JP6832349B2 - Il−2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット - Google Patents
Il−2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット Download PDFInfo
- Publication number
- JP6832349B2 JP6832349B2 JP2018515180A JP2018515180A JP6832349B2 JP 6832349 B2 JP6832349 B2 JP 6832349B2 JP 2018515180 A JP2018515180 A JP 2018515180A JP 2018515180 A JP2018515180 A JP 2018515180A JP 6832349 B2 JP6832349 B2 JP 6832349B2
- Authority
- JP
- Japan
- Prior art keywords
- biomarkers
- level
- hadsc
- biomarker
- individual
- 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
- 108010002350 Interleukin-2 Proteins 0.000 title claims description 556
- 238000000034 method Methods 0.000 title claims description 115
- 238000002560 therapeutic procedure Methods 0.000 title claims description 86
- 210000002901 mesenchymal stem cell Anatomy 0.000 title claims description 54
- 239000000090 biomarker Substances 0.000 claims description 312
- 108090000623 proteins and genes Proteins 0.000 claims description 257
- 230000014509 gene expression Effects 0.000 claims description 214
- 102000004169 proteins and genes Human genes 0.000 claims description 157
- -1 I L-32 Proteins 0.000 claims description 139
- 238000011282 treatment Methods 0.000 claims description 113
- 210000004027 cell Anatomy 0.000 claims description 78
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 claims description 73
- 101001096190 Homo sapiens Pleckstrin homology domain-containing family A member 1 Proteins 0.000 claims description 67
- 102100037862 Pleckstrin homology domain-containing family A member 1 Human genes 0.000 claims description 67
- 101000742579 Homo sapiens Vascular endothelial growth factor B Proteins 0.000 claims description 66
- 102000004889 Interleukin-6 Human genes 0.000 claims description 66
- 108090001005 Interleukin-6 Proteins 0.000 claims description 66
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 claims description 66
- 102100021633 Cathepsin B Human genes 0.000 claims description 65
- 101000898449 Homo sapiens Cathepsin B Proteins 0.000 claims description 65
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 claims description 63
- 102100022188 Dihydropyrimidinase-related protein 1 Human genes 0.000 claims description 62
- 101000900531 Homo sapiens Dihydropyrimidinase-related protein 1 Proteins 0.000 claims description 62
- 102100040683 Fermitin family homolog 1 Human genes 0.000 claims description 57
- 101000892670 Homo sapiens Fermitin family homolog 1 Proteins 0.000 claims description 57
- 101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 claims description 50
- 101001076407 Homo sapiens Interleukin-1 receptor antagonist protein Proteins 0.000 claims description 49
- 101001044895 Homo sapiens Interleukin-20 receptor subunit beta Proteins 0.000 claims description 49
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 claims description 49
- 102100022705 Interleukin-20 receptor subunit beta Human genes 0.000 claims description 49
- 102100031358 Urokinase-type plasminogen activator Human genes 0.000 claims description 49
- 101001096179 Homo sapiens Pleckstrin homology domain-containing family A member 6 Proteins 0.000 claims description 47
- 102100037869 Pleckstrin homology domain-containing family A member 6 Human genes 0.000 claims description 47
- 101000998139 Homo sapiens Interleukin-32 Proteins 0.000 claims description 45
- 230000002411 adverse Effects 0.000 claims description 45
- 102100033501 Interleukin-32 Human genes 0.000 claims description 44
- 239000000203 mixture Substances 0.000 claims description 38
- 206010028980 Neoplasm Diseases 0.000 claims description 29
- 238000003559 RNA-seq method Methods 0.000 claims description 28
- 201000011510 cancer Diseases 0.000 claims description 24
- 102100024454 Apoptosis regulatory protein Siva Human genes 0.000 claims description 23
- 101000688963 Homo sapiens Apoptosis regulatory protein Siva Proteins 0.000 claims description 23
- 238000003556 assay Methods 0.000 claims description 21
- 230000008859 change Effects 0.000 claims description 17
- 238000002054 transplantation Methods 0.000 claims description 15
- 238000000338 in vitro Methods 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 238000005259 measurement Methods 0.000 claims description 13
- 238000012286 ELISA Assay Methods 0.000 claims description 9
- 230000007423 decrease Effects 0.000 claims description 9
- 238000012360 testing method Methods 0.000 claims description 9
- 238000004949 mass spectrometry Methods 0.000 claims description 8
- 230000002055 immunohistochemical effect Effects 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 6
- 101100337774 Arabidopsis thaliana GRF2 gene Proteins 0.000 claims 5
- 102000008640 interleukin-21 receptor activity proteins Human genes 0.000 claims 5
- 108040002099 interleukin-21 receptor activity proteins Proteins 0.000 claims 5
- 238000001190 Q-PCR Methods 0.000 claims 4
- 238000003364 immunohistochemistry Methods 0.000 claims 1
- 102000000588 Interleukin-2 Human genes 0.000 description 524
- 230000000638 stimulation Effects 0.000 description 195
- 230000028327 secretion Effects 0.000 description 166
- 239000002609 medium Substances 0.000 description 104
- 238000011534 incubation Methods 0.000 description 96
- 239000000523 sample Substances 0.000 description 82
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 59
- 230000032683 aging Effects 0.000 description 58
- 101000827763 Drosophila melanogaster Fibroblast growth factor receptor homolog 1 Proteins 0.000 description 57
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 55
- 230000037361 pathway Effects 0.000 description 54
- 102100024289 Metalloproteinase inhibitor 4 Human genes 0.000 description 53
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 53
- 108010010057 TYK2 Kinase Proteins 0.000 description 53
- 108010017411 Interleukin-21 Receptors Proteins 0.000 description 52
- 102100030699 Interleukin-21 receptor Human genes 0.000 description 52
- 108050006579 Metalloproteinase inhibitor 4 Proteins 0.000 description 51
- 102000003815 Interleukin-11 Human genes 0.000 description 49
- 108090000177 Interleukin-11 Proteins 0.000 description 49
- 102100025234 Receptor of activated protein C kinase 1 Human genes 0.000 description 49
- 108010044157 Receptors for Activated C Kinase Proteins 0.000 description 49
- 229940074383 interleukin-11 Drugs 0.000 description 49
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 48
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 48
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 46
- 108010082684 Transforming Growth Factor-beta Type II Receptor Proteins 0.000 description 45
- 102000004060 Transforming Growth Factor-beta Type II Receptor Human genes 0.000 description 45
- 102100033096 Interleukin-17D Human genes 0.000 description 44
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 43
- 108091011896 CSF1 Proteins 0.000 description 43
- 102100028413 Fibroblast growth factor 11 Human genes 0.000 description 43
- 102100035292 Fibroblast growth factor 14 Human genes 0.000 description 43
- 101000917236 Homo sapiens Fibroblast growth factor 11 Proteins 0.000 description 43
- 101000878181 Homo sapiens Fibroblast growth factor 14 Proteins 0.000 description 43
- 101000655536 Homo sapiens Transforming growth factor-beta receptor-associated protein 1 Proteins 0.000 description 43
- 102100032349 Transforming growth factor-beta receptor-associated protein 1 Human genes 0.000 description 43
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 43
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 42
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 42
- 101000998176 Homo sapiens Interleukin-17D Proteins 0.000 description 42
- 210000004623 platelet-rich plasma Anatomy 0.000 description 36
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 35
- 230000010076 replication Effects 0.000 description 34
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 33
- 102000019034 Chemokines Human genes 0.000 description 27
- 108010012236 Chemokines Proteins 0.000 description 27
- 239000003446 ligand Substances 0.000 description 27
- 238000013508 migration Methods 0.000 description 24
- 230000001105 regulatory effect Effects 0.000 description 20
- 206010027476 Metastases Diseases 0.000 description 19
- 230000033115 angiogenesis Effects 0.000 description 19
- 230000004044 response Effects 0.000 description 19
- 238000003753 real-time PCR Methods 0.000 description 18
- 210000000130 stem cell Anatomy 0.000 description 18
- 230000005012 migration Effects 0.000 description 17
- 102000004127 Cytokines Human genes 0.000 description 16
- 108090000695 Cytokines Proteins 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 230000009401 metastasis Effects 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 230000008236 biological pathway Effects 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 239000003102 growth factor Substances 0.000 description 13
