JP2000511898A - Mhcクラスii抗原提示系及びcd4▲上+▼t細胞の活性化方法 - Google Patents
Mhcクラスii抗原提示系及びcd4▲上+▼t細胞の活性化方法Info
- Publication number
- JP2000511898A JP2000511898A JP10500616A JP50061698A JP2000511898A JP 2000511898 A JP2000511898 A JP 2000511898A JP 10500616 A JP10500616 A JP 10500616A JP 50061698 A JP50061698 A JP 50061698A JP 2000511898 A JP2000511898 A JP 2000511898A
- Authority
- JP
- Japan
- Prior art keywords
- molecule
- cells
- accessory
- mhc class
- 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.)
- Granted
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 160
- 238000000034 method Methods 0.000 title claims abstract description 159
- 230000003213 activating effect Effects 0.000 title claims description 16
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 title description 2
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 title description 2
- 210000004027 cell Anatomy 0.000 claims abstract description 357
- 239000011159 matrix material Substances 0.000 claims abstract description 53
- 239000000427 antigen Substances 0.000 claims abstract description 34
- 108091007433 antigens Proteins 0.000 claims abstract description 31
- 102000036639 antigens Human genes 0.000 claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 claims abstract description 29
- 108091054438 MHC class II family Proteins 0.000 claims description 200
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 195
- 108090000623 proteins and genes Proteins 0.000 claims description 168
- 102000043131 MHC class II family Human genes 0.000 claims description 156
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 101
- 239000013598 vector Substances 0.000 claims description 90
- 102000004127 Cytokines Human genes 0.000 claims description 54
- 108090000695 Cytokines Proteins 0.000 claims description 54
- 239000000833 heterodimer Substances 0.000 claims description 47
- 239000012634 fragment Substances 0.000 claims description 45
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 claims description 43
- 230000000139 costimulatory effect Effects 0.000 claims description 41
- 230000004044 response Effects 0.000 claims description 40
- 230000030741 antigen processing and presentation Effects 0.000 claims description 34
- 230000004083 survival effect Effects 0.000 claims description 31
- 241000238631 Hexapoda Species 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 24
- 108010008038 Synthetic Vaccines Proteins 0.000 claims description 23
- 238000000338 in vitro Methods 0.000 claims description 23
- 230000001939 inductive effect Effects 0.000 claims description 23
- 102000000588 Interleukin-2 Human genes 0.000 claims description 22
- 108010002350 Interleukin-2 Proteins 0.000 claims description 21
- 102000004388 Interleukin-4 Human genes 0.000 claims description 19
- 108090000978 Interleukin-4 Proteins 0.000 claims description 19
- 229940028885 interleukin-4 Drugs 0.000 claims description 19
- 238000011068 loading method Methods 0.000 claims description 17
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 claims description 16
- 102000003814 Interleukin-10 Human genes 0.000 claims description 16
- 108090000174 Interleukin-10 Proteins 0.000 claims description 16
- 229940076144 interleukin-10 Drugs 0.000 claims description 16
- 102100025221 CD70 antigen Human genes 0.000 claims description 15
- 108010074328 Interferon-gamma Proteins 0.000 claims description 12
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 12
- 230000000295 complement effect Effects 0.000 claims description 12
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 12
- 101710148794 Intercellular adhesion molecule 2 Proteins 0.000 claims description 11
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 108010064600 Intercellular Adhesion Molecule-3 Proteins 0.000 claims description 10
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 claims description 10
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 9
- 239000000725 suspension Substances 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 8
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 claims description 8
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 108010067902 Peptide Library Proteins 0.000 claims description 7
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 241000256248 Spodoptera Species 0.000 claims description 6
- 230000006052 T cell proliferation Effects 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- 102000008070 Interferon-gamma Human genes 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 230000004069 differentiation Effects 0.000 claims description 5
- 229930193140 Neomycin Natural products 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 239000002502 liposome Substances 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 229960004927 neomycin Drugs 0.000 claims description 4
- 229910052759 nickel Inorganic materials 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000035755 proliferation Effects 0.000 claims description 4
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 3
- 241000269821 Scombridae Species 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 229960003130 interferon gamma Drugs 0.000 claims description 3
- 235000020640 mackerel Nutrition 0.000 claims description 3
- 239000011148 porous material Substances 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 101150062179 II gene Proteins 0.000 claims description 2
- 230000021633 leukocyte mediated immunity Effects 0.000 claims description 2
- 206010028417 myasthenia gravis Diseases 0.000 claims description 2
- 230000009885 systemic effect Effects 0.000 claims description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 claims 8
- 230000001131 transforming effect Effects 0.000 claims 6
- 206010015150 Erythema Diseases 0.000 claims 1
- 206010025421 Macule Diseases 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 238000012358 sourcing Methods 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 210000004241 Th2 cell Anatomy 0.000 abstract description 4
