 claims description 2
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 claims description 2
- 229960003668 docetaxel Drugs 0.000 claims description 2
- 206010014599 encephalitis Diseases 0.000 claims description 2
- 229960003711 glyceryl trinitrate Drugs 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 231100000283 hepatitis Toxicity 0.000 claims description 2
- 229960001340 histamine Drugs 0.000 claims description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 2
- 229960002411 imatinib Drugs 0.000 claims description 2
- 229950005692 larotaxel Drugs 0.000 claims description 2
- SEFGUGYLLVNFIJ-QDRLFVHASA-N larotaxel dihydrate Chemical compound O.O.O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@@]23[C@H]1[C@@]1(CO[C@@H]1C[C@@H]2C3)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 SEFGUGYLLVNFIJ-QDRLFVHASA-N 0.000 claims description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 claims description 2
- 108010052968 leupeptin Proteins 0.000 claims description 2
- 210000004324 lymphatic system Anatomy 0.000 claims description 2
- YFCUZWYIPBUQBD-ZOWNYOTGSA-N n-[(3s)-7-amino-1-chloro-2-oxoheptan-3-yl]-4-methylbenzenesulfonamide;hydron;chloride Chemical compound Cl.CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 YFCUZWYIPBUQBD-ZOWNYOTGSA-N 0.000 claims description 2
- 229960001756 oxaliplatin Drugs 0.000 claims description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 2
- 108060006633 protein kinase Proteins 0.000 claims description 2
- 229940076279 serotonin Drugs 0.000 claims description 2
- 241000712461 unidentified influenza virus Species 0.000 claims description 2
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 claims 4
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 claims 2
- 229940123134 Nitric oxide inhibitor Drugs 0.000 claims 2
- 229960000711 alprostadil Drugs 0.000 claims 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims 2
- 102100035792 Kininogen-1 Human genes 0.000 claims 1
- RDFCSSHDJSZMTQ-ZDUSSCGKSA-N Tos-Lys-CH2Cl Chemical group CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 RDFCSSHDJSZMTQ-ZDUSSCGKSA-N 0.000 claims 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 claims 1
- 230000000149 penetrating effect Effects 0.000 claims 1
- 230000010118 platelet activation Effects 0.000 claims 1
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 230000001965 increasing effect Effects 0.000 abstract description 10
- 206010028980 Neoplasm Diseases 0.000 description 82
- 108090000765 processed proteins & peptides Proteins 0.000 description 65
- 229920001184 polypeptide Polymers 0.000 description 64
- 102000004196 processed proteins & peptides Human genes 0.000 description 64
- 210000004027 cell Anatomy 0.000 description 61
- 241000699670 Mus sp. Species 0.000 description 39
- 239000000203 mixture Substances 0.000 description 30
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 26
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 26
- 229960002930 sirolimus Drugs 0.000 description 26
- 230000004048 modification Effects 0.000 description 25
- 238000012986 modification Methods 0.000 description 25
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 24
- 229960004397 cyclophosphamide Drugs 0.000 description 24
- 230000004083 survival effect Effects 0.000 description 24
- 238000011282 treatment Methods 0.000 description 22
- 102100034170 Interferon-induced, double-stranded RNA-activated protein kinase Human genes 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 20
- 239000007924 injection Substances 0.000 description 20
- 238000002347 injection Methods 0.000 description 20
- 238000001802 infusion Methods 0.000 description 19
- 241000702244 Orthoreovirus Species 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 230000014509 gene expression Effects 0.000 description 17
- 239000002953 phosphate buffered saline Substances 0.000 description 16
- 230000006870 function Effects 0.000 description 15
- 150000007523 nucleic acids Chemical class 0.000 description 15
- 238000001990 intravenous administration Methods 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 201000011510 cancer Diseases 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000004913 activation Effects 0.000 description 9
- 125000003275 alpha amino acid group Chemical group 0.000 description 9
- 210000000234 capsid Anatomy 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- -1 2-aminophenoxy Chemical group 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000007912 intraperitoneal administration Methods 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 102000006601 Thymidine Kinase Human genes 0.000 description 7
- 108020004440 Thymidine kinase Proteins 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 210000005170 neoplastic cell Anatomy 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 208000035269 cancer or benign tumor Diseases 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000003018 immunosuppressive agent Substances 0.000 description 5
- 229940125721 immunosuppressive agent Drugs 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000002601 intratumoral effect Effects 0.000 description 5
- 230000003472 neutralizing effect Effects 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 230000006798 recombination Effects 0.000 description 5
- 238000005215 recombination Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 210000002845 virion Anatomy 0.000 description 5
- 108090000317 Chymotrypsin Proteins 0.000 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 238000000719 MTS assay Methods 0.000 description 4
- 231100000070 MTS assay Toxicity 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 108091023045 Untranslated Region Proteins 0.000 description 4
- 101800003344 Vaccinia growth factor Proteins 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 229960002376 chymotrypsin Drugs 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012737 fresh medium Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000003471 mutagenic agent Substances 0.000 description 4
- 231100000707 mutagenic chemical Toxicity 0.000 description 4
- 230000001613 neoplastic effect Effects 0.000 description 4
- 230000000174 oncolytic effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000001243 protein synthesis Methods 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 102100037651 AP-2 complex subunit sigma Human genes 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108090000565 Capsid Proteins Proteins 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 101000806914 Homo sapiens AP-2 complex subunit sigma Proteins 0.000 description 3
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 3
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 102100040247 Tumor necrosis factor Human genes 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000002706 hydrostatic effect Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 150000002605 large molecules Chemical class 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 3
- 239000000693 micelle Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108090000172 Interleukin-15 Proteins 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 102000002297 Laminin Receptors Human genes 0.000 description 2
- 108010000851 Laminin Receptors Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 241001042466 Mammalian orthoreovirus Species 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 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 2
- 241000700635 Orf virus Species 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 108700005078 Synthetic Genes Proteins 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 241000710924 Togaviridae Species 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 2
- 101150004676 VGF gene Proteins 0.000 description 2
- 101710157851 Zona occludens toxin Proteins 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000008051 alkyl sulfates Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000002962 chemical mutagen Substances 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000012055 enteric layer Substances 0.000 description 2
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 2
- 229960005542 ethidium bromide Drugs 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 230000003505 mutagenic effect Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012385 systemic delivery Methods 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 1
- ONJZYZYZIKTIEG-CFBQITSMSA-N (3s,6s,9r,10r,11s,12s,13e,15e,18s,21s)-18-[(2e,4e,8s,9s)-10-[(2s,3r,4s,5s,6r,9s,11s)-9-ethyl-4-hydroxy-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undecan-2-yl]-9-hydroxy-8-methyldeca-2,4-dien-2-yl]-10,12-dihydroxy-3-[(3-hydroxyphenyl)methyl]-11-methyl-9- Chemical compound N1C(=O)[C@@H](CC)C[C@H](C)[C@]21[C@@H](C)[C@@H](O)[C@@H](C)[C@H](C[C@H](O)[C@@H](C)CC\C=C\C=C(/C)[C@H]1OC(=O)[C@@H]3CCCN(N3)C(=O)[C@H](CC=3C=C(O)C=CC=3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(C)=O)[C@H](O)[C@@H](C)[C@@H](O)/C=C/C=C/C1)O2 ONJZYZYZIKTIEG-CFBQITSMSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- 101150096316 5 gene Proteins 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 241000712892 Arenaviridae Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241001533362 Astroviridae Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241001516406 Avian orthoreovirus Species 0.000 description 1
- FTEDXVNDVHYDQW-UHFFFAOYSA-N BAPTA Chemical compound OC(=O)CN(CC(O)=O)C1=CC=CC=C1OCCOC1=CC=CC=C1N(CC(O)=O)CC(O)=O FTEDXVNDVHYDQW-UHFFFAOYSA-N 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 241000701412 Baculoviridae Species 0.000 description 1
- 241001533460 Barnaviridae Species 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000714198 Caliciviridae Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000520666 Carmotetraviridae Species 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- 108090000426 Caspase-1 Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 0.000 description 1
- 241001533399 Circoviridae Species 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 241000701520 Corticoviridae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 101710201734 E3 protein Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000702463 Geminiviridae Species 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 101000633984 Homo sapiens Influenza virus NS1A-binding protein Proteins 0.000 description 1
- 101001010621 Homo sapiens Interleukin-21 Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000702394 Inoviridae Species 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 241000701377 Iridoviridae Species 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- ZDLDXNCMJBOYJV-YFKPBYRVSA-N L-arginine, methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N ZDLDXNCMJBOYJV-YFKPBYRVSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 101150027802 L2 gene Proteins 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000714210 Leviviridae Species 0.000 description 1
- 241000701365 Lipothrixviridae Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101150046652 M2 gene Proteins 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 102000016397 Methyltransferase Human genes 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000702318 Microviridae Species 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100381978 Mus musculus Braf gene Proteins 0.000 description 1
- 241000701553 Myoviridae Species 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 241000723741 Nodaviridae Species 0.000 description 1
- 101800000515 Non-structural protein 3 Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 241000701945 Parvoviridae Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000150350 Peribunyaviridae Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 241000701369 Plasmaviridae Species 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 101800000980 Protease nsP2 Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 101150040459 RAS gene Proteins 0.000 description 1
- 101800001758 RNA-directed RNA polymerase nsP4 Proteins 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 241000702247 Reoviridae Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 241000711931 Rhabdoviridae Species 0.000 description 1
- 108010041388 Ribonucleotide Reductases Proteins 0.000 description 1
- 102000000505 Ribonucleotide Reductases Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 101150027674 S1 gene Proteins 0.000 description 1
- 101150080963 S4 gene Proteins 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- ONJZYZYZIKTIEG-UHFFFAOYSA-N Sanglifehrin A Natural products N1C(=O)C(CC)CC(C)C21C(C)C(O)C(C)C(CC(O)C(C)CCC=CC=C(C)C1OC(=O)C3CCCN(N3)C(=O)C(CC=3C=C(O)C=CC=3)NC(=O)C(C(C)C)NC(=O)C(CCC(C)=O)C(O)C(C)C(O)C=CC=CC1)O2 ONJZYZYZIKTIEG-UHFFFAOYSA-N 0.000 description 1
- 241000961587 Secoviridae Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 102400000096 Substance P Human genes 0.000 description 1
- 101800003906 Substance P Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 241001533336 Tombusviridae Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108700024019 Vaccinia virus pK3 Proteins 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010093857 Viral Hemagglutinins Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000007416 antiviral immune response Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004900 c-terminal fragment Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000012054 flavored emulsion Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000020375 flavoured syrup Nutrition 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229950004923 fontolizumab Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 108010064833 guanylyltransferase Proteins 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002480 immunoprotective effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960005108 mepolizumab Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000008481 normal tissue growth Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000012379 oncolytic virotherapy Methods 0.000 description 1
- 229950010444 onercept Drugs 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000009057 passive transport Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001480 pro-metastatic effect Effects 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 108700042226 ras Genes Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 108010003189 recombinant human tumor necrosis factor-binding protein-1 Proteins 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 229930185087 sanglifehrin Natural products 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 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 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000006656 viral protein synthesis Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/765—Reovirus; Rotavirus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
-
- 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
-
- 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
- C12N2720/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsRNA viruses
- C12N2720/00011—Details
- C12N2720/12011—Reoviridae
- C12N2720/12032—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
Abstract
Description
実施例1 レオウイルス、パクリタキセル、及びカルボプラチンのヒト用プロトコール。
これは、レオウイルスをパクリタキセル及びカルボプラチンと共に3週毎に静脈内投与する研究計画である。
2〜5日目に、レオウイルスのみを、1日目に使用したのと同じ用量及び方法を使用して投与するだろう。
Chou及びTalalayの中央値効果原理(median-effect principle)(Chou and Talalay, Trends Pharmacol. Sci. 4:450-454 (1983))に基づく定率組み合わせ設計及び組み合わせ示標法(constant ratio combination design and combination index method)を使用して、ラパマイシンと組み合わせたレオウイルスのB16.F10細胞に対する効果を評価した。
Treg欠乏(PC−61)及び/又はIL−2を用いたC57Bl/6マウスのプレコンディショニングは、静脈内送達したレオウイルスの皮下定着B16腫瘍への局在化を増強した(図3)。しかしながら、この実験に使用した高用量のレオウイルス(3.75×109TCID50)は、毒性をもたらした。したがって、レオウイルスのウイルス用量を1回の注射当たり1×108TCID50に低減して、PC−61又はCPA(PC−61の効果を模倣する)+IL−2+レオウイルスの治療効能を試験した。これらの条件下で、PC−61+IL−2又はCPA+IL−2のいずれかを使用した皮下B16腫瘍の同様の療法が、どの対照治療よりも有意に良好なレベルであったことを観察した(P<0.01;図4A)。プレコンディショニング投薬計画及び静脈内レオウイルスで治療したマウスはいずれも、毒性を発生させなかった。しかしながら、観察可能な毒性の欠如にも関わらず、CPA+IL−2+レオウイルスで治療したマウスの肺及び心臓の両方から、レオウイルスが回収された。これは、ウイルスが肺からのみ回収され、心臓からは回収されなかった、PC−61+IL−2+レオウイルスで治療したマウスと対照的である。したがって、CPA+IL−2によるプレコンディショニングは、静脈内送達したレオウイルスの全身性送達によりもたらされた療法を、PC−61+IL−2により誘導されたものと判別不能なレベルへと増強した。
Claims (43)
- 対象体の増殖性障害を治療するための方法であって、
(a)前記対象体の間質圧力を減少させるステップと、
(b)1つ又は複数の腫瘍崩壊性ウイルスを前記対象体に投与するステップとを含む方法。 - およそ103〜1012プラーク形成単位(PFU)の前記腫瘍崩壊性ウイルスが前記対象体に投与される、請求項1に記載の方法。
- およそ108〜1012プラーク形成単位(PFU)の前記腫瘍崩壊性ウイルスが前記対象体に投与される、請求項2に記載の方法。
- およそ108〜1012TCID50の前記腫瘍崩壊性ウイルスが前記対象体に投与される、請求項1に記載の方法。
- ステップ(a)が、間質圧力を減少させる作用剤を前記対象体に投与することにより実施される、請求項1に記載の方法。
- およそ5〜1000mg/m2の前記間質圧力を減少させる作用剤が、前記対象体に投与される、請求項5に記載の方法。
- 体重1kg当たりおよそ0.001〜10,000mgの前記間質圧力を減少させる作用剤が、前記対象体に投与される、請求項5に記載の方法。
- 前記間質圧力を減少させる作用剤が血管透過性を増加させる、請求項5に記載の方法。
- 前記間質圧力を減少させる作用剤がタキサンである、請求項5に記載の方法。
- 前記タキサンが、ラロタキセル、パクリタキセル、及びドセタキセルからなる群から選択される、請求項6に記載の方法。
- およそ40〜300mg/m2の前記タキサンが前記対象体に投与される、請求項9に記載の方法。
- およそ130〜225mg/m2の前記タキサンが前記対象体に投与される、請求項9に記載の方法。
- およそ175〜200mg/m2の前記パクリタキセルが前記対象体に投与される、請求項10に記載の方法。
- 前記作用剤が、インターロイキン−1(IL−1)、インターフェロン−K(IFN−K)、サブスタンスP、プロティナーゼ阻害剤、血管内皮増殖因子(VEGF)、ニトログリセリン、セロトニン、血漿キニン、血小板活性化因子(PAF)、プロスタグランジンE1(PGE1)、ヒスタミン、イマチニブ、閉鎖帯毒素(ZOT)、インターロイキン−2、一酸化窒素阻害剤、及びヒト成長因子受容体チロシンキナーゼ阻害剤からなる群から選択される、請求項5に記載の方法。
- 前記プロティナーゼ阻害剤が、N−アルファ−トシル−L−リシル−クロロメチル−ケトン(TLCK)、トシルフェニルアラニルクロロメチルケトン(TPCK)、又はロイペプチンである、請求項14に記載の方法。
- 前記血漿キニンがブラジキニンである、請求項14に記載の方法。
- 前記一酸化窒素阻害剤が、L−N−モノメチルアルギニン(L−NMMA)又はL−N−ニトロ−アルギニンメチルエステル(L−NAME)である、請求項14に記載の方法。
- ステップ(a)が、低カルシウムイオン濃度液体を前記対象体に投与することにより実施される、請求項1に記載の方法。
- 前記液体が、50Tmol/L〜200Tmol/Lのカルシウムイオン濃度を含む、請求項18に記載の方法。
- ステップ(a)が、増殖性障害の部位又はその付近の過剰間質液を除去することにより実施される、請求項1に記載の方法。
- 前記過剰間質液が、人工リンパ系(ALS)により除去される、請求項20に記載の方法。
- ステップ(a)が、透過化光線力学療法用薬剤を前記対象体に投与することにより実行される、請求項1に記載の方法。
- ステップ(a)が、ステップ(b)と同時に、ステップ(b)の前に、又はステップ(b)の後で実施される、請求項1〜22のいずれか一項に記載の方法。
- 前記間質圧力を減少させる作用剤が、前記腫瘍崩壊性ウイルスの前に投与される、請求項5に記載の方法。
- 前記作用剤が、前記腫瘍崩壊性ウイルスの1〜12時間前に投与される、請求項24に記載の方法。
- 前記ウイルスが複数回投与で投与される、請求項1〜22のいずれか一項に記載の方法。
- 前記間質圧力を減少させる作用剤が複数回投与で投与される、請求項5に記載の方法。
- 炎症促進性サイトカインを阻害する作用剤を前記対象体に投与するステップをさらに含む、請求項5に記載の方法。
- 前記作用剤が炎症促進性サイトカインを阻害するが、NARAの産生を阻害しないか又は最小限にしか阻害しない、請求項28に記載の方法。
- 前記炎症促進性サイトカインを阻害する作用剤が白金化合物である、請求項28に記載の方法。
- 前記白金化合物が、シスプラチン、カルボプラチン、及びオキサリプラチンからなる群から選択される、請求項30に記載の方法。
- およそ5〜1000mg/m2の前記白金化合物が前記対象体に投与される、請求項30に記載の方法。
- 1分当たり2〜7mg/mL(AUC)の前記カルボプラチンが前記対象体に投与される、請求項31に記載の方法。
- 1分当たり5〜6mg/mL(AUC)の前記カルボプラチンが前記対象体に投与される、請求項31に記載の方法。
- 前記間質圧力を低下させる作用剤がパクリタキセルであり、前記炎症促進性サイトカインを阻害する作用剤がカルボプラチンであり、前記腫瘍崩壊性ウイルスがレオウイルスである、請求項28に記載の方法。
- 前記間質圧力を減少させる作用剤が、前記腫瘍崩壊性ウイルス投与の4時間前の時点で最初に投与され、前記炎症促進性サイトカインを阻害する作用剤が、前記腫瘍崩壊性ウイルス投与の1時間前の時点で2番目に投与される、請求項28に記載の方法。
- 前記ウイルスが、前記二本鎖RNA活性化プロテインキナーゼ(PKR)を阻害しないように1つ又は複数の突然変異又は欠失を有する、請求項1に記載の方法。
- 前記腫瘍崩壊性ウイルスが、レオウイルス、シンドビスウイルス、Delta24、水疱性口内炎ウィルス(VSV)、ニューカッスル病ウィルス(NDV)、ワクシニアウイルス、脳炎ウイルス、帯状疱疹ウイルス、肝炎ウイルス、インフルエンザウイルス、水痘ウイルス、及び麻疹ウイルスからなる群から選択される、請求項1に記載の方法。
- 前記レオウイルスが哺乳動物レオウイルスである、請求項38に記載の方法。
- 前記レオウイルスがヒトレオウイルスである、請求項38に記載の方法。
- 前記ヒトレオウイルスが、血清型1レオウイルス、血清型2レオウイルス、及び血清型3レオウイルスからなる群から選択される、請求項40に記載の方法。
- 前記ヒトレオウイルスが、血清型3レオウイルスである、請求項40に記載の方法。
- 前記レオウイルスが、IDAC寄託番号190907−01を有する、請求項38に記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5627608P | 2008-05-27 | 2008-05-27 | |
US61/056,276 | 2008-05-27 | ||
US11384508P | 2008-11-12 | 2008-11-12 | |
US61/113,845 | 2008-11-12 | ||
PCT/CA2009/000720 WO2009143610A1 (en) | 2008-05-27 | 2009-05-27 | Modulating interstitial pressure and oncolytic viral delivery and distribution |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013249892A Division JP2014040490A (ja) | 2008-05-27 | 2013-12-03 | 間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2011520993A true JP2011520993A (ja) | 2011-07-21 |
Family
ID=41376508
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011510787A Pending JP2011520993A (ja) | 2008-05-27 | 2009-05-27 | 間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 |
JP2013249892A Pending JP2014040490A (ja) | 2008-05-27 | 2013-12-03 | 間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013249892A Pending JP2014040490A (ja) | 2008-05-27 | 2013-12-03 | 間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 |
Country Status (11)
Country | Link |
---|---|
US (1) | US20110086005A1 (ja) |
EP (1) | EP2296678A4 (ja) |
JP (2) | JP2011520993A (ja) |
CN (1) | CN102695520A (ja) |
AU (1) | AU2009253682B2 (ja) |
CA (1) | CA2723580A1 (ja) |
IL (1) | IL208381A (ja) |
MX (1) | MX339014B (ja) |
TW (1) | TW200951143A (ja) |
WO (1) | WO2009143610A1 (ja) |
ZA (1) | ZA201008018B (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3176971A1 (en) * | 2013-06-14 | 2014-12-18 | Psioxus Therapeutics Limited | A dosing regime and formulations for type b adenoviruses |
CA3183645A1 (en) | 2013-10-25 | 2015-04-30 | Psioxus Therapeutics Limited | Oncolytic adenoviruses armed with heterologous genes |
EP3068411B1 (en) * | 2013-11-15 | 2020-03-18 | Oncolytics Biotech Inc. | Oncolytic viruses and increased cancer treatment regimens |
WO2016174200A1 (en) | 2015-04-30 | 2016-11-03 | Psioxus Therapeutics Limited | Oncolytic adenovirus encoding a b7 protein |
WO2017103291A1 (en) | 2015-12-17 | 2017-06-22 | Psioxus Therapeutics Limited | Virus encoding an anti-tcr-complex antibody or fragment |
GB201713765D0 (en) | 2017-08-28 | 2017-10-11 | Psioxus Therapeutics Ltd | Modified adenovirus |
JP2024510871A (ja) * | 2021-01-15 | 2024-03-12 | エヌエックスティー バイオメディカル,エルエルシー | 間質空間を介して生理学的状態を評価および変更するための方法およびデバイス |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002502399A (ja) * | 1997-06-02 | 2002-01-22 | バイオファウシア、アクチボラグ | プライマー化合物による抗癌剤の固形癌への増強された送達 |
JP2004043471A (ja) * | 2002-07-11 | 2004-02-12 | Health Res Inc | 患部組織への薬物送達を補助するために血管の透過性を増強させるための光線力学療法 |
JP2004517966A (ja) * | 2001-02-20 | 2004-06-17 | オンコリティクス バイオテック, インコーポレイティッド | レオウイルスを用いる化学療法薬剤耐性新生物細胞の感作 |
US20040131590A1 (en) * | 2002-12-26 | 2004-07-08 | Nagarajan Ramesh | Methods and reagents for the enhancement of virus transduction in the bladder epithelium |
WO2007093036A1 (en) * | 2006-02-13 | 2007-08-23 | Oncolytics Biotech Inc. | Use of local immune suppression to enhance oncolytic viral therapy |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4554101A (en) * | 1981-01-09 | 1985-11-19 | New York Blood Center, Inc. | Identification and preparation of epitopes on antigens and allergens on the basis of hydrophilicity |
US5023252A (en) * | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
US5484399A (en) * | 1992-02-27 | 1996-01-16 | Sloan-Kettering Institute For Cancer Research | Process and device to reduce interstitial fluid pressure in tissue |
US6110461A (en) * | 1997-08-13 | 2000-08-29 | Oncolytics Biotech Inc. | Reovirus for the treatment of neoplasia |
US6565831B1 (en) * | 1999-02-24 | 2003-05-20 | Oncolytics Biotech Inc. | Methods for preventing reovirus recognition for the treatment of cellular proliferative disorders |
US6136307A (en) * | 1997-08-13 | 2000-10-24 | Oncolytics Biotech Inc. | Reovirus for the treatment of cellular proliferative disorders |
US6376471B1 (en) * | 1997-10-10 | 2002-04-23 | Johns Hopkins University | Gene delivery compositions and methods |
WO2001035970A1 (en) * | 1999-11-12 | 2001-05-25 | Oncolytics Biotech Inc. | Viruses for the treatment of cellular proliferative disorders |
US6547777B2 (en) * | 2000-02-17 | 2003-04-15 | Sloan-Kettering Institute For Cancer Research | Apparatus and method for reducing interstitial fluid pressure and enhancing delivery of a therapeutic agent |
US7306902B2 (en) * | 2002-06-28 | 2007-12-11 | Oncolyties Biotech Inc. | Oncolytic viruses as phenotyping agents for neoplasms |
TWI289158B (en) * | 2000-08-10 | 2007-11-01 | Oncolytics Biotech Inc | Method of producing infectious reovirus |
JP4087712B2 (ja) * | 2001-03-16 | 2008-05-21 | オンコリティクス バイオテック, インコーポレイティッド | 細胞培養物からウイルスを抽出する方法 |
US6942633B2 (en) * | 2002-03-22 | 2005-09-13 | Twin Star Medical, Inc. | System for treating tissue swelling |
MXPA04011007A (es) * | 2002-05-09 | 2005-02-14 | Oncolytics Biotech Inc | Metodo para reducir el dolor usando virus oncoliticos. |
EP2269618A1 (en) * | 2002-08-12 | 2011-01-05 | Jennerex Biotherapeutics ULC | An oncolytic vaccinia virus for use in combination with a chemotherapy for treating cancer. |
CA2598239C (en) * | 2005-02-18 | 2019-10-29 | Abraxis Bioscience, Inc. | Nanoparticulate formulations of taxanes and carrier proteins for use in combination chemotherapy |
JP5577103B2 (ja) * | 2007-03-12 | 2014-08-20 | オンコリティクス バイオテク,インコーポレーテッド | 改変配列を有するレオウイルス |
AR066649A1 (es) * | 2007-05-21 | 2009-09-02 | Oncolytics Biotech Inc | Reovirus mutantes y metodos de elaboracion y uso de los mismos |
CA2699805A1 (en) * | 2007-10-22 | 2009-04-30 | Oncolytics Biotech Inc. | Treatment regime for proliferative disorders |
-
2009
- 2009-05-27 JP JP2011510787A patent/JP2011520993A/ja active Pending
- 2009-05-27 WO PCT/CA2009/000720 patent/WO2009143610A1/en active Application Filing
- 2009-05-27 AU AU2009253682A patent/AU2009253682B2/en active Active
- 2009-05-27 US US12/994,119 patent/US20110086005A1/en not_active Abandoned
- 2009-05-27 TW TW098117651A patent/TW200951143A/zh unknown
- 2009-05-27 CN CN2009801191554A patent/CN102695520A/zh active Pending
- 2009-05-27 MX MX2010012858A patent/MX339014B/es active IP Right Grant
- 2009-05-27 EP EP09753371A patent/EP2296678A4/en not_active Withdrawn
- 2009-05-27 CA CA2723580A patent/CA2723580A1/en not_active Abandoned
-
2010
- 2010-10-03 IL IL208381A patent/IL208381A/en active IP Right Grant
- 2010-11-09 ZA ZA2010/08018A patent/ZA201008018B/en unknown
-
2013
- 2013-12-03 JP JP2013249892A patent/JP2014040490A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002502399A (ja) * | 1997-06-02 | 2002-01-22 | バイオファウシア、アクチボラグ | プライマー化合物による抗癌剤の固形癌への増強された送達 |
JP2004517966A (ja) * | 2001-02-20 | 2004-06-17 | オンコリティクス バイオテック, インコーポレイティッド | レオウイルスを用いる化学療法薬剤耐性新生物細胞の感作 |
JP2004043471A (ja) * | 2002-07-11 | 2004-02-12 | Health Res Inc | 患部組織への薬物送達を補助するために血管の透過性を増強させるための光線力学療法 |
US20040131590A1 (en) * | 2002-12-26 | 2004-07-08 | Nagarajan Ramesh | Methods and reagents for the enhancement of virus transduction in the bladder epithelium |
WO2007093036A1 (en) * | 2006-02-13 | 2007-08-23 | Oncolytics Biotech Inc. | Use of local immune suppression to enhance oncolytic viral therapy |
Non-Patent Citations (6)
Title |
---|
JPN6013043386; Press Release Details-Oncolytics Biotech Inc. Starts Patient Enrolment in U.K. Combination REOLYSIN/ , 20070529 * |
JPN6013043389; Cancer Research, 1999, Vol.59, pp.3776-3782 * |
JPN6013043394; Ann. Surg. Oncol., 2007, Vol.14, No.8, pp.2411-2421 * |
JPN6013043398; Nature Reviews, Cancer, 2004, Vol.4, No.10, pp.806-813 * |
JPN6013043402; Clinical Cancer Research, 2005, Vol.11, pp.1527-1533 * |
JPN6013043405; Br. J. Cancer, 1992, Vol.66, No.4, pp.717-719 * |
Also Published As
Publication number | Publication date |
---|---|
WO2009143610A1 (en) | 2009-12-03 |
CN102695520A (zh) | 2012-09-26 |
EP2296678A4 (en) | 2012-03-21 |
TW200951143A (en) | 2009-12-16 |
CA2723580A1 (en) | 2009-12-03 |
IL208381A0 (en) | 2010-12-30 |
AU2009253682B2 (en) | 2015-09-17 |
MX2010012858A (es) | 2010-12-20 |
IL208381A (en) | 2014-03-31 |
JP2014040490A (ja) | 2014-03-06 |
AU2009253682A1 (en) | 2009-12-03 |
ZA201008018B (en) | 2012-01-25 |
US20110086005A1 (en) | 2011-04-14 |
EP2296678A1 (en) | 2011-03-23 |
MX339014B (es) | 2016-05-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8658158B2 (en) | Sensitization of chemotherapeutic agent resistant neoplastic cells with a virus | |
JP2014040490A (ja) | 間質圧力の調節並びに腫瘍崩壊性ウイルスの送達及び分布 | |
AU2002234453A1 (en) | Sensitization of chemotherapeutic agent resistant neoplastic cells with reovirus | |
AU2007215328A1 (en) | Use of local immune suppression to enhance oncolytic viral therapy | |
EP3068411B1 (en) | Oncolytic viruses and increased cancer treatment regimens | |
US20130243732A1 (en) | Abrogating proinflammatory cytokine production during oncolytic reovirus therapy | |
WO2015017915A1 (en) | Methods of treating taxane naïve subjects with primary tumors or with metastatic cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120525 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130903 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131203 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140714 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141114 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20141128 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20141219 |