CA2249412A1 - Methods for inducing immune responsiveness in a subject - Google Patents
Methods for inducing immune responsiveness in a subject Download PDFInfo
- Publication number
- CA2249412A1 CA2249412A1 CA002249412A CA2249412A CA2249412A1 CA 2249412 A1 CA2249412 A1 CA 2249412A1 CA 002249412 A CA002249412 A CA 002249412A CA 2249412 A CA2249412 A CA 2249412A CA 2249412 A1 CA2249412 A1 CA 2249412A1
- Authority
- CA
- Canada
- Prior art keywords
- cells
- disease
- cell
- blood
- dendritic
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 181
- 230000001939 inductive effect Effects 0.000 title description 3
- 230000004043 responsiveness Effects 0.000 title description 2
- 210000004443 dendritic cell Anatomy 0.000 claims abstract description 310
- 239000000427 antigen Substances 0.000 claims abstract description 199
- 108091007433 antigens Proteins 0.000 claims abstract description 199
- 102000036639 antigens Human genes 0.000 claims abstract description 199
- 210000004369 blood Anatomy 0.000 claims abstract description 145
- 239000008280 blood Substances 0.000 claims abstract description 145
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 100
- 239000000203 mixture Substances 0.000 claims abstract description 57
- 210000005259 peripheral blood Anatomy 0.000 claims abstract description 14
- 239000011886 peripheral blood Substances 0.000 claims abstract description 14
- 230000001976 improved effect Effects 0.000 claims abstract description 13
- 230000000899 immune system response Effects 0.000 claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims description 353
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 220
- 201000010099 disease Diseases 0.000 claims description 216
- 239000012636 effector Substances 0.000 claims description 121
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 61
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 50
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 46
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 46
- 206010028980 Neoplasm Diseases 0.000 claims description 42
- 210000001519 tissue Anatomy 0.000 claims description 31
- 108091054437 MHC class I family Proteins 0.000 claims description 29
- 102000004127 Cytokines Human genes 0.000 claims description 27
- 108090000695 Cytokines Proteins 0.000 claims description 27
- 102000043129 MHC class I family Human genes 0.000 claims description 25
- 108090000623 proteins and genes Proteins 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 21
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 19
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 18
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical group C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 claims description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 15
- 238000002955 isolation Methods 0.000 claims description 12
- 230000028993 immune response Effects 0.000 claims description 11
- 230000001965 increasing effect Effects 0.000 claims description 10
- 102000013462 Interleukin-12 Human genes 0.000 claims description 9
- 108010065805 Interleukin-12 Proteins 0.000 claims description 9
- 108090000978 Interleukin-4 Proteins 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 9
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- -1 TNF-ALPHA Proteins 0.000 claims description 8
- 210000004881 tumor cell Anatomy 0.000 claims description 8
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 claims description 7
- 230000004913 activation Effects 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 230000020477 pH reduction Effects 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 230000003472 neutralizing effect Effects 0.000 claims description 4
- 108010077805 Bacterial Proteins Proteins 0.000 claims description 3
- 108010004889 Heat-Shock Proteins Proteins 0.000 claims description 3
- 102000002812 Heat-Shock Proteins Human genes 0.000 claims description 3
- 108010067390 Viral Proteins Proteins 0.000 claims description 3
- 238000011176 pooling Methods 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000010362 Protozoan Infections Diseases 0.000 claims description 2
- 108010042038 Protozoan Proteins Proteins 0.000 claims description 2
- 230000002934 lysing effect Effects 0.000 claims description 2
- 230000006472 autoimmune response Effects 0.000 claims 2
- 230000003211 malignant effect Effects 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 102100029966 HLA class II histocompatibility antigen, DP alpha 1 chain Human genes 0.000 claims 1
- 101000864089 Homo sapiens HLA class II histocompatibility antigen, DP alpha 1 chain Proteins 0.000 claims 1
- 101000930802 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 1 chain Proteins 0.000 claims 1
- 101000968032 Homo sapiens HLA class II histocompatibility antigen, DR beta 3 chain Proteins 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 43
- 230000004044 response Effects 0.000 description 42
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 42