- 210000000447 Th1 cell Anatomy 0.000 abstract description 3
- 230000009210 ongoing activation Effects 0.000 abstract 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 123
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 123
- 102000004196 processed proteins & peptides Human genes 0.000 description 88
- 239000013615 primer Substances 0.000 description 66
- 230000014509 gene expression Effects 0.000 description 63
- 239000013604 expression vector Substances 0.000 description 60
- 239000002773 nucleotide Substances 0.000 description 60
- 125000003729 nucleotide group Chemical group 0.000 description 60
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 53
- 238000001994 activation Methods 0.000 description 36
- 229920001184 polypeptide Polymers 0.000 description 34
- 102000004169 proteins and genes Human genes 0.000 description 34
- 239000013612 plasmid Substances 0.000 description 33
- 230000004913 activation Effects 0.000 description 32
- 235000018102 proteins Nutrition 0.000 description 32
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 31
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 31
- 108020004414 DNA Proteins 0.000 description 30
- 239000002299 complementary DNA Substances 0.000 description 28
- 238000003752 polymerase chain reaction Methods 0.000 description 28
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 27
- 108091028043 Nucleic acid sequence Proteins 0.000 description 24
- 238000003199 nucleic acid amplification method Methods 0.000 description 22
- 230000006044 T cell activation Effects 0.000 description 21
- 230000003321 amplification Effects 0.000 description 21
- 102000054766 genetic haplotypes Human genes 0.000 description 18
- 230000001105 regulatory effect Effects 0.000 description 17
- 238000003556 assay Methods 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 150000007523 nucleic acids Chemical class 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 14
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 14
- 125000000539 amino acid group Chemical group 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 238000013518 transcription Methods 0.000 description 14
- 230000035897 transcription Effects 0.000 description 14
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- 238000010367 cloning Methods 0.000 description 13
- 210000004698 lymphocyte Anatomy 0.000 description 13
- 108020004707 nucleic acids Proteins 0.000 description 13
- 102000039446 nucleic acids Human genes 0.000 description 13
- 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 12
- 241001529936 Murinae Species 0.000 description 12
- 108091008874 T cell receptors Proteins 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 12
- 229940024606 amino acid Drugs 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 108020004511 Recombinant DNA Proteins 0.000 description 11
- 238000010276 construction Methods 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 241000700605 Viruses Species 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 101150026150 mt gene Proteins 0.000 description 10
- 230000010076 replication Effects 0.000 description 10
- 108090001008 Avidin Proteins 0.000 description 9
- 239000003155 DNA primer Substances 0.000 description 9
- 210000003719 b-lymphocyte Anatomy 0.000 description 9
- 239000011324 bead Substances 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 230000008488 polyadenylation Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 102000003792 Metallothionein Human genes 0.000 description 8
- 108090000157 Metallothionein Proteins 0.000 description 8
- 239000006057 Non-nutritive feed additive Substances 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 101150067366 adh gene Proteins 0.000 description 8
- 230000000890 antigenic effect Effects 0.000 description 8
- 238000004113 cell culture Methods 0.000 description 8
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 102100037850 Interferon gamma Human genes 0.000 description 7
- 108700005092 MHC Class II Genes Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 238000012408 PCR amplification Methods 0.000 description 7
- 230000016396 cytokine production Effects 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 108700012293 Drosophila APC Proteins 0.000 description 6
- 108010033276 Peptide Fragments Proteins 0.000 description 6
- 102000007079 Peptide Fragments Human genes 0.000 description 6
- 230000005867 T cell response Effects 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 229960002685 biotin Drugs 0.000 description 6
- 235000020958 biotin Nutrition 0.000 description 6
- 239000011616 biotin Substances 0.000 description 6
- 230000020411 cell activation Effects 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 5
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241000255601 Drosophila melanogaster Species 0.000 description 5
- 241000222722 Leishmania <genus> Species 0.000 description 5
- 108010058846 Ovalbumin Proteins 0.000 description 5
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 5
- 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 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 210000004970 cd4 cell Anatomy 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000004186 co-expression Effects 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 210000003162 effector t lymphocyte Anatomy 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 239000013613 expression plasmid Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 210000002443 helper t lymphocyte Anatomy 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000004816 latex Substances 0.000 description 5
- 229920000126 latex Polymers 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100027207 CD27 antigen Human genes 0.000 description 4
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 4
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 4
- 101000946850 Homo sapiens T-lymphocyte activation antigen CD86 Proteins 0.000 description 4
