FI85867B - Foerfarande foer framstaellning av ett preparat berikat med en lymfokin kallad leukoregulin. - Google Patents
Foerfarande foer framstaellning av ett preparat berikat med en lymfokin kallad leukoregulin. Download PDFInfo
- Publication number
- FI85867B FI85867B FI854803A FI854803A FI85867B FI 85867 B FI85867 B FI 85867B FI 854803 A FI854803 A FI 854803A FI 854803 A FI854803 A FI 854803A FI 85867 B FI85867 B FI 85867B
- Authority
- FI
- Finland
- Prior art keywords
- cells
- leukoregulin
- human
- lymphokine
- cell
- Prior art date
Links
- 108010002060 leukoregulin Proteins 0.000 title claims abstract description 194
- 210000004027 cell Anatomy 0.000 claims abstract description 200
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 62
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 30
- 230000012010 growth Effects 0.000 claims abstract description 18
- 238000001155 isoelectric focusing Methods 0.000 claims abstract description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 15
- 108091005804 Peptidases Proteins 0.000 claims abstract description 12
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 230000035479 physiological effects, processes and functions Effects 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims description 77
- 238000002360 preparation method Methods 0.000 claims description 30
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 102000035195 Peptidases Human genes 0.000 claims description 11
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 claims description 7
- 239000011780 sodium chloride Substances 0.000 claims description 7
- 238000002523 gelfiltration Methods 0.000 claims description 5
- 238000004255 ion exchange chromatography Methods 0.000 claims description 5
- 238000012258 culturing Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 108010047620 Phytohemagglutinins Proteins 0.000 claims description 3
- 238000001962 electrophoresis Methods 0.000 claims description 3
- 230000001885 phytohemagglutinin Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 239000001963 growth medium Substances 0.000 claims description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 230000032823 cell division Effects 0.000 claims 1
- 230000002934 lysing effect Effects 0.000 claims 1
- 235000019833 protease Nutrition 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 24
- 230000009089 cytolysis Effects 0.000 abstract description 12
- 230000001404 mediated effect Effects 0.000 abstract description 12
- 239000004365 Protease Substances 0.000 abstract description 11
- 230000035699 permeability Effects 0.000 abstract description 11
- 210000003719 b-lymphocyte Anatomy 0.000 abstract description 8
- 210000005259 peripheral blood Anatomy 0.000 abstract description 7
- 239000011886 peripheral blood Substances 0.000 abstract description 7
- 230000004663 cell proliferation Effects 0.000 abstract description 5
- 210000004408 hybridoma Anatomy 0.000 abstract description 5
- 210000000822 natural killer cell Anatomy 0.000 abstract description 5
- 210000001185 bone marrow Anatomy 0.000 abstract description 3
- 230000000711 cancerogenic effect Effects 0.000 abstract description 3
- 210000001519 tissue Anatomy 0.000 abstract description 3
- 210000002798 bone marrow cell Anatomy 0.000 abstract description 2
- 230000009466 transformation Effects 0.000 abstract description 2
- 229960005486 vaccine Drugs 0.000 abstract description 2
- 239000013598 vector Substances 0.000 abstract description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 abstract 1
- 102000005348 Neuraminidase Human genes 0.000 abstract 1
- 108010006232 Neuraminidase Proteins 0.000 abstract 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract 1
- 238000005571 anion exchange chromatography Methods 0.000 abstract 1
- 231100000315 carcinogenic Toxicity 0.000 abstract 1
- 238000010494 dissociation reaction Methods 0.000 abstract 1
- 230000005593 dissociations Effects 0.000 abstract 1
- 102000006240 membrane receptors Human genes 0.000 abstract 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 80
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 80
- 239000002609 medium Substances 0.000 description 41
- 238000002474 experimental method Methods 0.000 description 23
- 239000000523 sample Substances 0.000 description 23
- 210000000265 leukocyte Anatomy 0.000 description 22
- 102000014150 Interferons Human genes 0.000 description 21
- 108010050904 Interferons Proteins 0.000 description 21
- 229940079322 interferon Drugs 0.000 description 21
- 241000699800 Cricetinae Species 0.000 description 20
- 238000003556 assay Methods 0.000 description 19
- 239000012091 fetal bovine serum Substances 0.000 description 19
- 230000035945 sensitivity Effects 0.000 description 19
- 230000005764 inhibitory process Effects 0.000 description 15
- 230000003217 anti-cancerogenic effect Effects 0.000 description 14
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 229920001223 polyethylene glycol Polymers 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 102000008072 Lymphokines Human genes 0.000 description 12
- 108010074338 Lymphokines Proteins 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 12
- 230000001461 cytolytic effect Effects 0.000 description 12
- 210000004698 lymphocyte Anatomy 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 230000001085 cytostatic effect Effects 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- 239000012980 RPMI-1640 medium Substances 0.000 description 10
- 238000010367 cloning Methods 0.000 description 10
- 230000003013 cytotoxicity Effects 0.000 description 10
- 231100000135 cytotoxicity Toxicity 0.000 description 10
- 239000000499 gel Substances 0.000 description 10
- 210000002540 macrophage Anatomy 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 230000004565 tumor cell growth Effects 0.000 description 10
- 230000000875 corresponding effect Effects 0.000 description 9
- 239000002158 endotoxin Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 235000019419 proteases Nutrition 0.000 description 8
- 102000008070 Interferon-gamma Human genes 0.000 description 7
- 108010074328 Interferon-gamma Proteins 0.000 description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 description 7
- 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 7
- 230000004071 biological effect Effects 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 201000000050 myeloid neoplasm Diseases 0.000 description 7
- 238000001959 radiotherapy Methods 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 201000009030 Carcinoma Diseases 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- 102000006992 Interferon-alpha Human genes 0.000 description 6
- 108010047761 Interferon-alpha Proteins 0.000 description 6
- 102000015696 Interleukins Human genes 0.000 description 6
- 108010063738 Interleukins Proteins 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- 230000003213 activating effect Effects 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 229940047122 interleukins Drugs 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 5
- 241000699673 Mesocricetus auratus Species 0.000 description 5
- 108010059712 Pronase Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000007758 minimum essential medium Substances 0.000 description 5
- 230000005855 radiation Effects 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 229920001817 Agar Polymers 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 206010039491 Sarcoma Diseases 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 238000000149 argon plasma sintering Methods 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000000824 cytostatic agent Substances 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 239000012224 working solution Substances 0.000 description 4
- CHADEQDQBURGHL-UHFFFAOYSA-N (6'-acetyloxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 CHADEQDQBURGHL-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 241000283707 Capra Species 0.000 description 3
- 206010057248 Cell death Diseases 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000000593 degrading effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 229940044627 gamma-interferon Drugs 0.000 description 3
- 230000009422 growth inhibiting effect Effects 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000017095 negative regulation of cell growth Effects 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 238000001374 small-angle light scattering Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102100021022 Gastrin Human genes 0.000 description 2
- 108010052343 Gastrins Proteins 0.000 description 2
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241001460678 Napo <wasp> Species 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229960003896 aminopterin Drugs 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(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](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 210000002950 fibroblast Anatomy 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
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 210000003953 foreskin Anatomy 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 102000055277 human IL2 Human genes 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229950000038 interferon alfa Drugs 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 230000002101 lytic effect Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000017066 negative regulation of growth Effects 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012898 sample dilution Substances 0.000 description 2
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical class CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 2
- 210000001626 skin fibroblast Anatomy 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101000782236 Bothrops leucurus Thrombin-like enzyme leucurobin Proteins 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000651236 Homo sapiens NCK-interacting protein with SH3 domain Proteins 0.000 description 1
- 101000801481 Homo sapiens Tissue-type plasminogen activator Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- FSNCEEGOMTYXKY-JTQLQIEISA-N Lycoperodine 1 Natural products N1C2=CC=CC=C2C2=C1CN[C@H](C(=O)O)C2 FSNCEEGOMTYXKY-JTQLQIEISA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000013967 Monokines Human genes 0.000 description 1
- 108010050619 Monokines Proteins 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108010089814 Plant Lectins Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000473945 Theria <moth genus> Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 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 1
- 241000607626 Vibrio cholerae Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Substances [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- -1 argon ion Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000000211 autoradiogram Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 231100000147 cell transformation assay Toxicity 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 239000003145 cytotoxic factor Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 208000018554 digestive system carcinoma Diseases 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000010359 gene isolation Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 231100000001 growth retardation Toxicity 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 102000051179 human NCKIPSD Human genes 0.000 description 1
- 102000057041 human TNF Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000014726 immortalization of host cell Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 231100000405 induce cancer Toxicity 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940087875 leukine Drugs 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- ZBJWWKFMHOAPNS-UHFFFAOYSA-N loretin Chemical compound C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 ZBJWWKFMHOAPNS-UHFFFAOYSA-N 0.000 description 1
- 229950010248 loretin Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 230000031942 natural killer cell mediated cytotoxicity Effects 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000037311 normal skin Effects 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
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000005304 optical glass Substances 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- AXFBAIOSECPASO-UHFFFAOYSA-N pentacyclo[6.6.2.02,7.04,16.011,15]hexadeca-1(14),2(7),3,5,8(16),9,11(15),12-octaene Chemical compound C1=C(C=C23)C4=C5C3=CC=CC5=CC=C4C2=C1 AXFBAIOSECPASO-UHFFFAOYSA-N 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000003726 plant lectin Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 108010038379 sargramostim Proteins 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 208000005925 vesicular stomatitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (3)
1. Förfarande för framställning av ett preparat berikat med en lymfokin kallad leukoregulin, vilket pro-5 tein har följande egenskaper: (i) förmäga att reglera en malign tumörs fysiologi och tillväxt utan att pävarka tillväxten hos normala celler; (ii) förmäga att direkt lysera humana HT-29 och
10 RPMI 2650 tumörceller; (iii) oförmäga att lysera musceller aL 929; (iv) förm&ga att dämpa celldelningen hos de humana tumörcellerna K 526 och RPMI 2650; (v) varvid aktiviteterna enligt punkterna (i) 15 - (iv) är känsliga för behandling av proteinet med pro- teinas - men inte med neuramidas; (vi) en molekylvikt p& 120 000 - 140 000 Dalton; (vii) en isoelektrisk punkt inom omrädet 4,8 - 5,5 och/eller inom omrädet 7,5 - 8,3; 20 (viii) eluerbar med jonbytarkromatografi mellan 0,07 och 0,12 mol/1 NaCl; kännetecknat därav, att man a) odlar lymfokinproducerande celler; b) frigör den lymfokininnehällande proteinfrak-25 tionen frän de lymfokinproducerande cellerna; c) separerar proteinerna i proteinfraktionen enligt molekylstorlek och/eller molekylladdning; och d) efter varje selektionssteg enligt punkt c) väljer ut den proteinfraktion som har nämnda egenskaper. 30 2. Förfarande enligt patentkravet 1, känne tecknat därav, att punkt c) omfattar ätminstone ett av följande separationsätgärder: (aa) HPLC (bb) jonbytarkromatografi 35 (cc) elektrofores i: 59 85867 (dd) gelfiltrering (ee) isoelektrisk fokusering.
3. Förfarande enligt patentkravet 1 eller 2, kännetecknat därav, att den lymfokininnehäl-5 lande proteinfraktionen är koncentrerat odlingsmedium frän en odling av humana perifera mononukleära blodceller som behandlats med fytohemagglutinin för att stimulera produk-tionen av leukoregulin.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60030384A | 1984-04-13 | 1984-04-13 | |
| US60030384 | 1984-04-13 | ||
| US8500626 | 1985-04-11 | ||
| PCT/US1985/000626 WO1985004662A1 (en) | 1984-04-13 | 1985-04-11 | Leukoregulin, an antitumor lymphokine, and its therapeutic uses |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI854803A FI854803A (fi) | 1985-12-04 |
| FI854803A0 FI854803A0 (fi) | 1985-12-04 |
| FI85867B true FI85867B (fi) | 1992-02-28 |
| FI85867C FI85867C (sv) | 1992-06-10 |
Family
ID=24403068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI854803A FI85867C (sv) | 1984-04-13 | 1985-12-04 | Förfarande för framställning av ett preparat berikat med en lymfokin k allad leukoregulin |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0179127B1 (sv) |
| JP (2) | JP2562014B2 (sv) |
| AT (1) | ATE48617T1 (sv) |
| AU (2) | AU592529B2 (sv) |
| DE (1) | DE3574710D1 (sv) |
| DK (2) | DK170781B1 (sv) |
| FI (1) | FI85867C (sv) |
| NO (1) | NO170423C (sv) |
| WO (1) | WO1985004662A1 (sv) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3574710D1 (de) * | 1984-04-13 | 1990-01-18 | Litton Bionetics Inc | Leukoregulin, ein antitumor-lymphokin und dessen verwendung als heilmittel. |
| US5683688A (en) * | 1984-05-31 | 1997-11-04 | Genentech, Inc. | Unglycosylated recombinant human lymphotoxin polypeptides and compositions |
| US6087166A (en) | 1997-07-03 | 2000-07-11 | Basf Aktiengesellschaft | Transcriptional activators with graded transactivation potential |
| JP2009537139A (ja) | 2006-05-15 | 2009-10-29 | パラテック ファーマシューティカルズ インコーポレイテッド | 置換されたテトラサイクリン化合物を用いて、遺伝子または遺伝子産物の発現を制御する方法 |
| WO2012156535A1 (en) | 2011-05-19 | 2012-11-22 | Fundación Progreso Y Salud | Highly inducible dual-promoter lentiviral tet-on system |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4394448A (en) * | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4403035A (en) * | 1981-06-19 | 1983-09-06 | Regents Of The University Of Minnesota | In vitro DNA-Protein viral assembly and gene cloning system |
| DE3138230A1 (de) * | 1981-09-25 | 1983-04-07 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | Verfahren zur gewinnung von makrophagen- aktivierungsfaktor (maf) |
| JPS6011889B2 (ja) * | 1981-10-28 | 1985-03-28 | 電気化学工業株式会社 | 継代可能なリンホカイン産生ヒトｔ細胞融合株及びその取得方法 |
| US4464465A (en) * | 1982-04-05 | 1984-08-07 | Genetic Systems Corporation | Cell-driven viral transfer in eukaryotes |
| US4443427A (en) * | 1982-06-21 | 1984-04-17 | Sidney Farber Cancer Institute, Inc. | Monoclonal antibody |
| ZA834976B (en) * | 1982-07-30 | 1984-08-29 | Genentech Inc | Human lymphotoxin |
| EP0135797A3 (de) * | 1983-08-30 | 1987-11-11 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Verfahren zur Herstellung von Lymphotoxin und von Lymphotoxin-mRNA |
| DE3574710D1 (de) * | 1984-04-13 | 1990-01-18 | Litton Bionetics Inc | Leukoregulin, ein antitumor-lymphokin und dessen verwendung als heilmittel. |
-
1985
- 1985-04-11 DE DE8585902248T patent/DE3574710D1/de not_active Expired - Fee Related
- 1985-04-11 EP EP85902248A patent/EP0179127B1/en not_active Expired
- 1985-04-11 AT AT85902248T patent/ATE48617T1/de not_active IP Right Cessation
- 1985-04-11 AU AU42341/85A patent/AU592529B2/en not_active Ceased
- 1985-04-11 WO PCT/US1985/000626 patent/WO1985004662A1/en active IP Right Grant
- 1985-04-11 JP JP60501862A patent/JP2562014B2/ja not_active Expired - Lifetime
- 1985-12-04 FI FI854803A patent/FI85867C/sv not_active IP Right Cessation
- 1985-12-04 DK DK562285A patent/DK170781B1/da active
- 1985-12-12 NO NO85854994A patent/NO170423C/no unknown
-
1990
- 1990-04-18 AU AU53653/90A patent/AU641386B2/en not_active Ceased
-
1992
- 1992-08-04 DK DK098692A patent/DK170423B1/da not_active IP Right Cessation
-
1993
- 1993-11-30 JP JP5300409A patent/JP2564245B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DK98692D0 (da) | 1992-08-04 |
| JPS61501853A (ja) | 1986-08-28 |
| DK562285D0 (da) | 1985-12-04 |
| EP0179127A1 (en) | 1986-04-30 |
| JPH06253832A (ja) | 1994-09-13 |
| DK98692A (da) | 1992-08-04 |
| FI85867C (sv) | 1992-06-10 |
| DK170781B1 (da) | 1996-01-15 |
| NO170423C (no) | 1992-10-14 |
| DK562285A (da) | 1985-12-04 |
| AU641386B2 (en) | 1993-09-23 |
| AU4234185A (en) | 1985-11-01 |
| NO854994L (no) | 1985-12-12 |
| WO1985004662A1 (en) | 1985-10-24 |
| AU5365390A (en) | 1990-09-20 |
| AU592529B2 (en) | 1990-01-18 |
| DE3574710D1 (de) | 1990-01-18 |
| DK170423B1 (da) | 1995-08-28 |
| JP2562014B2 (ja) | 1996-12-11 |
| FI854803A (fi) | 1985-12-04 |
| NO170423B (no) | 1992-07-06 |
| FI854803A0 (fi) | 1985-12-04 |
| EP0179127A4 (en) | 1986-08-21 |
| JP2564245B2 (ja) | 1996-12-18 |
| EP0179127B1 (en) | 1989-12-13 |
| ATE48617T1 (de) | 1989-12-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Fu et al. | Induction of in vitro differentiation and immunoglobulin synthesis of human leukemic B lymphocytes. | |
| Perussia et al. | Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells. | |
| JPH06501456A (ja) | 表面複合リンホトキシン | |
| US20040247594A1 (en) | Use of cd28-specific monoclonal antibodies for stimulating blood cells that lack cd28 | |
| WO2022222846A1 (zh) | 靶向cd19的嵌合抗原受体、制备方法及其应用 | |
| Nelson et al. | Effects of CKS-17, a synthetic retroviral envelope peptide, on cell-mediated immunity in vivo: immunosuppression, immunogenicity, and relation to immunosuppressive tumor products | |
| US6265214B1 (en) | Methods and compositions for inducing monocyte cytotoxicity | |
| FI85867B (fi) | Foerfarande foer framstaellning av ett preparat berikat med en lymfokin kallad leukoregulin. | |
| Burakoff et al. | Induction of secondary cytotoxic T lymphocytes by liposomes containing HLA-DR antigens | |
| Zhou et al. | Effect of tumor necrosis factor-alpha on the proliferation of leukemic cells from children with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL): studies of primary leukemic cells and BCP-ALL cell lines | |
| US5082657A (en) | Leukoregulin, an antitumor lymphokine, and its therapeutic uses | |
| US4849506A (en) | Leukoregulin, an antitumor lymphokine, and its therapeutic uses | |
| Cerny et al. | Specific susceptibility of sensitized (memory) B cells to suppression and antigenic alteration by murine leukemia virus | |
| Österborg et al. | Monoclonal and biclonal immunoglobulin‐producing disorders | |
| US4977245A (en) | Methods and compositions for inducing monocyte cytotoxicity | |
| Bystryn et al. | Double-antibody radioimmunoassay for B16 melanoma antibodies | |
| Hu et al. | Interleukin 2 up-regulates its own production. | |
| Suyama et al. | Effects of murine tumor necrosis factor on friend erythroleukemic cells | |
| JPH01126558A (ja) | 抗体依存性細胞性細胞毒性の測定方法 | |
| Kikuchi et al. | Effects of tumor necrosis factor α, interferon α and interferon γ on non-lymphoid leukemia cell lines: Growth inhibition, differentiation induction and drug sensitivity modulation | |
| EP4427761A1 (en) | Vaccine against pancreatic cancer, and medical use thereof | |
| Inglot et al. | Tumor-associated antigens are cytokine inducers and hyporeactivity factors to the immune system | |
| KR950008569B1 (ko) | 신규 림포카인(lymphokine) 및 그 제조방법과 사용방법 | |
| Bell et al. | Neutralising antibodies in patients with multiple myeloma receiving maintenance therapy with interferon α2b | |
| Jones et al. | Characterization of a human monocyte cytotoxicity-inducing factor (MCF) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: AKZO N.V. |