- 102000004196 processed proteins & peptides Human genes 0.000 description 37
- SQBBOVROCFXYBN-UHFFFAOYSA-N methoxypsoralen Natural products C1=C2OC(=O)C(OC)=CC2=CC2=C1OC=C2 SQBBOVROCFXYBN-UHFFFAOYSA-N 0.000 description 22
- 239000002243 precursor Substances 0.000 description 22
- BUNGCZLFHHXKBX-UHFFFAOYSA-N 8-methoxypsoralen Natural products C1=CC(=O)OC2=C1C=C1CCOC1=C2OC BUNGCZLFHHXKBX-UHFFFAOYSA-N 0.000 description 20
- QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical compound C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 20
- 229960004469 methoxsalen Drugs 0.000 description 20
- 241000282414 Homo sapiens Species 0.000 description 18
- 238000012258 culturing Methods 0.000 description 18
- 238000011068 loading method Methods 0.000 description 18
- 238000005119 centrifugation Methods 0.000 description 16
- 238000000338 in vitro Methods 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 15
- 210000000712 G cell Anatomy 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 14
- 241000282320 Panthera leo Species 0.000 description 13
- 101150115433 SLC26A5 gene Proteins 0.000 description 13
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 108091034117 Oligonucleotide Proteins 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 150000002500 ions Chemical class 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 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 9
- 238000010828 elution Methods 0.000 description 9
- 210000000265 leukocyte Anatomy 0.000 description 9
- 102000004388 Interleukin-4 Human genes 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 238000002255 vaccination Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 102100040247 Tumor necrosis factor Human genes 0.000 description 7
- 238000004113 cell culture Methods 0.000 description 7
- 238000001802 infusion Methods 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 230000004614 tumor growth Effects 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 231100000588 tumorigenic Toxicity 0.000 description 6
- 230000000381 tumorigenic effect Effects 0.000 description 6
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 5
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 5
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- BGEBZHIAGXMEMV-UHFFFAOYSA-N 5-methoxypsoralen Chemical compound O1C(=O)C=CC2=C1C=C1OC=CC1=C2OC BGEBZHIAGXMEMV-UHFFFAOYSA-N 0.000 description 4
- 108091054438 MHC class II family Proteins 0.000 description 4
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 4
- 230000001594 aberrant effect Effects 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 230000030741 antigen processing and presentation Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 239000013043 chemical agent Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000011081 inoculation Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010001857 Cell Surface Receptors Proteins 0.000 description 3
- 102000000844 Cell Surface Receptors Human genes 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- YFONKFDEZLYQDH-OPQQBVKSSA-N N-[(1R,2S)-2,6-dimethyindan-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine Chemical compound C[C@@H](F)C1=NC(N)=NC(N[C@H]2C3=CC(C)=CC=C3C[C@@H]2C)=N1 YFONKFDEZLYQDH-OPQQBVKSSA-N 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000001464 adherent effect Effects 0.000 description 3
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 3
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 3
- 229960000830 captopril Drugs 0.000 description 3
- 230000032823 cell division Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 210000004700 fetal blood Anatomy 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000011132 hemopoiesis Effects 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 2
- RRJCLYMGCZJLBQ-UHFFFAOYSA-N 5-amino-8-(diaminomethylideneamino)-2-[(4-hydroxyphenyl)methyl]-4-oxooctanoic acid Chemical compound NC(N)=NCCCC(N)C(=O)CC(C(O)=O)CC1=CC=C(O)C=C1 RRJCLYMGCZJLBQ-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 2
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 210000003771 C cell Anatomy 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 2
- 101710197836 HLA class I histocompatibility antigen, alpha chain G Proteins 0.000 description 2
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000004125 Interleukin-1alpha Human genes 0.000 description 2
- 108010082786 Interleukin-1alpha Proteins 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960002045 bergapten Drugs 0.000 description 2
- KGZDKFWCIPZMRK-UHFFFAOYSA-N bergapten Natural products COC1C2=C(Cc3ccoc13)C=CC(=O)O2 KGZDKFWCIPZMRK-UHFFFAOYSA-N 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 229940030156 cell vaccine Drugs 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 108091092356 cellular DNA Proteins 0.000 description 2
- 230000004670 cellular proteolysis Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052804 chromium Inorganic materials 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000006862 enzymatic digestion Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 150000004032 porphyrins Chemical class 0.000 description 2