- 101000638161 Homo sapiens Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 101710182846 Polyhedrin Proteins 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 229960000723 ampicillin Drugs 0.000 description 4
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000036755 cellular response Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 210000003527 eukaryotic cell Anatomy 0.000 description 4
- 230000004992 fission Effects 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 102000049849 human CD86 Human genes 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 108010028930 invariant chain Proteins 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 229940092253 ovalbumin Drugs 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 230000009696 proliferative response Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001541 thymus gland Anatomy 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 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 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 108020004635 Complementary DNA Proteins 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 108090000204 Dipeptidase 1 Proteins 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 3
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 108091054437 MHC class I family Proteins 0.000 description 3
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 3
- 241000700618 Vaccinia virus Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 230000009918 complex formation Effects 0.000 description 3
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- 230000002998 immunogenetic effect Effects 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000004073 interleukin-2 production Effects 0.000 description 3
- 230000017307 interleukin-4 production Effects 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 230000010473 stable expression Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000011277 treatment modality Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- UVGHPGOONBRLCX-NJSLBKSFSA-N (2,5-dioxopyrrolidin-1-yl) 6-[5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)NCCCCCC(=O)ON1C(=O)CCC1=O UVGHPGOONBRLCX-NJSLBKSFSA-N 0.000 description 2
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 241001454374 Drosophila <fruit fly, subgenus> Species 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- 108010039471 Fas Ligand Protein Proteins 0.000 description 2
- 102000015212 Fas Ligand Protein Human genes 0.000 description 2
- DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 108010047214 HLA-DRB1*03:01 antigen Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 2
- 101100321817 Human parvovirus B19 (strain HV) 7.5K gene Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102100025390 Integrin beta-2 Human genes 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 235000019687 Lamb Nutrition 0.000 description 2
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 2
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 2
- 241000233870 Pneumocystis Species 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 241000256251 Spodoptera frugiperda Species 0.000 description 2
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 2
- 241000283068 Tapiridae Species 0.000 description 2
- 241000723873 Tobacco mosaic virus Species 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000003092 anti-cytokine Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000011712 cell development Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 238000004182 chemical digestion Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229960002376 chymotrypsin Drugs 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 230000004940 costimulation Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 229940044627 gamma-interferon Drugs 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 102000043559 human ICAM1 Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000002132 lysosomal effect Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- -1 nucleoside triphosphates Chemical class 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 201000000317 pneumocystosis Diseases 0.000 description 2
- 229920002704 polyhistidine Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000005737 synergistic response Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 235000011178 triphosphate Nutrition 0.000 description 2
- 241001515965 unidentified phage Species 0.000 description 2
- OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
- BFFPVEVGHKMWLT-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;3,7-dihydropurin-6-one Chemical compound O=C1NC=NC2=C1NC=N2.O=C1NC(N)=NC2=C1NC=N2 BFFPVEVGHKMWLT-UHFFFAOYSA-N 0.000 description 1
- YVOOPGWEIRIUOX-UHFFFAOYSA-N 2-azanyl-3-sulfanyl-propanoic acid Chemical compound SCC(N)C(O)=O.SCC(N)C(O)=O YVOOPGWEIRIUOX-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 102100029457 Adenine phosphoribosyltransferase Human genes 0.000 description 1
- 108010024223 Adenine phosphoribosyltransferase Proteins 0.000 description 1
- 241001385733 Aesculus indica Species 0.000 description 1
- 241000156724 Antirhea Species 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241001203868 Autographa californica Species 0.000 description 1
- 108010045634 B7 Antigens Proteins 0.000 description 1
- 102000005738 B7 Antigens Human genes 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 241000255789 Bombyx mori Species 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- ZKTPOUXCUHYLDZ-SAYNGHPTSA-N C(CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@H]12)(=O)NCCCCNC(=O)C1CCC(CC1)CN1C(C=CC1=O)=O Chemical compound C(CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@H]12)(=O)NCCCCNC(=O)C1CCC(CC1)CN1C(C=CC1=O)=O ZKTPOUXCUHYLDZ-SAYNGHPTSA-N 0.000 description 1
- 108091028026 C-DNA Proteins 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241000701489 Cauliflower mosaic virus Species 0.000 description 1
- 101001026137 Cavia porcellus Glutathione S-transferase A Proteins 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 101000936738 Coturnix japonica Astacin-like metalloendopeptidase Proteins 0.000 description 1
