JP6437988B2 - リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 - Google Patents
リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 Download PDFInfo
- Publication number
- JP6437988B2 JP6437988B2 JP2016239572A JP2016239572A JP6437988B2 JP 6437988 B2 JP6437988 B2 JP 6437988B2 JP 2016239572 A JP2016239572 A JP 2016239572A JP 2016239572 A JP2016239572 A JP 2016239572A JP 6437988 B2 JP6437988 B2 JP 6437988B2
- Authority
- JP
- Japan
- Prior art keywords
- stem cells
- cells
- disease
- days
- cell
- 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
- 210000000130 stem cell Anatomy 0.000 title claims description 423
- 210000001280 germinal center Anatomy 0.000 title claims description 104
- 210000003563 lymphoid tissue Anatomy 0.000 title claims description 54
- 239000000203 mixture Substances 0.000 title claims description 25
- 230000002401 inhibitory effect Effects 0.000 title claims description 16
- 238000000034 method Methods 0.000 title description 59
- 230000001172 regenerating effect Effects 0.000 title description 8
- 210000000952 spleen Anatomy 0.000 claims description 121
- 210000004027 cell Anatomy 0.000 claims description 118
- 210000001185 bone marrow Anatomy 0.000 claims description 67
- 239000003814 drug Substances 0.000 claims description 43
- 210000001519 tissue Anatomy 0.000 claims description 35
- 210000000056 organ Anatomy 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 26
- 229940124597 therapeutic agent Drugs 0.000 claims description 21
- 210000001165 lymph node Anatomy 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 230000001400 myeloablative effect Effects 0.000 claims description 17
- 238000009168 stem cell therapy Methods 0.000 claims description 17
- 229960003957 dexamethasone Drugs 0.000 claims description 16
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 16
- 230000003394 haemopoietic effect Effects 0.000 claims description 16
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 16
- 238000009580 stem-cell therapy Methods 0.000 claims description 16
- 238000002560 therapeutic procedure Methods 0.000 claims description 16
- 238000011069 regeneration method Methods 0.000 claims description 14
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 238000011084 recovery Methods 0.000 claims description 13
- 230000008929 regeneration Effects 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 10
- 238000002512 chemotherapy Methods 0.000 claims description 9
- 230000005855 radiation Effects 0.000 claims description 9
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 8
- 210000001178 neural stem cell Anatomy 0.000 claims description 7
- 210000000845 cartilage Anatomy 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 210000004263 induced pluripotent stem cell Anatomy 0.000 claims description 5
- 210000001986 peyer's patch Anatomy 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 238000011275 oncology therapy Methods 0.000 claims description 4
- 208000032467 Aplastic anaemia Diseases 0.000 claims description 3
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 3
- 206010004659 Biliary cirrhosis Diseases 0.000 claims description 3
- 208000010392 Bone Fractures Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 208000016192 Demyelinating disease Diseases 0.000 claims description 3
- 201000010046 Dilated cardiomyopathy Diseases 0.000 claims description 3
- 206010016654 Fibrosis Diseases 0.000 claims description 3
- 206010017076 Fracture Diseases 0.000 claims description 3
- 206010018691 Granuloma Diseases 0.000 claims description 3
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 3
- 206010019663 Hepatic failure Diseases 0.000 claims description 3
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 3
- 206010028289 Muscle atrophy Diseases 0.000 claims description 3
- 201000002481 Myositis Diseases 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 206010031264 Osteonecrosis Diseases 0.000 claims description 3
- 206010033661 Pancytopenia Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 claims description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 3
- 206010039491 Sarcoma Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 3
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 3
- 206010043395 Thalassaemia sickle cell Diseases 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 208000025997 central nervous system neoplasm Diseases 0.000 claims description 3
- 230000007882 cirrhosis Effects 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 208000024389 cytopenia Diseases 0.000 claims description 3
- 230000007850 degeneration Effects 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 208000016253 exhaustion Diseases 0.000 claims description 3
- 230000035876 healing Effects 0.000 claims description 3
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 208000007903 liver failure Diseases 0.000 claims description 3
- 231100000835 liver failure Toxicity 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 208000008585 mastocytosis Diseases 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 208000002865 osteopetrosis Diseases 0.000 claims description 3
- 208000007056 sickle cell anemia Diseases 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000017701 Endocrine disease Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 206010049287 Lipodystrophy acquired Diseases 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 208000023178 Musculoskeletal disease Diseases 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- 208000025966 Neurological disease Diseases 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims description 2
- 208000018631 connective tissue disease Diseases 0.000 claims description 2
- 230000007547 defect Effects 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims description 2
- 208000016097 disease of metabolism Diseases 0.000 claims description 2
- 208000030172 endocrine system disease Diseases 0.000 claims description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 208000006132 lipodystrophy Diseases 0.000 claims description 2
- 208000030159 metabolic disease Diseases 0.000 claims description 2
- 208000017445 musculoskeletal system disease Diseases 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 208000019553 vascular disease Diseases 0.000 claims description 2
- 210000002514 epidermal stem cell Anatomy 0.000 claims 1
- 210000004966 intestinal stem cell Anatomy 0.000 claims 1
- 210000002510 keratinocyte Anatomy 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 description 164
- 210000005087 mononuclear cell Anatomy 0.000 description 64
- 241000699670 Mus sp. Species 0.000 description 60
- 239000008280 blood Substances 0.000 description 50
- 210000004369 blood Anatomy 0.000 description 49
- 210000003719 b-lymphocyte Anatomy 0.000 description 39
- 241000282414 Homo sapiens Species 0.000 description 38
- 210000001744 T-lymphocyte Anatomy 0.000 description 38
- 102000036639 antigens Human genes 0.000 description 38
- 108091007433 antigens Proteins 0.000 description 38
- 239000000427 antigen Substances 0.000 description 37
- 230000001965 increasing effect Effects 0.000 description 25
- 238000002347 injection Methods 0.000 description 24
- 239000007924 injection Substances 0.000 description 24
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 23
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 23
- 239000000556 agonist Substances 0.000 description 23
- 101150013553 CD40 gene Proteins 0.000 description 22
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 18
- 238000001802 infusion Methods 0.000 description 18
- 102000004169 proteins and genes Human genes 0.000 description 18
- 102000005962 receptors Human genes 0.000 description 18
- 108020003175 receptors Proteins 0.000 description 18
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 17
- 102100032937 CD40 ligand Human genes 0.000 description 17
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 17
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 239000002671 adjuvant Substances 0.000 description 17
- 230000004087 circulation Effects 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 17
- 102000001708 Protein Isoforms Human genes 0.000 description 16
- 108010029485 Protein Isoforms Proteins 0.000 description 16
- 210000004504 adult stem cell Anatomy 0.000 description 16
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 15
- -1 amino, carboxyl Chemical group 0.000 description 15
- 230000014509 gene expression Effects 0.000 description 15
- 238000010253 intravenous injection Methods 0.000 description 15
- 238000010254 subcutaneous injection Methods 0.000 description 15
- 239000007929 subcutaneous injection Substances 0.000 description 15
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 108010029697 CD40 Ligand Proteins 0.000 description 13
- 102100037241 Endoglin Human genes 0.000 description 13
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 13
- 101000881679 Homo sapiens Endoglin Proteins 0.000 description 13
- 101001008874 Homo sapiens Mast/stem cell growth factor receptor Kit Proteins 0.000 description 13
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 13
- 230000001064 anti-interferon Effects 0.000 description 13
- 230000002354 daily effect Effects 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 210000003743 erythrocyte Anatomy 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 238000009825 accumulation Methods 0.000 description 11
- 238000001994 activation Methods 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 210000004700 fetal blood Anatomy 0.000 description 11
- 238000002054 transplantation Methods 0.000 description 11