- 230000002103 transcriptional effect Effects 0.000 description 13
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 12
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 12
- 210000001744 T-lymphocyte Anatomy 0.000 description 12
- 230000002424 anti-apoptotic effect Effects 0.000 description 12
- 230000002519 immonomodulatory effect Effects 0.000 description 12
- 230000003827 upregulation Effects 0.000 description 12
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 11
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 11
- 230000000875 corresponding effect Effects 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- 238000013518 transcription Methods 0.000 description 11
- 230000035897 transcription Effects 0.000 description 11
- 102100031775 Leptin receptor Human genes 0.000 description 10
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 108010019813 leptin receptors Proteins 0.000 description 10
- 230000003248 secreting effect Effects 0.000 description 10
- 102000006573 Chemokine CXCL12 Human genes 0.000 description 9
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 9
- 102000003968 Fibroblast growth factor 6 Human genes 0.000 description 9
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 description 9
- 102000007005 Interleukin-1 Type II Receptors Human genes 0.000 description 9
- 108010008144 Interleukin-1 Type II Receptors Proteins 0.000 description 9
- 102100026016 Interleukin-1 receptor type 1 Human genes 0.000 description 9
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 9
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 9
- 102100022205 Tumor necrosis factor receptor superfamily member 21 Human genes 0.000 description 9
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 9
- 230000010094 cellular senescence Effects 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 description 8
- 101000679921 Homo sapiens Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 description 8
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 8
- 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 8
- 102100024481 Signal transducer and activator of transcription 5A Human genes 0.000 description 8
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 8
- 230000003110 anti-inflammatory effect Effects 0.000 description 8
- 230000009087 cell motility Effects 0.000 description 8
- 230000004069 differentiation Effects 0.000 description 8
- 230000003828 downregulation Effects 0.000 description 8
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 8
- 229940100601 interleukin-6 Drugs 0.000 description 8
- 230000011664 signaling Effects 0.000 description 8
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 7
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 7
- 102000006576 Chemokine CXCL16 Human genes 0.000 description 7
- 108010008957 Chemokine CXCL16 Proteins 0.000 description 7
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 7
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 7
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 7
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 7
- 102000004375 Insulin-like growth factor-binding protein 1 Human genes 0.000 description 7
- 108090000957 Insulin-like growth factor-binding protein 1 Proteins 0.000 description 7
- 102100035010 Interleukin-18 receptor accessory protein Human genes 0.000 description 7
- 102000004890 Interleukin-8 Human genes 0.000 description 7
- 108090001007 Interleukin-8 Proteins 0.000 description 7
- 102100026871 Interleukin-9 Human genes 0.000 description 7
- 108010002335 Interleukin-9 Proteins 0.000 description 7
- 102000016267 Leptin Human genes 0.000 description 7
- 108010092277 Leptin Proteins 0.000 description 7
- 102000004230 Neurotrophin 3 Human genes 0.000 description 7
- 108090000742 Neurotrophin 3 Proteins 0.000 description 7
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 7
- 108010057464 Prolactin Proteins 0.000 description 7
- 102000003946 Prolactin Human genes 0.000 description 7
- 102100040247 Tumor necrosis factor Human genes 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000012292 cell migration Effects 0.000 description 7
- 230000001419 dependent effect Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 229940098448 fibroblast growth factor 7 Drugs 0.000 description 7
- 229940118526 interleukin-9 Drugs 0.000 description 7
- 229940039781 leptin Drugs 0.000 description 7
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 7
- 229940032018 neurotrophin 3 Drugs 0.000 description 7
- 230000003389 potentiating effect Effects 0.000 description 7
- 229940097325 prolactin Drugs 0.000 description 7
- 108010075348 Activated-Leukocyte Cell Adhesion Molecule Proteins 0.000 description 6
- 108010049976 Bone Morphogenetic Protein 5 Proteins 0.000 description 6
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 description 6
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 6
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 6
- 102100024210 CD166 antigen Human genes 0.000 description 6
- 208000005623 Carcinogenesis Diseases 0.000 description 6
- 102100028892 Cardiotrophin-1 Human genes 0.000 description 6
- 102100037241 Endoglin Human genes 0.000 description 6
- 101000830594 Homo sapiens Tumor necrosis factor ligand superfamily member 14 Proteins 0.000 description 6
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 6
- 101710112634 Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 6
- 101710138729 Interleukin-18 receptor accessory protein Proteins 0.000 description 6
- 102000004388 Interleukin-4 Human genes 0.000 description 6
- 108090000978 Interleukin-4 Proteins 0.000 description 6
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 6
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 6
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 6
- 101710204736 Platelet endothelial cell adhesion molecule Proteins 0.000 description 6
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 6
- 102000001708 Protein Isoforms Human genes 0.000 description 6
- 108010029485 Protein Isoforms Proteins 0.000 description 6
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 6
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 6
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 6
- 102000009618 Transforming Growth Factors Human genes 0.000 description 6
- 108010009583 Transforming Growth Factors Proteins 0.000 description 6
- 102100024586 Tumor necrosis factor ligand superfamily member 14 Human genes 0.000 description 6
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 6
- 230000036952 cancer formation Effects 0.000 description 6
- 231100000504 carcinogenesis Toxicity 0.000 description 6
- 108010041776 cardiotrophin 1 Proteins 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000029578 entry into host Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 230000001617 migratory effect Effects 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 6
- 108010064733 Angiotensins Proteins 0.000 description 5
- 102000015427 Angiotensins Human genes 0.000 description 5
- 108050006947 CXC Chemokine Proteins 0.000 description 5
- 102000019388 CXC chemokine Human genes 0.000 description 5
- 102100027995 Collagenase 3 Human genes 0.000 description 5
- 108010036395 Endoglin Proteins 0.000 description 5
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 5
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 5
- 101001128456 Homo sapiens Myosin regulatory light polypeptide 9 Proteins 0.000 description 5
- 101000582936 Homo sapiens Pleckstrin Proteins 0.000 description 5
- 102100039065 Interleukin-1 beta Human genes 0.000 description 5
- 108050001109 Interleukin-1 receptor type 1 Proteins 0.000 description 5
- 102000000646 Interleukin-3 Human genes 0.000 description 5
- 108010002386 Interleukin-3 Proteins 0.000 description 5
- 102100039897 Interleukin-5 Human genes 0.000 description 5
- 108010002616 Interleukin-5 Proteins 0.000 description 5
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 5
- 108010076503 Matrix Metalloproteinase 13 Proteins 0.000 description 5
- 108010016160 Matrix Metalloproteinase 3 Proteins 0.000 description 5
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 5
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 5
- 102100030264 Pleckstrin Human genes 0.000 description 5
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 5
- 102100030416 Stromelysin-1 Human genes 0.000 description 5
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 5
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 5
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 5
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 5
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 5
- 230000000735 allogeneic effect Effects 0.000 description 5
- 230000002001 anti-metastasis Effects 0.000 description 5
- 230000021164 cell adhesion Effects 0.000 description 5
