JP6494594B2 - 樹状細胞を含有する医薬およびその製造方法 - Google Patents
樹状細胞を含有する医薬およびその製造方法 Download PDFInfo
- Publication number
- JP6494594B2 JP6494594B2 JP2016505286A JP2016505286A JP6494594B2 JP 6494594 B2 JP6494594 B2 JP 6494594B2 JP 2016505286 A JP2016505286 A JP 2016505286A JP 2016505286 A JP2016505286 A JP 2016505286A JP 6494594 B2 JP6494594 B2 JP 6494594B2
- Authority
- JP
- Japan
- Prior art keywords
- galcer
- cells
- disease
- dendritic cells
- medicament
- 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
- 210000004443 dendritic cell Anatomy 0.000 title claims description 75
- 239000003814 drug Substances 0.000 title claims description 27
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- VQFKFAKEUMHBLV-BYSUZVQFSA-N 1-O-(alpha-D-galactosyl)-N-hexacosanoylphytosphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)[C@H](O)CCCCCCCCCCCCCC)CO[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQFKFAKEUMHBLV-BYSUZVQFSA-N 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 37
- 208000010125 myocardial infarction Diseases 0.000 claims description 26
- 210000005087 mononuclear cell Anatomy 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 16
- 238000012258 culturing Methods 0.000 claims description 14
- 108010002350 Interleukin-2 Proteins 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 8
- 206010063837 Reperfusion injury Diseases 0.000 claims description 7
- 210000004748 cultured cell Anatomy 0.000 claims description 7
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 5
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 201000010099 disease Diseases 0.000 description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 43
- 210000000581 natural killer T-cell Anatomy 0.000 description 26
- 102000004127 Cytokines Human genes 0.000 description 25
- 108090000695 Cytokines Proteins 0.000 description 25
- 230000002861 ventricular Effects 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 20
- 208000024172 Cardiovascular disease Diseases 0.000 description 15
- 206010019280 Heart failures Diseases 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 239000002609 medium Substances 0.000 description 12
- 230000007574 infarction Effects 0.000 description 11
- 206010061216 Infarction Diseases 0.000 description 10
- 208000028867 ischemia Diseases 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 230000000302 ischemic effect Effects 0.000 description 9
- 230000010410 reperfusion Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000028993 immune response Effects 0.000 description 7
- 208000031225 myocardial ischemia Diseases 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 238000009169 immunotherapy Methods 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 6
- 239000002504 physiological saline solution Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 5
- 210000004351 coronary vessel Anatomy 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 210000005240 left ventricle Anatomy 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 210000004165 myocardium Anatomy 0.000 description 4
- 239000013049 sediment Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 208000000435 Heart Rupture Diseases 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000002617 apheresis Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000004217 heart function Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 229960001412 pentobarbital Drugs 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 238000004904 shortening Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001631 vena cava inferior Anatomy 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- VJLLLMIZEJJZTE-VNQXHBPZSA-N HexCer(d18:1/16:0) Chemical class CCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)COC1OC(CO)C(O)C(O)C1O VJLLLMIZEJJZTE-VNQXHBPZSA-N 0.000 description 2
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 208000033774 Ventricular Remodeling Diseases 0.000 description 2
- 208000002223 abdominal aortic aneurysm Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 208000007474 aortic aneurysm Diseases 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000002592 echocardiography Methods 0.000 description 2
- 230000005713 exacerbation Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 102000046157 human CSF2 Human genes 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000013227 male C57BL/6J mice Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- LCJINPXTMHVZGV-UHFFFAOYSA-N 2,3,5-triphenyl-1h-tetrazol-4-ium;chloride Chemical compound [Cl-].[NH2+]1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 LCJINPXTMHVZGV-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010007513 Cardiac aneurysm Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010013012 Dilatation ventricular Diseases 0.000 description 1
- 208000021866 Dressler syndrome Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 206010033698 Papillary muscle rupture Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000013546 non-drug therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 208000004124 rheumatic heart disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Images
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
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
-
- 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
- A61K38/193—Colony stimulating factors [CSF]
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/34—Sugars
-
- 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/30—Organic components
- C12N2500/36—Lipids
-
- 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
- C12N2501/22—Colony stimulating factors (G-CSF, GM-CSF)
-
- 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)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
単核球細胞をGM−CSFおよびIL−2の存在下で培養する工程、ならびに
培養された細胞をα−ガラクトシルセラミドでパルスする工程
を含む方法により得られる樹状細胞を含有する、心血管病の予防および/または治療のための医薬。
(2)
前記心血管病が心筋梗塞もしくはその合併症、虚血再灌流障害または動脈瘤である、(1)に記載の医薬。
(3)
単核球細胞をGM−CSFおよびIL−2の存在下で培養する工程、ならびに
培養された細胞をα−ガラクトシルセラミドでパルスする工程
を含む、心血管病の予防および/または治療のための医薬の製造方法。
α−GalCerをパルスした樹状細胞は、非特許文献11に記載の方法に従って調製した。以下に具体的な手順を示す。
(1)単核球細胞の調製
健常成人ドナーから連続式血液成分分離装置を用いてアフェレーシス細胞液を採取した。50mL遠心チューブ中のFicoll−Paque PREMIUM(GEヘルスケア・ジャパン)20mLにアフェレーシス細胞液26.6mLを積層し、400×gで30分間、20℃で遠心し、単核球細胞層を回収した。単核球細胞層を同量の生理食塩水で洗浄し、400×gで10分間、20℃で遠心した。沈渣にアルブミネート加AIM−V培地(AIM−V培地(GIBCO Invitrogen Corporation)20容量に対して4.4%献血アルブミネート(日本製薬)1容量を添加したもの)を加えて液量を45mLにした懸濁液を再度遠心した。この操作をさらに1回繰り返した後、得られた沈渣を自己血漿加アルブミネート加AIM−V培地(AIM−V培地40容量に対して健常成人ドナーの血漿を1容量、4.4%献血アルブミネートを2容量添加したもの)に懸濁し、細胞濃度が2.7×108個/mL以下となるように液量を調節して、細胞浮遊液とした。
(1)で凍結保存した単核球細胞を37℃で解凍し、2倍容量の4.4%献血アルブミネートを加えて洗浄した後、400×gで5分間、20℃で遠心した。沈渣にアルブミネート加生理食塩水45mLを加えて再度洗浄、遠心分離を行い、単核球細胞の沈渣を得た。
α−GalCer/DCの心筋梗塞に対する治療効果を評価するため、心筋梗塞モデルマウスを用いた試験を行った。心筋梗塞モデルマウスは非特許文献8に記載の方法に従って作成した。すなわち、10〜12週齢の雄性C57BL/6Jマウスにペントバルビタール(50mg/kg体重)を投与して麻酔した後、左側胸部を開胸し、8−0糸を使用して冠動脈左前下行枝を結紮し、心筋梗塞を発生させた。
α−GalCer/DCの虚血再灌流に対する治療効果を評価するため、心筋虚血再灌流モデルマウスを用いた試験を行った。試験に使用したマウスα−GalCer/DCおよびα−GalCer非添加マウスDCは、マウス末梢血から分離した単核球細胞を用いて、実施例1と同様の手順で調製した。
Claims (2)
- 単核球細胞をGM−CSFおよびIL−2の存在下で培養する工程
、ならびに
培養された細胞をα−ガラクトシルセラミドでパルスする工程
を含む方法により得られる樹状細胞を有効成分として含有する、心筋梗塞もしくはその合併症または虚血再灌流障害の予防および/または治療のための医薬。 - 単核球細胞をGM−CSFおよびIL−2の存在下で培養する工程
、ならびに
培養された細胞をα−ガラクトシルセラミドでパルスする工程
を含む、心筋梗塞もしくはその合併症または虚血再灌流障害の予防および/または治療のためのα−ガラクトシルセラミドでパルスされた樹状細胞を有効成分として含有する医薬の製造方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014036070 | 2014-02-26 | ||
JP2014036070 | 2014-02-26 | ||
PCT/JP2015/055547 WO2015129791A1 (ja) | 2014-02-26 | 2015-02-26 | 樹状細胞を含有する医薬およびその製造方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2015129791A1 JPWO2015129791A1 (ja) | 2017-03-30 |
JP6494594B2 true JP6494594B2 (ja) | 2019-04-03 |
Family
ID=54009105
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016505286A Active JP6494594B2 (ja) | 2014-02-26 | 2015-02-26 | 樹状細胞を含有する医薬およびその製造方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US10022401B2 (ja) |
EP (1) | EP3111945B1 (ja) |
JP (1) | JP6494594B2 (ja) |
KR (1) | KR102376846B1 (ja) |
WO (1) | WO2015129791A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6779616B2 (ja) * | 2015-12-25 | 2020-11-04 | 富士ソフト株式会社 | Nkt細胞活性化医薬組成物、その製造方法、及び抗原提示細胞の保存方法 |