- IPJDHSYCSQAODE-UHFFFAOYSA-N 5-chloromethylfluorescein diacetate Chemical compound O1C(=O)C2=CC(CCl)=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 IPJDHSYCSQAODE-UHFFFAOYSA-N 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 230000012178 germinal center formation Effects 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 210000004698 lymphocyte Anatomy 0.000 description 10
- 210000001778 pluripotent stem cell Anatomy 0.000 description 10
- 229960004641 rituximab Drugs 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 108010029961 Filgrastim Proteins 0.000 description 9
- 239000012190 activator Substances 0.000 description 9
- 239000002256 antimetabolite Substances 0.000 description 9
- 239000002246 antineoplastic agent Substances 0.000 description 9
- 210000004204 blood vessel Anatomy 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 210000002216 heart Anatomy 0.000 description 9
- 230000004217 heart function Effects 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 230000000340 anti-metabolite Effects 0.000 description 8
- 229940100197 antimetabolite Drugs 0.000 description 8
- 239000003018 immunosuppressive agent Substances 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 229940045513 CTLA4 antagonist Drugs 0.000 description 7
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 7
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 7
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 7
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 7
- 102100040120 Prominin-1 Human genes 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 7
- 229960002964 adalimumab Drugs 0.000 description 7
- 230000000139 costimulatory effect Effects 0.000 description 7
- 229940127089 cytotoxic agent Drugs 0.000 description 7
- 230000002708 enhancing effect Effects 0.000 description 7
- 230000003325 follicular Effects 0.000 description 7
- 108020001507 fusion proteins Proteins 0.000 description 7
- 102000037865 fusion proteins Human genes 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- 230000028993 immune response Effects 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 7
- 229940029345 neupogen Drugs 0.000 description 7
- 108010038379 sargramostim Proteins 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 6
- 102100032768 Complement receptor type 2 Human genes 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 6
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 6
- 102000017095 Leukocyte Common Antigens Human genes 0.000 description 6
- 108010013709 Leukocyte Common Antigens Proteins 0.000 description 6
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 6
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 6
- 210000000577 adipose tissue Anatomy 0.000 description 6
- 230000002137 anti-vascular effect Effects 0.000 description 6
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 6
- 210000000601 blood cell Anatomy 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 229960003444 immunosuppressant agent Drugs 0.000 description 6
- 229940087875 leukine Drugs 0.000 description 6
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 6
- 210000002894 multi-fate stem cell Anatomy 0.000 description 6
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 6
- 210000000440 neutrophil Anatomy 0.000 description 6
- 210000005259 peripheral blood Anatomy 0.000 description 6
- 239000011886 peripheral blood Substances 0.000 description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 6
- 229960005330 pimecrolimus Drugs 0.000 description 6
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- 210000004988 splenocyte Anatomy 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 5
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 5
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 5
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 5
- 108010036949 Cyclosporine Proteins 0.000 description 5
- 101000941929 Homo sapiens Complement receptor type 2 Proteins 0.000 description 5
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 5
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 5
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 5
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 5
- 102100040247 Tumor necrosis factor Human genes 0.000 description 5
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 5
- 210000000612 antigen-presenting cell Anatomy 0.000 description 5
- 229960002170 azathioprine Drugs 0.000 description 5
- 210000001772 blood platelet Anatomy 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 5
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 230000003308 immunostimulating effect Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 229940100602 interleukin-5 Drugs 0.000 description 5
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 229960000470 omalizumab Drugs 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 150000003212 purines Chemical class 0.000 description 5
- 230000006824 pyrimidine synthesis Effects 0.000 description 5
- 230000008439 repair process Effects 0.000 description 5
- 229940031439 squalene Drugs 0.000 description 5
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 5
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 5
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 4
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 229920001917 Ficoll Polymers 0.000 description 4
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 4
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 4
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 4
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 4
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 102100032818 Integrin alpha-4 Human genes 0.000 description 4
- 102100025304 Integrin beta-1 Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 102100038081 Signal transducer CD24 Human genes 0.000 description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 description 4
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 4
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 description 4
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 4
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 210000001789 adipocyte Anatomy 0.000 description 4
- 229960002833 aflibercept Drugs 0.000 description 4
- 108010081667 aflibercept Proteins 0.000 description 4
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 4
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000001028 anti-proliverative effect Effects 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 229960001265 ciclosporin Drugs 0.000 description 4
- 229930182912 cyclosporin Natural products 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 239000004052 folic acid antagonist Substances 0.000 description 4
- 210000000285 follicular dendritic cell Anatomy 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- 210000001654 germ layer Anatomy 0.000 description 4
- 239000003862 glucocorticoid Substances 0.000 description 4
- 229960001743 golimumab Drugs 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000011132 hemopoiesis Effects 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 230000001861 immunosuppressant effect Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 229960003130 interferon gamma Drugs 0.000 description 4
- 229940124829 interleukin-23 Drugs 0.000 description 4
- 229960000681 leflunomide Drugs 0.000 description 4
- 210000002751 lymph Anatomy 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 210000000822 natural killer cell Anatomy 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 210000004180 plasmocyte Anatomy 0.000 description 4
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 4
- 230000006825 purine synthesis Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 210000001562 sternum Anatomy 0.000 description 4
- 229960003433 thalidomide Drugs 0.000 description 4
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 3
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 108010008165 Etanercept Proteins 0.000 description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 3
- 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 3
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 3
- 101000633778 Homo sapiens SLAM family member 5 Proteins 0.000 description 3
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 3
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 3
- 101000622304 Homo sapiens Vascular cell adhesion protein 1 Proteins 0.000 description 3
- 108010073816 IgE Receptors Proteins 0.000 description 3
- 102100032816 Integrin alpha-6 Human genes 0.000 description 3
- 102100025390 Integrin beta-2 Human genes 0.000 description 3
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 3
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 3
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 3
- 102100030704 Interleukin-21 Human genes 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
- 102100029216 SLAM family member 5 Human genes 0.000 description 3
- 102100029215 Signaling lymphocytic activation molecule Human genes 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 3
- 208000035199 Tetraploidy Diseases 0.000 description 3
- 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 description 3
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 3
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 3
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 230000000735 allogeneic effect Effects 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000002391 anti-complement effect Effects 0.000 description 3
- 230000003432 anti-folate effect Effects 0.000 description 3
- 108010008730 anticomplement Proteins 0.000 description 3
- 229940127074 antifolate Drugs 0.000 description 3
- 210000000702 aorta abdominal Anatomy 0.000 description 3
- 230000001174 ascending effect Effects 0.000 description 3