- 230000024245 cell differentiation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229940076264 interleukin-3 Drugs 0.000 description 5
- 229940028885 interleukin-4 Drugs 0.000 description 5
- 229940100602 interleukin-5 Drugs 0.000 description 5
- 238000010232 migration assay Methods 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 5
- 229940072041 transforming growth factor beta 2 Drugs 0.000 description 5
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 4
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 4
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 4
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 4
- 101000897959 Homo sapiens Endothelial cell-specific molecule 1 Proteins 0.000 description 4
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 4
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 4
- 102100039060 Interleukin enhancer-binding factor 2 Human genes 0.000 description 4
- 108010057368 Interleukin-1 Type I Receptors Proteins 0.000 description 4
- 108010065805 Interleukin-12 Proteins 0.000 description 4
- 102000013462 Interleukin-12 Human genes 0.000 description 4
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 4
- 101800003050 Interleukin-16 Proteins 0.000 description 4
- 102000049772 Interleukin-16 Human genes 0.000 description 4
- 108010060632 Interleukin-2 Receptor beta Subunit Proteins 0.000 description 4
- 102000008193 Interleukin-2 Receptor beta Subunit Human genes 0.000 description 4
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 4
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 4
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 description 4
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 4
- 102100031787 Myosin regulatory light polypeptide 9 Human genes 0.000 description 4
- 108010025020 Nerve Growth Factor Proteins 0.000 description 4
- 102000007072 Nerve Growth Factors Human genes 0.000 description 4
- 108700031302 Nuclear Factor 45 Proteins 0.000 description 4
- 102100029837 Probetacellulin Human genes 0.000 description 4
- 108010019674 Proto-Oncogene Proteins c-sis Proteins 0.000 description 4
- 102100032350 Protransforming growth factor alpha Human genes 0.000 description 4
- 101150058731 STAT5A gene Proteins 0.000 description 4
- 101150063267 STAT5B gene Proteins 0.000 description 4
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 4
- 108010092867 Transforming Growth Factor beta Receptors Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 238000002659 cell therapy Methods 0.000 description 4
- 102000008373 cell-cell adhesion mediator activity proteins Human genes 0.000 description 4
- 108040002566 cell-cell adhesion mediator activity proteins Proteins 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 210000002950 fibroblast Anatomy 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 102000046949 human MSC Human genes 0.000 description 4
- 101150095658 ilf2 gene Proteins 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000003900 neurotrophic factor Substances 0.000 description 4
- 238000010606 normalization Methods 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 238000003908 quality control method Methods 0.000 description 4
- 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 3
- 102100025240 CD320 antigen Human genes 0.000 description 3
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 3
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 108010024212 E-Selectin Proteins 0.000 description 3
- 102100023471 E-selectin Human genes 0.000 description 3
- 102000012545 EGF-like domains Human genes 0.000 description 3
- 108050002150 EGF-like domains Proteins 0.000 description 3
- 102100021860 Endothelial cell-specific molecule 1 Human genes 0.000 description 3
- 102000003969 Fibroblast growth factor 4 Human genes 0.000 description 3
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 3
- 102100020715 Fms-related tyrosine kinase 3 ligand protein Human genes 0.000 description 3
- 101710162577 Fms-related tyrosine kinase 3 ligand protein Proteins 0.000 description 3
- 102100020997 Fractalkine Human genes 0.000 description 3
- 101000934335 Homo sapiens CD320 antigen Proteins 0.000 description 3
- 101001044940 Homo sapiens Insulin-like growth factor-binding protein 2 Proteins 0.000 description 3
- 101001010600 Homo sapiens Interleukin-12 subunit alpha Proteins 0.000 description 3
- 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 3
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 3
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 3
- 101000830598 Homo sapiens Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 3
- 101000830600 Homo sapiens Tumor necrosis factor ligand superfamily member 13 Proteins 0.000 description 3
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 3
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 102100022710 Insulin-like growth factor-binding protein 2 Human genes 0.000 description 3
- 102000004369 Insulin-like growth factor-binding protein 4 Human genes 0.000 description 3
- 108090000969 Insulin-like growth factor-binding protein 4 Proteins 0.000 description 3
- 102000004883 Insulin-like growth factor-binding protein 6 Human genes 0.000 description 3
- 108090001014 Insulin-like growth factor-binding protein 6 Proteins 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102000013691 Interleukin-17 Human genes 0.000 description 3
- 108050003558 Interleukin-17 Proteins 0.000 description 3
- 102100035017 Interleukin-18-binding protein Human genes 0.000 description 3
- 108010067003 Interleukin-33 Proteins 0.000 description 3
- 102000017761 Interleukin-33 Human genes 0.000 description 3
- 102000010786 Interleukin-5 Receptors Human genes 0.000 description 3
- 108010038484 Interleukin-5 Receptors Proteins 0.000 description 3
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 108010092694 L-Selectin Proteins 0.000 description 3
- 102100033467 L-selectin Human genes 0.000 description 3
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 3
- 102000003683 Neurotrophin-4 Human genes 0.000 description 3
- 108090000099 Neurotrophin-4 Proteins 0.000 description 3
- 206010067482 No adverse event Diseases 0.000 description 3
- 108010010424 Nuclear Factor 90 Proteins Proteins 0.000 description 3
- 102000015863 Nuclear Factor 90 Proteins Human genes 0.000 description 3
- 102100024474 Signal transducer and activator of transcription 5B Human genes 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 102000043168 TGF-beta family Human genes 0.000 description 3
- 108091085018 TGF-beta family Proteins 0.000 description 3
- 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 description 3
- 102100024585 Tumor necrosis factor ligand superfamily member 13 Human genes 0.000 description 3
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 3
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 3
- 102100024537 Tyrosine-protein kinase Fer Human genes 0.000 description 3
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 3
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 3
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 3
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 3
- 101150030763 Vegfa gene Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000006909 anti-apoptosis Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000003491 array Methods 0.000 description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 230000008472 epithelial growth Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 108010019691 inhibin beta A subunit Proteins 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 102000044166 interleukin-18 binding protein Human genes 0.000 description 3
- 108010070145 interleukin-18 binding protein Proteins 0.000 description 3
- 108040006849 interleukin-2 receptor activity proteins Proteins 0.000 description 3
- 229940096397 interleukin-8 Drugs 0.000 description 3
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000003147 molecular marker Substances 0.000 description 3
- 229940097998 neurotrophin 4 Drugs 0.000 description 3
- 230000003076 paracrine Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108010067366 proto-oncogene protein c-fes-fps Proteins 0.000 description 3
- 230000003716 rejuvenation Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 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 3
- 238000011222 transcriptome analysis Methods 0.000 description 3
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 2
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 2
- 102100036409 Activated CDC42 kinase 1 Human genes 0.000 description 2
- 102100034594 Angiopoietin-1 Human genes 0.000 description 2
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 2
- 101710131689 Angiopoietin-1 receptor Proteins 0.000 description 2
- 102100034608 Angiopoietin-2 Human genes 0.000 description 2
- 102100025672 Angiopoietin-related protein 2 Human genes 0.000 description 2
- 102100034599 Angiopoietin-related protein 6 Human genes 0.000 description 2