- 241000256113 Culicidae Species 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 108700010895 Drosophila ADH Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 101001026109 Gallus gallus Glutathione S-transferase Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102100040485 HLA class II histocompatibility antigen, DRB1 beta chain Human genes 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 108010048896 HLA-D Antigens Proteins 0.000 description 1
- 102000009485 HLA-D Antigens Human genes 0.000 description 1
- 108010010378 HLA-DP Antigens Proteins 0.000 description 1
- 108010062347 HLA-DQ Antigens Proteins 0.000 description 1
- 108010039343 HLA-DRB1 Chains Proteins 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101000599858 Homo sapiens Intercellular adhesion molecule 2 Proteins 0.000 description 1
- 101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 101001062793 Homo sapiens Protein FAM171A1 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- LFVLUOAHQIVABZ-UHFFFAOYSA-N Iodofenphos Chemical compound COP(=S)(OC)OC1=CC(Cl)=C(I)C=C1Cl LFVLUOAHQIVABZ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical group 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 101710105759 Major outer membrane porin Proteins 0.000 description 1
- 101710164702 Major outer membrane protein Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 101100261636 Methanothermobacter marburgensis (strain ATCC BAA-927 / DSM 2133 / JCM 14651 / NBRC 100331 / OCM 82 / Marburg) trpB2 gene Proteins 0.000 description 1
- 101150076359 Mhc gene Proteins 0.000 description 1
- 108010086093 Mung Bean Nuclease Proteins 0.000 description 1
- 101001082628 Mus musculus H-2 class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 101500006448 Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97) Endonuclease PI-MboI Proteins 0.000 description 1
- 101000944608 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Chaperonin GroEL 2 Proteins 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 241001477931 Mythimna unipuncta Species 0.000 description 1
- 101000794562 Naegleria gruberi Calmodulin, flagellar Proteins 0.000 description 1
- 241001045988 Neogene Species 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108010019759 OVA 323-339 Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 229940122060 Ornithine decarboxylase inhibitor Drugs 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 238000003527 Peterson olefination reaction Methods 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 102100030534 Protein FAM171A1 Human genes 0.000 description 1
- 241000205160 Pyrococcus Species 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 101100109192 Rhizobium galegae apt gene Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000020385 T cell costimulation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 101710165202 T-cell surface antigen CD2 Proteins 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 229920008262 Thermoplastic starch Polymers 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 108091005956 Type II transmembrane proteins Proteins 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- VJBCNMFKFZIXHC-UHFFFAOYSA-N azanium;2-(4-methyl-5-oxo-4-propan-2-yl-1h-imidazol-2-yl)quinoline-3-carboxylate Chemical compound N.N1C(=O)C(C(C)C)(C)N=C1C1=NC2=CC=CC=C2C=C1C(O)=O VJBCNMFKFZIXHC-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000009133 cooperative interaction Effects 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 108010052621 fas Receptor Proteins 0.000 description 1
- 102000018823 fas Receptor Human genes 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 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 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 102000053826 human CD70 Human genes 0.000 description 1
- 102000056475 human ICAM2 Human genes 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000007834 ligase chain reaction Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000010841 mRNA extraction Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229940041669 mercury Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 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 1
- 239000011325 microbead Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- 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 1
- 101150091879 neo gene Proteins 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 108010087904 neutravidin Proteins 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940124276 oligodeoxyribonucleotide Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000002818 ornithine decarboxylase inhibitor Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 101150081616 trpB gene Proteins 0.000 description 1
- 101150111232 trpB-1 gene Proteins 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- C12N5/0601—Invertebrate cells or tissues, e.g. insect cells; Culture media therefor
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/81—Drug, bio-affecting and body treating compositions involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Cell Biology (AREA)