- 230000037452 priming Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- FMHHVULEAZTJMA-UHFFFAOYSA-N trioxsalen Chemical compound CC1=CC(=O)OC2=C1C=C1C=C(C)OC1=C2C FMHHVULEAZTJMA-UHFFFAOYSA-N 0.000 description 2
- 229960000850 trioxysalen Drugs 0.000 description 2
- 229950009811 ubenimex Drugs 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 101150029062 15 gene Proteins 0.000 description 1
- WBIICVGYYRRURR-UHFFFAOYSA-N 3-(aminomethyl)-2,5,9-trimethylfuro[3,2-g]chromen-7-one Chemical compound O1C(=O)C=C(C)C2=C1C(C)=C1OC(C)=C(CN)C1=C2 WBIICVGYYRRURR-UHFFFAOYSA-N 0.000 description 1
- 238000011640 AKR mouse Methods 0.000 description 1
- 208000004881 Amebiasis Diseases 0.000 description 1
- 206010001980 Amoebiasis Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 208000035049 Blood-Borne Infections Diseases 0.000 description 1
- 108700031361 Brachyury Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000016355 Granulocyte-Macrophage Colony-Stimulating Factor Receptors Human genes 0.000 description 1
- 108010092372 Granulocyte-Macrophage Colony-Stimulating Factor Receptors Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101100045405 Homo sapiens TAP2 gene Proteins 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 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
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- BAQCROVBDNBEEB-UBYUBLNFSA-N Metrizamide Chemical compound CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C(=O)N[C@@H]2[C@H]([C@H](O)[C@@H](CO)OC2O)O)=C1I BAQCROVBDNBEEB-UBYUBLNFSA-N 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 201000011152 Pemphigus Diseases 0.000 description 1
- ZPHBZEQOLSRPAK-UHFFFAOYSA-N Phosphoramidon Natural products C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O ZPHBZEQOLSRPAK-UHFFFAOYSA-N 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101000884281 Rattus norvegicus Signal transducer CD24 Proteins 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108010036928 Thiorphan Proteins 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 208000005448 Trichomonas Infections Diseases 0.000 description 1
- 206010044620 Trichomoniasis Diseases 0.000 description 1
- XJLATMLVMSFZBN-VYDXJSESSA-N actinonin Chemical compound CCCCC[C@H](CC(=O)NO)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1CO XJLATMLVMSFZBN-VYDXJSESSA-N 0.000 description 1
- XJLATMLVMSFZBN-UHFFFAOYSA-N actinonine Natural products CCCCCC(CC(=O)NO)C(=O)NC(C(C)C)C(=O)N1CCCC1CO XJLATMLVMSFZBN-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000011166 aliquoting Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000003173 antianemic agent Substances 0.000 description 1
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- OIPMQULDKWSNGX-UHFFFAOYSA-N bis[[ethoxy(oxo)phosphaniumyl]oxy]alumanyloxy-ethoxy-oxophosphanium Chemical compound [Al+3].CCO[P+]([O-])=O.CCO[P+]([O-])=O.CCO[P+]([O-])=O OIPMQULDKWSNGX-UHFFFAOYSA-N 0.000 description 1
- 210000005208 blood dendritic cell Anatomy 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 208000037516 chromosome inversion disease Diseases 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001887 cortisones Chemical class 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000005188 flotation Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000000937 inactivator Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229960000554 metrizamide Drugs 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 201000001976 pemphigus vulgaris Diseases 0.000 description 1
- RJSZPKZQGIKVAU-UXBJKDEOSA-N peptide f Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C(C)C)C(C)C)C1=CC=CC=C1 RJSZPKZQGIKVAU-UXBJKDEOSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 108010072906 phosphoramidon Proteins 0.000 description 1
- BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003220 pyrenes Chemical class 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000012899 standard injection Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940031626 subunit vaccine Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 201000002311 trypanosomiasis Diseases 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2026—IL-4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/208—IL-12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/605—MHC molecules or ligands thereof
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US62110996A | 1996-03-22 | 1996-03-22 | |
US08/621,109 | 1996-03-22 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2249412A1 true CA2249412A1 (en) | 1997-09-25 |
Family
ID=24488765
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002249412A Abandoned CA2249412A1 (en) | 1996-03-22 | 1997-03-18 | Methods for inducing immune responsiveness in a subject |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0896506A4 (ja) |
JP (1) | JP2000508628A (ja) |
AU (1) | AU2331597A (ja) |