- 108010081589 Becaplermin Proteins 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 108010049974 Bone Morphogenetic Protein 6 Proteins 0.000 description 2
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 2
- 102100036848 C-C motif chemokine 20 Human genes 0.000 description 2
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 2
- 102100031184 C-Maf-inducing protein Human genes 0.000 description 2
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 2
- 102100036153 C-X-C motif chemokine 6 Human genes 0.000 description 2
- 102100032528 C-type lectin domain family 11 member A Human genes 0.000 description 2
- 102100035793 CD83 antigen Human genes 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102100038768 Carbohydrate sulfotransferase 3 Human genes 0.000 description 2
- 102100024940 Cathepsin K Human genes 0.000 description 2
- 108010019961 Cysteine-Rich Protein 61 Proteins 0.000 description 2
- 102000005889 Cysteine-Rich Protein 61 Human genes 0.000 description 2
- 102100038591 Endothelial cell-selective adhesion molecule Human genes 0.000 description 2
- 102100021579 Enhancer of filamentation 1 Human genes 0.000 description 2
- 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 2
- 101100393214 Escherichia coli O157:H7 gnu gene Proteins 0.000 description 2
- 102100023637 FYVE, RhoGEF and PH domain-containing protein 6 Human genes 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 description 2
- 101710088083 Glomulin Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 101000928956 Homo sapiens Activated CDC42 kinase 1 Proteins 0.000 description 2
- 101000924552 Homo sapiens Angiopoietin-1 Proteins 0.000 description 2
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 2
- 101000693081 Homo sapiens Angiopoietin-related protein 2 Proteins 0.000 description 2
- 101000924549 Homo sapiens Angiopoietin-related protein 6 Proteins 0.000 description 2
- 101000713099 Homo sapiens C-C motif chemokine 20 Proteins 0.000 description 2
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 2
- 101000993081 Homo sapiens C-Maf-inducing protein Proteins 0.000 description 2
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 2
- 101000942297 Homo sapiens C-type lectin domain family 11 member A Proteins 0.000 description 2
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 2
- 101000882992 Homo sapiens Carbohydrate sulfotransferase 3 Proteins 0.000 description 2
- 101000761509 Homo sapiens Cathepsin K Proteins 0.000 description 2
- 101000740970 Homo sapiens Cathepsin O Proteins 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101000882622 Homo sapiens Endothelial cell-selective adhesion molecule Proteins 0.000 description 2
- 101000898310 Homo sapiens Enhancer of filamentation 1 Proteins 0.000 description 2
- 101000827814 Homo sapiens FYVE, RhoGEF and PH domain-containing protein 6 Proteins 0.000 description 2
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 description 2
- 101000903806 Homo sapiens Inactive glycosyltransferase 25 family member 3 Proteins 0.000 description 2
- 101001002695 Homo sapiens Integrin-linked protein kinase Proteins 0.000 description 2
- 101000852483 Homo sapiens Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 2
- 101000977768 Homo sapiens Interleukin-1 receptor-associated kinase 3 Proteins 0.000 description 2
- 101001008949 Homo sapiens Kinesin-like protein KIF14 Proteins 0.000 description 2
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 2
- 101000645296 Homo sapiens Metalloproteinase inhibitor 2 Proteins 0.000 description 2
- 101000831266 Homo sapiens Metalloproteinase inhibitor 4 Proteins 0.000 description 2
- 101001128156 Homo sapiens Nanos homolog 3 Proteins 0.000 description 2
- 101001124309 Homo sapiens Nitric oxide synthase, endothelial Proteins 0.000 description 2
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 2
- 101001126234 Homo sapiens Phospholipid phosphatase 3 Proteins 0.000 description 2
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 2
- 101000605122 Homo sapiens Prostaglandin G/H synthase 1 Proteins 0.000 description 2
- 101001051777 Homo sapiens Protein kinase C alpha type Proteins 0.000 description 2
- 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 2
- 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 2
- 101000852716 Homo sapiens T-cell immunomodulatory protein Proteins 0.000 description 2
- 101000598030 Homo sapiens Talin-2 Proteins 0.000 description 2
- 101000723923 Homo sapiens Transcription factor HIVEP2 Proteins 0.000 description 2
- 101000635938 Homo sapiens Transforming growth factor beta-1 proprotein Proteins 0.000 description 2
- 101000894525 Homo sapiens Transforming growth factor-beta-induced protein ig-h3 Proteins 0.000 description 2
- 101000800807 Homo sapiens Tumor necrosis factor alpha-induced protein 8 Proteins 0.000 description 2
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 2
- 101000801228 Homo sapiens Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 2
- 101000679903 Homo sapiens Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 description 2
- 101000965721 Homo sapiens Volume-regulated anion channel subunit LRRC8A Proteins 0.000 description 2
- 101000723920 Homo sapiens Zinc finger protein 40 Proteins 0.000 description 2
- 101150083678 IL2 gene Proteins 0.000 description 2
- 102100022966 Inactive glycosyltransferase 25 family member 3 Human genes 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 102100027004 Inhibin beta A chain Human genes 0.000 description 2
- 102100020944 Integrin-linked protein kinase Human genes 0.000 description 2
- 108010064600 Intercellular Adhesion Molecule-3 Proteins 0.000 description 2
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 2
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 2
- 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 2
- 102100023530 Interleukin-1 receptor-associated kinase 3 Human genes 0.000 description 2
- 108010017550 Interleukin-10 Receptors Proteins 0.000 description 2
- 102000004551 Interleukin-10 Receptors Human genes 0.000 description 2
- 102000003810 Interleukin-18 Human genes 0.000 description 2
- 108090000171 Interleukin-18 Proteins 0.000 description 2
- 108010066979 Interleukin-27 Proteins 0.000 description 2
- 102100021592 Interleukin-7 Human genes 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 102100027631 Kinesin-like protein KIF14 Human genes 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 2
- 102100030450 Phospholipid phosphatase 3 Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 2
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
- 101710164680 Platelet-derived growth factor receptor beta Proteins 0.000 description 2
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 2
- 101710186503 Probetacellulin Proteins 0.000 description 2
- 102100023832 Prolyl endopeptidase FAP Human genes 0.000 description 2
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 2
- 102100024924 Protein kinase C alpha type Human genes 0.000 description 2
- 108010026552 Proteome Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 2
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 2
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 2
- 102100029957 Sialic acid-binding Ig-like lectin 5 Human genes 0.000 description 2
- 101710110535 Sialic acid-binding Ig-like lectin 5 Proteins 0.000 description 2
- 229940126530 T cell activator Drugs 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- 102100036378 T-cell immunomodulatory protein Human genes 0.000 description 2
- 102100036980 Talin-2 Human genes 0.000 description 2
- 102000036693 Thrombopoietin Human genes 0.000 description 2
- 108010041111 Thrombopoietin Proteins 0.000 description 2
- 102100028438 Transcription factor HIVEP2 Human genes 0.000 description 2
- 102100030742 Transforming growth factor beta-1 proprotein Human genes 0.000 description 2
- 102100021398 Transforming growth factor-beta-induced protein ig-h3 Human genes 0.000 description 2
- 102100033649 Tumor necrosis factor alpha-induced protein 8 Human genes 0.000 description 2
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 2
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 2
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 2
- 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 description 2
- 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 2
- 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 2
- 102100040985 Volume-regulated anion channel subunit LRRC8A Human genes 0.000 description 2
- 102100028440 Zinc finger protein 40 Human genes 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 108010023082 activin A Proteins 0.000 description 2
- 108700025316 aldesleukin Proteins 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 230000008235 cell cycle pathway Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 230000003399 chemotactic effect Effects 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 230000001427 coherent effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000009274 differential gene expression Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 238000011124 ex vivo culture Methods 0.000 description 2
- 238000010195 expression analysis Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 102000002467 interleukin receptors Human genes 0.000 description 2
- 108010093036 interleukin receptors Proteins 0.000 description 2
- 229940117681 interleukin-12 Drugs 0.000 description 2
- 229940100994 interleukin-7 Drugs 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000013074 reference sample Substances 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- BWRRWBIBNBVHQF-UHFFFAOYSA-N 4-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2N=CC=CC=2)=N1 BWRRWBIBNBVHQF-UHFFFAOYSA-N 0.000 description 1
- ROMPPAWVATWIKR-UHFFFAOYSA-N 4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2C=CC(Cl)=CC=2)=N1 ROMPPAWVATWIKR-UHFFFAOYSA-N 0.000 description 1
- 102100022464 5'-nucleotidase Human genes 0.000 description 1
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- 108091023043 Alu Element Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102100023703 C-C motif chemokine 15 Human genes 0.000 description 1
- 102000000905 Cadherin Human genes 0.000 description 1
- 108050007957 Cadherin Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102100024851 Cell growth regulator with EF hand domain protein 1 Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108010082548 Chemokine CCL11 Proteins 0.000 description 1
- 102000006383 Chemokine CCL24 Human genes 0.000 description 1
- 108010083647 Chemokine CCL24 Proteins 0.000 description 1
- 108010083698 Chemokine CCL26 Proteins 0.000 description 1
- 102000006440 Chemokine CCL26 Human genes 0.000 description 1
- 102000014464 Chemokine CX3CL1 Human genes 0.000 description 1
- 108010014423 Chemokine CXCL6 Proteins 0.000 description 1
- 102100035396 Cingulin-like protein 1 Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 102000005754 Cytokine Receptor gp130 Human genes 0.000 description 1
- 108010006197 Cytokine Receptor gp130 Proteins 0.000 description 1
- 102100028630 Cytoskeleton-associated protein 2 Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000978376 Homo sapiens C-C motif chemokine 15 Proteins 0.000 description 1
- 101000947177 Homo sapiens C-X-C motif chemokine 6 Proteins 0.000 description 1
- 101000979919 Homo sapiens Cell growth regulator with EF hand domain protein 1 Proteins 0.000 description 1
- 101000737619 Homo sapiens Cingulin-like protein 1 Proteins 0.000 description 1
- 101000766848 Homo sapiens Cytoskeleton-associated protein 2 Proteins 0.000 description 1
- 101000881679 Homo sapiens Endoglin Proteins 0.000 description 1
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 description 1
- 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 1
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 1
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101000960952 Homo sapiens Interleukin-1 receptor accessory protein Proteins 0.000 description 1
- 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 description 1
- 101001003140 Homo sapiens Interleukin-15 receptor subunit alpha Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101000804764 Homo sapiens Lymphotactin Proteins 0.000 description 1
- 101000987144 Homo sapiens Molybdenum cofactor sulfurase Proteins 0.000 description 1
- 101001126417 Homo sapiens Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 101001073427 Homo sapiens Prostaglandin E2 receptor EP1 subtype Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101100421141 Homo sapiens SELENON gene Proteins 0.000 description 1
- 101000864743 Homo sapiens Secreted frizzled-related protein 1 Proteins 0.000 description 1
- 101000701446 Homo sapiens Stanniocalcin-2 Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 101000772194 Homo sapiens Transthyretin Proteins 0.000 description 1
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 description 1
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 101000606129 Homo sapiens Tyrosine-protein kinase receptor TYRO3 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000004372 Insulin-like growth factor binding protein 2 Human genes 0.000 description 1
- 108090000964 Insulin-like growth factor binding protein 2 Proteins 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102100025304 Integrin beta-1 Human genes 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102100039880 Interleukin-1 receptor accessory protein Human genes 0.000 description 1
- 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 description 1
- 101710194995 Interleukin-12 subunit alpha Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 102100020789 Interleukin-15 receptor subunit alpha Human genes 0.000 description 1
- 108010058010 Interleukin-18 Receptor beta Subunit Proteins 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 101710197067 Lectin 5 Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102100035304 Lymphotactin Human genes 0.000 description 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
- 241000590503 Melanitis Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108050006599 Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 108050006602 Metalloproteinase inhibitor 2 Proteins 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 206010050513 Metastatic renal cell carcinoma Diseases 0.000 description 1
- 102100030979 Methylmalonyl-CoA mutase, mitochondrial Human genes 0.000 description 1
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
- 101000597780 Mus musculus Tumor necrosis factor ligand superfamily member 18 Proteins 0.000 description 1
- 101150031207 NOS3 gene Proteins 0.000 description 1
- 102100031893 Nanos homolog 3 Human genes 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 1
- 102100035842 Prostaglandin E2 receptor EP1 subtype Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 235000014443 Pyrus communis Nutrition 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 101710146873 Receptor-binding protein Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 101150052608 SIVA1 gene Proteins 0.000 description 1
- 102100030058 Secreted frizzled-related protein 1 Human genes 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 102100023781 Selenoprotein N Human genes 0.000 description 1
- 108010042291 Serum Response Factor Proteins 0.000 description 1
- 102100022056 Serum response factor Human genes 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 230000033540 T cell apoptotic process Effects 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 1
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 102100029290 Transthyretin Human genes 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 101710187751 Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 1
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 1
- 102100039127 Tyrosine-protein kinase receptor TYRO3 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 102000013814 Wnt Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 102000019997 adhesion receptor Human genes 0.000 description 1
- 108010013985 adhesion receptor Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 229960005310 aldesleukin Drugs 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 208000010928 autoimmune thyroid disease Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 210000000803 cardiac myoblast Anatomy 0.000 description 1
- 230000022159 cartilage development Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000021953 cytokinesis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- WOERBKLLTSWFBY-UHFFFAOYSA-M dihydrogen phosphate;tetramethylazanium Chemical compound C[N+](C)(C)C.OP(O)([O-])=O WOERBKLLTSWFBY-UHFFFAOYSA-M 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000010201 enrichment analysis Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000002431 foraging effect Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 230000037189 immune system physiology Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 230000024949 interleukin-17 production Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000004132 lipogenesis Effects 0.000 description 1
- 238000007443 liposuction Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000003643 myeloid progenitor cell Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 235000003170 nutritional factors Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000002135 phase contrast microscopy Methods 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000010469 pro-virus integration Effects 0.000 description 1
- 229940087463 proleukin Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 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 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
- 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
- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
- C07K16/246—IL-2
-
- 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