- Pulmonology (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.CD4+T細胞の活性化ための合成抗原提示細胞(APC)であって、 a)ベクター内の第一のプロモーターに機能的に結合した、MHCクラスIIα 鎖を発現することができるMHCクラスIIα鎖遺伝子、 b)ベクター内の第二のプロモーターに機能的に結合した、MHCクラスIIβ 鎖を発現することができるMHCクラスIIβ鎖遺伝子(ここでα鎖およびβ鎖遺 伝子が発現したとき、当該α鎖およびβ鎖は、ペプチドをローディングすること ができるMHCクラスIIヘテロダイマーを形成する)および、 c)ベクター内の第三のプロモーターに機能的に結合した、アクセサリー分子 を発現することができる少なくとも1つのアクセサリー分子遺伝子を含み、クラ スII遺伝子およびアクセサリー分子遺伝子の少なくとも1つを欠いていることを 特徴とする細胞。 2.当該α鎖およびβ鎖遺伝子がヒト起源である請求項1のAPC。 3.少なくとも1つのプロモーターが誘導性である請求項1のAPC。 4.当該α鎖、β鎖およびアクセサリー分子遺伝子が同じベクターに存在する請 求項1のAPC。 5.当該α鎖、β鎖およびアクセサリー分子遺伝子の少なくとも1つが別のベク ターに存在する請求項1のAPC。 6.当該APCが昆虫細胞である請求項1のAPC。 7.当該昆虫細胞がスポドプテラおよびドロソフィラからなる群から選ばれる請 求項6のAPC。 8.さらにベクターに機能的に結合したネオマイシン耐性遺伝子を含む請求項1 のAPC。 9.当該アクセサリー分子遺伝子が同時刺激分子をコードする請求項1のAPC 。 10.当該同時刺激分子がB7.1またはB7.2である請求項9のAPC。 11.当該アクセサリー分子遺伝子が付着分子をコードする請求項1のAPC。 12.当該付着分子がICAM−1、ICAM−2、ICAM−3またはLFA− 3である請求項11のAPC。 13.当該アクセサリー分子遺伝子がサバイバル分子をコードする請求項1のAP C。 14.当該サバイバル分子がFasリガンドまたはCD70である請求項13のA PC。 15.第一のアクセサリー分子のための遺伝子および第二のアクセサリー分子のた めの遺伝子を有する請求項1のAPC。 16.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子が付着分子である請求項15のAPC。 17.当該同時刺激分子がB7.1またはB7.2で、当該付着分子がICAM− 1である請求項16のAPC。 18.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子がサバイバル分子である請求項15のAPC。 19.当該第一のアクセサリー分子がサバイバル分子で、当該第二のアクセサリー 分子が付着分子である請求項15のAPC。 20.当該サバイバル分子がCD70で、当該付着分子がICAM−1である請求 項19のAPC。 21.当該第一および第二のアクセサリー分子が同時刺激分子である請求項15のA PC。 22.当該同時刺激分子がB7.1およびB7.2である請求項21のAPC。 23.第一のアクセサリー分子のための遺伝子、第二のアクセサリー分子のための 遺伝子および第三のアクセサリー分子のための遺伝子を有する請求項1のAPC 。 24.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子が付着分子で、当該第三のアクセサリー分子がサバイバル分子である請求項23 のAPC。 25.当該同時刺激分子がB7.2で、当該付着分子がICAM−1で、当該サバ イバル分子がCD70である請求項24のAPC。 26.当該MHCクラスIIヘテロダイマーおよびアクセサリー分子が、ペプチドが 当該ヘテロダイマー上にローディングされるときにCD4+T細胞を活性化させ るために十分な量で当該APCの外側表面に存在する請求項1のAPC。 27.当該ペプチドが細胞外でローディングされる請求項26のAPC。 28.当該ペプチドが細胞内でローディングされる請求項26のAPC。 29.ベクター内の第四のプロモーターに機能的に結合した、抗原プロセシング補 助分子を発現することができる抗原プロセシング補助遺伝子をさらに含む請求項 1のAPC。 30.CD4+T細胞を活性化するために細胞フラグメント上に機能的に結合した MHCクラスIIヘテロダイマーおよび少なくとも1つのアクセサリー分子を有す る請求項1のAPC由来の細胞フラグメント。 31.当該MHCクラスIIヘテロダイマーがエンプティである請求項30の細胞フラ グメント。 32.ペプチドが当該MHCクラスIIヘテロダイマー上にローディングされる請求 項30の細胞フラグメント。 33.CD4+T細胞を活性化するための合成抗原提示マトリックスであって、 a)担体、 b)担体に機能的に連結され、さらに選択ペプチドをローディングすることが できるMHCクラスIIヘテロダイマーの細胞外部分、および、 c)ペプチドが当該ヘテロダイマーの細胞外部分にローディングされたときに CD4+T細胞を活性化させるために十分な数で当該MHCクラスIIヘテロダイ マーおよびアクセサリー分子の細胞外部分が当該マトリックス上に存在するよう に、当該担体に機能的に結合した少なくとも1つのアクセサリー分子の細胞外部 分を含むことを特徴とするマトリックス。 34.当該担体が細胞フラグメントである請求項33のマトリックス。 35.当該担体が細胞である請求項33のマトリックス。 36.当該MHC分子の細胞外部分が、当該MHCクラスIIヘテロダイマーのトラ ンスメンブレンドメインによって当該細胞に結合している請求項35のマトリック ス。 37.当該担体がリポソームである請求項33のマトリックス。 38.当該担体が固体表面である請求項33のマトリックス。 39.当該MHCクラスIIヘテロダイマーの細胞外部分が、当該担体に当該部分 を連結させるために抗体と反応するエピトープに結合している請求項33のマトリ ックス。 40.当該MHCクラスIIヘテロダイマーの細胞外部分が、当該担体に当該部分が 連結させるためにニッケルと反応する(His)6に結合している請求項33のマ トリックス。 41.当該担体が多孔性物質である請求項33のマトリックス。 42.当該ペプチドがMHCクラスIIヘテロダイマーの細胞外部分にローディング される請求項33のマトリックス。 43.当該MHCクラスIIヘテロダイマーの細胞外部分がエンプティである請求項 33のマトリックス。 44.当該アクセサリー分子が同時刺激分子である請求項33のマトリックス。 45.当該同時刺激分子がB7.1またはB7.2である請求項44のマトリックス 。 46.当該アクセサリー分子が付着分子である請求項33のマトリックス。 47.当該付着分子がICAM−1、ICAM−2、ICAM−3またはLFA− 3である請求項46のマトリックス。 48.当該アクセサリー分子がサバイバル分子である請求項33のマトリックス。 49.当該サバイバル分子がFasリガンドまたはCD70である請求項48のマト リックス。 50.第一のアクセサリー分子および第二のアクセサリー分子を有する請求項33の マトリックス。 51.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子が付着分子である請求項50のマトリックス。 52.当該同時刺激分子がB7.1またはB7.2で、当該付着分子がICAM− 1である請求項51のマトリックス。 53.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子がサバイバル分子である請求項50のマトリックス。 54.当該第一のアクセサリー分子がサバイバル分子で、当該第二のアクセサリー 分子が付着分子である請求項50のマトリックス。 55.当該サバイバル分子がCD70で、当該付着分子がICAM−1である請求 項54のマトリックス。 56.当該第一および第二のアクセサリー分子が同時刺激分子である請求項50のマ トリックス。 57.当該同時刺激分子がB7.1およびB7.2である請求項56のマトリックス 。 58.さらに第三のアクセサリー分子を含む請求項50のマトリックス。 59.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子が付着分子で、当該第三のアクセサリー分子がサバイバル分子である請求項58 のマトリックス。 60.当該同時刺激分子がB7.2で、当該付着分子がICAM−1で、当該サバ イバル分子がCD70である請求項59のマトリックス。 61.合成抗原提示細胞(APC)を製造する方法であって、 a)ベクター内の第一のプロモーターに機能的に結合した、MHCクラスIIα 鎖を発現することができる発現可能MHCクラスIIα鎖遺伝子で細胞を形質転換 する工程、 b)ベクター内の第二のプロモーターに機能的に結合した、MHCクラスIIβ 鎖を発現することができる発現可能MHCクラスIIβ鎖遺伝子で細胞を形質転換 する工程、および、 c)ベクター内の第三のプロモーターに機能的に結合した、アクセサリー分子 を発現することができる発現可能なアクセサリー分子遺伝子で細胞を形質転換す る工程を特徴とする方法。 62.当該細胞が、当該α鎖、β鎖およびアクセサリー分子遺伝子の少なくとも1 つをコードする遺伝子を欠く請求項61の方法。 63.さらに、ベクター内の第四のプロモーターに機能的に結合した、抗原プロセ シング補助分子を発現することができる発現可能な抗原プロセシング補助遺伝子 で細胞を形質転換する工程を含む請求項61の方法。 64.当該α鎖およびβ鎖遺伝子がヒト起源である請求項61の方法。 65.少なくとも1つのプロモーターが誘導性である請求項61の方法。 66.当該α鎖、β鎖およびアクセサリー分子遺伝子が同じベクターに存在する請 求項61の方法。 67.当該α鎖、β鎖およびアクセサリー分子遺伝子が別個のベクターに存在する 請求項61の方法。 68.当該細胞が昆虫細胞である請求項61の方法。 69.当該昆虫細胞がスポドプテラおよびドロソフィラからなる群から選ばれる請 求項61の方法。 70.さらにベクターに機能的に結合した発現可能なネオマイシン耐性遺伝子で細 胞を形質転換する工程を含む請求項61の方法。 71.当該アクセサリー分子遺伝子が同時刺激分子をコードする請求項61の方法。 72.当該同時刺激分子がB7.1またはB7.2である請求項71の方法。 73.当該アクセサリー分子遺伝子が付着分子をコードする請求項61の方法。 74.当該付着分子がICAM−1、ICAM−2、ICAM−3またはLFA− 3である請求項73の方法。 75.当該アクセサリー分子遺伝子がサバイバル分子をコードする請求項61の方法 。 76.当該サバイバル分子がFasリガンドまたはCD70である請求項75の方法 。 77.さらに、第二のアクセサリー分子のための遺伝子で細胞を形質転換する工程 を含む請求項61の方法。 78.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子が付着分子である請求項77の方法。 79.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子がサバイバル分子である請求項77の方法。 80.当該第一のアクセサリー分子がサバイバル分子で、当該第二のアクセサリー 分子が付着分子である請求項77の方法。 81.さらに、第三のアクセサリー分子のための遺伝子で細胞を形質転換する工程 を含む請求項77の方法。 82.当該第一のアクセサリー分子が同時刺激分子で、当該第二のアクセサリー分 子が付着分子で、当該第三のアクセサリー分子がサバイバル分子である請求項81 の方法。 83.合成抗原提示細胞(APC)を製造する方法であって、 a)MHCクラスIIα鎖、MHCクラスIIβ鎖およびアクセサリー分子の少な くとも1つをコードする遺伝子を欠く細胞を提供する工程、及び、 b)当該細胞に欠けている(a)の遺伝子の各々のために発現可能であって、 当該遺伝子を発現する能力を有するベクター内のプロモーターに機能的に結合し た遺伝子で当該細胞を形質転換する工程からなることを特徴とする方法。 84.合成抗原提示細胞(APC)を製造する方法であって、 a)MHCクラスIIα鎖、MHCクラスIIβ鎖、アクセサリー分子および 抗原プロセシング補助分子の少なくとも1つをコードする遺伝子を欠く細胞を提 供しする工程、及び、 b)当該細胞に欠けている(a)の遺伝子の各々のために発現可能であって、 当該遺伝子を発現する能力を有するベクター内の機能できる第一のプロモーター に結合した遺伝子で当該細胞を形質転換する工程からなることを特徴とする方法 。 85.合成抗原提示マトリックスを製造する方法であって、 a)組換えMHCクラスIIヘテロダイマーの細胞外部分を提供する工程、 b)少なくとも1つの組換えアクセサリー分子の細胞外部分を提供する工程、 及び、 c)MHCクラスIIヘテロダイマーにペプチドがローディングされたときにC D4+T細胞を活性化させるために十分な数で、担体に当該MHCクラスIIヘテ ロダイマーおよびアクセサリー分子を結合する工程からなることを特徴とする方 法。 86.当該アクセサリー分子が同時刺激分子である請求項85の方法。 87.当該同時刺激分子がB7.1またはB7.2である請求項86の方法。 88.当該アクセサリー分子が付着分子である請求項86の方法。 89.当該付着分子がICAM−1、ICAM−2、ICAM−3またはLFA− 3である請求項88の方法。 90.当該アクセサリー分子がサバイバル分子である請求項85の方法。 91.当該サバイバル分子がFasリガンドまたはCD70である請求項90の方法 。 92.インビトロでCD4+T細胞を活性化させる方法であって、 a)請求項26のAPCを提供する工程、及び b)工程a)のAPCをCD4+T細胞と接触させ、それによって接触CD4+ T細胞を増殖させ、さらに活性化CD4+T細胞に分化させる工程からなること を特徴とする方法。 93.さらに、c)当該APCから活性化CD4+T細胞を分離する工程を含む請 求項92の方法。 94.さらに、当該活性化CD4+T細胞を許容可能な担体または賦形剤に添加し 懸濁物を生成する工程を含む請求項93の方法。 95.さらに、当該懸濁物を患者に投与する工程を含む請求項94の方法。 96.インビトロでCD4+T細胞を活性化させる方法であって、 a)請求項30の細胞フラグメントを提供する工程、 b)当該MHCクラスIIヘテロダイマーにペプチドをローディングする工程、 および、 c)当該ペプチドがローディングした細胞フラグメントをCD4+T細胞と接 触させ、それによって当該接触CD4+T細胞の増殖および活性化CD4+T細胞 への分化を誘発する工程からなるを特徴とする方法。 97.さらに、当該細胞フラグメントから活性化CD4+T細胞を分離する工程を 含む請求項96の方法。 98.さらに、当該活性化CD4+T細胞を許容可能な担体または賦形剤に添加し 懸濁物を生成する工程を含む請求項97の方法。 99.さらに、当該懸濁物を患者に投与する工程を含む請求項98の方法。 100.インビトロでCD4+T細胞を活性化させる方法であって、 a)請求項33のマトリックスを提供する工程、 b)当該MHCクラスIIヘテロダイマーにペプチドをローディングする工程、 および、 c)当該ペプチドをローディングした細胞マトリックスをCD4+T細胞と接 触させ、それによって当該接触CD4+T細胞の増殖および活性化CD4+T細胞 への分化を誘発する工程からなることを特徴とする方法。 101.さらに、当該マトリックスから活性化CD4+T細胞を分離する工程を含む 請求項100の方法。 102.さらに、当該活性化CD4+T細胞を許容可能な担体または賦形剤に添加し 懸濁物を生成する工程を含む請求項101の方法。 103.さらに、当該懸濁物を患者に投与する工程を含む請求項102の方法。 104.インビトロでCD4+T細胞を活性化させる方法であって、 a)請求項1のAPC、請求項30の細胞フラグメントまたは請求項33のマトリ ックスを十分な量でペプチドライブラリーとインビトロで十分な時間接触させ、 ペプチドがローディングしたMHCクラスIIヘテロダイマーを作製する工程、 及び、 b)工程b)のペプチド積載MHCクラスIIヘテロダイマーをCD4+T細胞 と接触させ、それによって当該接触CD4+T細胞の増殖および活性化CD4+T 細胞への分化を誘発する工程からなることを特徴とする方法。 105.CD4+T細胞仲介免疫反応を変化させて患者の症状を治療する方法であっ て、 a)患者に固有のサイトカインプロフィールについて患者を分析する工程、 b)当該患者からCD4+T細胞を採取する工程、 c)当該CD4+T細胞を請求項26のAPCと十分な量で十分な時間インビ トロで接触させ、それによって当該接触CD4+T細胞の増殖分裂および、工程 a)で得られたプロフィールに機能的に対抗するサイトカインプロフィールを産 生する活性化CD4+T細胞への分化を誘発する工程、および、 d)当該活性化CD4+T細胞を当該患者に戻す工程からなることを特徴とす る方法。 106.当該症状が自己免疫疾患である請求項105の方法。 107.当該免疫疾患が、糖尿病、多発性硬化症、自己免疫性甲状腺炎、全身性紅 斑性狼瘡、重症筋無力症、クローン病および炎症性大腸症候群から成る群から選 ばれる請求項106の方法。 108.当該患者に固有のサイトカインプロフィールがCD4+Th1型応答によっ て生じる請求項106の方法。 109.当該患者に固有のサイトカインプロフィールが、インターロイキン−2、 インターフェロン−γおよび腫瘍壊死因子からなる群から選ばれるサイトカイン を含む請求項108の方法。 110.当該症状がアレルギーである請求項105の方法。 111.当該アレルギーが、喘息および接触過敏症からなる群から選ばれる請求項1 10の方法。 112.当該患者に固有のサイトカインプロフィールがCD4+Th2型応答によっ て生じる請求項110の方法。 113.当該患者に固有のサイトカインプロフィールが、インターロイキン−4お よびインターロイキン−10からなる群から選ばれるサイトカインを含む請求項 112の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1817596P | 1996-05-23 | 1996-05-23 | |
US60/018,175 | 1996-05-23 | ||
PCT/US1997/008697 WO1997046256A1 (en) | 1996-05-23 | 1997-05-22 | Mhc class ii antigen-presenting systems and methods for activating cd4+ t cells |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012077703A Division JP2012143245A (ja) | 1996-05-23 | 2012-03-29 | Mhcクラスii抗原提示系及びcd4+t細胞の活性化方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2000511898A true JP2000511898A (ja) | 2000-09-12 |
JP2000511898A5 JP2000511898A5 (ja) | 2005-01-13 |
JP5006998B2 JP5006998B2 (ja) | 2012-08-22 |
Family
ID=21786645
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP50061698A Expired - Lifetime JP5006998B2 (ja) | 1996-05-23 | 1997-05-22 | Mhcクラスii抗原提示系及びcd4+t細胞の活性化方法 |
JP2012077703A Withdrawn JP2012143245A (ja) | 1996-05-23 | 2012-03-29 | Mhcクラスii抗原提示系及びcd4+t細胞の活性化方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012077703A Withdrawn JP2012143245A (ja) | 1996-05-23 | 2012-03-29 | Mhcクラスii抗原提示系及びcd4+t細胞の活性化方法 |
Country Status (12)
Country | Link |
---|---|
US (4) | US6355479B1 (ja) |
EP (1) | EP0969865B1 (ja) |
JP (2) | JP5006998B2 (ja) |
AT (1) | ATE347588T1 (ja) |
AU (1) | AU723355B2 (ja) |
CA (1) | CA2254975C (ja) |
DE (1) | DE69737070T2 (ja) |
DK (1) | DK0969865T3 (ja) |
ES (1) | ES2278390T3 (ja) |
IL (1) | IL126843A (ja) |
PT (1) | PT969865E (ja) |
WO (1) | WO1997046256A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010505845A (ja) * | 2006-10-04 | 2010-02-25 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 不活性化された人工抗原提示細胞の調製および細胞治療におけるそれらの使用 |
Families Citing this family (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997046256A1 (en) * | 1996-05-23 | 1997-12-11 | The Scripps Research Institute | Mhc class ii antigen-presenting systems and methods for activating cd4+ t cells |
US6291430B1 (en) * | 1997-09-12 | 2001-09-18 | Ludwig Institute For Cancer Research | Mage-3 peptides presented by HLA class II molecules |
CA2330678C (en) | 1998-05-11 | 2009-04-07 | Miltenyi Biotec Gmbh | Method of direct selection of antigen-specific t cells |
US6230662B1 (en) | 1998-06-22 | 2001-05-15 | Theresa Miale | Animal lift and transport apparatus and method for using the same |
CA2340085A1 (en) * | 1998-08-10 | 2000-02-24 | Chiron Corporation | Engineered antigen-presenting cells expressing an array of antigens and uses thereof |
WO2000023053A2 (en) * | 1998-10-20 | 2000-04-27 | Salvatore Albani | Artificial antigen-specific cells and related methods |
US7807377B2 (en) | 1998-10-20 | 2010-10-05 | Salvatore Albani | Method of isolating antigen-specific T cells employing artificial antigen presenting cells |
US6225443B1 (en) * | 1999-05-19 | 2001-05-01 | Wisconsin Alumni Research Foundation | Cytotoxic T lymphocyte epitopes of the major outer membrane protein of chlamydia trachomatis |
US7521202B2 (en) | 1999-12-17 | 2009-04-21 | The Board Of Regents Of The University Of Oklahoma | Method and apparatus for the production of soluble MHC antigens and uses thereof |
DE10009341A1 (de) * | 2000-02-22 | 2001-09-06 | Florian Kern | Verfahren zur antigen-spezifischen Stimulation von T-Lymphozyten |
US7541184B2 (en) * | 2000-02-24 | 2009-06-02 | Invitrogen Corporation | Activation and expansion of cells |
AU2000243137A1 (en) * | 2000-04-20 | 2001-11-07 | Salvatore Albani | Methods for isolation, quantification, characterization and modulation of antigen-specific t cells |
CA2433194C (en) | 2000-10-10 | 2012-04-03 | The Board Of Regents Of The University Of Oklahoma | Comparative ligand mapping from mhc positive cells |
US20070026433A1 (en) | 2001-03-09 | 2007-02-01 | Hildebrand William H | Epitope testing using soluble HLA |
WO2002056908A2 (en) * | 2001-01-16 | 2002-07-25 | Hildebrand William H | Artificial antigen-presenting cells |
WO2002079396A2 (en) * | 2001-02-13 | 2002-10-10 | Mosca Joseph D | Biological carriers for induction of immune responses |
US20040071671A1 (en) * | 2001-02-20 | 2004-04-15 | Leturcq Didier J. | Cell therapy method for the treatment of tumors |
EP2016930B1 (en) * | 2001-02-20 | 2014-10-15 | Janssen Pharmaceuticals, Inc. | CD8 cell suspension for use in the treatment of melanoma |
FR2824567B1 (fr) * | 2001-05-11 | 2003-08-08 | Inst Nat Sante Rech Med | Procede d'obtention de lymphocytes tr1 regulateurs specifiques d'antigene |
US7745140B2 (en) | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
US7670781B2 (en) * | 2002-01-03 | 2010-03-02 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an agent that provides a primary activation signal and another agent that provides a co-stimulatory signal |
US7638326B2 (en) | 2002-01-03 | 2009-12-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform |
US20040072262A1 (en) * | 2002-10-11 | 2004-04-15 | Montero-Julian Felix A. | Methods and systems for detecting MHC class I binding peptides |
ES2282355T3 (es) | 2002-10-11 | 2007-10-16 | Sentoclone Ab | Inmunoterapia de cancer. |