CA (1) | CA2249412A1 (ja) |
WO (1) | WO1997034472A1 (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5651993A (en) | 1992-11-18 | 1997-07-29 | Yale University | Specific immune system modulation |
US7402307B2 (en) | 1998-03-31 | 2008-07-22 | Geron Corporation | Method for identifying and killing cancer cells |
US20020142974A1 (en) * | 1998-09-11 | 2002-10-03 | Leonard D. Kohn | Immune activation by double-stranded polynucleotides |
US7109031B2 (en) | 1999-04-20 | 2006-09-19 | Yale University | Methods for inducing the differentiation of monocytes into functional dendritic cells and immunotherapeutic compositions including such dendritic cells |
US8313945B2 (en) | 1999-04-20 | 2012-11-20 | Yale University | Methods for inducing the differentiation of blood monocytes into functional dendritic cells |
WO2000062818A1 (en) | 1999-04-20 | 2000-10-26 | Richard Leslie Edelson | Differentiation of monocytes into functional dendritic cells |
DE19960705A1 (de) * | 1999-12-16 | 2001-06-21 | Laser & Med Tech Gmbh | Verfahren und Vorrichtung zur Herstellung eines autologen Immunisierungsimpfstoffes gegen Krebserkrankungen (Tumorvakzine) |
DE10053783B4 (de) * | 2000-07-10 | 2007-06-14 | Eppendorf Ag | Verfahren zur Modifizierung von dendritischen Zellen |
US7727523B2 (en) | 2001-08-13 | 2010-06-01 | Yale University | Method for suppressing immune system response to transplanted tissue or cells |
ES2339752T3 (es) | 2001-08-13 | 2010-05-25 | Yale University | Metodo para inducir una respuesta inmune selectivamente suprimida. |
EP1592441B1 (en) * | 2003-02-06 | 2012-04-11 | Aduro Biotech | Listeria attenuated for entry into non-phagocytic cells, vaccines comprising the listeria, and methods of use thereof |
US8524495B2 (en) | 2007-05-16 | 2013-09-03 | Yale University | Methods for inducing the differentiation of blood monocytes into functional dendritic cells |
EP4255576A2 (en) * | 2020-12-07 | 2023-10-11 | The Trustees of Indiana University | Methods to sensitize cancer cells to immune attack using atractylenolide i |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL85746A (en) * | 1988-03-15 | 1994-05-30 | Yeda Res & Dev | Preparations comprising t-lymphocyte cells treated with 8-methoxypsoralen or cell membranes separated therefrom for preventing or treating autoimmune diseases |
AU687733B2 (en) * | 1992-04-01 | 1998-03-05 | Rockefeller University, The | Method for in vitro proliferation of dendritic cell precursors and their use to produce immunogens |
US5651993A (en) * | 1992-11-18 | 1997-07-29 | Yale University | Specific immune system modulation |
US5820872A (en) * | 1992-11-18 | 1998-10-13 | Yale University | Methods and compositions for improving the effectiveness of X-irradiation therapy for the treatment of an internal solid tumor |
CA2192655A1 (en) * | 1994-06-14 | 1995-12-21 | Edgar G. Engleman | Methods for in vivo t cell activation by antigen-pulsed dendritic cells |
-
1997
- 1997-03-18 CA CA002249412A patent/CA2249412A1/en not_active Abandoned
- 1997-03-18 AU AU23315/97A patent/AU2331597A/en not_active Abandoned
- 1997-03-18 EP EP97916046A patent/EP0896506A4/en not_active Withdrawn
- 1997-03-18 WO PCT/US1997/004285 patent/WO1997034472A1/en not_active Application Discontinuation
- 1997-03-18 JP JP9533616A patent/JP2000508628A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
JP2000508628A (ja) | 2000-07-11 |
WO1997034472A1 (en) | 1997-09-25 |
EP0896506A4 (en) | 2003-06-18 |
EP0896506A1 (en) | 1999-02-17 |
AU2331597A (en) | 1997-10-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10226519B2 (en) | Cancer vaccines and vaccination methods | |
AU722328B2 (en) | Methods for generating cytotoxic T cells in vitro | |
US5820872A (en) | Methods and compositions for improving the effectiveness of X-irradiation therapy for the treatment of an internal solid tumor | |
CA2368855C (en) | Differentiation of monocytes into functional dendritic cells | |
US20020155108A1 (en) | Method for ex vivo loading of antigen presenting cells with antigen, and a vaccine comprising the loaded cells | |
US8673296B2 (en) | Method and composition for producing a cellular allogeneic vaccine | |
EA023106B1 (ru) | Способ получения частично зрелых дендритных клеток, обладающих повышенной экспрессией интерлейкина il-12 | |
CA2249412A1 (en) | Methods for inducing immune responsiveness in a subject | |
US6703016B1 (en) | Apoptotic bodies, monocyte derived cells containing the same, a process for their preparation and their uses as vaccines | |
US20100303868A1 (en) | Ex vivo, fast and efficient process to obtain activated antigen-presenting cells that are useful for therapies against cancer and immune system-related diseases | |
CN100421727C (zh) | 方法 | |
US20040022813A1 (en) | Shed antigen vaccine with dendritic cells adjuvant | |
AU5394801A (en) | Methods for inducing immune responsiveness in a subject | |
MXPA98007775A (en) | Methods to induce immune responses in a suj |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
FZDE | Discontinued |