- 210000002798 bone marrow cell Anatomy 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000007975 buffered saline Substances 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 235000013601 eggs Nutrition 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 229960001388 interferon-beta Drugs 0.000 description 3
- 229940117681 interleukin-12 Drugs 0.000 description 3
- 108010074108 interleukin-21 Proteins 0.000 description 3
- 229940028885 interleukin-4 Drugs 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 229960005386 ipilimumab Drugs 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 238000007885 magnetic separation Methods 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 210000003519 mature b lymphocyte Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 3
- 229960000951 mycophenolic acid Drugs 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 210000005155 neural progenitor cell Anatomy 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 230000002688 persistence Effects 0.000 description 3
- 210000002826 placenta Anatomy 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 229960003254 reslizumab Drugs 0.000 description 3
- 230000000250 revascularization Effects 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000011476 stem cell transplantation Methods 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 229960001967 tacrolimus Drugs 0.000 description 3
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 3
- 229960000235 temsirolimus Drugs 0.000 description 3
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 3
- 210000000115 thoracic cavity Anatomy 0.000 description 3
- 229950007217 tremelimumab Drugs 0.000 description 3
- 210000000689 upper leg Anatomy 0.000 description 3
- 229960003824 ustekinumab Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 description 2
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 2
- 108010082808 4-1BB Ligand Proteins 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 2
- 101150084229 ATXN1 gene Proteins 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 230000003844 B-cell-activation Effects 0.000 description 2
- 229920002498 Beta-glucan Polymers 0.000 description 2
- 102100039398 C-X-C motif chemokine 2 Human genes 0.000 description 2
- 102100040840 C-type lectin domain family 7 member A Human genes 0.000 description 2
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 2
- 102100027207 CD27 antigen Human genes 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 102100036008 CD48 antigen Human genes 0.000 description 2
- 101150015280 Cel gene Proteins 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 206010010099 Combined immunodeficiency Diseases 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- 241000699800 Cricetinae Species 0.000 description 2
- 108010069514 Cyclic Peptides Proteins 0.000 description 2
- 102000001189 Cyclic Peptides Human genes 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- 208000008960 Diabetic foot Diseases 0.000 description 2
- 108010052167 Dihydroorotate Dehydrogenase Proteins 0.000 description 2
- 102100032823 Dihydroorotate dehydrogenase (quinone), mitochondrial Human genes 0.000 description 2
- 229940123907 Disease modifying antirheumatic drug Drugs 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 2
- 101000823298 Homo sapiens Broad substrate specificity ATP-binding cassette transporter ABCG2 Proteins 0.000 description 2
- 101000889128 Homo sapiens C-X-C motif chemokine 2 Proteins 0.000 description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 2
- 101000994369 Homo sapiens Integrin alpha-5 Proteins 0.000 description 2
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 2
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 2
- 101000633786 Homo sapiens SLAM family member 6 Proteins 0.000 description 2
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 2
- 101000845170 Homo sapiens Thymic stromal lymphopoietin Proteins 0.000 description 2
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 2
- 241001135569 Human adenovirus 5 Species 0.000 description 2
- 102000009438 IgE Receptors Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- 102100032817 Integrin alpha-5 Human genes 0.000 description 2
- 108010041012 Integrin alpha4 Proteins 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 108010017411 Interleukin-21 Receptors Proteins 0.000 description 2
- 102100030699 Interleukin-21 receptor Human genes 0.000 description 2
- 108010065637 Interleukin-23 Proteins 0.000 description 2
- 102000013264 Interleukin-23 Human genes 0.000 description 2
- 102100039897 Interleukin-5 Human genes 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 2
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 2
- 241000186779 Listeria monocytogenes Species 0.000 description 2
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- 241000282553 Macaca Species 0.000 description 2
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 2
- 241000186366 Mycobacterium bovis Species 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 2
- 102000001759 Notch1 Receptor Human genes 0.000 description 2
- 108010042215 OX40 Ligand Proteins 0.000 description 2
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 2
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 2
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 2
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
- 108010039491 Ricin Proteins 0.000 description 2
- 102100029197 SLAM family member 6 Human genes 0.000 description 2
- 102100029198 SLAM family member 7 Human genes 0.000 description 2
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102100033447 T-lymphocyte surface antigen Ly-9 Human genes 0.000 description 2
- 101150052863 THY1 gene Proteins 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 102100031294 Thymic stromal lymphopoietin Human genes 0.000 description 2
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 2
- 101710183280 Topoisomerase Proteins 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 2
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 2
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 2
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 229940122803 Vinca alkaloid Drugs 0.000 description 2
- ZVLWUMPAHCEZAW-KRNLDFAISA-N [(2r)-3-[2-[[(2s)-2-[[(4r)-4-[[(2s)-2-[[(2r)-2-[(2r,3r,4r,5r)-2-acetamido-4,5,6-trihydroxy-1-oxohexan-3-yl]oxypropanoyl]amino]propanoyl]amino]-5-amino-5-oxopentanoyl]amino]propanoyl]amino]ethoxy-hydroxyphosphoryl]oxy-2-hexadecanoyloxypropyl] hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O)C(N)=O ZVLWUMPAHCEZAW-KRNLDFAISA-N 0.000 description 2
- 229960003697 abatacept Drugs 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 229940037003 alum Drugs 0.000 description 2
- NTGGOTYRTOXKMQ-UHFFFAOYSA-K aluminum;potassium;phosphate Chemical compound [Al+3].[K+].[O-]P([O-])([O-])=O NTGGOTYRTOXKMQ-UHFFFAOYSA-K 0.000 description 2
- 210000004381 amniotic fluid Anatomy 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 229960004238 anakinra Drugs 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 238000002617 apheresis Methods 0.000 description 2
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000002459 blastocyst Anatomy 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000009583 bone marrow aspiration Methods 0.000 description 2
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 229950006754 cedelizumab Drugs 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 229950007409 dacetuzumab Drugs 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- 229960002344 dexamethasone sodium phosphate Drugs 0.000 description 2
- PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-FCJDYXGNSA-L 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
- 230000002222 downregulating effect Effects 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 238000002592 echocardiography Methods 0.000 description 2
- 229960000284 efalizumab Drugs 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229960000403 etanercept Drugs 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 229960004177 filgrastim Drugs 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 210000001102 germinal center b cell Anatomy 0.000 description 2
- 150000002313 glycerolipids Chemical class 0.000 description 2
- 210000000224 granular leucocyte Anatomy 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229960002706 gusperimus Drugs 0.000 description 2
- IDINUJSAMVOPCM-UHFFFAOYSA-N gusperimus Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 229950002183 lebrikizumab Drugs 0.000 description 2
- 210000002414 leg Anatomy 0.000 description 2
- 229960004942 lenalidomide Drugs 0.000 description 2
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000001806 memory b lymphocyte Anatomy 0.000 description 2
- 210000003071 memory t lymphocyte Anatomy 0.000 description 2
- 229960005108 mepolizumab Drugs 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 229960005225 mifamurtide Drugs 0.000 description 2
- 108700007621 mifamurtide Proteins 0.000 description 2
- 230000001483 mobilizing effect Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229940014456 mycophenolate Drugs 0.000 description 2
- 229960005027 natalizumab Drugs 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 238000012633 nuclear imaging Methods 0.000 description 2
- 239000007764 o/w emulsion Substances 0.000 description 2
- 229940035567 orencia Drugs 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229950011485 pascolizumab Drugs 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 229950003203 pexelizumab Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229960002169 plerixafor Drugs 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 108010046141 rilonacept Proteins 0.000 description 2
- 229960001886 rilonacept Drugs 0.000 description 2
- 229930182490 saponin Natural products 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 235000017709 saponins Nutrition 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical class C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229940055944 soliris Drugs 0.000 description 2
- 210000001082 somatic cell Anatomy 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 2
- 238000010911 splenectomy Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 229960000331 teriflunomide Drugs 0.000 description 2
- UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 description 2
- 230000002381 testicular Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 239000003970 toll like receptor agonist Substances 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 2
- 229950004616 tribromoethanol Drugs 0.000 description 2
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 229940099073 xolair Drugs 0.000 description 2
- JPSHPWJJSVEEAX-OWPBQMJCSA-N (2s)-2-amino-4-fluoranylpentanedioic acid Chemical compound OC(=O)[C@@H](N)CC([18F])C(O)=O JPSHPWJJSVEEAX-OWPBQMJCSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- 108010093960 2-((1-(3,5-dichlorobenzenesulfonyl)pyrrolidine-2-carbonyl)amino)-4-(4-methyl-2-(methyl-(2-(4-(3-o-tolylureido)phenyl)acetyl)amino)pentanoylamino)butyric acid Proteins 0.000 description 1
- AOYNUTHNTBLRMT-MXWOLSILSA-N 2-Deoxy-2(F-18)fluoro-2-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H]([18F])C=O AOYNUTHNTBLRMT-MXWOLSILSA-N 0.000 description 1
- JLTPSDHKZGWXTD-UHFFFAOYSA-N 2-[6-(dicyanomethylidene)naphthalen-2-ylidene]propanedinitrile Chemical compound N#CC(C#N)=C1C=CC2=CC(=C(C#N)C#N)C=CC2=C1 JLTPSDHKZGWXTD-UHFFFAOYSA-N 0.000 description 1
- BALXSYQWXWVVJJ-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;phosphoric acid Chemical compound OP(O)(O)=O.O=C1NC(N)=NC2=C1NC=N2 BALXSYQWXWVVJJ-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100025683 Alkaline phosphatase, tissue-nonspecific isozyme Human genes 0.000 description 1
- 101710161969 Alkaline phosphatase, tissue-nonspecific isozyme Proteins 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 1
- 241001156002 Anthonomus pomorum Species 0.000 description 1
- 101710145634 Antigen 1 Proteins 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
- 102000016605 B-Cell Activating Factor Human genes 0.000 description 1
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108010064528 Basigin Proteins 0.000 description 1
- 102000015279 Basigin Human genes 0.000 description 1
- 102100032412 Basigin Human genes 0.000 description 1
- 101150017888 Bcl2 gene Proteins 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
- 102100024263 CD160 antigen Human genes 0.000 description 1
- 102100024210 CD166 antigen Human genes 0.000 description 1
- 102000007499 CD27 Ligand Human genes 0.000 description 1
- 108010046080 CD27 Ligand Proteins 0.000 description 1
- 102100038078 CD276 antigen Human genes 0.000 description 1
- 101710185679 CD276 antigen Proteins 0.000 description 1
- 102000004634 CD30 Ligand Human genes 0.000 description 1
- 108010017987 CD30 Ligand Proteins 0.000 description 1
- 108010063916 CD40 Antigens Proteins 0.000 description 1
- 108010038940 CD48 Antigen Proteins 0.000 description 1
- 102100027221 CD81 antigen Human genes 0.000 description 1
- 102100027217 CD82 antigen Human genes 0.000 description 1
- 102100022436 CMRF35-like molecule 8 Human genes 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 102000004003 Chemokine CCL11 Human genes 0.000 description 1
- 108010082548 Chemokine CCL11 Proteins 0.000 description 1
- 108010014414 Chemokine CXCL2 Proteins 0.000 description 1
- 102000016951 Chemokine CXCL2 Human genes 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 1
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 description 1
- 108091029430 CpG site Proteins 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 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
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 101100239628 Danio rerio myca gene Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102100031984 Ephrin type-B receptor 6 Human genes 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 108010040721 Flagellin Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102100020715 Fms-related tyrosine kinase 3 ligand protein Human genes 0.000 description 1
- 101710162577 Fms-related tyrosine kinase 3 ligand protein Proteins 0.000 description 1
- 229920000855 Fucoidan Polymers 0.000 description 1
- 230000010337 G2 phase Effects 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 208000011616 HELIX syndrome Diseases 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 101100028493 Haloferax volcanii (strain ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM B-1768 / DS2) pan2 gene Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010007712 Hepatitis A Virus Cellular Receptor 1 Proteins 0.000 description 1
- 101710185991 Hepatitis A virus cellular receptor 1 homolog Proteins 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 1
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000749325 Homo sapiens C-type lectin domain family 7 member A Proteins 0.000 description 1
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 1
- 101000980840 Homo sapiens CD166 antigen Proteins 0.000 description 1
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 1
- 101000914479 Homo sapiens CD81 antigen Proteins 0.000 description 1
- 101000914469 Homo sapiens CD82 antigen Proteins 0.000 description 1
- 101000901669 Homo sapiens CMRF35-like molecule 8 Proteins 0.000 description 1
- 101001064451 Homo sapiens Ephrin type-B receptor 6 Proteins 0.000 description 1
- 101001068136 Homo sapiens Hepatitis A virus cellular receptor 1 Proteins 0.000 description 1
- 101001032602 Homo sapiens Homeobox protein goosecoid Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 1
- 101000599858 Homo sapiens Intercellular adhesion molecule 2 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 1
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 1
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 1
- 101000980823 Homo sapiens Leukocyte surface antigen CD53 Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 101000928479 Homo sapiens Microtubule organization protein AKNA Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
- 101001094700 Homo sapiens POU domain, class 5, transcription factor 1 Proteins 0.000 description 1
- 101000734646 Homo sapiens Programmed cell death protein 6 Proteins 0.000 description 1
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
- 101000797623 Homo sapiens Protein AMBP Proteins 0.000 description 1
- 101000633792 Homo sapiens SLAM family member 9 Proteins 0.000 description 1
- 101001133085 Homo sapiens Sialomucin core protein 24 Proteins 0.000 description 1
- 101000713275 Homo sapiens Solute carrier family 22 member 3 Proteins 0.000 description 1
- 101000648544 Homo sapiens Sushi domain-containing protein 2 Proteins 0.000 description 1
- 101000837401 Homo sapiens T-cell leukemia/lymphoma protein 1A Proteins 0.000 description 1
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 1
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 description 1
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 1
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 1
- 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 1
- 101000597779 Homo sapiens Tumor necrosis factor ligand superfamily member 18 Proteins 0.000 description 1
- 101000764263 Homo sapiens Tumor necrosis factor ligand superfamily member 4 Proteins 0.000 description 1
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 1
- 101000795167 Homo sapiens Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 description 1
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 101000648507 Homo sapiens Tumor necrosis factor receptor superfamily member 14 Proteins 0.000 description 1
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 1
- 101000801228 Homo sapiens Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 101000801232 Homo sapiens Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
- 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 101000611185 Homo sapiens Tumor necrosis factor receptor superfamily member 5 Proteins 0.000 description 1
- 101000760781 Homo sapiens Tyrosyl-DNA phosphodiesterase 2 Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020707 Hyperparathyroidism primary Diseases 0.000 description 1
- 102100034980 ICOS ligand Human genes 0.000 description 1
- 101710093458 ICOS ligand Proteins 0.000 description 1
- GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 description 1
- 102000017182 Ikaros Transcription Factor Human genes 0.000 description 1
- 108010013958 Ikaros Transcription Factor Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 1
- 108010016648 Immunophilins Proteins 0.000 description 1
- 102000000521 Immunophilins Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 1
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 1
- 102100033467 L-selectin Human genes 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 102100021747 Leukemia inhibitory factor receptor Human genes 0.000 description 1
- 101710142062 Leukemia inhibitory factor receptor Proteins 0.000 description 1
- 102100024221 Leukocyte surface antigen CD53 Human genes 0.000 description 1
- 102100027361 Lithostathine-1-alpha Human genes 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- 102000003959 Lymphotoxin-beta Human genes 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108030000089 Metallocarboxypeptidases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241000202985 Methanobrevibacter smithii Species 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 102100036470 Microtubule organization protein AKNA Human genes 0.000 description 1
- 108091006442 Mitochondrial phosphate transporters Proteins 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 101100381525 Mus musculus Bcl6 gene Proteins 0.000 description 1
- 101100328148 Mus musculus Cd300a gene Proteins 0.000 description 1
- 101100354351 Mus musculus Ptprc gene Proteins 0.000 description 1
- 101000597780 Mus musculus Tumor necrosis factor ligand superfamily member 18 Proteins 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- RTGDFNSFWBGLEC-UHFFFAOYSA-N Mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1CC=C(C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-UHFFFAOYSA-N 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical class OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 108010029755 Notch1 Receptor Proteins 0.000 description 1
- 108010068425 Octamer Transcription Factor-3 Proteins 0.000 description 1
- 102000002584 Octamer Transcription Factor-3 Human genes 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102100023472 P-selectin Human genes 0.000 description 1
- 102100040444 P2X purinoceptor 1 Human genes 0.000 description 1
- 101710189973 P2X purinoceptor 1 Proteins 0.000 description 1
- 102100037601 P2X purinoceptor 4 Human genes 0.000 description 1
- 101710189967 P2X purinoceptor 4 Proteins 0.000 description 1
- 101710189965 P2X purinoceptor 7 Proteins 0.000 description 1
- 102100037602 P2X purinoceptor 7 Human genes 0.000 description 1
- 238000012879 PET imaging Methods 0.000 description 1
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- 201000000981 Primary Hyperparathyroidism Diseases 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 102100034785 Programmed cell death protein 6 Human genes 0.000 description 1
- 102100024448 Prostaglandin E2 receptor EP2 subtype Human genes 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 102100032859 Protein AMBP Human genes 0.000 description 1
- 101710150336 Protein Rex Proteins 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 108010073443 Ribi adjuvant Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 102100029196 SLAM family member 9 Human genes 0.000 description 1
- 101150086694 SLC22A3 gene Proteins 0.000 description 1
- 208000006117 ST-elevation myocardial infarction Diseases 0.000 description 1
- 101150099493 STAT3 gene Proteins 0.000 description 1
- 241000242677 Schistosoma japonicum Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 102100034258 Sialomucin core protein 24 Human genes 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- GDVNLLJNADMLLR-BBRMVZONSA-N Spergualin Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)C[C@@H](O)CCCCN=C(N)N GDVNLLJNADMLLR-BBRMVZONSA-N 0.000 description 1
- JBVZQDJNGFOSNX-UHFFFAOYSA-N Spergualin Natural products NCCCNCCCCNC(=O)C(O)NC(=O)CC(O)CCCCNC(=CN)N JBVZQDJNGFOSNX-UHFFFAOYSA-N 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102100028854 Sushi domain-containing protein 2 Human genes 0.000 description 1
- 230000020385 T cell costimulation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 102100039367 T-cell immunoglobulin and mucin domain-containing protein 4 Human genes 0.000 description 1
- 101710174757 T-cell immunoglobulin and mucin domain-containing protein 4 Proteins 0.000 description 1
- 102100028676 T-cell leukemia/lymphoma protein 1A Human genes 0.000 description 1
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 1
- 101710114141 T-lymphocyte surface antigen Ly-9 Proteins 0.000 description 1
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 description 1
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 229940123384 Toll-like receptor (TLR) agonist Drugs 0.000 description 1
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 1
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 1
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 1
- 102000012883 Tumor Necrosis Factor Ligand Superfamily Member 14 Human genes 0.000 description 1
- 108010065158 Tumor Necrosis Factor Ligand Superfamily Member 14 Proteins 0.000 description 1
- 102100035283 Tumor necrosis factor ligand superfamily member 18 Human genes 0.000 description 1
- 102100029675 Tumor necrosis factor receptor superfamily member 13B Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
- 102100024578 Tyrosyl-DNA phosphodiesterase 2 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 1
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 102000013127 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101001029301 Xenopus tropicalis Forkhead box protein D3 Proteins 0.000 description 1
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
- YGPZYYDTPXVBRA-RTDBHSBRSA-N [(2r,3s,4r,5r,6s)-2-[[(2r,3r,4r,5s,6r)-3-[[(3r)-3-dodecanoyloxytetradecanoyl]amino]-6-(hydroxymethyl)-5-phosphonooxy-4-[(3r)-3-tetradecanoyloxytetradecanoyl]oxyoxan-2-yl]oxymethyl]-3,6-dihydroxy-5-[[(3r)-3-hydroxytetradecanoyl]amino]oxan-4-yl] (3r)-3-hydr Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](O)O1 YGPZYYDTPXVBRA-RTDBHSBRSA-N 0.000 description 1
- VSGXHMIIKRQAGL-UHFFFAOYSA-N [Br-].CC(CCCCCCCCC)([NH+](CCCCCCCC)CCCCCCCC)C Chemical compound [Br-].CC(CCCCCCCCC)([NH+](CCCCCCCC)CCCCCCCC)C VSGXHMIIKRQAGL-UHFFFAOYSA-N 0.000 description 1
- JQHRAVMDTJQGTD-UHFFFAOYSA-J [Na+].[Al+3].OP([O-])([O-])=O.OP([O-])([O-])=O Chemical compound [Na+].[Al+3].OP([O-])([O-])=O.OP([O-])([O-])=O JQHRAVMDTJQGTD-UHFFFAOYSA-J 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 229960001683 abetimus Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229940119059 actemra Drugs 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 229960002459 alefacept Drugs 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229940047712 aluminum hydroxyphosphate Drugs 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 210000003663 amniotic stem cell Anatomy 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 229940094361 arcalyst Drugs 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- 229960002594 arsenic trioxide Drugs 0.000 description 1
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical class C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229960003270 belimumab Drugs 0.000 description 1
- 229940022836 benlysta Drugs 0.000 description 1
- 229950010015 bertilimumab Drugs 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 210000004703 blastocyst inner cell mass Anatomy 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
- 229940046731 calcineurin inhibitors Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 210000003321 cartilage cell Anatomy 0.000 description 1
- 208000015100 cartilage disease Diseases 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 229940107810 cellcept Drugs 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003588 centroblast Anatomy 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 210000001268 chyle Anatomy 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229950002334 clenoliximab Drugs 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 108010025838 dectin 1 Proteins 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 210000003074 dental pulp Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 229960002224 eculizumab Drugs 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 210000001174 endocardium Anatomy 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 108060002566 ephrin Proteins 0.000 description 1
- 102000012803 ephrin Human genes 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 230000008378 epithelial damage Effects 0.000 description 1
- 229950004292 erlizumab Drugs 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 210000000646 extraembryonic cell Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 229950001488 faralimomab Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000000604 fetal stem cell Anatomy 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229950001109 galiximab Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000002710 gonadal effect Effects 0.000 description 1
- 230000007085 granulocyte colony-stimulating factor production Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000005745 host immune response Effects 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- OWLCGJBUTJXNOF-HDNKIUSMSA-N hydron;2-morpholin-4-ylethyl (e)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1h-2-benzofuran-5-yl)-4-methylhex-4-enoate;chloride Chemical compound Cl.COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 OWLCGJBUTJXNOF-HDNKIUSMSA-N 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000001571 immunoadjuvant effect Effects 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 229940073062 imuran Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229940055742 indium-111 Drugs 0.000 description 1
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229950007937 inolimomab Drugs 0.000 description 1
- 235000013902 inosinic acid Nutrition 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 108010043603 integrin alpha4beta7 Proteins 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940076264 interleukin-3 Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002608 intravascular ultrasound Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 229940054136 kineret Drugs 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000012731 long-acting form Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229950004563 lucatumumab Drugs 0.000 description 1
- 229950000128 lumiliximab Drugs 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 210000003738 lymphoid progenitor cell Anatomy 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000004579 marble Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229950005555 metelimumab Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 229940074923 mozobil Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229960003816 muromonab-cd3 Drugs 0.000 description 1
- 210000001665 muscle stem cell Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 229940087560 mycophenolate mofetil hydrochloride Drugs 0.000 description 1