US7435592B2 (en) | 2003-05-13 | 2008-10-14 | Immunovative Therapies, Ltd. | Compositions for allogeneic cell therapy |
US20050095655A1 (en) * | 2003-11-03 | 2005-05-05 | Montero-Julian Felix A. | Solution-based methods for detecting MHC-binding peptides |
DK2573166T3 (da) | 2004-02-26 | 2016-07-04 | Immunovative Therapies Ltd | Fremgangsmåder til fremstilling af T-celler til celleterapi |
US7592431B2 (en) | 2004-02-26 | 2009-09-22 | Immunovative Therapies, Ltd. | Biodegradable T-cell Activation device |
US20050287611A1 (en) * | 2004-05-07 | 2005-12-29 | Nugent C T Iv | MHC bridging system for detecting CTL-mediated lysis of antigen presenting cells |
EP2295588B1 (en) | 2004-05-27 | 2018-03-07 | The Trustees Of The University Of Pennsylvania | Novel artificial antigen presenting cells and uses thefor |
EP1781313A4 (en) * | 2004-06-17 | 2009-08-26 | Beckman Coulter Inc | MYCOBACTERIUM TUBERCULOSIS EPITOPES AND METHODS OF USE |
EP1712615A1 (en) * | 2005-04-15 | 2006-10-18 | Txcell | In vitro production of a cell population using feeder cells |
KR101600225B1 (ko) | 2005-06-08 | 2016-03-04 | 다나-파버 캔서 인스티튜트 인크. | 예정 세포사 1(pd-1) 경로를 억제함으로써 지속 감염 및 암을 치료하기 위한 방법 및 조성물 |
WO2006138449A2 (en) * | 2005-06-16 | 2006-12-28 | The Wistar Institute | Method for identifying a mhc class ii-dependent tumor-associated t helper cell antigen |
RU2399382C2 (ru) | 2005-12-21 | 2010-09-20 | Сентоклон Аб | Улучшенный способ увеличения числа опухоле-реактивных т-лимфоцитов в иммунотерапии онкологических больных |
WO2007071410A1 (en) | 2005-12-21 | 2007-06-28 | Sentoclone Ab | Method for treating urinary bladder cancer |
EP1966370B1 (en) | 2005-12-21 | 2013-02-20 | SentoClone International AB | Method for obtaining T-lymphocytes |
WO2007071390A1 (en) | 2005-12-21 | 2007-06-28 | Sentoclone Ab | Method for treating malignant melanoma |
AU2007222080B2 (en) | 2006-03-01 | 2012-08-16 | Janssen Pharmaceutica N.V. | Cancer treatment combining lymphodepleting agent with CTLs and cytokines |
JP5623747B2 (ja) * | 2006-12-27 | 2014-11-12 | エモリー ユニバーシティ | 感染症および腫瘍を処置するための組成物および方法 |
US20120034155A1 (en) * | 2010-08-03 | 2012-02-09 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Artificial cells |
CA2744449C (en) | 2008-11-28 | 2019-01-29 | Emory University | Methods for the treatment of infections and tumors |
US8075895B2 (en) * | 2009-09-22 | 2011-12-13 | Janssen Pharmaceutica N.V. | Identification of antigenic peptides from multiple myeloma cells |
EP2404618A1 (en) | 2010-07-07 | 2012-01-11 | Stichting Katholieke Universiteit meer in het bijzonder Radboud Universiteit Nijmegen | Immunomodulatory protein constructs with a helical polymeric backbone. |
WO2012017678A1 (ja) * | 2010-08-06 | 2012-02-09 | 株式会社ケーナインラボ | 免疫機能の強化剤 |
US9233156B2 (en) | 2011-05-03 | 2016-01-12 | Immunovative Therapies Ltd. | Induction of IL-12 using immunotherapy |
KR102202460B1 (ko) | 2011-05-03 | 2021-01-14 | 이뮤노베이티브 테라피스, 엘티디. | 생세포를 포함하는 생물학적 약물을 처리하기 위한 방법 |
EP2841563B1 (en) | 2012-04-24 | 2019-06-12 | Dan S. Kaufman | Method for developing natural killer cells from stem cells |
JP6463577B2 (ja) | 2013-05-14 | 2019-02-06 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 改変キメラ抗原受容体(car)t細胞のヒト応用 |
CN106232807A (zh) * | 2013-12-16 | 2016-12-14 | 美利坚合众国, 由健康及人类服务部部长代表 | 通过使用vlp复制子投递ii类mhc抗原的癌症免疫疗法 |
CN106414748B (zh) | 2014-02-14 | 2021-05-28 | 得克萨斯州大学系统董事会 | 嵌合抗原受体及制备方法 |
US10857219B2 (en) | 2014-03-28 | 2020-12-08 | The Board Of Regents Of The University Of Oklahoma | Compositions comprising soluble HLA/M. tuberculosis-specific ligand complexes and methods of production and use thereof |
JP2017514471A (ja) | 2014-04-23 | 2017-06-08 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | キメラ抗原受容体(car)並びにその製造及び使用方法 |
KR20200138445A (ko) | 2014-04-24 | 2020-12-09 | 보드 오브 리전츠, 더 유니버시티 오브 텍사스 시스템 | 입양 세포 요법 생성물을 생성하기 위한 유도 만능 줄기 세포의 응용 |
EP3536707A1 (en) | 2014-11-05 | 2019-09-11 | Board of Regents, The University of Texas System | Gene modified immune effector cells and engineered cells for expansion of immune effector cells |
ES2806126T3 (es) | 2014-11-05 | 2021-02-16 | Univ Texas | Receptores de antígenos quiméricos (CAR) dirigidos de forma selectiva a complejos proteicos |
FR3031519B1 (fr) | 2015-01-14 | 2016-12-30 | Arkema France | Composition a base de terpolymere electroactif |
DK3271382T3 (da) * | 2015-03-16 | 2020-05-04 | Max Delbrueck Centrum Fuer Molekulare Medizin Helmholtz Gemeinschaft | Fremgangsmåde til detektion af nye immunogene T-celleepitoper og isolering af nye antigenspecifikke T-cellereceptorer ved hjælp af et MHC-cellebibliotek |
EP3368075B1 (en) | 2015-10-27 | 2020-01-29 | Board of Regents, The University of Texas System | Chimeric antigen receptor molecules and uses thereof |
SG11201810640RA (en) | 2016-06-08 | 2018-12-28 | Intrexon Corp | Cd33 specific chimeric antigen receptors |
AU2017301887A1 (en) | 2016-07-29 | 2019-02-07 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies against anti-CD19 antibodies |
CA3043356A1 (en) | 2016-11-09 | 2018-05-17 | Musc Foundation For Research Development | Cd38-nad+ regulated metabolic axis in anti-tumor immunotherapy |
WO2018132494A1 (en) | 2017-01-10 | 2018-07-19 | Intrexon Corporation | Modulating expression of polypeptides via new gene switch expression systems |
US11285196B2 (en) | 2017-03-13 | 2022-03-29 | Eslam Abbas Baseuny | Multivalent biologic constructs for inducing a therapeutic modulation of cellular response and uses thereof |
WO2018195175A1 (en) | 2017-04-18 | 2018-10-25 | FUJIFILM Cellular Dynamics, Inc. | Antigen-specific immune effector cells |
IL306102A (en) | 2017-06-07 | 2023-11-01 | Precigen Inc | Expression of new cell markers |
SG11202105609RA (en) | 2018-11-28 | 2021-06-29 | Univ Texas | Multiplex genome editing of immune cells to enhance functionality and resistance to suppressive environment |
EP3886874A1 (en) | 2018-11-29 | 2021-10-06 | Board of Regents, The University of Texas System | Methods for ex vivo expansion of natural killer cells and use thereof |
JP2023500671A (ja) | 2019-11-06 | 2023-01-10 | ベイラー カレッジ オブ メディスン | がんのt細胞治療のための細胞傷害性エフェクターメモリーt細胞の産生方法 |
WO2021163191A1 (en) | 2020-02-10 | 2021-08-19 | Board Of Regents, The University Of Texas System | Methods for rapid cloning and expression of hla class i cells |
CA3179599A1 (en) | 2020-05-27 | 2021-12-02 | Marco ALESSANDRINI | Adapter molecules to re-direct car t cells to an antigen of interest |
US20220194999A1 (en) | 2020-12-23 | 2022-06-23 | Janssen Biotech, Inc. | Neoantigen Peptide Mimics |
WO2023211972A1 (en) | 2022-04-28 | 2023-11-02 | Medical University Of South Carolina | Chimeric antigen receptor modified regulatory t cells for treating cancer |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5242687A (en) | 1989-03-15 | 1993-09-07 | Tkb Associates Limited Partnership | Method of reducing cellular immune response involving T-cells using CD8-bearing antigen presenting cells |
US5395760A (en) | 1989-09-05 | 1995-03-07 | Immunex Corporation | DNA encoding tumor necrosis factor-α and -β receptors |
JP2683461B2 (ja) * | 1991-07-05 | 1997-11-26 | 住友電気工業株式会社 | 光ファイバケーブルの製造方法 |
US5583031A (en) * | 1992-02-06 | 1996-12-10 | President And Fellows Of Harvard College | Empty major histocompatibility class II heterodimers |
US5314813A (en) * | 1992-02-19 | 1994-05-24 | Scripps Research Institute | Drosophila cell lines expressing genes encoding MHC class I antigens and B2-microglobulin and capable of assembling empty complexes and methods of making said cell lines |
WO1996012009A2 (en) * | 1994-10-14 | 1996-04-25 | Tykocinski Mark L | Methods for engineering antigen-presenting cells |
WO1997046256A1 (en) * | 1996-05-23 | 1997-12-11 | The Scripps Research Institute | Mhc class ii antigen-presenting systems and methods for activating cd4+ t cells |
-
1997
- 1997-05-22 WO PCT/US1997/008697 patent/WO1997046256A1/en active IP Right Grant
- 1997-05-22 AT AT97927709T patent/ATE347588T1/de active
- 1997-05-22 IL IL126843A patent/IL126843A/en not_active IP Right Cessation
- 1997-05-22 EP EP97927709A patent/EP0969865B1/en not_active Expired - Lifetime
- 1997-05-22 DK DK97927709T patent/DK0969865T3/da active
- 1997-05-22 AU AU32103/97A patent/AU723355B2/en not_active Expired
- 1997-05-22 CA CA002254975A patent/CA2254975C/en not_active Expired - Lifetime
- 1997-05-22 PT PT97927709T patent/PT969865E/pt unknown
- 1997-05-22 JP JP50061698A patent/JP5006998B2/ja not_active Expired - Lifetime
- 1997-05-22 DE DE69737070T patent/DE69737070T2/de not_active Expired - Lifetime
- 1997-05-22 US US09/194,285 patent/US6355479B1/en not_active Expired - Lifetime
- 1997-05-22 ES ES97927709T patent/ES2278390T3/es not_active Expired - Lifetime
-
2000
- 2000-11-17 US US09/715,891 patent/US7074617B1/en not_active Expired - Fee Related
-
2004
- 2004-04-08 US US10/822,173 patent/US7439335B2/en not_active Expired - Fee Related
- 2004-07-29 US US10/903,213 patent/US7402430B2/en not_active Expired - Fee Related
-
2012
- 2012-03-29 JP JP2012077703A patent/JP2012143245A/ja not_active Withdrawn
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010505845A (ja) * | 2006-10-04 | 2010-02-25 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 不活性化された人工抗原提示細胞の調製および細胞治療におけるそれらの使用 |
Also Published As
Publication number | Publication date |
---|---|
US20050059144A1 (en) | 2005-03-17 |
DK0969865T3 (da) | 2007-03-19 |
DE69737070D1 (de) | 2007-01-18 |
US6355479B1 (en) | 2002-03-12 |
JP5006998B2 (ja) | 2012-08-22 |
AU723355B2 (en) | 2000-08-24 |
WO1997046256A1 (en) | 1997-12-11 |
JP2012143245A (ja) | 2012-08-02 |
EP0969865A4 (en) | 2001-07-11 |
AU3210397A (en) | 1998-01-05 |
PT969865E (pt) | 2007-02-28 |
DE69737070T2 (de) | 2007-06-21 |
IL126843A (en) | 2007-06-17 |
US20050054090A1 (en) | 2005-03-10 |
EP0969865A1 (en) | 2000-01-12 |
US7074617B1 (en) | 2006-07-11 |
EP0969865B1 (en) | 2006-12-06 |
ES2278390T3 (es) | 2007-08-01 |
CA2254975A1 (en) | 1997-12-11 |
IL126843A0 (en) | 1999-09-22 |
CA2254975C (en) | 2008-12-16 |
US7402430B2 (en) | 2008-07-22 |
ATE347588T1 (de) | 2006-12-15 |
US7439335B2 (en) | 2008-10-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5006998B2 (ja) | Mhcクラスii抗原提示系及びcd4+t細胞の活性化方法 | |
ES2201177T3 (es) | Sistema de presentacion de antigenos y activacion de celulas-t. | |
EP1249490B1 (en) | In vitro activation of cytotoxic T cells | |
US6001365A (en) | In vitro activation of cytotoxic T cells | |
US20120315269A1 (en) | Immunoglobulin-like transcript (ilt) receptors as cd8 antagonists | |
JP2003502387A (ja) | プライミングされた抗原特異的t細胞またはb細胞を用いる自己養子免疫療法 | |
AU755156B2 (en) | Methods for enhanced antigen presentation on antigen-presenting cells and compositions produced thereby | |
US20020065241A1 (en) | Antigenic peptide concatomers |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040520 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040520 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070508 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070808 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20070914 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071108 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090303 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090521 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090629 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090624 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090803 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090903 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20091027 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100507 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100512 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120223 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120302 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120329 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120528 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150601 Year of fee payment: 3 |
|
R150 | Certificate of patent or registration of utility model |
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 |
|
EXPY | Cancellation because of completion of term |