WO2018043660A1 (ja) * | 2016-09-01 | 2018-03-08 | 株式会社理研免疫再生医学 | ナチュラルキラーt(nkt)細胞を刺激する樹状細胞の製造方法、およびnkt細胞を刺激する樹状細胞とnkt細胞とを含む細胞組成物の製造方法 |
JP6712042B1 (ja) * | 2019-03-04 | 2020-06-17 | 国立大学法人北海道大学 | α−ガラクトシルセラミド及び/又はα−ガラクトシルセラミドでパルスされた樹状細胞を含有する医薬組成物 |
WO2020179104A1 (ja) * | 2019-03-04 | 2020-09-10 | 国立大学法人北海道大学 | α-ガラクトシルセラミド及び/又はα-ガラクトシルセラミドでパルスされた樹状細胞を含有する医薬組成物 |
JPWO2021010344A1 (ja) * | 2019-07-12 | 2021-01-21 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100527950B1 (ko) * | 1997-04-10 | 2005-11-09 | 기린 비루 가부시키가이샤 | 알파-글리코실세라미드를 함유하는 엔케이티 세포활성화제 |
EP1437358B1 (en) | 2001-08-16 | 2006-10-18 | Daiichi Asubio Pharma Co., Ltd. | Novel glycolipid and remedial agent for autoimmune disease containing the same as active ingredient |
JP2005536982A (ja) * | 2001-11-07 | 2005-12-08 | 麒麟麦酒株式会社 | インビトロにおけるt細胞増幅および増幅されたt細胞集団 |
WO2007043630A1 (ja) * | 2005-10-06 | 2007-04-19 | Riken | 上気道粘膜下に投与されるnkt細胞刺激剤 |
US7928077B2 (en) | 2008-07-11 | 2011-04-19 | Academia Sinica | Alpha-galactosyl ceramide analogs and their use as immunotherapies |
WO2012018950A1 (en) * | 2010-08-03 | 2012-02-09 | Beth Israel Deaconess Medical Center | Methods and compositions for treatment of metabolic disorders |
CN102978160A (zh) * | 2012-12-13 | 2013-03-20 | 上海柯莱逊生物技术有限公司 | 一种体外诱导扩增nkt细胞的方法 |
-
2015
- 2015-02-26 JP JP2016505286A patent/JP6494594B2/ja active Active
- 2015-02-26 WO PCT/JP2015/055547 patent/WO2015129791A1/ja active Application Filing
- 2015-02-26 US US15/121,557 patent/US10022401B2/en active Active
- 2015-02-26 EP EP15754438.8A patent/EP3111945B1/en active Active
- 2015-02-26 KR KR1020167025967A patent/KR102376846B1/ko active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
EP3111945A4 (en) | 2017-08-09 |
KR102376846B1 (ko) | 2022-03-21 |
JPWO2015129791A1 (ja) | 2017-03-30 |
US20160361358A1 (en) | 2016-12-15 |
WO2015129791A1 (ja) | 2015-09-03 |
EP3111945A1 (en) | 2017-01-04 |
KR20160130403A (ko) | 2016-11-11 |
US10022401B2 (en) | 2018-07-17 |
EP3111945B1 (en) | 2021-07-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6494594B2 (ja) | 樹状細胞を含有する医薬およびその製造方法 | |
JP6803339B2 (ja) | 治療用のプールされた血液アポトーシス細胞調製物及びそれらの使用 | |
KR20180041229A (ko) | 줄기 세포 이식을 위한 방법 | |
TW202102540A (zh) | 包含抗il-6受體抗體之bbb功能低下之抑制劑 | |
WO2007043630A1 (ja) | 上気道粘膜下に投与されるnkt細胞刺激剤 | |
WO2022249535A1 (ja) | 癌悪液質の改善剤および癌悪液質の改善方法 | |
US20210393628A1 (en) | Compositions and methods for modulating t cell exhaustion | |
US20220088015A1 (en) | Methods and pharmaceutical compositions for the treatment of age-related cardiometabolic diseases | |
WO2022213870A1 (zh) | 通过口服给药抑制CD4+Treg细胞的药物和方法 | |
WO2020179104A1 (ja) | α-ガラクトシルセラミド及び/又はα-ガラクトシルセラミドでパルスされた樹状細胞を含有する医薬組成物 | |
JP2019031470A (ja) | Nk細胞培養上清を含む抗腫瘍組成物およびその製造方法 | |
JP5807769B2 (ja) | 頭頚部癌の治療に用いる、腫瘍栄養動脈に投与される抗癌細胞組成物の使用 | |
EP3466422B1 (en) | Use of z-butylidenephthalide in activating autoimmune system | |
WO2021010344A1 (ja) | 心筋収縮改善治療法および心筋細胞死抑制法の開発 | |
JP6712042B1 (ja) | α−ガラクトシルセラミド及び/又はα−ガラクトシルセラミドでパルスされた樹状細胞を含有する医薬組成物 | |
JPWO2016195086A1 (ja) | アレルギー性疾患の治療薬 | |
WO2023080001A1 (ja) | 固形悪性腫瘍治療用組成物、及び固形悪性腫瘍治療用キット | |
US20240131027A1 (en) | Pharmaceutical composition comprising novel sd911 compound as active ingredient for prevention or treatment of transplant rejection | |
JP6992984B2 (ja) | 腫瘍内静脈形成促進剤 | |
Mokrenko et al. | CYTOKINE PROFILE OF RAT BLOOD SERUM DURING EXPERIMENTAL BRONCHOPULMONARY INFLAMMATION AND IMMUNOMODULATOR ADMINISTRATION | |
WO2019156145A1 (ja) | 改良されたαβT加工細胞製造方法 | |
TW202120531A (zh) | 小孢子靈芝免疫調節蛋白與鑰孔蟲戚血藍蛋白用於製備治療上皮細胞癌的醫藥組合物及用途 | |
JPWO2021214497A5 (ja) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20160804 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180206 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20180206 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180207 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181030 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181225 |
|
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: 20190212 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190305 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6494594 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |