DK1441591T3 - Sammensætninger og fremgangsmåder til priming af monocytiske dendritiske celler og T-celler for TH-1-respons - Google Patents
Sammensætninger og fremgangsmåder til priming af monocytiske dendritiske celler og T-celler for TH-1-respons Download PDFInfo
- Publication number
- DK1441591T3 DK1441591T3 DK02761594.7T DK02761594T DK1441591T3 DK 1441591 T3 DK1441591 T3 DK 1441591T3 DK 02761594 T DK02761594 T DK 02761594T DK 1441591 T3 DK1441591 T3 DK 1441591T3
- Authority
- DK
- Denmark
- Prior art keywords
- cells
- antigen
- dendritic cells
- bcg
- immature
- Prior art date
Links
- 210000004443 dendritic cell Anatomy 0.000 title claims description 328
- 210000001744 T-lymphocyte Anatomy 0.000 title claims description 112
- 238000000034 method Methods 0.000 title claims description 36
- 230000004044 response Effects 0.000 title description 32
- 239000000203 mixture Substances 0.000 title description 14
- 230000037452 priming Effects 0.000 title description 6
- 239000000427 antigen Substances 0.000 claims description 146
- 108091007433 antigens Proteins 0.000 claims description 146
- 102000036639 antigens Human genes 0.000 claims description 146
- 210000004027 cell Anatomy 0.000 claims description 86
- 230000035800 maturation Effects 0.000 claims description 62
- 239000002243 precursor Substances 0.000 claims description 55
- 108010065805 Interleukin-12 Proteins 0.000 claims description 49
- 102000013462 Interleukin-12 Human genes 0.000 claims description 49
- 102000003814 Interleukin-10 Human genes 0.000 claims description 46
- 108090000174 Interleukin-10 Proteins 0.000 claims description 46
- 229940076144 interleukin-10 Drugs 0.000 claims description 45
- 229940117681 interleukin-12 Drugs 0.000 claims description 39
- 206010028980 Neoplasm Diseases 0.000 claims description 31
- 102000004388 Interleukin-4 Human genes 0.000 claims description 27
- 108090000978 Interleukin-4 Proteins 0.000 claims description 27
- 229940028885 interleukin-4 Drugs 0.000 claims description 27
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 230000001580 bacterial effect Effects 0.000 claims description 18
- 241000282414 Homo sapiens Species 0.000 claims description 15
- 238000000338 in vitro Methods 0.000 claims description 15
- 210000004881 tumor cell Anatomy 0.000 claims description 14
- 102000008070 Interferon-gamma Human genes 0.000 claims description 12
- 108010074328 Interferon-gamma Proteins 0.000 claims description 12
- 229960003130 interferon gamma Drugs 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 239000003104 tissue culture media Substances 0.000 claims description 12
- 241001467552 Mycobacterium bovis BCG Species 0.000 claims description 11
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 claims description 11
- 238000012258 culturing Methods 0.000 claims description 10
- 230000028993 immune response Effects 0.000 claims description 10
- 239000012528 membrane Substances 0.000 claims description 10
- 102000003816 Interleukin-13 Human genes 0.000 claims description 9
- 108090000176 Interleukin-13 Proteins 0.000 claims description 9
- 239000013592 cell lysate Substances 0.000 claims description 8
- 230000003612 virological effect Effects 0.000 claims description 6
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 claims 10
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims 2
- 102000004127 Cytokines Human genes 0.000 description 29
- 108090000695 Cytokines Proteins 0.000 description 29
- 239000000758 substrate Substances 0.000 description 23
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 17
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 17
- 201000011510 cancer Diseases 0.000 description 13
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 13
- 210000001616 monocyte Anatomy 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 230000005867 T cell response Effects 0.000 description 10
- 230000016396 cytokine production Effects 0.000 description 10
- 230000003308 immunostimulating effect Effects 0.000 description 10
- 230000031261 interleukin-10 production Effects 0.000 description 10
- 230000019734 interleukin-12 production Effects 0.000 description 10
- 210000000265 leukocyte Anatomy 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 7
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 210000000612 antigen-presenting cell Anatomy 0.000 description 7
- 230000000139 costimulatory effect Effects 0.000 description 7
- 230000004069 differentiation Effects 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 7
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 6
- -1 IFNy Proteins 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 5
- 230000006044 T cell activation Effects 0.000 description 5
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 102000054766 genetic haplotypes Human genes 0.000 description 5
- 206010022000 influenza Diseases 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- CBHOWTTXCQAOID-UHFFFAOYSA-L sodium ethane formaldehyde mercury(2+) molecular iodine 2-sulfidobenzoate Chemical compound [Na+].[Hg++].C[CH2-].II.C=O.[O-]C(=O)c1ccccc1[S-] CBHOWTTXCQAOID-UHFFFAOYSA-L 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 4
- 102100035793 CD83 antigen Human genes 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 4
- 102000003812 Interleukin-15 Human genes 0.000 description 4
- 108090000172 Interleukin-15 Proteins 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000004041 dendritic cell maturation Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009169 immunotherapy Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 3
- 241000712431 Influenza A virus Species 0.000 description 3
- 108010002616 Interleukin-5 Proteins 0.000 description 3
- 102000000743 Interleukin-5 Human genes 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- 102000043129 MHC class I family Human genes 0.000 description 3
- 108091054437 MHC class I family Proteins 0.000 description 3
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000012228 culture supernatant Substances 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000001821 langerhans cell Anatomy 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 210000003563 lymphoid tissue Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- VHVVPYOJIIQCKS-QEJZJMRPSA-N Ala-Leu-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 VHVVPYOJIIQCKS-QEJZJMRPSA-N 0.000 description 2
- KQBVNNAPIURMPD-PEFMBERDSA-N Asp-Ile-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KQBVNNAPIURMPD-PEFMBERDSA-N 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 238000012286 ELISA Assay Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 241000186366 Mycobacterium bovis Species 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 2
- PMCMLDNPAZUYGI-DCAQKATOSA-N Ser-Lys-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O PMCMLDNPAZUYGI-DCAQKATOSA-N 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 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 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 102000055135 Vasoactive Intestinal Peptide Human genes 0.000 description 2
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 238000002619 cancer immunotherapy Methods 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 238000000432 density-gradient centrifugation Methods 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000037797 influenza A Diseases 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000003071 memory t lymphocyte Anatomy 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 2
- 230000007420 reactivation Effects 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 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
- 241000271566 Aves Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 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 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- BDISFWMLMNBTGP-NUMRIWBASA-N Glu-Thr-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O BDISFWMLMNBTGP-NUMRIWBASA-N 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- KEVYYIMVELOXCT-KBPBESRZSA-N Leu-Gly-Phe Chemical compound CC(C)C[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 KEVYYIMVELOXCT-KBPBESRZSA-N 0.000 description 1
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-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
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- HBZBPFLJNDXRAY-FXQIFTODSA-N Ser-Ala-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O HBZBPFLJNDXRAY-FXQIFTODSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound 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 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 210000000173 T-lymphoid precursor cell Anatomy 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- OHAJHDJOCKKJLV-LKXGYXEUSA-N Thr-Asp-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O OHAJHDJOCKKJLV-LKXGYXEUSA-N 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- YKNOJPJWNVHORX-UNQGMJICSA-N Val-Phe-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(O)=O)CC1=CC=CC=C1 YKNOJPJWNVHORX-UNQGMJICSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000002617 apheresis Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940126587 biotherapeutics Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 230000002338 cryopreservative effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 210000004544 dc2 Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 102000046689 human FOLH1 Human genes 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 108010061181 influenza matrix peptide (58-66) Proteins 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000007193 modulation by symbiont of host erythrocyte aggregation Effects 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000029069 type 2 immune response Effects 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
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005135 veiled cell Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- 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
-
- 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
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5428—IL-10
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5434—IL-12
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/57—IFN-gamma
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
-
- 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
- A61K2039/5158—Antigen-pulsed cells, e.g. T-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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55522—Cytokines; Lymphokines; Interferons
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55588—Adjuvants of undefined constitution
- A61K2039/55594—Adjuvants of undefined constitution from bacteria
-
- 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2500/00—Specific components of cell culture medium
- C12N2500/70—Undefined extracts
- C12N2500/72—Undefined extracts from bacteria
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/24—Interferons [IFN]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Urology & Nephrology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
Claims (10)
1. En ex vivo- eller in vitro-metode til frembringelse af en moden dendritisk cellepopulation, der frembringer et forhøjet forhold mellem Interleukin 12 og Interleukin 10, hvor det forhøjede forhold mellem Interleukin 12 og Interleukin 10 er forhøjet i forhold til en umoden dendritisk cellepopulation, der ikke er bragt i kontakt med Bacillus-Calmette-Guerin (BCG) og Interferon y (IFNy) under modning, der omfatter: kontakt gav umodne dendritiske celler en effektiv mængde Bacillus-Calmette-Guerin (BCG) bestående af 105 til 107 cfu pr. ml vævskulturmedier og 100 til 1000 enheder Interferon gamma (IFNy) pr. ml vævskulturmedier under kulturbetingelser, der er egnet til modning af de umodne dendritiske celler for at danne den modne dendritiske cellepopulation.
2. En ex vivo- eller in vitro-metode til frembringelse af en moden dendritisk cellepopulation, hvori den modne dendritiske cellepopulation frembringer en type 1-immunresponse, der omfatter: kontakt gav umodne dendritiske celler en effektiv mængde Bacillus-Calmette-Guerin (BCG) bestående af 105 til 107 cfu pr. ml vævskulturmedier og 100 til 1000 enheder Interferon gamma (IFNy) pr. ml vævskulturmedier under kulturbetingelser, der er egnet til modning af de umodne dendritiske celler for at danne den modne dendritiske cellepopulation.
3. En ex vivo- eller in vitro-metode til frembringelse af aktiverede T-celler, der omfatter: kontakt gav umodne dendritiske celler et forudbestemt antigen; og kontakt gav de umodne dendritiske celler en mængde Bacillus-Calmette-Guerin (BCG), bestående af 105 til 107 cfu pr. ml vævskulturmedier og 100 til 1000 enheder Interferon gamma (IFNy) pr. ml vævskulturmedier under kulturbetingelser, der er egnet til modning af de umodne dendritiske celler for at danne den modne dendritiske cellepopulation. hvori den modne dendritiske cellepopulation frembringer et forhøjet forhold mellem Interleukin 12 og Interleukin 10, og kontakt mellem de modne dendritiske celler og naive T-celler for at danne aktiverede T-celler til frembringelse af IFNy, og hvori den aktiverede T-cellepopulation frembringer en type 1-immunrespons.
4. Metoden i ifølge ethvert af kravene 1 til 3, hvori de modne dendritiske celler frembringer et forhold mellem IL-12 og IL-10 på mindst ca. 1:1, mindst ca. 10:1 eller mindst ca. 100: 1.
5. Metoden ifølge ethvert af kravene 1 til 3, der desuden omfatter: dyrkning af isolerede monocytiske dendritiske celleprækursorer ved tilstedeværelse af en monocytisk dendritisk celledifferentierende agent for at danne de umodne dendritiske celler.
6. Metoden i krav 5, hvori den differentierende agent er GM-CSF, Interleukin 4, en kombination af GM-CSF og Interleukin 4 eller Interleukin 13.
7. Metoden i krav 5, hvori de monocytiske dendritiske celleprækursorer er humane monocytiske dendritiske celleprækursorer.
8. Metoden i krav 3, hvori et forudbestemt antigen er et tumorspecifikt antigen, et tumorassocieret antigen, et viralt antigen, et bakterielt antigen, tumorceller, bakterieceller, rekombinante celler, der udtrykker et antigen, et cellelysat, et membranpræparat, et rekombinant produceret antigen, et peptidantigen eller et isoleret antigen.
9. Metoden i ifølge ethvert af kravene 3 til 8, hvori de umodne dendritiske celler bringes i samtidig kontakt med det forudbestemte antigen, BCG og IFNy eller bringes i kontakt med det forudbestemte antigen, før de bringes i kontakt med BCG og IFNy.
10. Metoden i ifølge ethvert af kravene 3 og 8 til 9, hvori de umodne dendritiske celler og T-cellerne er autologe i forhold til hinanden.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US31759201P | 2001-09-06 | 2001-09-06 | |
PCT/US2002/028620 WO2003022215A2 (en) | 2001-09-06 | 2002-09-06 | Compositions and methods for priming monocytic dendritic cells and t cells for th-1 response |
Publications (1)
Publication Number | Publication Date |
---|---|
DK1441591T3 true DK1441591T3 (da) | 2017-05-22 |
Family
ID=32654226
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK02761594.7T DK1441591T3 (da) | 2001-09-06 | 2002-09-06 | Sammensætninger og fremgangsmåder til priming af monocytiske dendritiske celler og T-celler for TH-1-respons |
DK10181985.2T DK2322603T3 (da) | 2001-09-06 | 2002-09-06 | Sammensætninger og fremgangsmåder til aktivering af monocytiske dendritiske celler og t-celler for th1-respons |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK10181985.2T DK2322603T3 (da) | 2001-09-06 | 2002-09-06 | Sammensætninger og fremgangsmåder til aktivering af monocytiske dendritiske celler og t-celler for th1-respons |
Country Status (18)
Country | Link |
---|---|
US (2) | US20050059151A1 (da) |
EP (3) | EP2322603B1 (da) |
JP (3) | JP2005505270A (da) |
KR (3) | KR101803702B1 (da) |
CN (2) | CN102973928B (da) |
AU (1) | AU2008221592B2 (da) |
BR (1) | BRPI0212545B8 (da) |
CA (1) | CA2459713C (da) |
DK (2) | DK1441591T3 (da) |
ES (2) | ES2766299T3 (da) |
HK (1) | HK1079989A1 (da) |
IL (3) | IL160720A0 (da) |
MX (1) | MXPA04002147A (da) |
NO (2) | NO338147B1 (da) |
NZ (1) | NZ531530A (da) |
PL (1) | PL372098A1 (da) |
PT (2) | PT1441591T (da) |
WO (1) | WO2003022215A2 (da) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT412145B (de) * | 2002-09-13 | 2004-10-25 | Forsch Krebskranke Kinder | Verfahren zur herstellung eines zellulären immuntherapeutikums auf basis von il-12-freisetzenden dendritischen zellen |
US20040057935A1 (en) * | 2002-09-20 | 2004-03-25 | Cedars-Sinai Medical Center | Intratumoral delivery of dendritic cells |
RU2348418C2 (ru) * | 2002-12-06 | 2009-03-10 | Норсуэст Байотерапьютикс, Инк. | Введение дендритных клеток, подвергнутых частичному созреванию in vitro, для лечения опухолей |
ATE420946T1 (de) * | 2003-02-27 | 2009-01-15 | Northwest Biotherapeutics Inc | Erzeugung dendritischer zellen aus monozytischen dendritischen vorläuferzellen mit gm-csf ohne anwesenheit zusätzlicher zytokine |
EP1484064A1 (en) | 2003-06-04 | 2004-12-08 | Gesellschaft für Biotechnologische Forschung | Therapeutical composition containing dentritic cells and use thereof |
JP2007507543A (ja) * | 2003-10-06 | 2007-03-29 | セダーズ−シナイ メディカル センター | 樹状細胞治療によって誘導されるt細胞アネルギーを予防するためのcox−2インヒビターの使用 |
WO2005043155A1 (en) * | 2003-10-21 | 2005-05-12 | Cedars-Sinai Medical Center | System and method for the treatment of cancer, including cancers of the central nervous system |
AU2004286144A1 (en) * | 2003-11-04 | 2005-05-12 | Dnavec Research Inc. | Method for producing gene transferred dendritic cells |
JP5296983B2 (ja) | 2004-06-24 | 2013-09-25 | 株式会社ディナベック研究所 | Rnaウイルスが導入された樹状細胞を含む抗癌剤 |
WO2007067782A2 (en) * | 2005-12-08 | 2007-06-14 | Northwest Biotherapeutics, Inc. | Compositions and methods for inducing the activation of immature monocytic dendritic cells |
EP1840206A1 (en) * | 2006-03-28 | 2007-10-03 | Gsf-Forschungszentrum Für Umwelt Und Gesundheit, Gmbh | Compositions for the preparation of mature dendritic cells |
CA2700573C (en) | 2006-09-26 | 2016-11-22 | Cedars-Sinai Medical Center | Cancer stem cell antigen vaccines and methods |
CA2700579A1 (en) | 2006-09-28 | 2008-04-03 | Cedars-Sinai Medical Center | Cancer vaccines and vaccination methods |
EP2328923B1 (en) * | 2008-09-02 | 2016-01-13 | Cedars-Sinai Medical Center | Cd133 epitopes |
EP2427485B1 (en) | 2009-05-07 | 2016-12-07 | ImmunoCellular Therapeutics, Ltd. | Cd133 epitopes |
SG11201404543UA (en) * | 2012-02-02 | 2014-08-28 | California Stem Cell Inc | Pluripotent germ layer origin antigen presenting cancer vaccine |
KR101704745B1 (ko) | 2012-05-31 | 2017-02-08 | 제이더블유크레아젠 주식회사 | 수지상세포 성숙화 조성물 및 이를 이용하여 항원 특이적 수지상세포를 제조하는 방법 |
AU2020203845C1 (en) * | 2012-09-06 | 2022-08-11 | Orbis Health Solutions, Llc | Tumor lysate loaded particles |
US20140065173A1 (en) * | 2012-09-06 | 2014-03-06 | Orbis Health Solutions Llc | Tumor lysate loaded particles |
JP6121561B2 (ja) | 2012-12-12 | 2017-04-26 | オービス ヘルス ソリューションズ エルエルシー | 組織再生のための組成物および方法 |
EP2956544B1 (en) | 2013-02-14 | 2017-11-01 | Immunocellular Therapeutics Ltd. | Cancer vaccines and vaccination methods |
CN112891522A (zh) * | 2013-09-05 | 2021-06-04 | 奥比思健康解决方案有限责任公司 | 装载了肿瘤裂解物的微粒 |
SG11201607368XA (en) | 2014-03-05 | 2016-10-28 | Orbis Health Solutions Llc | Vaccine delivery systems using yeast cell wall particles |
US10373259B1 (en) | 2014-05-20 | 2019-08-06 | State Farm Mutual Automobile Insurance Company | Fully autonomous vehicle insurance pricing |
US9972054B1 (en) | 2014-05-20 | 2018-05-15 | State Farm Mutual Automobile Insurance Company | Accident fault determination for autonomous vehicles |
US10599155B1 (en) | 2014-05-20 | 2020-03-24 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle operation feature monitoring and evaluation of effectiveness |
US10223479B1 (en) | 2014-05-20 | 2019-03-05 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle operation feature evaluation |
US11669090B2 (en) | 2014-05-20 | 2023-06-06 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle operation feature monitoring and evaluation of effectiveness |
US10540723B1 (en) | 2014-07-21 | 2020-01-21 | State Farm Mutual Automobile Insurance Company | Methods of providing insurance savings based upon telematics and usage-based insurance |
US20210118249A1 (en) | 2014-11-13 | 2021-04-22 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle salvage and repair |
WO2017002045A1 (en) | 2015-06-30 | 2017-01-05 | Stemlab, Sa | A viable cell population, method for production and uses thereof |
MX2018000056A (es) * | 2015-06-30 | 2018-05-28 | Northwest Biotherapeutics Inc | Celulas dendriticas optimamente activadas que inducen una respuesta inmunologica antitumoral mayor o mejorada. |
US9805601B1 (en) | 2015-08-28 | 2017-10-31 | State Farm Mutual Automobile Insurance Company | Vehicular traffic alerts for avoidance of abnormal traffic conditions |
US11242051B1 (en) | 2016-01-22 | 2022-02-08 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle action communications |
US10308246B1 (en) | 2016-01-22 | 2019-06-04 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle signal control |
US10395332B1 (en) | 2016-01-22 | 2019-08-27 | State Farm Mutual Automobile Insurance Company | Coordinated autonomous vehicle automatic area scanning |
US10324463B1 (en) | 2016-01-22 | 2019-06-18 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle operation adjustment based upon route |
US11441916B1 (en) | 2016-01-22 | 2022-09-13 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle trip routing |
US11719545B2 (en) | 2016-01-22 | 2023-08-08 | Hyundai Motor Company | Autonomous vehicle component damage and salvage assessment |
US10134278B1 (en) | 2016-01-22 | 2018-11-20 | State Farm Mutual Automobile Insurance Company | Autonomous vehicle application |
KR102038114B1 (ko) * | 2016-02-26 | 2019-10-30 | 주식회사 엘지화학 | 광학 점착제용 (메타)아크릴레이트기 함유 벤조페논의 제조방법 및 광학 점착제 조성물 |
WO2018160666A1 (en) * | 2017-02-28 | 2018-09-07 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Short-term activated dc1s and methods for their production and use |
AU2020363707A1 (en) * | 2019-10-07 | 2022-04-28 | Northwest Biotherapeutics, Inc. | In vitro methods and compositions for enhancing the activation of dendritic cells and t cells, and for inducing a th-1 immune response |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5162504A (en) * | 1988-06-03 | 1992-11-10 | Cytogen Corporation | Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients |
US5366866A (en) * | 1991-07-25 | 1994-11-22 | Duke University | Method of diagnosing ovarian and endometrial cancer with monoclonal antibodies OXA and OXB |
US5227471A (en) * | 1992-01-30 | 1993-07-13 | Eastern Virginia Medical School Of The Medical College Of Hampton Roads | Monoclonal antibody PD41 that binds to a prostate mucin antigen that is expressed in human prostatic carcinoma |
US5788963A (en) | 1995-07-31 | 1998-08-04 | Pacific Northwest Cancer Foundation | Isolation and/or preservation of dendritic cells for prostate cancer immunotherapy |
NZ321039A (en) * | 1995-10-04 | 2001-03-30 | Immunex Corp | Use of flt3-ligand to augment immunizing effects of known cytokines by stimulating myeloid precursor cells, monocytic cells, macrophages, B-cells and dendritic cells from CD34+ bone marrow progenitors |
US7659119B2 (en) * | 1996-02-12 | 2010-02-09 | Argos Therapeutics, Inc. | Method and compositions for obtaining mature dendritic cells |
DE69840739D1 (de) * | 1997-10-27 | 2009-05-28 | Merix Bioscience Inc | Methode und Zusammensetzung zur Herstellung von reifen dendritischen Zellen |
JP2000143534A (ja) * | 1998-11-13 | 2000-05-23 | Asahi Chem Ind Co Ltd | 樹状細胞ワクチン及びその製造方法 |
JP2000279181A (ja) * | 1999-04-01 | 2000-10-10 | Japan Science & Technology Corp | ヒト樹状細胞の発現遺伝子群 |
US20030108527A1 (en) * | 1999-12-28 | 2003-06-12 | Tsukasa Seya | Maturation-promoting agent for immature dendrtic cells |
US6247378B1 (en) * | 2000-01-06 | 2001-06-19 | Deere & Company | Operator control device for an infinitely variable transmission |
US20030175247A1 (en) * | 2000-05-12 | 2003-09-18 | Michael Salgaller | Method to increase class I presentation of exogenous antigens by human dendritic cells |
ES2254527T3 (es) * | 2001-01-15 | 2006-06-16 | I.D.M. Immuno-Designed Molecules | Metodo para la preparacion de suspensiones de particulas submicronicas de agentes farmaceuticos. |
WO2003010292A2 (en) * | 2001-07-25 | 2003-02-06 | Northwest Biotherapeutics, Inc. | Methods and apparatus for enrichment and culture of monocytic dendritic cell precursors |
-
2002
- 2002-09-06 BR BRPI0212545A patent/BRPI0212545B8/pt not_active IP Right Cessation
- 2002-09-06 ES ES10181985T patent/ES2766299T3/es not_active Expired - Lifetime
- 2002-09-06 PL PL02372098A patent/PL372098A1/xx not_active Application Discontinuation
- 2002-09-06 US US10/488,744 patent/US20050059151A1/en not_active Abandoned
- 2002-09-06 EP EP10181985.2A patent/EP2322603B1/en not_active Expired - Lifetime
- 2002-09-06 EP EP02761594.7A patent/EP1441591B1/en not_active Expired - Lifetime
- 2002-09-06 IL IL16072002A patent/IL160720A0/xx unknown
- 2002-09-06 JP JP2003526345A patent/JP2005505270A/ja active Pending
- 2002-09-06 KR KR1020147023675A patent/KR101803702B1/ko active IP Right Grant
- 2002-09-06 PT PT2761594T patent/PT1441591T/pt unknown
- 2002-09-06 KR KR1020117012621A patent/KR20110081341A/ko not_active Application Discontinuation
- 2002-09-06 CA CA2459713A patent/CA2459713C/en not_active Expired - Lifetime
- 2002-09-06 DK DK02761594.7T patent/DK1441591T3/da active
- 2002-09-06 ES ES02761594.7T patent/ES2598109T3/es not_active Expired - Lifetime
- 2002-09-06 KR KR1020047003386A patent/KR20050027163A/ko not_active Application Discontinuation
- 2002-09-06 EP EP19202820.7A patent/EP3653055A1/en not_active Withdrawn
- 2002-09-06 MX MXPA04002147A patent/MXPA04002147A/es active IP Right Grant
- 2002-09-06 WO PCT/US2002/028620 patent/WO2003022215A2/en active Application Filing
- 2002-09-06 NZ NZ531530A patent/NZ531530A/en not_active IP Right Cessation
- 2002-09-06 PT PT101819852T patent/PT2322603T/pt unknown
- 2002-09-06 DK DK10181985.2T patent/DK2322603T3/da active
- 2002-09-06 CN CN201210470111.XA patent/CN102973928B/zh not_active Expired - Fee Related
- 2002-09-06 CN CN028198174A patent/CN1636229B/zh not_active Expired - Fee Related
-
2004
- 2004-03-03 IL IL160720A patent/IL160720A/en active IP Right Grant
- 2004-03-05 NO NO20040965A patent/NO338147B1/no not_active IP Right Cessation
-
2006
- 2006-01-04 HK HK06100064.5A patent/HK1079989A1/xx not_active IP Right Cessation
-
2008
- 2008-05-29 US US12/129,549 patent/US20080254064A1/en not_active Abandoned
- 2008-09-19 AU AU2008221592A patent/AU2008221592B2/en not_active Ceased
-
2011
- 2011-07-04 JP JP2011148711A patent/JP5777956B2/ja not_active Expired - Fee Related
-
2012
- 2012-04-18 IL IL219266A patent/IL219266A/en active IP Right Grant
-
2015
- 2015-03-02 JP JP2015040165A patent/JP6114768B2/ja not_active Expired - Fee Related
- 2015-11-16 NO NO20151562A patent/NO20151562A1/no not_active Application Discontinuation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DK1441591T3 (da) | Sammensætninger og fremgangsmåder til priming af monocytiske dendritiske celler og T-celler for TH-1-respons | |
CA2632263C (en) | Compositions and methods for inducing the activation of immature monocytic dendritic cells | |
JP4762887B2 (ja) | 付加的なサイトカインの非存在下でgm−csfを用いる単球樹状前駆細胞からの樹状細胞の産生 | |
JP2009518045A5 (da) | ||
AU2013201707B2 (en) | Compositions and methods for priming monocytic dendritic cells and T cells for Th-1 response | |
AU2002326846A1 (en) | Compositions and methods for priming monocytic dendritic cells and T cells for Th-1 response | |
AU2013206016B2 (en) | Compositions and methods for inducing the activation of immature monocytic dendritic cells |