- 230000003039 myelosuppressive effect Effects 0.000 description 1
- 229940083410 myfortic Drugs 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 1
- XEPXGZZWVKNRGS-GQYPCLOQSA-N n-[(3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]octanamide Chemical compound CCCCCCCC(=O)NC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XEPXGZZWVKNRGS-GQYPCLOQSA-N 0.000 description 1
- 210000004296 naive t lymphocyte Anatomy 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 230000007896 negative regulation of T cell activation Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229940071846 neulasta Drugs 0.000 description 1
- 230000007372 neural signaling Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229950005751 ocrelizumab Drugs 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- 210000001706 olfactory mucosa Anatomy 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 230000033667 organ regeneration Effects 0.000 description 1
- 229940029358 orthoclone okt3 Drugs 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 101150081585 panB gene Proteins 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 108010044644 pegfilgrastim Proteins 0.000 description 1
- 238000013146 percutaneous coronary intervention Methods 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000012831 peritoneal equilibrium test Methods 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 238000012636 positron electron tomography Methods 0.000 description 1
- 238000012877 positron emission topography Methods 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 210000001948 pro-b lymphocyte Anatomy 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940124272 protein stabilizer Drugs 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 238000011363 radioimmunotherapy Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229940116176 remicade Drugs 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000019254 respiratory burst Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 210000004176 reticulum cell Anatomy 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 108090000064 retinoic acid receptors Proteins 0.000 description 1
- 102000003702 retinoic acid receptors Human genes 0.000 description 1
- 238000010242 retro-orbital bleeding Methods 0.000 description 1
- 229950009092 rovelizumab Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 229960002530 sargramostim Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229940068638 simponi Drugs 0.000 description 1
- 229940115586 simulect Drugs 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000010374 somatic cell nuclear transfer Methods 0.000 description 1
- 210000001988 somatic stem cell Anatomy 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000009120 supportive therapy Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000007755 survival signaling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229950004218 talizumab Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229950010127 teplizumab Drugs 0.000 description 1
- 229940034915 thalomid Drugs 0.000 description 1
- 230000033912 thigmotaxis Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 210000003014 totipotent stem cell Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940079023 tysabri Drugs 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960002166 vinorelbine tartrate Drugs 0.000 description 1
- GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IWWDSPBFSA-N 0.000 description 1
- 239000000277 virosome Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 229950009002 zanolimumab Drugs 0.000 description 1
- 229940043785 zortress Drugs 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 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
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/289—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD45
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Gastroenterology & Hepatology (AREA)
- Reproductive Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Gynecology & Obstetrics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Materials For Medical Uses (AREA)
Description
幹細胞がリンパ組織、特にリンパ組織の胚中心へ結合することを阻害する剤(エージェント)は、放射線、化学療法剤、免疫抑制剤、ならびにCD45に対するアンタゴニストおよびCD26に対するアンタゴニストを含む。全血または骨髄からの単核画分内で見いだされる幹細胞、または全血もしくは骨髄から精製された幹細胞は、脾臓の白脾髄領域、さらに具体的には脾臓を含むリンパ組織の白脾髄における胚中心、さらにより具体的には脾臓の白脾髄における活性胚中心へ結合する。CD45、特に30−F11ラットIgG2b抗マウス抗CD45モノクローナル抗体により識別されるエピトープに対する抗体は、脾臓の特定された場所への幹細胞の結合を減少させ、標的損傷器官への生体内分布のために幹細胞をより利用可能にし、組織の再生の機能回復を増進する。
本発明の実施態様を表すために用いられる定義。
本明細書で用いられるアゴニストという用語は、特定の受容体、または当該受容体の効果(単数または複数)を媒介するために必須な下流シグナル伝達経路を活性化する、すべての実体を意味する。アゴニストは、抗体、抗体断片、可溶性リガンド、小分子、環状ペプチド、架橋剤を含みうるがこれらに限定されない。
リンパ組織は、リンパ系における、多数のリンパ球を含有する特殊化された形態の網様結合組織である。この組織型は、脾臓、胸腺、扁桃腺、ならびに、すべてが消化管の粘膜と関連する内臓リンパ節、パイエル板および乳糜管を構成する。
他の特定の実施態様は、脾臓をcluster of differentiation45(CD45)抗原に対するアンタゴニストの溶液へ暴露することにより、幹細胞が脾臓に結合することを調整する方法を提供する。CD45抗原に対するアンタゴニストの溶液は、30−F11エピトープに結合するように構成または処方されうる。CD45抗原に対するアンタゴニストの溶液は、損傷組織または器官への幹細胞の輸送を増強することにより再生治療を促進するように処方されうる。CD45抗原に対する抗体を含む溶液は、30−F11エピトープおよび30F−11のヒト相当物に結合するように処方されうる。
本発明の別の実施態様は、胚中心の増殖を阻害もしくは下方制御し、または胚中心を破壊もしくは除去することにより、幹細胞がリンパ組織に結合することを阻害することである。胚中心(GC)は、T依存性抗原によるB細胞の活性化の後、動的に発達する。B細胞を活性化し、それによって胚中心の増殖を誘導するT細胞抗原は、B細胞上に存在するCD40受容体に結合するCD40L(CD154としても知られる)である。CD40受容体へのCD40のこの結合は、B細胞を活性化するだけでなく、胚中心の増殖もまた誘導する。それゆえに、本発明のその他の実施態様は、CD40へのCD40Lの結合を阻害する剤を個体へ投与することが含まれる。そのような剤の例として、CD40またはCD40Lに対するアンタゴニスト性抗体がある。
タクロリムスは、T細胞によるインターロイキン−2(IL−2)の産生を減少する。好ましくは幹細胞投与の3〜4日前に、カプセルまたは注入の形態で、0.10〜0.15mg/kg/日(Astellas Pharma US、Inc.Deerfield、IL)。
本発明の範囲内の幹細胞という用語は、所望の組織に分化可能な細胞を包含する。かかる細胞には、多能性幹細胞、胚性幹細胞、複能性成体幹細胞、および始原細胞と前駆細胞が含まれる。「幹細胞」は、一定の条件下で、長期間、または、成体幹細胞の場合、生物体の寿命の全体にわたって、それ自体を再生する能力を有する、胚、胎児、もしくは成体の細胞である。また、身体の組織および器官を構成する、特殊化した細胞を生じさせることもできる。
幹細胞治療は、多くの疾患の治療について調査され、改善されている。幹細胞治療から利益を得ることができ得る症状には、次に示すものが含まれる:眼疾患、神経疾患、胃腸疾患、筋骨格疾患、代謝性疾患、内分泌疾患、血管疾患、肺疾患、心臓疾患、心血管疾患、免疫媒介疾患、自己免疫媒介疾患、心血管疾患、および再生治療が有用なすべての疾患。NIHのウェブサイト(www.clinicaltrials.gov)上に含まれる臨床試験情報は、3000を越えるの幹細胞試験を列挙する。評価段階にある疾患には、次に示すものが含まれる:脈管炎、内皮始原細胞を使用するリウマチ障害、結合組織疾患患者における自家単核細胞の移植による新血管新生の治療、進行性核上麻痺患者における血液幹細胞動員のための顆粒球コロニー刺激因子の連続投与、大脳皮質基底核変性症、および多系統萎縮症;血液悪性腫瘍、白血病、リンパ腫、癌、大理石病、再生不良性貧血および血球減少症、鎌状赤血球病およびサラセミア、角膜上皮幹細胞疲弊症、乳癌、急性心筋梗塞(米国特許第7,862,810号:c−kit陽性心臓幹細胞の単離および培養を参照)、冠動脈疾患(米国特許第7,470,538号:臍帯血から単離されたCD133+/CD34+/CXCR4−細胞を増強させる、冠動脈への注入による単離および投与を参照)末梢血管疾患、心不全、I型糖尿病(米国特許出願公開第2011000830号:糖尿病の治療のための間葉系幹細胞を作製するヒト脂肪由来インスリンを参照)、2型糖尿病、脳卒中、脊髄損傷、神経芽腫、多発性硬化症(米国特許出願公開第20100166712号:MSを治療するための自家間葉系幹細胞由来神経前駆細胞の投与を参照)、全身性硬化症、紅斑性狼瘡、慢性創傷治癒、熱傷、骨折治癒、軟骨修復、CNS腫瘍、変形性関節炎、腎不全、パーキンソン病(米国特許出願公開第20100010087号:幹細胞移動の誘導およびEC−18による特殊化のための方法を参照)、骨髄腫、糖尿病性足疾患、肝硬変および胆汁性肝硬変、拡張型心筋症、貧血、色素性網膜炎、クローン病、糖尿病性ニューロパシー、肥満細胞症、卵巣癌、てんかん、重症筋無力症、自己免疫疾患、肉芽腫性疾患、骨壊死、肝不全、PMD疾患、脂質異栄養症(lypodystrophy)、脱髄疾患、軟骨欠陥、網膜疾患、ループス腎炎、アルツハイマー病、外傷性脳損傷、肉腫、筋炎、高血糖、黄斑変性、潰瘍性大腸炎、筋変性、ならびにその他。これらの幹細胞治療に対する制約としては、標的が特定の損傷した器官であろうと骨髄および脾臓の造血中心であろうと、幹細胞を最適に送達し移植する能力がないことが挙げられる。
幹細胞は、多くの経路によって患者に送達することができる。例えば、幹細胞は、幹細胞生存率を最適化し細胞集塊をなくす適切な賦形剤に含めて、静脈内に、動脈内に、筋肉内に、皮内に、皮下に、腹腔内に、心膜内に、眼内に、血管に、経心内膜に、経心的に、経中隔に、心外膜に、冠動脈内に、経皮的経心筋血行再建術によって、鞘内に、器官内に、鼻腔内に、心室内に、または、針、カテーテルもしくは他の最小侵襲性の方法によって硬膜外に、投与することができる。また、幹細胞は、注入部位で幹細胞の維持を支援するように設計された、「マトリックス」混合物または懸濁混合物(例えば、コラーゲン、フィブリノーゲン、フィブロネクチン、ラミニン、アルギン酸塩、アガロース、メチルセルロース、リポソーム、ナノ粒子、ミセル、アルブミン泡、脂肪酸、または他の半固体懸濁製剤)で、これらの経路によって投与することもできる。
幹細胞によって患者を治療する他の方法は、自分の身体の幹細胞を動員させて、骨髄等の器官を出て循環させるようにすることを含む。例えば、ニューポジェン(Neupogen)またはニューラスタ(Neulasta)等の長期活性型として販売される、顆粒球コロニー刺激因子(G−CSF;フィルグラスチム(Filgrastim))、リューカイン(Leukine)として販売される、顆粒球マクロファージコロニー刺激因子(GM−CFS;サルグラモスチム(Sargramostim))、ジェンザイム(Genzyme)社によってモゾビル(Mozobil)/プレリキサフォル(Plerixafor)として販売される、AMD3100等の治療法は、循環内の幹細胞数を増加させる。ニューポジェンは、300マイクログラムまたは480マイクログラムのいずれか一方のフィルグラスチムを含む、単回使用バイアルまたは単回使用シリンジで存在する。賦形剤は、酢酸塩、ソルビトール、ポリソルベート80、ナトリウム、および注射用蒸留水からなる。ニューポジェンは、1日2回静脈内に、1日1回皮下に、または慢性的皮下治療として、臨床的に使用される。ニューポジェンは、骨髄抑制化学療法を受ける癌患者、誘導または統合化学療法を受ける急性骨髄白血病患者、骨髄移植を受ける癌患者、重症慢性好中球減少症患者、および末梢血始原細胞の収集および治療を受ける患者の好中球数の回復を促進するために、承認されている。ニューポジェンは、一般に、体重1キログラム当たり3マイクログラムから69マイクログラム、毎日投与され、2日から20日間継続する治療による化学療法4日後に開始する。ニューポジェンの添付文書によれば、G−CSFは、骨髄内の好中球の生産を調節し、好中球始原細胞の増殖、分化、および選択された終末細胞の機能活性化(食細胞の能力の増強、呼吸バーストに関連する細胞の代謝の準備刺激、抗体依存性致死、および、細胞表面抗原に関連する一部の機能のうちの発現の増加を含む)に影響を与える。また、G−CSFは、次に示すものによって、循環に幹細胞を動員することも示されている:CXCR4のN末端のクリッピングをもたらすことによる(1)、骨髄においてVCAM発現を低減することによる(2)、骨髄間質におけるCXCL12発現を低減し、CXCR4発現を低減するその作用。G−CSFは、CX
CR2の同系統のリガンドである、CXCL2を増加させることが示されている。臨床的治療のための承認であるので、G−CSFは、循環において非常に小さい胚様幹細胞の数を増加させることも示されている。
幹細胞によって患者を治療する他の方法は、自発的に放出された内因性幹細胞が、リンパ組織で隔離されることを防ぐことを含む。幹細胞および始原細胞は、毎日、血液循環に自発的に放出される。並体結合マウスを使用する試験は、脾臓が、幹細胞および始原細胞を容易に循環とやりとりすることが示されている。さらに、病状(例えば、特に、高コレステロール血症、心臓発作、STEMIまたはCAD、動脈結紮または一過性虚血、中程度の滞留、原発性副甲状腺機能亢進症、および、網膜色素上皮損傷)は、幹細胞および始原細胞の循環のレベルを増加させることが示されている。自発的に放出された幹細胞または疾患により誘導された幹細胞が、リンパ組織で隔離されることを防ぐことによって、より多くの幹細胞が、損傷を受けた組織または器官の再生のために利用可能となる。
本発明は、放射または化学療法の後に、リンパ組織の胚中心を再生し、再若幼化し、リンパ組織の胚中心の数を増加させる方法および組成物を提供することによって、この必要性を満たす。本発明による、リンパ組織の胚中心を再若幼化(Rejuvenate)するかまたは再生(Regenerate)する治療法は、免疫活性化剤、共刺激分子、免疫アジュバント、およびこれらの組合せを含む。
アルミニウムカリウムホスフェートは、約0.17mgの用量で投与することができる。
SBAS−2は、MPLとQS21の水中油型エマルションである。
BCG−CWSと呼ばれるBCG準備刺激免疫(マイコバクテリウム・ボビス)は、成体ではバイアル当たり1から8×108コロニー形成単位(CFU)、子供ではその用量の半分である。
最大100塩基の長さ(最も好ましくは、20塩基の長さ)のCpGオリゴヌクレオチドは、体重20グラムから25グラム当たり1、10、100、500マイクログラムで投与される。好ましい用量は、体重20mgから25mg当たり10μgである。
リンパ組織内の胚中心の再生を誘導する治療剤の投与は、静脈内、動脈内、経口、筋肉内、エアロゾル、吸入、皮内、皮下、腹腔内、心膜内、眼内、血管、経心内膜、経心的、経中隔、心外膜、冠動脈内、経皮的経心筋血行再建術、鞘内、器官内、鼻腔内、心室内、または、針、カテーテルもしくは他の最小侵襲性の方法による硬膜外を含む方法によって行うことができる。
雄129S1/SvlmJマウスの骨髄および全血単核細胞画分を、ヒストパクを使用して単離し、混合した。細胞を、37℃、5%CO2で、4日間インキュベートして、分化した体細胞を致死させ、これによって、単核細胞(MNC)中の幹細胞画分を濃縮した。次いで、得られた細胞を、メーカーの説明書に従って、セルトラッカーオレンジ(cell tracker orange)(CTO、インビトロゲン(Invitrogen)社製)によって標識した。およそ1000万の標識細胞を、レシピエント同腹子に眼窩後方注射によって投与し、90分後、マウスを放血し、血液を収集し、残存する赤血球を血管から洗い流し、および脾臓を採取した。脾臓を、1%PFA中で一晩固定し、次いで、これを低溶融低ゲル化温度アガロースに埋め込み、切片当たり200ミクロンの厚さに切片化した。脾臓に結合したMNC幹細胞を、免疫蛍光法を用いて視覚化した。標識MNC含有幹細胞画分は、脾臓の白脾髄の端部におけるB細胞領域に結合した。失血中に収集した全血のMNC画分の免疫蛍光試験は、注射した標識細胞1000万のうちのおよそ40,000が、注射90分後に循環で継続してみられることを示した。
雄マウスの骨髄および全血の単核細胞画分を、ヒストパクを使用して単離し、混合した。次いで、セルトラッカーグリーン(CTG、インビトロゲン社製)によって標識したMNC細胞を、CD34、ckit、およびCD105に対するビオチン標識抗体と共にインキュベートし、メーカーの推奨に従って、ミルテニー磁力分離カラムを使用して、精製した。単離されたMNCの一部を、CTOによって別個に標識した。100万のCTO標識MNCを、100ミクロンから200ミクロンの厚さの新鮮な脾臓切片上で、205,000CTG標識精製幹細胞と共に、4℃で12時間から18時間、インキュベートした。脾臓切片を十分に洗浄して、未結合の細胞を除去し、1時間、1%PFA中で固定し、次いで、蛍光イメージングのために湿式マウントした。メタモルフ(MetaMorph)ソフトウェアを使用して、生じた赤色(MNC)と緑色(幹細胞)の結合を捉え、重ね合わせた。
骨髄および全血単核細胞(MNC)を、ヒストパクを使用して、成体マウスから単離する。得られた単核細胞を、メーカーの推奨に従って、セルトラッカーオレンジ、グリーンまたはブルー、DiIまたはカルセインオレンジまたはブルー等の細胞追跡用色素によって染色する。FITC標識PNA(10μg)、IgD(10μg)、または抗CD21(10μg)を使用して、白脾髄の特定のB細胞領域を識別する。PNAは胚中心を標識し、IgDは濾胞帯を標識し、また、抗CD21は、辺縁帯および暗殻帯を標識する。FITC標識抗CD3(200ngから1μg)を使用して、白脾髄のT細胞領域を特定する。十分な洗浄後、結合細胞および抗体を、1%PFAを使用して、4℃で1時間、脾臓切片上で固定する。湿式マウント切片を、蛍光について観察し、メタモルフソフトウェアを使用して撮影する。
マウス全血および骨髄からの単核細胞画分を組み合わせ、CTOによって標識し、次いで、ビオチン化抗CD34、抗CD117、および抗CD105と共にインキュベートし、その後、抗体に結合した細胞を、メーカーの説明書に従って、ミルテニー磁力細胞分離カラムを使用して、単離した。回収されたCD34+CD105+CD117+幹細胞の数は、開始MNC画分の0.3%から3%であった。
脾臓切片へのMNCおよび幹細胞の結合は、ラットモノクローナルIgG2b抗マウス抗CD45(800ナノグラムから4マイクログラム)によってブロックされるが、抗CD45R(10マイクログラム)、または抗CD3抗体(1マイクログラム)によってはブロックされない。30−F11ラット抗マウス抗CD45抗体(サンタクルーズバイオテクノロジー(Santa Cruz Biotechnology)社製)、または17A2抗CD3抗体(サンタクルーズバイオテクノロジー社製)を、1:50または1:10に希釈し、1時間、250,000のCTO標識MNCと共にインキュベートした。MNC結合を、結合するニッチの数、およびニッチのサイズとして視覚的に計測した。CTO−MNC対照の新鮮な脾臓切片は、切片当たり3〜6個の中程度から大きいサイズのMNC結合ニッチを有していた。抗CD3抗体は、MNC結合ニッチの数またはサイズのいずれにも影響を与えなかった。1:50希釈における抗CD45 30−F11抗体は、MNC結合ニッチの数およびサイズを共に半分に減少させた。1:10希釈における抗CD45 30−F11抗体は、新鮮な脾臓切片に結合するCTO−MNCを完全に消失させた。
[30−F11は、マウスCD45のすべてのアイソフォームに結合する。]
30−F11エピトープの正確な結合は、マッピングされていない。30−F11は、マウスの脾臓および胸腺細胞を用いた免疫化によって生成されたものである。マウスCD45アイソフォーム1の細胞外ドメインは、アミノ酸24〜564からなる。アイソフォーム2は、アミノ酸31〜73を欠いているが、アイソフォーム3は、アミノ酸31〜169を欠いている。
30−F11は、マウスCD45のすべてのアイソフォームに結合すると報告されているので、結合するエピトープは、アイソフォーム1のアミノ酸170〜564に存在するはずである。タンパク質の抗原領域は、疎水性(Kyte Doolittle)、およびSwisProtウェブサイトでみられるアクセス可能性アルゴリズムを用いて予測することができる。抗原領域は、低い疎水性と高いアクセス可能性の領域でみられる可能性が最も高いと考えられる。ヒト配列の501〜521付近のアミノ酸残基には、タンパク質のこの領域を潜在的抗原性部位として示す、低い疎水性予測がある。また、この領域は、マウスからヒトまで十分に保存される。(Okumura M.らの文献:1996年8月15日;157(4):1569-75を参照。)
不完全フロイントアジュバントまたはRibiを使用した意図的な免疫化によって、活性胚中心を正常なマウスに誘発させた。第0日目に、マウスに、PBSまたは0.5mlのRIBIアジュバントと1:1で混合した0.5mlの不完全フロイントアジュバント(FIA)を腹腔内に(IP)注射した。免疫化7日または14日後に、マウスを、アベルチン麻酔前に、100Uの腹腔内ヘパリンによって30分間ヘパリン処置した。マウスを、眼窩後部出血によって放血し、全1.5mlから1.8mlの全血を得て、これを15mlコニカルチューブ中で200μlの5U/mlヘパリンに加えた。その後、腹大動脈および大静脈を切断し、残存する血液を、上行性胸部大静脈を介して、10mlの5U/mLヘパリンの遅い押出し注入によって、完全に血管から外に洗い流した。脾臓を除去し、増殖培地に入れ、その後、軟寒天に埋め込み、また、これを切片化して、200ミクロンの厚さの均一な切片を得た。胸骨および大腿骨骨髄を、ハンク緩衝食塩水によって骨から洗い流し、全血および骨髄の単核幹細胞画分を、ヒストパクを使用して単離し、混合した。FITC標識抗PNA(10μg)を使用して、4℃で一晩インキュベーションすることによって、脾臓切片上で胚中心を特定した。PNAとの一晩のインキュベーション後、洗浄せずに、CTO標識単核幹細胞画分を4℃で1時間切片に加えた。十分な洗浄後、結合細胞および標識PNAを、1%PFAを使用して、4℃で1時間、脾臓切片上に固定する。湿式マウント切片を、蛍光について観察しメタモルフソフトウェアを使用して撮影する。
マウスを、脾臓切片に結合する幹細胞のエクスビボ分析のための脾臓および幹細胞の採取7日前に、腹腔内注射により、エタノール(1部)およびPBS(9部)中に溶解した1mgデキサメタゾンによって処置した。対照マウスは、全容積1mlのエタノール(1部)およびPBS(9部)のみによって処置した。第7日目に、実施例7に詳述するように、マウスを採取し処置した。対照マウスの単核幹細胞画分を、対照およびデキサメタゾン処置脾臓切片に関する結合試験に使用した。第7日目に結合する単核幹細胞は、試験7日前に供したデキサメタゾンによる1回1mgの処置の後では、30%から40%減少した。
未処置の対照マウスを、アベルチン麻酔前に30分間、100Uの腹腔内ヘパリンによってヘパリン処理した。マウスを、眼窩後部出血によって放血し、全1.5mlから1.8mlの全血を得て、これを15mlコニカルチューブ中で200μlの5U/mlヘパリンに加えた。その後、腹大動脈および大静脈を切断し、残存する血液を、上行性胸部大静脈を介して、10mlの5U/mLヘパリンの遅い押出し注入によって、完全に血管から外に洗い流した。胸骨および大腿骨骨髄を、ハンク緩衝食塩水によって骨から洗い流し、全血および骨髄の単核幹細胞画分を、ヒストパクを使用して単離し、混合した。単核幹細胞画分を増殖培地(10%FBS添加DMEM)中で再懸濁し、37℃、5%CO2で、一晩インキュベートした。翌朝、単核幹細胞を、メーカーの説明書に従って、セルトラッカーグリーン(CTG)によって標識した。
(理論実験例(prophetic))
ヒトボランティアを、確立された臨床試験計画書に従って、薬剤のすべての悪影響を制限するか、または完全に回避するために選択された用量を用いて、プレドニゾン等の市販の一般的な免疫反応抑制剤によって、予防的に処置する。別のヒトボランティア群を、5 mg/kgから100 mg/kgの用量で、HCD−122抗CD40 mAb等のCD40に対する抗体によって処置する。
(理論実験例)
3ヶ月および12ヶ月齢のPNおよび129S1/SvlmJマウスに、抗CD40L mAb(ファルマミンゲン(PharMingen)社製)または対照ハムスターIg(ピアス(Pierce)社製、ロックフォード、イリノイ州)を静脈内注射(i.v.;第0日、2日および4日目の注射当たり250mg)する。全血および骨髄単核画分幹細胞を、未処置の同腹子マウスから収集し、CTO等の細胞追跡用色素によって標識し、次いで、幹細胞を、ビオチン化抗CD34、抗CD105、抗SSEA1、および抗CD117抗体を使用して、ミルテニー磁力分離カラムによって精製する。第5日目に、100,000から1Mの精製幹細胞を、試験マウスの眼窩後部または静脈内に注射する。15時間から24時間後に、マウスを放血し、血液を収集し、血管に残存する赤血球を洗浄し、また、脾臓を、幹細胞蓄積の蛍光イメージングのために収集する。幹細胞蓄積は、対照のIG処置PNマウスの活性PNA+胚中心において明らかであり、129S1マウスよりも有意に多い活性胚中心数、そしてその結果としての、結合する幹細胞の増加を示す。抗CD40L mAb処置129S1マウスは、明白な活性胚中心が、あったとしても少数であり、幹細胞結合はほとんどないか全くない。抗CD40L mAb処置PNマウスは、Ig処置対照マウスと比較して、活性胚中心の数の減少を示し、このため、これに並行して、幹細胞結合の減少を示す。
(理論実験例)
梗塞急性期におけるステント移植による経皮的冠動脈インターベンションによって良好に治療された、急性ST部上昇型MI患者が、試験に適格である。患者を、第1日目に、30分のIV注入によって、5、10、20または100 mg/kgで、抗CD40L mAbレプリツマブ(Replizumab)により処置する。
雄129S1/SvlmJマウスの骨髄および全血単核細胞画分を、ヒストパクを使用して単離し、混合し、メーカーの説明書に従って、CTOによって標識した。脾臓を、単個細胞浮遊液に解離し、CTBによって標識した。MNCを7日間、増殖培地で培養し、その後、7日間、FBSを含まない増殖培地(120 ng/ml幹細胞因子および25%ウマ血清を添加)で培養し、非接着性細胞を採取することによって、幹細胞を得た。典型的には、非接着性細胞の最大40%が、CD34、CD105、SSEA1、および/またはCD117を発現する。幹細胞をCTOによって標識した。
[1]
幹細胞がリンパ組織に結合することを阻害する方法であって、前記リンパ組織への前記幹細胞の結合を阻害する治療剤とともに当該幹細胞を投与することを含む方法。
[2]
前記リンパ組織が脾臓、パイエル板およびリンパ節を含む、[1]に記載の方法。
[3]
前記治療剤は、前記幹細胞の、前記リンパ組織内の胚中心への結合を阻害する、[1]に記載の方法。
[4]
前記胚中心は、脾臓、パイエル板およびリンパ節組織からなる群から選択されるリンパ組織に存在する、[3]に記載の方法。
[5]
前記胚中心は活性化している、[3]に記載の方法。
[6]
前記治療剤は、プリン類の合成を妨げる剤、抗代謝産物、脾臓への放射線照射、化学療法剤、免疫抑制剤、グルココルチコイド、抗ベータアミロイド剤、抗Rh因子、抗TNF剤、抗エオタキシン、抗T細胞受容体(TCR)剤、抗インターフェロン剤、抗インターフェロンアルファ剤、抗インターフェロンベータ剤、抗インターフェロンガンマ剤、抗TGF剤、抗TGFアルファ剤、抗TGFベータ剤、抗インテグリン剤、抗アルファ4剤、抗インターロイキン剤、抗インターロイキン1剤、抗インターロイキン2剤、抗インターロイキン4剤、抗インターロイキン5剤、抗インターロイキン6剤、抗インターロイキン12剤、抗インターロイキン13剤、抗インターロイキン23剤、抗IgE剤、抗血管接着タンパク質(VAP)剤、抗B7剤、抗血管内皮増殖因子(VEGF)剤、抗BAFF(BLyS)剤、抗CTLA4剤、抗補体剤、抗CD2剤、抗CD3剤、抗CD4剤、抗CD5剤、抗CD20剤、抗CD23剤、抗CD25a剤、抗CD40剤、抗CD154(CD40L)剤、抗CD62L剤、抗CD80剤、抗CD147剤、抗LFA1剤、抗(CD11a)剤、抗CD18剤、プリン類合成阻害剤、ピリミジン合成阻害剤、抗増殖剤、抗代謝剤、抗葉酸在、および抗mTOR剤、
からなる群から選択される、[1]の方法。
[7]
前記治療剤は、アザチオプリン、ミコフェノール酸、レフルノミド、テリフルノミド、メトトレキサート、タクロリムス、シクロスポリン、ピメクロリムス、アベチムス、グスペリムス、サリドマイド、レナリドマイド、アナキンラ、シロリムス、デフォロリウムス、エベロリムス、テムシロリムス、ゾタロリムス、ビオリムス A9、エクリズマブ、インフリキシマブ、アダリムマブ、セルトリズマブ ペゴル、アフェリモマブ、ゴリムマブ、メポリズマブ、オマリズマブ、ネレリモマブ、ファラリモマブ、エルシリモマブ、レブリキズマブ、ウステキヌマブ、ムロモナブ−CD3、オテリキシズマブ、テプリズマブ、ビジリズマブ、クレノリキシマブ、ケリキシマブ、ザノリムマブ、エファリズマブ、エルリズマブ、アフツズマブ、オクレリズマブ、パスコリズマブ、ルミリキシマブ、テネリキシマブ、トラリズマブ、アセリズマブ、ガリキシマブ、ガビリモマブ、ルプリズマブ、ベリムマブ、イピリムマブ、トレメリムマブ、ベルチリムマブ、レルデリムマブ、メテリムマブ、ナタリズマブ、トシリズマブ、オヅリモマブ、バシリキシマブ、ダクリズマブ、イノリモマブ、ゾリモマブアリトックス、アトロリムマブ、セデリズマブ、ドルリキシズマブ、フォントリズマブ、ガンテネルマブ、ゴミリキシマブ、マスリモマブ、モロリムマブ、ペキセリズマブ、レスリズマブ、ロベリズマブ、シプリズマブ、タリズマブ、テリモマブアリトックス、バパリキシマブ、ベパリモマブ、アバタセプト、ベラタセプト、エタネルセプト、ペグスネルセプト、アフリベルセプト、アレファセプト、リロナセプト、リンフォトキシンアルファおよびベータ阻害剤、ダセツズマブSGN−40、HCD−12、
からなる群から選択される、[1]に記載の方法。
[8]
前記幹細胞の前記リンパ組織への結合が、CD45抗原を下方制御するかまたは妨げる治療剤を投与することにより阻害される、[1]に記載の方法。
[9]
前記治療剤は、放射線である、[1]に記載の方法。
[10]
前記幹細胞は、外因性または内因性の幹細胞である、[1]に記載の方法。
[11]
前記治療剤は、化学療法剤である、[1]に記載の方法。
[12]
前記幹細胞は、血液悪性腫瘍、白血病、リンパ腫、癌、大理石骨病、再生不良性貧血および血球減少症、鎌状赤血球病およびサラセミア、角膜上皮幹細胞疲弊症、乳癌、急性心筋梗塞、冠状動脈疾患、末梢血管疾患、心不全、1型糖尿病、2型糖尿病、脳卒中、脊髄損傷、神経芽細胞腫、多発性硬化症、全身性硬化症、エリテマトーデス、慢性創傷治癒、火傷、骨折治癒、軟骨修復、CNS腫瘍、変形性関節症、腎不全、パーキンソン病、骨髄腫、糖尿病足、肝硬変および胆汁性肝硬変、拡張型心筋症、貧血、網膜色素変性症、クローン病、糖尿病性神経障害、肥満細胞症、卵巣癌、てんかん、重症筋無力症、自己免疫性疾患、肉芽腫性疾患、骨壊死、肝不全、PMD疾患、脂肪異栄養症、脱髄疾患、軟骨疾患、網膜疾患、ループス腎炎、アルツハイマー病、外傷性脳損傷、肉腫、筋炎、高血糖症、黄斑変性症、潰瘍性大腸炎および筋肉変性、
からなる群から選択される疾患を治療するために投与される、[1]に記載の方法。
[13]
個体において、幹細胞がリンパ組織へ結合することを阻害するための方法であって、リンパ組織に存在する胚中心の形成を阻害すること、またはリンパ組織の胚中心を破壊もしくは除去することを含む方法。
[14]
胚芽細胞(germinal cells)の形成を阻害する、または胚芽細胞の破壊もしくは除去を促進する治療剤が個体に投与され、前記治療剤は、プリン類の合成を妨げる剤、抗代謝産物、放射線、免疫抑制剤、グルココルチコイド、抗ベータアミロイド剤、抗Rh因子、抗TNF剤、抗エオタキシン、抗T細胞受容体(TCR)剤、抗インターフェロン剤、抗インターフェロンアルファ剤、抗インターフェロンベータ剤、抗インターフェロンガンマ剤、抗TGF剤、抗TGFアルファ剤、抗TGFベータ剤、抗インテグリン剤、抗アルファ4剤、抗インターロイキン剤、抗インターロイキン1剤、抗インターロイキン2剤、抗インターロイキン4剤、抗インターロイキン5剤、抗インターロイキン6剤、抗インターロイキン12剤、抗インターロイキン13剤、抗インターロイキン23剤、抗IgE剤、抗血管接着タンパク質(VAP)剤、抗B7剤、抗血管内皮増殖因子(VEGF)剤、抗BAFF(BLyS)剤、抗CTLA4剤、抗補体剤、抗CD2剤、抗CD3剤、抗CD4剤、抗CD5剤、抗CD20剤、抗CD23剤、抗CD25a剤、抗CD40剤、抗CD154(CD40L)剤、抗CD62L剤、抗CD80剤、抗CD147剤、抗LFA1剤、抗(CD11a)剤、抗CD18剤、プリン類合成阻害剤、ピリミジン合成阻害剤、抗増殖剤、抗代謝剤、抗葉酸在、および抗mTOR剤、からなる群から選択される、[13]に記載の方法。
[15]
前記治療剤は、化学療法剤である、[13]に記載の方法。
[16]
リンパ組織の胚中心を再生するための方法であって、前記胚中心は化学剤、生物剤により、または放射線により損傷されたものであって、胚中心の再生を刺激する1つ以上の剤を投与することを含む方法。
上述するように、本発明の好適な実施態様が示され、説明されたが、上で述べた通り、多くの変更を、本発明の趣旨および範囲から逸脱することなしに、行うことができる。したがって、本発明の範囲は、好適な実施態様の開示によって限定されない。代わりに、本発明は、次に示す特許請求の範囲を参照することによって専ら決定されるべきである。
Claims (6)
- 損傷した組織または器官を有する対象において、循環する幹細胞がリンパ組織に結合することを阻害して幹細胞治療を補助するための組成物であって、
前記対象はリンパ組織内に活性胚中心を有する対象であり、
前記幹細胞治療は、癌治療、非骨髄破壊的治療、または骨髄破壊的治療に伴う造血回復のためのものではなく、前記癌治療、非骨髄破壊的治療、または骨髄破壊的治療は、化学療法、放射線、またはその組合せを含み、
前記組成物は、前記幹細胞の投与の後ではなく前記幹細胞の投与の前または前記幹細胞の投与と一緒に投与され、
前記組成物は、前記幹細胞が前記活性胚中心に結合することを阻害する治療物質であって、それによってより多くの幹細胞を前記損傷した組織または器官の再生のために利用可能にする、治療物質を含み、
前記治療物質はデキサメタゾンである、
組成物。 - 前記リンパ組織は、脾臓、パイエル板、およびリンパ節を含む、請求項1に記載の組成物。
- 前記幹細胞は、間葉系幹細胞、中胚葉系幹細胞、脂肪幹細胞、間質血管幹細胞、人工多能性幹細胞、胚性幹細胞、嗅幹細胞、表皮幹細胞、神経幹細胞、角膜上皮幹細胞、皮膚幹細胞、心臓幹細胞、骨格幹細胞、筋芽幹細胞、卵形幹細胞、肝臓幹細胞、上皮幹細胞、腸管幹細胞、膵臓幹細胞、角膜幹細胞、およびケラチノサイト幹細胞からなる群から選択される、請求項1または2に記載の組成物。
- 前記対象は、血液悪性腫瘍、白血病、リンパ腫、癌、大理石骨病、白血病、再生不良性貧血および血球減少症、鎌状赤血球病およびサラセミア、乳癌、神経芽細胞腫、CNS腫瘍、卵巣癌、骨髄腫、エリテマトーデス、ループス腎炎、多発性硬化症、肉芽腫性疾患、全身性硬化症、筋炎、潰瘍性大腸炎、胆汁性肝硬変、クローン病、自己免疫性疾患、および肉腫からなる群から選択される状態に罹患した対象ではない、請求項1〜3のいずれか1項に記載の組成物。
- 前記対象は、神経疾患、胃腸疾患、筋骨格疾患、代謝性疾患、内分泌疾患、血管疾患、肺疾患、心臓疾患、心血管疾患、大理石骨病、角膜上皮幹細胞疲弊症、急性心筋梗塞、冠状動脈疾患、末梢血管疾患、心不全、2型糖尿病、脳卒中、脊髄損傷、慢性創傷治癒、火傷、骨折治癒、軟骨変性、結合組織疾患、変形性関節症、腎不全、パーキンソン病、肝硬変、拡張型心筋症、網膜色素変性症、肥満細胞症、てんかん、重症筋無力症、骨壊死、肝不全、PMD疾患、脂肪異栄養症、脱髄疾患、軟骨欠陥、網膜疾患、アルツハイマー病、外傷性脳損傷、高血糖症、黄斑変性症、および筋肉変性からなる群から選択される状態に罹患した対象である、請求項1〜3のいずれか1項に記載の組成物。
- 損傷した組織または器官を有する対象において、循環する自家幹細胞がリンパ組織に結合することを阻害して幹細胞治療を補助するための組成物であって、
前記対象はリンパ組織内に活性胚中心を有する対象であり、
前記幹細胞治療は、癌治療、非骨髄破壊的治療、または骨髄破壊的治療に伴う造血回復のためのものではなく、前記癌治療、非骨髄破壊的治療、または骨髄破壊的治療は、化学療法、放射線、またはその組合せを含み、
前記組成物は、前記自家幹細胞の投与の前または前記幹細胞の投与とともに投与され、
前記組成物は、前記自家幹細胞が前記活性胚中心に結合することを阻害する治療物質であって、それによってより多くの幹細胞を前記損傷した組織または器官の再生のために利用可能にする、治療物質を含み、
前記治療物質はデキサメタゾンである、
組成物。
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37494310P | 2010-08-18 | 2010-08-18 | |
US61/374,943 | 2010-08-18 | ||
US201161441485P | 2011-02-10 | 2011-02-10 | |
US61/441,485 | 2011-02-10 | ||
US201161449372P | 2011-03-04 | 2011-03-04 | |
US61/449,372 | 2011-03-04 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013524985A Division JP6096116B2 (ja) | 2010-08-18 | 2011-08-18 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法。 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018214418A Division JP6716668B2 (ja) | 2010-08-18 | 2018-11-15 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017081948A JP2017081948A (ja) | 2017-05-18 |
JP6437988B2 true JP6437988B2 (ja) | 2018-12-12 |
Family
ID=45594254
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013524985A Active JP6096116B2 (ja) | 2010-08-18 | 2011-08-18 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法。 |
JP2016239572A Active JP6437988B2 (ja) | 2010-08-18 | 2016-12-09 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 |
JP2018214418A Active JP6716668B2 (ja) | 2010-08-18 | 2018-11-15 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013524985A Active JP6096116B2 (ja) | 2010-08-18 | 2011-08-18 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法。 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018214418A Active JP6716668B2 (ja) | 2010-08-18 | 2018-11-15 | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 |
Country Status (19)
Country | Link |
---|---|
US (2) | US20120045435A1 (ja) |
EP (2) | EP2605765B1 (ja) |
JP (3) | JP6096116B2 (ja) |
KR (3) | KR101833204B1 (ja) |
CN (1) | CN103167870B (ja) |
AU (1) | AU2011291651B2 (ja) |
BR (1) | BR112013003169B1 (ja) |
CA (1) | CA2844109C (ja) |
CR (1) | CR20130117A (ja) |
DO (1) | DOP2013000043A (ja) |
ES (1) | ES2738115T3 (ja) |
IL (1) | IL224727B (ja) |
MX (1) | MX368272B (ja) |
MY (1) | MY179491A (ja) |
NZ (1) | NZ607906A (ja) |
RU (1) | RU2645069C2 (ja) |
SG (2) | SG10201600621VA (ja) |
WO (1) | WO2012024519A2 (ja) |
ZA (2) | ZA201301800B (ja) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10426740B1 (en) * | 2010-08-18 | 2019-10-01 | Avm Biotechnology, Llc | Compositions and methods to inhibit stem cell and progenitor cell binding to lymphoid tissue and for regenerating germinal centers in lymphatic tissues |
EP2767549A1 (en) * | 2013-02-19 | 2014-08-20 | Adienne S.A. | Anti-CD26 antibodies and uses thereof |
US11242399B2 (en) | 2013-02-19 | 2022-02-08 | Adienne S.A. | Anti-CD26 antibodies |
WO2016022656A1 (en) * | 2014-08-05 | 2016-02-11 | Wayne State University | Compositions and methods for treatment of sickle cell disease |
EP3355914B1 (en) | 2015-09-29 | 2024-03-06 | The General Hospital Corporation | A composition comprising bcg for reducing cholesterol. |
EP3373929A4 (en) * | 2015-11-09 | 2019-07-03 | The General Hospital Corporation d/b/a Massachusetts General Hospital | UNIT DOSE FORMULATIONS FOR USE AS ANTI-FUGETACTIC AGENT |
CN107034272B (zh) * | 2016-12-14 | 2020-09-29 | 河北医科大学第四医院(河北省肿瘤医院) | Cxcl2在制备诊断或治疗肺腺癌工具中的应用 |
AU2018243753A1 (en) * | 2017-04-01 | 2019-10-10 | Avm Biotechnology, Llc | Replacement of cytotoxic preconditioning before cellular immunotherapy |
CN110944668A (zh) | 2017-06-16 | 2020-03-31 | 学校法人同志社 | 用于治疗或预防眼部症状、障碍或疾病的包含mTOR抑制剂的药物及其应用 |
WO2018230713A1 (ja) * | 2017-06-16 | 2018-12-20 | 学校法人同志社 | カスパーゼ阻害活性を有する化合物、これらの化合物を含む、角膜内皮の症状、障害または疾患を治療または予防するための医薬およびその応用 |
AU2018374283A1 (en) * | 2017-11-29 | 2020-06-04 | Magenta Therapeutics, Inc. | Compositions and methods for the depletion of CD5+ cells |
RU2707281C1 (ru) * | 2018-09-17 | 2019-11-26 | Гордейчук Владимир Евгеньевич | Способ иммунотерапии раковых заболеваний |
EP3488851A1 (en) | 2018-10-03 | 2019-05-29 | AVM Biotechnology, LLC | Immunoablative therapies |
CN113301923A (zh) * | 2018-10-30 | 2021-08-24 | 美真达治疗公司 | 同种异体造血干细胞移植的方法 |
KR20220130253A (ko) | 2018-11-14 | 2022-09-26 | 에이브이엠 바이오테크놀로지, 엘엘씨 | 안정한 글루코코르티코이드 제제 |
JOP20210298A1 (ar) | 2019-05-14 | 2023-01-30 | Provention Bio Inc | طرق وتركيبات للوقاية من مرض السكري من النوع الأول |
WO2021211450A1 (en) * | 2020-04-13 | 2021-10-21 | Fred Hutchinson Cancer Research Center | Conditioning regimens for in vivo gene therapy |
US20210353685A1 (en) * | 2020-05-14 | 2021-11-18 | Brain Cancer Research Institute | Augmentation of Cell Therapy Efficacy by Inhibition of Complement Activation Pathways |
KR20230092863A (ko) | 2020-06-11 | 2023-06-26 | 프로벤션 바이오, 인코포레이티드 | 제1형 당뇨병을 예방하기 위한 방법 및 조성물 |
KR102285160B1 (ko) * | 2020-12-24 | 2021-08-03 | 주식회사 타임바이오 | 전구세포에서 유래한 다기능성 엑소좀을 포함하는 피부염 예방 또는 치료용 약학적 조성물 |
CN116549629A (zh) * | 2022-01-30 | 2023-08-08 | 江苏众红生物工程创药研究院有限公司 | Cd45作为生物标志物在筛查cd26抗体或其衍生物治疗肿瘤有效性和精准性中的应用 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5486359A (en) | 1990-11-16 | 1996-01-23 | Osiris Therapeutics, Inc. | Human mesenchymal stem cells |
US5837539A (en) | 1990-11-16 | 1998-11-17 | Osiris Therapeutics, Inc. | Monoclonal antibodies for human mesenchymal stem cells |
GB9323199D0 (en) * | 1993-11-10 | 1994-01-05 | Falkenberg J H F | Leukaemia treatment |
US7862810B2 (en) | 2000-07-31 | 2011-01-04 | New York Medical College | Methods and compositions for the repair and/or regeneration of damaged myocardium |
EP1395274A2 (en) * | 2001-05-22 | 2004-03-10 | Duke University | Compositions and methods for inhibiting metastasis |
IL146970A0 (en) * | 2001-12-06 | 2002-08-14 | Yeda Res & Dev | Migration of haematopoietic stem cells and progenitor cells to the liver |
CN1697655B (zh) * | 2002-05-17 | 2013-09-18 | 细胞基因公司 | 使用免疫调节性化合物用于治疗和控制癌症和其它疾病的方法及组合物 |
US7470538B2 (en) | 2002-12-05 | 2008-12-30 | Case Western Reserve University | Cell-based therapies for ischemia |
US20040247574A1 (en) * | 2003-05-27 | 2004-12-09 | Christopherson Kent W. | Methods for enhancing stem cell engraftment during transplantation |
JP5425399B2 (ja) * | 2004-12-23 | 2014-02-26 | エシコン・インコーポレイテッド | 産褥由来細胞を用いたパーキンソン病および関連の障害の治療 |
US20080138415A1 (en) * | 2006-09-26 | 2008-06-12 | Mehboob Hussain | Composition and method for producing composition for constructing tissue, and tissue construct |
US8642331B2 (en) | 2006-11-03 | 2014-02-04 | Multiple Sclerosis Research Center Of New York | Bone marrow-derived mesenchymal stem cells as a source of neural progenitors |
AU2008210988B2 (en) * | 2007-02-01 | 2012-09-06 | Allocure, Inc. | Potentiation of stem cell homing and treatment of organ dysfunction or organ failure |
JP4865868B2 (ja) * | 2007-03-14 | 2012-02-01 | 国立大学法人 東京大学 | 悪性中皮種の治療方法 |
JP4743215B2 (ja) | 2008-02-07 | 2011-08-10 | 株式会社ジェイ・エム・エス | 血液透析装置 |
US20090299269A1 (en) | 2008-05-29 | 2009-12-03 | John Foley | Vascular stimulation to aid intravascular cell replacement therapy |
WO2010006261A1 (en) | 2008-07-10 | 2010-01-14 | Hong John J | Methods for inducing stem cell migration and specialization with ec-18 |
-
2011
- 2011-08-18 AU AU2011291651A patent/AU2011291651B2/en not_active Ceased
- 2011-08-18 KR KR1020137006660A patent/KR101833204B1/ko active IP Right Grant
- 2011-08-18 ES ES11752017T patent/ES2738115T3/es active Active
- 2011-08-18 CN CN201180050123.0A patent/CN103167870B/zh active Active
- 2011-08-18 JP JP2013524985A patent/JP6096116B2/ja active Active
- 2011-08-18 KR KR1020187005163A patent/KR102173938B1/ko active IP Right Grant
- 2011-08-18 US US13/212,916 patent/US20120045435A1/en not_active Abandoned
- 2011-08-18 EP EP11752017.1A patent/EP2605765B1/en active Active
- 2011-08-18 RU RU2013110492A patent/RU2645069C2/ru not_active Application Discontinuation
- 2011-08-18 MX MX2013001835A patent/MX368272B/es active IP Right Grant
- 2011-08-18 EP EP19165292.4A patent/EP3530274A1/en active Pending
- 2011-08-18 MY MYPI2013000477A patent/MY179491A/en unknown
- 2011-08-18 BR BR112013003169-7A patent/BR112013003169B1/pt active IP Right Grant
- 2011-08-18 KR KR1020197003901A patent/KR20190017065A/ko active Application Filing
- 2011-08-18 CA CA2844109A patent/CA2844109C/en active Active
- 2011-08-18 SG SG10201600621VA patent/SG10201600621VA/en unknown
- 2011-08-18 WO PCT/US2011/048297 patent/WO2012024519A2/en active Application Filing
- 2011-08-18 SG SG2013010863A patent/SG187840A1/en unknown
- 2011-08-18 NZ NZ607906A patent/NZ607906A/en not_active IP Right Cessation
-
2013
- 2013-02-14 DO DO2013000043A patent/DOP2013000043A/es unknown
- 2013-02-14 IL IL224727A patent/IL224727B/en active IP Right Grant
- 2013-03-08 ZA ZA2013/01800A patent/ZA201301800B/en unknown
- 2013-03-15 CR CR20130117A patent/CR20130117A/es unknown
-
2014
- 2014-04-02 ZA ZA2014/02419A patent/ZA201402419B/en unknown
-
2016
- 2016-12-09 JP JP2016239572A patent/JP6437988B2/ja active Active
-
2017
- 2017-01-19 US US15/410,759 patent/US9962408B2/en active Active
-
2018
- 2018-11-15 JP JP2018214418A patent/JP6716668B2/ja active Active
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6716668B2 (ja) | リンパ組織に幹細胞および前駆細胞が結合することを阻害する組成および方法、ならびにリンパ組織の胚中心を再生させるための組成および方法 | |
US20220054554A1 (en) | Scalable Production of Standardized Extracellular Vesicles, Extracellular Vesicle Preparations and Uses Thereof | |
EP2893002B1 (en) | Methods of expanding and assessing b cells and using expanded b cells to treat disease | |
KR20220005075A (ko) | 키메라 항원 수용체 면역요법의 투여 방법 | |
US10426740B1 (en) | Compositions and methods to inhibit stem cell and progenitor cell binding to lymphoid tissue and for regenerating germinal centers in lymphatic tissues | |
US20240158488A1 (en) | Methods of restoring functional capacity and lineage composition of an aging blood and vascular system | |
KR101786862B1 (ko) | 류마티즘성 질환을 치료 또는 예방하는 방법 | |
TW202128741A (zh) | 嵌合抗原受體t細胞療法 | |
Delemarre et al. | Autologous bone marrow transplantation restores immune tolerance in experimental arthritis by renewal and modulation of the T effector compartment | |
Sala | Mesenchymal stem cells: mechanisms involved in the treatment of Inflammatory Bowel Disease | |
Ehrlich | IL-3-Mediated Osteoblast Inhibition in Multiple Myeloma |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180213 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180510 |
|
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: 20181016 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181115 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6437988 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 |