- C12N5/0018—Culture media for cell or tissue culture
-
- 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)
-
- 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
- C12N5/0667—Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2302—Interleukin-2 (IL-2)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/65—MicroRNA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4703—Regulators; Modulating activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/475—Assays involving growth factors
- G01N2333/495—Transforming growth factor [TGF]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/55—IL-2
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
- G01N2333/91205—Phosphotransferases in general
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96466—Cysteine endopeptidases (3.4.22)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96486—Metalloendopeptidases (3.4.24)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Developmental Biology & Embryology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
Description
本出願は、2015年6月3日に出願された米国仮出願番号第62/170,604号、2015年6月3日に出願された米国仮出願番号第62/170,619号、および2015年6月12日に出願された米国仮出願番号第62/175,203号に基づく優先権を主張しており、これら仮出願の各々は、それらの全体が参考として本明細書中に援用される。
インターロイキン2(IL−2)は、免疫系におけるサイトカインシグナル伝達分子の一種であり、治療法として使用される。IL−2は、組換えDNA技術を使用して製造され、アルデスロイキン(Proleukin(登録商標)の商標)と呼ばれるタンパク質治療薬として販売されている。IL−2は、がん(転移性メラノーマおよび腎細胞癌)およびHIVの処置のために数か国で承認されている。
ヒト間葉系幹細胞(MSC)は現在、種々の状態を処置するための移植のための幹細胞の主要供給源の1つである(Kucerova、Cancer Res 2007年7月1日、67巻;6304頁)。in vivoでの炎症誘発性または他の面で快適でない環境の存在下におけるこのような移植された幹細胞は、望まれない有害事象を生じ得る。MSCの有益な特性が、その局所的環境によって影響される程度については、ほとんど知られていない。
IL−2に基づく治療法を受けるのに適格な個体またはIL−2に基づく治療法を既に受けている個体が、このIL−2に基づく治療法に伴う有害事象を経験する可能性があるか決定するためのコンパニオン方法およびキットが、本明細書に記載されている。個体が、がん等、根底にある疾患の根絶よりもむしろ、腫瘍発生または転移のリスク増加等、有害事象を経験し得ることが決定された場合、処置決断は、さらなるIL−2に基づく治療法を全く行わないものとすることができる。同様に、個体が、IL−2に基づく治療法に伴う有害事象を経験しない可能性が高いことが決定された場合、IL−2に基づく治療法の投与を開始するか、または続けるように決断を為すことができる。
I.方法
1.序文
IL−2に基づく治療法および間葉系幹細胞に基づく治療法に有用なコンパニオン方法およびキットが、本明細書に提供される。
2.SEN−MSCおよびSR−MSC
3.目的のバイオマーカーの検出
4.目的のバイオマーカーの同一性
5.IL−2治療法のためのコンパニオン方法
6.細胞に基づく治療法における使用に先立つMSCの品質管理
II.キットおよび製造品
材料および方法
この実施例は、本発明の例示的な方法を提供し、実施例2〜10で後に使用される材料および方法を提供する。
MSCの単離、培養および特徴付け
老化関連のSA−βガラクトシダーゼアッセイ
遊走および浸潤アッセイ
酵素結合免疫吸着検定法(ELISA)
リアルタイム定量的ポリメラーゼ連鎖反応
RNA−seqデータ分析
(実施例2)
MSC老化表現型の特徴付け
(実施例3)
SEN−MSCは、遊走のより高い傾向を示す
(実施例4)
複製老化の際のヒト脂肪由来MSCにおけるIl−2刺激への差次的応答
(実施例5)
Il−2刺激後のhADSCの栄養特性は、ex vivo複製加齢に感受性である
IL−2に曝露させたヒトMSCの抗炎症および免疫調節特性
(実施例7)
複製老化の際のIL−2刺激hADSCの抗アポトーシスおよび転移促進特性
(実施例8)
転写プロファイリングは、複製老化の際にIL−2刺激hADSCで強化された遊走および血管新生を調節する遺伝子標的を示す
(実施例9)
プロテオーム抗体アレイデータ
特定の実施形態では、例えば以下の項目が提供される。
(項目1)
IL−2に基づく治療法を受けるのに適格な個体が、前記IL−2に基づく治療法に伴う有害事象を経験し得るか決定する方法であって、
(a)前記個体由来の試料における、バイオマーカーのパネルから選択される少なくとも2種のバイオマーカーの発現レベルを測定するステップであって、(1)前記個体が、少なくとも1用量のIL−2に基づく治療法を受けたことがある、または(2)前記試料が、in vitroでIL−2と組み合わされるのいずれかであり、前記バイオマーカーのパネルが、TIE−1、TIE−2、TIMP−4、FGF1、LIF、TGFBR2、CSF1、TGFα、TGFβ1、IL17D、SDF2、TGFBRAP1、FGF11、TNFSF13B、FGF14、IL1β、IL−11、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、GNB2L1、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むステップと、
(b)前記バイオマーカーのレベルを参照レベルと比較するステップであって、前記参照レベルを上回る前記レベルの増加が、前記個体が前記IL−2に基づく治療法に伴う有害事象を経験し得ることを示し、前記参照レベルと比較した前記レベルの減少または変化なしが、前記個体が前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることを示すステップと
を含む方法。
(項目2)
前記個体が、少なくとも1用量のIL−2に基づく治療法を受けたことがある、項目1に記載の方法。
(項目3)
前記個体が、がんの処置のために前記IL−2に基づく治療法を受けたことがある、項目2に記載の方法。
(項目4)
前記試料が、前記IL−2に基づく治療法を受けてから24、48または72時間後に前記個体から得られた、項目2に記載の方法。
(項目5)
前記試料が、in vitroでIL−2と組み合わされる、項目1に記載の方法。
(項目6)
前記試料が、IL−2と約24時間組み合わされる、項目5に記載の方法。
(項目7)
前記発現レベルが、前記試料からのIL−2の除去から24、48または72時間後に測定される、項目5に記載の方法。
(項目8)
前記バイオマーカーのパネル由来の少なくとも3種のバイオマーカーの発現レベルを測定するステップを含む、項目1に記載の方法。
(項目9)
前記バイオマーカーのパネル由来の少なくとも4種のバイオマーカーの発現レベルを測定するステップを含む、項目1に記載の方法。
(項目10)
前記バイオマーカーのパネル由来の少なくとも5種のバイオマーカーの発現レベルを測定するステップを含む、項目1に記載の方法。
(項目11)
TIE−1、TIE−2、TIMP−4、VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSB、PLEKHA6、GNB2L1およびTGFβ1の発現レベルを測定するステップを含む、項目1に記載の方法。
(項目12)
SIVA1のレベルを測定するステップをさらに含む、項目1に記載の方法。
(項目13)
前記バイオマーカーのタンパク質レベルを測定するステップを含む、項目1に記載の方法。
(項目14)
前記測定ステップが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により為される、項目13に記載の方法。
(項目15)
前記バイオマーカーのRNAレベルを測定するステップを含む、項目1に記載の方法。
(項目16)
前記測定ステップが、Q−PCRアッセイまたはRNA−seqにより為される、項目15に記載の方法。
(項目17)
前記個体から試料を得るステップをさらに含む、項目1に記載の方法。
(項目18)
前記試料が、血液、血漿または血清試料である、項目1に記載の方法。
(項目19)
ステップ(b)において、前記個体が、前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることが決定された場合、有効量の前記IL−2に基づく治療法を前記個体に投与するステップをさらに含む、項目1に記載の方法。
(項目20)
ステップ(b)において、前記個体が、前記IL−2に基づく治療法に伴う有害事象を経験し得ることが決定された場合、前記個体に若返り治療法を投与するステップをさらに含む、項目1に記載の方法。
(項目21)
IL−2に基づく治療法によりがんに関して個体を処置する方法であって、
(a)前記個体由来の試料における、バイオマーカーのパネルから選択される少なくとも2種のバイオマーカーの発現レベルを測定するステップであって、(1)前記個体が、少なくとも1用量のIL−2に基づく治療法を受けたことがある、または(2)前記試料が、in vitroでIL−2と組み合わされるのいずれかであり、前記バイオマーカーのパネルが、TIE−1、TIE−2、TIMP−4、FGF1、LIF、TGFBR2、CSF1、TGFα、TGFβ1、IL17D、SDF2、TGFBRAP1、FGF11、TNFSF13B、FGF14、IL1B、IL−11、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、GNB2L1、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むステップと、
(b)前記バイオマーカーのレベルを参照レベルと比較するステップであって、前記レベルの変化なしまたは前記参照レベルを下回る減少が、前記個体が、前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることを示すステップと、
(c)ステップ(b)において、前記個体が、前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることが決定された場合、有効量の前記IL−2に基づく治療法を前記個体に投与するステップと
を含む方法。
(項目22)
前記個体が、少なくとも1用量のIL−2に基づく治療法を受けたことがある、項目21に記載の方法。
(項目23)
前記個体が、がんの処置のために前記IL−2に基づく治療法を受けたことがある、項目22に記載の方法。
(項目24)
前記試料が、前記IL−2に基づく治療法を受けてから24、48または72時間後に前記個体から得られた、項目22に記載の方法。
(項目25)
前記試料が、in vitroでIL−2と組み合わされる、項目21に記載の方法。
(項目26)
前記試料が、IL−2と約24時間組み合わされる、項目25に記載の方法。
(項目27)
前記発現レベルが、前記試料からのIL−2の除去から24、48または72時間後に測定される、項目25に記載の方法。
(項目28)
前記バイオマーカーのパネル由来の少なくとも3種のバイオマーカーの発現レベルを測定するステップを含む、項目21に記載の方法。
(項目29)
前記バイオマーカーのパネル由来の少なくとも4種のバイオマーカーの発現レベルを測定するステップを含む、項目21に記載の方法。
(項目30)
前記バイオマーカーのパネル由来の少なくとも5種のバイオマーカーの発現レベルを測定するステップを含む、項目21に記載の方法。
(項目31)
TIE−1、TIE−2、TIMP−4、VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSB、PLEKHA6、GNB2L1およびTGFβ1の発現レベルを測定するステップを含む、項目21に記載の方法。
(項目32)
SIVA1のレベルを測定するステップをさらに含む、項目21に記載の方法。
(項目33)
前記バイオマーカーのタンパク質レベルを測定するステップを含む、項目21に記載の方法。
(項目34)
前記測定ステップが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により為される、項目33に記載の方法。
(項目35)
前記バイオマーカーのRNAレベルを測定するステップを含む、項目21に記載の方法。
(項目36)
前記測定ステップが、Q−PCRアッセイまたはRNA−seqにより為される、項目35に記載の方法。
(項目37)
前記個体から試料を得るステップをさらに含む、項目21に記載の方法。
(項目38)
前記試料が、血液、血漿または血清試料を含む、項目21に記載の方法。
(項目39)
IL−2に基づく治療法によりがんに関して個体を処置する方法であって、少なくとも2種のバイオマーカーの発現レベルが、前記個体由来の試料において、参照レベルと比較して減少するか、または変化を示さない場合、有効量の前記IL−2に基づく治療法を前記個体に投与するステップであって、(1)前記個体が、少なくとも1用量のIL−2に基づく治療法を受けたことがある、または(2)前記試料が、in vitroでIL−2と組み合わされるのいずれかであり、前記バイオマーカーのパネルが、TIE−1、TIE−2、TIMP−4、FGF1、LIF、TGFBR2、CSF1、TGFα、TGFβ1、IL17D、SDF2、TGFBRAP1、FGF11、TNFSF13B、FGF14、IL1B、IL−11、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、GNB2L1、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むステップを含む方法。
(項目40)
前記個体が、少なくとも1用量のIL−2に基づく治療法を受けたことがある、項目39に記載の方法。
(項目41)
前記個体が、がんの処置のために前記IL−2に基づく治療法を受けたことがある、項目40に記載の方法。
(項目42)
前記試料が、前記IL−2に基づく治療法を受けてから24、48または72時間後に前記個体から得られた、項目39に記載の方法。
(項目43)
前記試料が、in vitroでIL−2と組み合わされる、項目39に記載の方法。
(項目44)
前記試料が、IL−2と約24時間組み合わされる、項目43に記載の方法。
(項目45)
前記発現レベルが、in vitroにおける前記試料からのIL−2の除去から24、48または72時間後に測定される、項目43に記載の方法。
(項目46)
前記バイオマーカーのパネル由来の少なくとも3種のバイオマーカーの発現レベルを測定するステップを含む、項目39に記載の方法。
(項目47)
前記バイオマーカーのパネル由来の少なくとも4種のバイオマーカーの発現レベルを測定するステップを含む、項目39に記載の方法。
(項目48)
前記バイオマーカーのパネル由来の少なくとも5種のバイオマーカーの発現レベルを測定するステップを含む、項目39に記載の方法。
(項目49)
TIE−1、TIE−2、TIMP−4、VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSB、PLEKHA6、GNB2L1およびTGFβ1の発現レベルを測定するステップを含む、項目39に記載の方法。
(項目50)
SIVA1のレベルを測定するステップをさらに含む、項目39に記載の方法。
(項目51)
前記バイオマーカーのタンパク質レベルを測定するステップを含む、項目39に記載の方法。
(項目52)
前記測定ステップが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により為される、項目51に記載の方法。
(項目53)
前記バイオマーカーのRNAレベルを測定するステップを含む、項目39に記載の方法。
(項目54)
前記測定ステップが、Q−PCRアッセイまたはRNA−seqにより為される、項目53に記載の方法。
(項目55)
前記試料が、血液、血漿または血清試料を含む、項目39に記載の方法。
(項目56)
間葉系幹細胞(MSC)の集団が、MSCに基づく治療法のための個体への投与に適するか決定する方法であって、
(a)前記MSCの集団と共にIL−2をインキュベートするステップと、
(b)前記MSCにおける、バイオマーカーのパネルから選択される少なくとも2種のバイオマーカーの発現レベルを測定するステップであって、前記バイオマーカーのパネルが、TIE−1、TIE−2、TIMP−4、FGF1、LIF、TGFBR2、CSF1、TGFα、TGFβ1、IL17D、SDF2、TGFBRAP1、FGF11、TNFSF13B、FGF14、IL1B、IL−11、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、GNB2L1、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むステップと、
(c)前記バイオマーカーのレベルを参照レベルと比較するステップであって、前記参照レベルを上回る前記レベルの増加が、前記MSCが、個体への投与に適さないことを示し、前記レベルの変化なしまたは前記参照レベルを下回る減少が、前記MSCが、個体への投与に適することを示すステップと
を含む方法。
(項目57)
前記バイオマーカーのパネル由来の少なくとも3種のバイオマーカーの発現レベルを測定するステップを含む、項目56に記載の方法。
(項目58)
前記バイオマーカーのパネル由来の少なくとも4種のバイオマーカーの発現レベルを測定するステップを含む、項目56に記載の方法。
(項目59)
前記バイオマーカーのパネル由来の少なくとも5種のバイオマーカーの発現レベルを測定するステップを含む、項目56に記載の方法。
(項目60)
TIE−1、TIE−2、TIMP−4、VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSB、PLEKHA6、GNB2L1およびTGFβ1の発現レベルを測定するステップを含む、項目56に記載の方法。
(項目61)
SIVA1のレベルを測定するステップをさらに含む、項目56に記載の方法。
(項目62)
前記バイオマーカーのタンパク質レベルを測定するステップを含む、項目56に記載の方法。
(項目63)
前記測定ステップが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により為される、項目62に記載の方法。
(項目64)
前記バイオマーカーのRNAレベルを測定するステップを含む、項目56に記載の方法。
(項目65)
前記測定ステップが、Q−PCRアッセイまたはRNA−seqにより為される、項目64に記載の方法。
(項目66)
前記細胞が、前記IL−2と共に約24時間インキュベートされる、項目56に記載の方法。
(項目67)
前記測定ステップが、前記IL−2の除去から24、48または72時間後に行われる、項目56に記載の方法。
(項目68)
前記細胞の集団を前記個体に投与するステップをさらに含む、項目56に記載の方法。
(項目69)
前記細胞を若返らせるステップをさらに含む、項目56に記載の方法。
(項目70)
移植に対するMSCの集団の適合性を評価するための、またはIL−2に基づく治療法を投与するべきか決定するためのキットであって、試料におけるバイオマーカーのパネルから選択される少なくとも2種のバイオマーカーの発現レベルを測定するための試薬を含み、前記バイオマーカーのパネルが、TIE−1、TIE−2、TIMP−4、FGF1、LIF、TGFBR2、CSF1、TGFα、TGFβ1、IL17D、SDF2、TGFBRAP1、FGF11、TNFSF13B、FGF14、IL1β、IL−11、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、GNB2L1、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むキット。
(項目71)
前記試料における少なくとも3種のバイオマーカーの発現レベルを測定するための試薬を含む、項目70に記載のキット。
(項目72)
前記試料における少なくとも4種のバイオマーカーの発現レベルを測定するための試薬を含む、項目70に記載のキット。
(項目73)
前記試料における少なくとも5種のバイオマーカーの発現レベルを測定するための試薬を含む、項目70に記載のキット。
(項目74)
TIE−1、TIE−2、TIMP−4、VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSB、PLEKHA6、GNB2L1およびTGFβ1を測定するための試薬を含む、項目70に記載のキット。
(項目75)
IL−2をさらに含む、項目70に記載のキット。
(項目76)
移植に対するMSCの集団の適合性を評価するための、項目70に記載のキット。
(項目77)
IL−2に基づく治療法を投与するべきか決定するための、項目70に記載のキット。
Claims (54)
- バイオマーカーの発現レベルを、IL−2に基づく治療法を受けるのに適格な個体が、前記IL−2に基づく治療法に伴う有害事象を経験し得るか決定するための指標とする方法であって、
(a)ヒト脂肪由来間葉系幹細胞(hADSC)を含む前記個体由来の試料における、バイオマーカーのパネルから選択される少なくとも3種のバイオマーカーの発現レベルを測定するステップであって、前記試料が、in vitroでIL−2と組み合わされ、前記バイオマーカーのパネルが、FGF1、FGF11、FGF14、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むステップと、
(b)前記バイオマーカーのレベルを参照レベルと比較するステップであって、前記参照レベルを上回る前記レベルの増加が、前記個体が前記IL−2に基づく治療法に伴う有害事象を経験し得ることを示し、前記参照レベルと比較した前記レベルの減少または変化なしが、前記個体が前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることを示すステップと
を含む方法。 - 前記試料が、IL−2と約24時間組み合わされる、請求項1に記載の方法。
- 前記発現レベルが、前記試料からのIL−2の除去から24、48または72時間後に測定される、請求項1に記載の方法。
- 前記バイオマーカーのパネルからの少なくとも4種のバイオマーカーの発現レベルを測定するステップを含む、請求項1に記載の方法。
- 前記バイオマーカーのパネルからの少なくとも5種のバイオマーカーの発現レベルを測定するステップを含む、請求項1に記載の方法。
- VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSBおよびPLEKHA6の発現レベルを測定するステップを含む、請求項1に記載の方法。
- SIVA1のレベルを測定するステップをさらに含む、請求項1に記載の方法。
- 前記バイオマーカーのタンパク質レベルを測定するステップを含む、請求項1に記載の方法。
- 前記測定ステップが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により為される、請求項8に記載の方法。
- 前記バイオマーカーのRNAレベルを測定するステップを含む、請求項1に記載の方法。
- 前記測定ステップが、Q−PCRアッセイまたはRNA−seqにより為される、請求項10に記載の方法。
- 試料が、前記個体から得られる、請求項1に記載の方法。
- ステップ(b)において、前記個体が、前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることが決定された場合、前記個体が、有効量の前記IL−2に基づく治療法を受けるために選択される、請求項1に記載の方法。
- IL−2またはその活性部分を含む、がんに関して個体を処置するための組成物であって、
i.hADSCを含む前記個体由来の試料における、バイオマーカーのパネルから選択される少なくとも3種のバイオマーカーの発現レベルが測定され、前記試料が、in vitroでIL−2と組み合わされ、前記バイオマーカーのパネルが、FGF1、FGF11、FGF14、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含み、
ii.前記バイオマーカーのレベルが、参照レベルと比較され、前記レベルの変化なしまたは前記参照レベルを下回る減少が、前記個体が、IL−2に基づく治療法に伴う有害事象を経験しない場合があることを示し、
iii.前記個体が、前記IL−2に基づく治療法に伴う有害事象を経験しない場合があることが示された場合、前記組成物が、前記個体に投与されることを特徴とし、
iv.前記参照レベルが、IL−2に曝露されていない個体由来の等価な試料、IL−2を全く受けたことがない健康な個体由来の試料、またはIL−2処置を受けたことがない個体の不均一な群を表す等価な試料の収集物からのものである、組成物。 - 前記試料が、IL−2と約24時間組み合わされる、請求項14に記載の組成物。
- 前記発現レベルが、前記試料からのIL−2の除去から24、48または72時間後に測定される、請求項14に記載の組成物。
- 前記バイオマーカーのパネルからの少なくとも4種のバイオマーカーの発現レベルが測定される、請求項14に記載の組成物。
- 前記バイオマーカーのパネルからの少なくとも5種のバイオマーカーの発現レベルが測定される、請求項14に記載の組成物。
- VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSBおよびPLEKHA6の発現レベルが測定される、請求項14に記載の組成物。
- SIVA1のレベルが測定される、請求項14に記載の組成物。
- 前記バイオマーカーのタンパク質レベルが測定される、請求項14に記載の組成物。
- 前記タンパク質レベルが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により測定される、請求項21に記載の組成物。
- 前記バイオマーカーのRNAレベルが測定される、請求項14に記載の組成物。
- 前記RNAレベルが、Q−PCRアッセイまたはRNA−seqにより測定される、請求項23に記載の組成物。
- 試料が、前記個体から得られる、請求項14に記載の組成物。
- IL−2またはその活性部分を含む、がんに関して個体を処置するための組成物であって、少なくとも3種のバイオマーカーの発現レベルが、hADSCを含む前記個体由来の試料において、参照レベルと比較して減少するか、または変化を示さない場合、前記組成物が、前記個体に投与されることを特徴とし、前記試料が、in vitroでIL−2と組み合わされ、前記バイオマーカーのパネルが、FGF1、FGF11、FGF14、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含み、前記参照レベルが、IL−2に曝露されていない個体由来の等価な試料、IL−2を全く受けたことがない健康な個体由来の試料、またはIL−2処置を受けたことがない個体の不均一な群を表す等価な試料の収集物からのものである、組成物。
- 前記試料が、IL−2と約24時間組み合わされる、請求項26に記載の組成物。
- 前記発現レベルが、in vitroにおける前記試料からのIL−2の除去から24、48または72時間後に測定される、請求項26に記載の組成物。
- 前記バイオマーカーのパネルからの少なくとも4種のバイオマーカーの発現レベルが測定される、請求項26に記載の組成物。
- 前記バイオマーカーのパネルからの少なくとも5種のバイオマーカーの発現レベルが測定される、請求項26に記載の組成物。
- VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSBおよびPLEKHA6の発現レベルが測定される、請求項26に記載の組成物。
- SIVA1のレベルが測定される、請求項26に記載の組成物。
- 前記バイオマーカーのタンパク質レベルが測定される、請求項26に記載の組成物。
- 前記タンパク質レベルが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により測定される、請求項33に記載の組成物。
- 前記バイオマーカーのRNAレベルが測定される、請求項26に記載の組成物。
- 前記RNAレベルが、Q−PCRアッセイまたはRNA−seqにより測定される、請求項35に記載の組成物。
- バイオマーカーの発現レベルを、間葉系幹細胞(MSC)の集団が、MSCに基づく治療法のための個体への投与に適するか決定するための指標とする方法であって、
(a)前記MSCの集団と共にIL−2をインキュベートするステップと、
(b)前記MSCにおける、バイオマーカーのパネルから選択される少なくとも3種のバイオマーカーの発現レベルを測定するステップであって、前記バイオマーカーのパネルが、FGF1、FGF11、FGF14、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むステップと、
(c)前記バイオマーカーのレベルを参照レベルと比較するステップであって、前記参照レベルを上回る前記レベルの増加が、前記MSCが、個体への投与に適さないことを示し、前記レベルの変化なしまたは前記参照レベルを下回る減少が、前記MSCが、個体への投与に適することを示すステップと
を含む方法。 - 前記バイオマーカーのパネルからの少なくとも4種のバイオマーカーの発現レベルを測定するステップを含む、請求項37に記載の方法。
- 前記バイオマーカーのパネルからの少なくとも5種のバイオマーカーの発現レベルを測定するステップを含む、請求項37に記載の方法。
- VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSBおよびPLEKHA6の発現レベルを測定するステップを含む、請求項37に記載の方法。
- SIVA1のレベルを測定するステップをさらに含む、請求項37に記載の方法。
- 前記バイオマーカーのタンパク質レベルを測定するステップを含む、請求項37に記載の方法。
- 前記測定ステップが、ELISAアッセイ、抗体プロテオミクスアレイ、免疫組織化学的検査または質量分析により為される、請求項42に記載の方法。
- 前記バイオマーカーのRNAレベルを測定するステップを含む、請求項37に記載の方法。
- 前記測定ステップが、Q−PCRアッセイまたはRNA−seqにより為される、請求項44に記載の方法。
- 前記細胞が、前記IL−2と共に約24時間インキュベートされる、請求項37に記載の方法。
- 前記測定ステップが、前記IL−2の除去から24、48または72時間後に行われる、請求項37に記載の方法。
- 移植に対するMSCの集団の適合性を評価するための、またはIL−2またはその活性部分を投与するべきか決定するためのキットであって、試料における、バイオマーカーのパネルから選択される少なくとも3種のバイオマーカーの発現レベルを測定するための試薬を含み、前記バイオマーカーのパネルが、FGF1、FGF11、FGF14、IL−32、IL−6、IL1RN、IL−20RB、IL−21R、PLAU、PLEKHA6、CTSB、FERMT1、CRMP1、VEGFB、VEGFAおよびPLEKHA1を含むキット。
- 前記試料における少なくとも4種のバイオマーカーの発現レベルを測定するための試薬を含む、請求項48に記載のキット。
- 前記試料における少なくとも5種のバイオマーカーの発現レベルを測定するための試薬を含む、請求項48に記載のキット。
- VEGFA、PLEKHA1、VEGFB、CRMP1、FERMT1、CTSBおよびPLEKHA6を測定するための試薬を含む、請求項48に記載のキット。
- IL−2をさらに含む、請求項48に記載のキット。
- 移植に対するMSCの集団の適合性を評価するための、請求項48に記載のキット。
- IL−2またはその活性部分を投与するべきか決定するための、請求項48に記載のキット。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562170619P | 2015-06-03 | 2015-06-03 | |
US201562170604P | 2015-06-03 | 2015-06-03 | |
US62/170,619 | 2015-06-03 | ||
US62/170,604 | 2015-06-03 | ||
US201562175203P | 2015-06-12 | 2015-06-12 | |
US62/175,203 | 2015-06-12 | ||
PCT/US2016/035472 WO2016196765A2 (en) | 2015-06-03 | 2016-06-02 | Companion methods and kits for il-2-based therapies and mesenchymal stem cell-based therapies |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021014388A Division JP7186251B2 (ja) | 2015-06-03 | 2021-02-01 | Il-2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018518692A JP2018518692A (ja) | 2018-07-12 |
JP2018518692A5 JP2018518692A5 (ja) | 2019-07-04 |
JP6832349B2 true JP6832349B2 (ja) | 2021-02-24 |
Family
ID=57441773
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018515180A Active JP6832349B2 (ja) | 2015-06-03 | 2016-06-02 | Il−2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット |
JP2018515181A Active JP7118886B2 (ja) | 2015-06-03 | 2016-06-02 | 幹細胞からの有益因子の産生および送達のための方法およびデバイス |
JP2021014388A Active JP7186251B2 (ja) | 2015-06-03 | 2021-02-01 | Il-2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット |
JP2022123879A Active JP7455165B2 (ja) | 2015-06-03 | 2022-08-03 | 幹細胞からの有益因子の産生および送達のための方法およびデバイス |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018515181A Active JP7118886B2 (ja) | 2015-06-03 | 2016-06-02 | 幹細胞からの有益因子の産生および送達のための方法およびデバイス |
JP2021014388A Active JP7186251B2 (ja) | 2015-06-03 | 2021-02-01 | Il-2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット |
JP2022123879A Active JP7455165B2 (ja) | 2015-06-03 | 2022-08-03 | 幹細胞からの有益因子の産生および送達のための方法およびデバイス |
Country Status (6)
Country | Link |
---|---|
US (2) | US20180136209A1 (ja) |
EP (3) | EP4015652A1 (ja) |
JP (4) | JP6832349B2 (ja) |
CN (2) | CN108699605A (ja) |
ES (1) | ES2906161T3 (ja) |
WO (2) | WO2016196774A1 (ja) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017147501A1 (en) | 2016-02-25 | 2017-08-31 | Massachusetts Institute Of Technology | Neuronal axon mimetics for in vitro analysis of neurological diseases, myelination, and drug screening |
US11293065B2 (en) | 2016-03-14 | 2022-04-05 | Aelan Cell Technologies, Inc. | Compositions and methods for the quality control of stem cell preparations |
CN105769911A (zh) * | 2016-03-23 | 2016-07-20 | 中国人民解放军第二军医大学 | 间充质干细胞诱导斑秃处毛发再生的方法及应用 |
KR20190126899A (ko) * | 2017-03-21 | 2019-11-12 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 누공을 치료하기 위한 방법 및 물질 |
JP2020514395A (ja) * | 2017-03-23 | 2020-05-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 老化細胞および細胞老化関連分泌形質による発毛の刺激 |
AU2018248071A1 (en) * | 2017-04-07 | 2019-10-17 | Cynata Therapeutics Limited | Method for treating a side effect of chimeric antigen receptor (CAR) T cell therapy |
US11535826B2 (en) | 2017-05-10 | 2022-12-27 | Massachusetts Institute Of Technology | Engineered 3D-printed artificial axons |
CN109777872B (zh) * | 2017-11-15 | 2021-04-02 | 北京大学 | 肺癌中的t细胞亚群及其特征基因 |
WO2019099800A1 (en) * | 2017-11-17 | 2019-05-23 | Stc.Unm | Genome edited ipsc-derived monocytes expressing trophic factors |
US11975024B2 (en) | 2017-12-19 | 2024-05-07 | Musc Foundation For Research Development | T regulatory (Treg) cell transplantation in osteogenesis imperfecta (OI) |
CN109010368B (zh) * | 2018-08-01 | 2021-09-03 | 徐妍 | 用于治疗“女运动员三联征”和修复女运动员卵巢功能的细胞制剂及其制备方法 |
CN109468380B (zh) * | 2018-10-31 | 2022-05-17 | 复旦大学附属肿瘤医院 | Il1r2在乳腺癌预后评估与靶向治疗中的应用 |
CN109568565B (zh) * | 2018-11-08 | 2022-02-22 | 中国医学科学院北京协和医院 | Nf90在制备调控骨髓间充质干细胞成骨分化的生物制剂中的应用 |
CN109536440A (zh) * | 2018-11-19 | 2019-03-29 | 深圳市第二人民医院 | 外泌体的提取方法 |
CN110358832B (zh) * | 2019-07-11 | 2021-01-15 | 江苏医药职业学院 | 检测ph结构域家族a成员6表达水平的试剂的应用和试剂盒 |
CN110585243A (zh) * | 2019-08-12 | 2019-12-20 | 丰泽康生物医药(深圳)有限公司 | 用于治疗糖皮质激素依赖性皮炎的多潜能细胞活性物与富血小板血浆复合物及制法和应用 |
IL272145A (en) * | 2020-01-20 | 2021-07-29 | Stem Cell Medicine Ltd | Cosmetic preparations with protein concentrate from a conditioned growth medium of stem cells from adipose tissue |
CN112430626A (zh) * | 2020-11-27 | 2021-03-02 | 成都康景生物科技有限公司 | 一种基因修饰的脐间充质干细胞、制备方法及应用 |
CN113265372A (zh) * | 2021-06-08 | 2021-08-17 | 河南中医药大学 | 一种体外诱导粘液高分泌模型及其构建方法 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2105378A1 (en) * | 1991-03-21 | 1992-09-22 | Paolo A. Paciucci | Compositions and methods of treatment of a variety of disorders utilizing etianate and agonists thereof |
US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
JP2007527242A (ja) * | 2004-03-05 | 2007-09-27 | カイロン コーポレーション | 治療剤の患者耐容性を予測するためのインビトロ試験システム |
WO2007033216A2 (en) * | 2005-09-12 | 2007-03-22 | Beth Israel Deaconess Medical Center | Methods and compositions for the treatment and diagnosis of diseases characterized by vascular leak, hypotension, or a procoagulant state |
SG182976A1 (en) * | 2007-06-29 | 2012-08-30 | Ahngook Pharmaceutical Co Ltd | Predictive markers for ovarian cancer |
EP2254586B1 (en) * | 2008-02-22 | 2015-04-08 | Agency For Science, Technology And Research (A*star) | Mesenchymal stem cell particles |
ES2351916B8 (es) * | 2009-07-30 | 2012-07-09 | Centro Nacional De Investigaciones Cardiovasculares (Cnic) | Metodo de identificacion de celulas madre mesenquimales senescentes |
GB0918615D0 (en) | 2009-10-23 | 2009-12-09 | Cellerix Sa | Cell populations having immunoregulatory activity, methods for the preparation and uses thereof |
WO2012088337A1 (en) * | 2010-12-23 | 2012-06-28 | Prometheus Laboratories Inc. | Drug selection for malignant cancer therapy using antibody-based arrays |
US9446075B2 (en) * | 2011-05-06 | 2016-09-20 | Bioregenerative Sciences | Compositions derived from stem cell released molecules and methods for formulation thereof |
US20130251670A1 (en) * | 2011-09-13 | 2013-09-26 | Aidan Products, Inc | Treatment of Macular Edema Utilizing Stem Cell and Conditioned Media Thereof |
AU2012323856B2 (en) * | 2011-10-13 | 2017-05-25 | EyePoint Pharmaceuticals, Inc. | Methods for treating Vascular Leak Syndrome and cancer |
EP2806883B1 (en) * | 2012-01-25 | 2019-04-24 | DNAtrix, Inc. | Biomarkers and combination therapies using oncolytic virus and immunomodulation |
ITTO20120859A1 (it) * | 2012-10-02 | 2014-04-03 | Univ Degli Studi Torino | Nuova applicazione terapeutica di un mezzo condizionato da cellule staminali mesenchimali placentari |
US10351910B2 (en) * | 2013-02-20 | 2019-07-16 | Pluristem Ltd | Gene and protein expression properties of adherent stromal cells cultured in 3D |
-
2016
- 2016-06-02 WO PCT/US2016/035487 patent/WO2016196774A1/en active Application Filing
- 2016-06-02 EP EP21207206.0A patent/EP4015652A1/en active Pending
- 2016-06-02 CN CN201680045707.1A patent/CN108699605A/zh active Pending
- 2016-06-02 US US15/579,186 patent/US20180136209A1/en active Pending
- 2016-06-02 CN CN201680045662.8A patent/CN108289937A/zh active Pending
- 2016-06-02 JP JP2018515180A patent/JP6832349B2/ja active Active
- 2016-06-02 JP JP2018515181A patent/JP7118886B2/ja active Active
- 2016-06-02 ES ES16804415T patent/ES2906161T3/es active Active
- 2016-06-02 WO PCT/US2016/035472 patent/WO2016196765A2/en active Application Filing
- 2016-06-02 EP EP16804415.4A patent/EP3303636B1/en active Active
- 2016-06-02 EP EP16804422.0A patent/EP3302541A4/en active Pending
-
2021
- 2021-02-01 JP JP2021014388A patent/JP7186251B2/ja active Active
-
2022
- 2022-03-31 US US17/710,539 patent/US20220370503A1/en active Pending
- 2022-08-03 JP JP2022123879A patent/JP7455165B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2022140711A (ja) | 2022-09-27 |
US20180136209A1 (en) | 2018-05-17 |
WO2016196765A9 (en) | 2017-09-21 |
WO2016196765A3 (en) | 2017-01-19 |
ES2906161T3 (es) | 2022-04-13 |
JP7455165B2 (ja) | 2024-03-25 |
EP3303636A2 (en) | 2018-04-11 |
EP4015652A1 (en) | 2022-06-22 |
WO2016196765A2 (en) | 2016-12-08 |
EP3303636B1 (en) | 2021-11-10 |
EP3302541A4 (en) | 2018-12-05 |
WO2016196774A1 (en) | 2016-12-08 |
US20220370503A1 (en) | 2022-11-24 |
JP7118886B2 (ja) | 2022-08-16 |
CN108289937A (zh) | 2018-07-17 |
JP7186251B2 (ja) | 2022-12-08 |
CN108699605A (zh) | 2018-10-23 |
EP3302541A1 (en) | 2018-04-11 |
JP2018518692A (ja) | 2018-07-12 |
EP3303636A4 (en) | 2018-11-21 |
JP2021089290A (ja) | 2021-06-10 |
JP2018516988A (ja) | 2018-06-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6832349B2 (ja) | Il−2に基づく治療法および間葉系幹細胞に基づく治療法のためコンパニオン方法およびキット | |
Choudhury et al. | Extravillous trophoblast and endothelial cell crosstalk mediates leukocyte infiltration to the early remodeling decidual spiral arteriole wall | |
Saeki et al. | Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases | |
Huang et al. | S100A9 regulates MDSCs-mediated immune suppression via the RAGE and TLR4 signaling pathways in colorectal carcinoma | |
Verginelli et al. | Transcription factors FOXG1 and Groucho/TLE promote glioblastoma growth | |
King et al. | Association of cytokines and chemokines in pathogenesis of breast cancer | |
Qu et al. | Upregulated monocytic expression of CXC chemokine ligand 10 (CXCL-10) and its relationship with serum interleukin-6 levels in the syndrome of frailty | |
Ahmad et al. | Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance | |
Baston-Büst et al. | Syndecan-1 knock-down in decidualized human endometrial stromal cells leads to significant changes in cytokine and angiogenic factor expression patterns | |
Roberti et al. | Protein expression changes during human triple negative breast cancer cell line progression to lymph node metastasis in a xenografted model in nude mice | |
Sparmann et al. | Generation and characterization of immortalized rat pancreatic stellate cells | |
Eyster et al. | Reciprocal communication between endometrial stromal cells and macrophages | |
Behm et al. | Soluble CD14 enhances the response of periodontal ligament stem cells to toll-like receptor 2 agonists | |
Xie et al. | Semaphorin 4D induces an imbalance of Th17/Treg cells by activating the aryl hydrocarbon receptor in ankylosing spondylitis | |
Luo et al. | Myeloid-derived suppressor cells recruited by chemokine (CC Motif) ligand 3 promote the progression of breast cancer via phosphoinositide 3-kinase-protein kinase b-mammalian target of rapamycin signaling | |
Niu et al. | Transcriptional profiling of interleukin-2-primed human adipose derived mesenchymal stem cells revealed dramatic changes in stem cells response imposed by replicative senescence | |
Jung et al. | MCP-1 and MIP-3α secreted from necrotic cell-treated glioblastoma cells promote migration/infiltration of microglia | |
Sarosiek et al. | Osteopontin (OPN) isoforms, diabetes, obesity, and cancer; what is one got to do with the other? A new role for OPN | |
Wasko et al. | Langerhans cells are essential components of the angiogenic niche during murine skin repair | |
Li et al. | Single-cell RNA sequencing depicts the local cell landscape in thyroid-associated ophthalmopathy | |
Nieminen et al. | Dendritic cells from Crohn’s disease patients show aberrant STAT1 and STAT3 signaling | |
Henn et al. | Functionally distinct subpopulations of CpG-activated memory B cells | |
Appaiah et al. | ITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast cancer | |
Wang et al. | Periodontal treatment modulates gene expression of endothelial progenitor cells in diabetic patients | |
Tokumoto et al. | Identification of tumour-reactive lymphatic endothelial cells capable of inducing progression of gastric cancer |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190603 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190603 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200305 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200407 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200703 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201007 |
|
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: 20201202 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20201228 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210201 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6832349 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |