JP5727458B2 - 改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 - Google Patents
改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 Download PDFInfo
- Publication number
- JP5727458B2 JP5727458B2 JP2012505149A JP2012505149A JP5727458B2 JP 5727458 B2 JP5727458 B2 JP 5727458B2 JP 2012505149 A JP2012505149 A JP 2012505149A JP 2012505149 A JP2012505149 A JP 2012505149A JP 5727458 B2 JP5727458 B2 JP 5727458B2
- Authority
- JP
- Japan
- Prior art keywords
- promoter
- tumor
- cells
- stem cell
- mesenchymal stem
- 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.)
- Active
Links
- 210000002901 mesenchymal stem cell Anatomy 0.000 title claims description 139
- 206010028980 Neoplasm Diseases 0.000 title claims description 101
- 238000000034 method Methods 0.000 title claims description 25
- 210000004027 cell Anatomy 0.000 claims description 99
- 108090000623 proteins and genes Proteins 0.000 claims description 69
- 210000000130 stem cell Anatomy 0.000 claims description 67
- 239000003145 cytotoxic factor Substances 0.000 claims description 39
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 36
- 210000001519 tissue Anatomy 0.000 claims description 35
- 229960002963 ganciclovir Drugs 0.000 claims description 33
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 31
- 201000002528 pancreatic cancer Diseases 0.000 claims description 31
- 108010055166 Chemokine CCL5 Proteins 0.000 claims description 30
- 102000001327 Chemokine CCL5 Human genes 0.000 claims description 30
- 239000013598 vector Substances 0.000 claims description 27
- 241000700584 Simplexvirus Species 0.000 claims description 25
- 108700026244 Open Reading Frames Proteins 0.000 claims description 23
- 239000003623 enhancer Substances 0.000 claims description 23
- 108020004440 Thymidine kinase Proteins 0.000 claims description 22
- 239000003550 marker Substances 0.000 claims description 21
- 102000006601 Thymidine Kinase Human genes 0.000 claims description 20
- 230000037396 body weight Effects 0.000 claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims description 15
- 230000001177 retroviral effect Effects 0.000 claims description 15
- 230000003612 virological effect Effects 0.000 claims description 15
- 108020004707 nucleic acids Proteins 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 14
- 150000007523 nucleic acids Chemical class 0.000 claims description 14
- 231100000433 cytotoxic Toxicity 0.000 claims description 12
- 230000001472 cytotoxic effect Effects 0.000 claims description 12
- 238000004806 packaging method and process Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 239000012212 insulator Substances 0.000 claims description 8
- 230000010415 tropism Effects 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 7
- 108010052285 Membrane Proteins Proteins 0.000 claims description 6
- 102000018697 Membrane Proteins Human genes 0.000 claims description 6
- 230000003211 malignant effect Effects 0.000 claims description 6
- 230000003115 biocidal effect Effects 0.000 claims description 5
- 230000001394 metastastic effect Effects 0.000 claims description 5
- 108010080611 Cytosine Deaminase Proteins 0.000 claims description 4
- 230000000735 allogeneic effect Effects 0.000 claims description 4
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 230000001566 pro-viral effect Effects 0.000 claims description 4
- 201000003076 Angiosarcoma Diseases 0.000 claims description 3
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 102000000311 Cytosine Deaminase Human genes 0.000 claims description 3
- 206010014733 Endometrial cancer Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 3
- 208000032612 Glial tumor Diseases 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 3
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 208000033383 Neuroendocrine tumor of pancreas Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 3
- 206010057644 Testis cancer Diseases 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 claims description 3
- 208000023958 prostate neoplasm Diseases 0.000 claims description 3
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 206010042863 synovial sarcoma Diseases 0.000 claims description 3
- 201000003120 testicular cancer Diseases 0.000 claims description 3
- 208000024719 uterine cervix neoplasm Diseases 0.000 claims description 3
- 230000014509 gene expression Effects 0.000 description 40
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 30
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 27
- 241000699670 Mus sp. Species 0.000 description 26
- 108010054624 red fluorescent protein Proteins 0.000 description 23
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 20
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 20
- 238000011282 treatment Methods 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 206010027476 Metastases Diseases 0.000 description 15
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 15
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 15
- 230000004614 tumor growth Effects 0.000 description 15
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 210000001185 bone marrow Anatomy 0.000 description 12
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 11
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 11
- 239000005090 green fluorescent protein Substances 0.000 description 11
- 108700008625 Reporter Genes Proteins 0.000 description 10
- 230000001939 inductive effect Effects 0.000 description 10
- 230000002757 inflammatory effect Effects 0.000 description 10
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 10
- 208000008443 pancreatic carcinoma Diseases 0.000 description 10
- 108700019146 Transgenes Proteins 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 210000002845 virion Anatomy 0.000 description 9
- 230000006378 damage Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 7
- 230000009401 metastasis Effects 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 210000002536 stromal cell Anatomy 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000001415 gene therapy Methods 0.000 description 6
- 210000000496 pancreas Anatomy 0.000 description 6
- 210000004303 peritoneum Anatomy 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- 229930189065 blasticidin Natural products 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 238000013508 migration Methods 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 238000007809 Boyden Chamber assay Methods 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 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 4
- 241000713666 Lentivirus Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 101710172711 Structural protein Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 229920001184 polypeptide Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 238000000729 Fisher's exact test Methods 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 3
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 3
- 102100034349 Integrase Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 102000046949 human MSC Human genes 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000002559 palpation Methods 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000010361 transduction Methods 0.000 description 3
- 230000026683 transduction Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 2
- 101100118916 Gibbon ape leukemia virus env gene Proteins 0.000 description 2
- 208000009889 Herpes Simplex Diseases 0.000 description 2
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 2
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 description 2
- 108010029973 Lymphocytic choriomeningitis virus glycoprotein peptide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 108091027981 Response element Proteins 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 101150003725 TK gene Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 241000711975 Vesicular stomatitis virus Species 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 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 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000000981 bystander Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000000651 myofibroblast Anatomy 0.000 description 2
- 108020001162 nitroreductase Proteins 0.000 description 2
- 210000003668 pericyte Anatomy 0.000 description 2
- 230000003836 peripheral circulation Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000004500 stellate cell Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 208000037816 tissue injury Diseases 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- WZRJTRPJURQBRM-UHFFFAOYSA-N 4-amino-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide;5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1.COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 WZRJTRPJURQBRM-UHFFFAOYSA-N 0.000 description 1
- 230000005730 ADP ribosylation Effects 0.000 description 1
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007272 Apoptosis Inducing Factor Human genes 0.000 description 1
- 108010033604 Apoptosis Inducing Factor Proteins 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000003849 Cytochrome P450 Human genes 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 101710121417 Envelope glycoprotein Proteins 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 101100215371 Homo sapiens ACTB gene Proteins 0.000 description 1
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 241000283923 Marmota monax Species 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- 206010051676 Metastases to peritoneum Diseases 0.000 description 1
- 101100025201 Mus musculus Msc 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
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102000004459 Nitroreductase Human genes 0.000 description 1
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 1
- 240000007019 Oxalis corniculata Species 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 101710101148 Probable 6-oxopurine nucleoside phosphorylase Proteins 0.000 description 1
- 239000004792 Prolene Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 102000030764 Purine-nucleoside phosphorylase Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 102100038081 Signal transducer CD24 Human genes 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 241000713880 Spleen focus-forming virus Species 0.000 description 1
- 244000166550 Strophanthus gratus Species 0.000 description 1
- 102000008579 Transposases Human genes 0.000 description 1
- 108010020764 Transposases Proteins 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 101900150902 Varicella-zoster virus Thymidine kinase Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 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
- 229940112129 campath Drugs 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108700004026 gag Genes Proteins 0.000 description 1
- 108010062699 gamma-Glutamyl Hydrolase Proteins 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 101150106093 gpt gene Proteins 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000005099 host tropism Effects 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- -1 olive oil Chemical compound 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229960003343 ouabain Drugs 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 208000010918 peritoneal neoplasm Diseases 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000007112 pro inflammatory response Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 238000009580 stem-cell therapy Methods 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
- C12N5/0663—Bone marrow mesenchymal stem cells (BM-MSC)
-
- 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
-
- 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
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0662—Stem cells
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- 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
- C12N2510/00—Genetically modified cells
-
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
- C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Developmental Biology & Embryology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Plant Pathology (AREA)
- Oncology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16878709P | 2009-04-13 | 2009-04-13 | |
| US61/168,787 | 2009-04-13 | ||
| PCT/EP2010/054844 WO2010119039A1 (en) | 2009-04-13 | 2010-04-13 | Engineered mesenchymal stem cells and method of using same to treat tumors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012523243A JP2012523243A (ja) | 2012-10-04 |
| JP2012523243A5 JP2012523243A5 (cg-RX-API-DMAC7.html) | 2013-05-23 |
| JP5727458B2 true JP5727458B2 (ja) | 2015-06-03 |
Family
ID=42270435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012505149A Active JP5727458B2 (ja) | 2009-04-13 | 2010-04-13 | 改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US9434925B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2419113B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5727458B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR20120088542A (cg-RX-API-DMAC7.html) |
| CN (1) | CN102695517B (cg-RX-API-DMAC7.html) |
| AU (1) | AU2010237130B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI1013771A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2758120C (cg-RX-API-DMAC7.html) |
| IL (1) | IL215581A0 (cg-RX-API-DMAC7.html) |
| RU (1) | RU2539099C2 (cg-RX-API-DMAC7.html) |
| SG (1) | SG175127A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2010119039A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100183558A1 (en) | 2008-10-17 | 2010-07-22 | Zhennan Lai | Safe lentiviral vectors for targeted delivery of multiple therapeutic molecules |
| US20130171115A1 (en) * | 2011-12-30 | 2013-07-04 | Gang Li | Cell-mediated gene therapy for cancer using mesenchymal stem cells expressing a suicide gene |
| CN105950630A (zh) * | 2012-02-01 | 2016-09-21 | 浦项工科大学校产学协力团 | 同时表达十二聚体trail及hsv-tk自杀基因的载体及利用其的抗癌干细胞治疗剂 |
| US20130203166A1 (en) * | 2012-02-06 | 2013-08-08 | Protobios Llc | Stimulation of multipotency of mesenchymal stem cells by chemokine ccl5 |
| GB201202319D0 (en) | 2012-02-10 | 2012-03-28 | Orbsen Therapeutics Ltd | Stromal stem cells |
| US20140065110A1 (en) | 2012-08-31 | 2014-03-06 | The Regents Of The University Of California | Genetically modified msc and therapeutic methods |
| ES2748662T3 (es) * | 2012-11-05 | 2020-03-17 | Institute For Res In Biomedicine Irb | Roedores inmunodeficientes modificados genéticamente y métodos de uso de los mismos |
| US10472647B2 (en) | 2012-12-21 | 2019-11-12 | The Administrators Of The Tulane Educational Fund | Primary mesenchymal stem cells as a vaccine platform |
| WO2015100268A1 (en) * | 2013-12-23 | 2015-07-02 | The Regents Of The University Of California | Mesenchymal stem cells for targeted cancer therapy |
| CA2936483A1 (en) * | 2014-01-17 | 2015-07-23 | Wake Forest University Health Sciences | Methods for enhancing the delivery of active agents |
| CA2956987C (en) * | 2014-08-18 | 2023-03-21 | Apceth Gmbh & Co. Kg | Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells |
| CA3003133C (en) * | 2014-10-24 | 2020-09-15 | StemImmune, Incorporated | Combination immunotherapy approach for treatment of cancer |
| CN104622903B (zh) * | 2015-01-20 | 2018-10-09 | 奥思达干细胞有限公司 | 抗恶性黑色素瘤的干细胞制剂及其制备方法 |
| EP3247808B1 (en) | 2015-01-21 | 2021-05-05 | Fred Hutchinson Cancer Research Center | Point-of-care and/or portable platform for gene therapy |
| WO2016138340A1 (en) * | 2015-02-27 | 2016-09-01 | Saint Louis University | Tumor suppressor sall1 as a therapeutic agent for treating cancer |
| EP3262159B1 (en) * | 2015-02-27 | 2019-07-24 | Apceth GmbH & Co. KG | Genetically modified mesenchymal stem cell expressing klotho |
| WO2016146819A1 (en) * | 2015-03-18 | 2016-09-22 | Apceth Gmbh & Co. Kg | Hypoxia-induced expression of therapeutic proteins in mesenchymal stem cells |
| JP6890831B2 (ja) | 2015-07-08 | 2021-06-18 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | Ｈｉｖ予備免疫化および免疫療法 |
| EA201800148A1 (ru) | 2015-08-11 | 2019-01-31 | Калиди Биотерапьютикс, Инк. | Оспенная вакцина для лечения рака |
| WO2017036925A1 (en) * | 2015-08-28 | 2017-03-09 | Apceth Gmbh & Co. Kg | Mesenchymal stem cells for the treatment of metastatic liver disease |
| US10137144B2 (en) | 2016-01-15 | 2018-11-27 | American Gene Technologies International Inc. | Methods and compositions for the activation of gamma-delta T-cells |
| JP7260898B2 (ja) | 2016-01-15 | 2023-04-19 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | ガンマデルタｔ細胞の活性化のための方法および組成物 |
| JP7153332B2 (ja) | 2016-02-08 | 2022-10-14 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | Ｈｉｖワクチン接種および免疫療法 |
| EP3426777B1 (en) | 2016-03-09 | 2022-02-16 | American Gene Technologies International Inc. | Combination vectors and methods for treating cancer |
| AU2017277499B2 (en) | 2016-06-07 | 2022-07-28 | The Pacific Heart, lung & Blood Institute | Compositions and methods for treating cancer |
| EP3468617A4 (en) | 2016-06-08 | 2020-01-22 | American Gene Technologies International Inc. | INTEGRATED VIRAL ADMINISTRATION SYSTEM AND RELATED METHODS |
| WO2018009246A1 (en) | 2016-07-08 | 2018-01-11 | American Gene Technologies International Inc. | Hiv pre-immunization and immunotherapy |
| JP7176756B2 (ja) | 2016-07-21 | 2022-11-22 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | パーキンソン病を処置するためのウイルスベクター |
| KR20190109389A (ko) | 2016-11-03 | 2019-09-25 | 엑소스템 바이오텍 리미티드 | 간엽 줄기 세포 집단, 이들의 산물 및 이들의 용도 |
| KR102737836B1 (ko) | 2017-04-03 | 2024-12-03 | 아메리칸 진 테크놀로지스 인터내셔널 인코포레이티드 | 페닐케톤뇨증을 치료하기 위한 조성물 및 방법 |
| EP4317422A3 (en) | 2017-04-13 | 2024-05-01 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| US11246890B2 (en) | 2018-04-03 | 2022-02-15 | The Board Of Trustees Of The Leland Stanford Junior University | Systemic targeting of inflammatory sites and enhanced immunomodulatory function by introducing the chimeric antigen receptor (CAR) into mesenchymal stem cells for inflammatory and autoimmune diseases |
| US11505782B2 (en) | 2018-06-04 | 2022-11-22 | Calidi Biotherapeutics, Inc. | Cell-based vehicles for potentiation of viral therapy |
| JP2021526865A (ja) * | 2018-06-14 | 2021-10-11 | ロマ・リンダ・ユニヴァーシティ | 急性骨髄性白血病の処置のための操作された造血幹細胞 |
| SG11202103317XA (en) | 2018-10-17 | 2021-05-28 | Senti Biosciences Inc | Combinatorial cancer immunotherapy |
| US11419898B2 (en) | 2018-10-17 | 2022-08-23 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| EP3876952A4 (en) | 2018-11-05 | 2022-08-24 | American Gene Technologies International Inc. | VECTOR SYSTEM FOR EXPRESSING REGULATORY RNA |
| KR20210091740A (ko) | 2018-11-06 | 2021-07-22 | 카리디 바이오테라퓨틱스, 인크. | 세포-매개된 종양용해 바이러스 요법용 향상된 시스템 |
| US20220241337A1 (en) * | 2019-02-22 | 2022-08-04 | The Trustees Of Columbia University In The City Of Newyork | Preparing tissues for delivery of therapeutic and diagnostic agents and delivering the agents |
| SG10201902002SA (en) * | 2019-03-06 | 2020-10-29 | Nat Univ Singapore | Non-viral modification of mesenchymal stem cells |
| EP4017512B1 (en) * | 2019-08-23 | 2025-04-02 | Orbsen Therapeutics Limited | Compositions for monocyte and macrophage polarization and methods of use |
| JP2023547728A (ja) | 2020-11-06 | 2023-11-13 | アーテック メディカル ジーエムビーエイチ | 間葉系幹細胞由来の細胞外小胞およびアルファ－１アンチトリプシンを含むウイルス感染症治療用組成物 |
| EP3995130A1 (en) | 2020-11-06 | 2022-05-11 | JunctuCell Biomed Manufacturing GmbH | A composition comprising extra-cellular vesicles from mesenchymal stem cells and alpha-1 antitrypsin for the treatment of viral infections |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6265564B1 (en) * | 1996-08-02 | 2001-07-24 | Regeneron Pharmaceuticals, Inc. | Expressed ligand-vascular intercellular signalling molecule |
| US7098185B2 (en) * | 1998-05-18 | 2006-08-29 | University College London | Polypeptide hormone phosphatonin |
| US20060057553A1 (en) * | 2000-05-30 | 2006-03-16 | Estuardo Aguilar-Cordova | Chimeric viral vectors for gene therapy |
| WO2002069953A1 (en) * | 2001-03-01 | 2002-09-12 | The Board Of Regents Of The University Of Texas System | Methods of treating lung inflammation |
| US20030165579A1 (en) * | 2002-02-27 | 2003-09-04 | Chih-Hui Lin | Euphorbia antiquorum extract, a pharmaceutical composition containing the same and methods for treatment of cancers |
| EP1544213B1 (en) * | 2003-12-19 | 2008-02-20 | Charité - Universitätsmedizin Berlin | Use of ligands of the antigen cd52 for the treatment of solid tumours and bone-related cancerous diseases |
| JP2006194752A (ja) * | 2005-01-14 | 2006-07-27 | Sumitomo Metal Mining Co Ltd | Ｘ線回折測定における試料固定方法および試料固定具 |
| KR101022401B1 (ko) * | 2005-09-29 | 2011-03-15 | 아주대학교산학협력단 | 자살유전자를 발현하는 중간엽 줄기세포를 포함하는 암치료용 조성물 |
| EP2851422A3 (en) | 2007-05-24 | 2015-06-24 | Apceth GmbH & Co. KG | CD34neg stem cells for the treatment of gastrointestinal disorders |
-
2010
- 2010-04-13 SG SG2011073418A patent/SG175127A1/en unknown
- 2010-04-13 WO PCT/EP2010/054844 patent/WO2010119039A1/en not_active Ceased
- 2010-04-13 KR KR1020117026918A patent/KR20120088542A/ko not_active Ceased
- 2010-04-13 RU RU2011146048/10A patent/RU2539099C2/ru not_active IP Right Cessation
- 2010-04-13 CN CN201080026333.1A patent/CN102695517B/zh not_active Expired - Fee Related
- 2010-04-13 US US13/264,084 patent/US9434925B2/en not_active Expired - Fee Related
- 2010-04-13 EP EP10713933.9A patent/EP2419113B1/en not_active Not-in-force
- 2010-04-13 AU AU2010237130A patent/AU2010237130B2/en not_active Ceased
- 2010-04-13 BR BRPI1013771A patent/BRPI1013771A2/pt not_active IP Right Cessation
- 2010-04-13 CA CA2758120A patent/CA2758120C/en not_active Expired - Fee Related
- 2010-04-13 JP JP2012505149A patent/JP5727458B2/ja active Active
-
2011
- 2011-10-06 IL IL215581A patent/IL215581A0/en unknown
-
2016
- 2016-08-31 US US15/253,353 patent/US20170015976A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20120087901A1 (en) | 2012-04-12 |
| JP2012523243A (ja) | 2012-10-04 |
| EP2419113A1 (en) | 2012-02-22 |
| AU2010237130A1 (en) | 2011-11-03 |
| BRPI1013771A2 (pt) | 2016-04-05 |
| WO2010119039A1 (en) | 2010-10-21 |
| US20170015976A1 (en) | 2017-01-19 |
| EP2419113B1 (en) | 2017-05-10 |
| IL215581A0 (en) | 2011-12-29 |
| CN102695517A (zh) | 2012-09-26 |
| KR20120088542A (ko) | 2012-08-08 |
| RU2011146048A (ru) | 2013-05-20 |
| RU2539099C2 (ru) | 2015-01-10 |
| US9434925B2 (en) | 2016-09-06 |
| SG175127A1 (en) | 2011-11-28 |
| AU2010237130B2 (en) | 2015-01-29 |
| CA2758120A1 (en) | 2010-10-21 |
| CN102695517B (zh) | 2015-01-28 |
| CA2758120C (en) | 2014-08-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5727458B2 (ja) | 改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 | |
| KR102526711B1 (ko) | 고효율 게놈 편집을 위한 아데노-관련 바이러스 벡터 변이체 및 이의 방법 | |
| US20220378822A1 (en) | Combinatorial cancer immunotherapy | |
| JP2021527405A (ja) | 合成肝臓指向性アデノ随伴ウイルスカプシドおよびその使用 | |
| JP2014088432A (ja) | Ｃｄ３４幹細胞に関連した方法および組成物 | |
| US11547729B2 (en) | Nanoparticle modification of human adipose-derived mesenchymal stem cells for treating brain cancer and other neurological diseases | |
| Li et al. | Integrin β1 increases stem cell survival and cardiac function after myocardial infarction | |
| CN116801890A (zh) | 用于增强治疗性免疫细胞功效的方法和组合物 | |
| JP5846650B2 (ja) | ベクター産生型腫瘍標的細胞 | |
| Annan et al. | Gene therapy in the treatment of human cancer | |
| JP2024529400A (ja) | Ｂ型肝炎ウイルス（ｈｂｖ）ノックアウト | |
| US20220387626A1 (en) | Compositions and methods comprising viral vector systems for multiplexed activation of endogenous genes as immunotherapy and viral-based immune-gene therapy | |
| NL2031110B1 (en) | Recombinant adeno-associated virus vector, recombinant adeno-associated virus aav8-pd1 and use thereof | |
| JP2025529540A (ja) | Ｔｅｔ２の両アレルノックアウト | |
| JP2025531296A (ja) | Ｐｄｃｄ１の両アレルノックアウト | |
| da Silva | Genetic engineering of Mesenchymal Stromal Cells to express anti-cancer proteins | |
| JP2025529547A (ja) | Ｃｉｉｔａの両アレルノックアウト | |
| JP2025529546A (ja) | Ｃｉｓｈの両アレルノックアウト | |
| WO2025179221A1 (en) | Compositions and methods for armored cell based therapies | |
| JP2025529542A (ja) | Ｈｌａ－ｅの両アレルノックアウト | |
| JP2025529544A (ja) | Ｃｔｌａ４の両アレルノックアウト | |
| JP2025529545A (ja) | Ｆａｓｌｇの両アレルノックアウト | |
| JP2024513232A (ja) | 薬物で調節可能な転写リプレッサー | |
| Le Guiner et al. | Effective Limb Transduction and Phenotypic Correction after Injection of rAAV8-U7 snRNA in GRMD Dogs | |
| Enhancer-Blocking | RNA ViRus VectoRs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130405 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130405 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140827 |
|
| RD13 | Notification of appointment of power of sub attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7433 Effective date: 20141118 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141125 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20141119 |
|
| 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: 20150317 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150402 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5727458 Country of ref document: JP 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 |