DK2534242T3 - Forbedret sammensætning til inhibition af tumorcelleproliferation - Google Patents
Forbedret sammensætning til inhibition af tumorcelleproliferation Download PDFInfo
- Publication number
- DK2534242T3 DK2534242T3 DK11702471.1T DK11702471T DK2534242T3 DK 2534242 T3 DK2534242 T3 DK 2534242T3 DK 11702471 T DK11702471 T DK 11702471T DK 2534242 T3 DK2534242 T3 DK 2534242T3
- Authority
- DK
- Denmark
- Prior art keywords
- cells
- tumor
- mature
- dcs
- cancer
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title description 30
- 210000004881 tumor cell Anatomy 0.000 title description 16
- 230000001976 improved effect Effects 0.000 title description 3
- 230000004663 cell proliferation Effects 0.000 title description 2
- 230000005764 inhibitory process Effects 0.000 title 1
- 210000004443 dendritic cell Anatomy 0.000 claims description 241
- 206010028980 Neoplasm Diseases 0.000 claims description 134
- 230000000770 proinflammatory effect Effects 0.000 claims description 110
- 210000004027 cell Anatomy 0.000 claims description 49
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 46
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 claims description 29
- 238000002347 injection Methods 0.000 claims description 27
- 239000007924 injection Substances 0.000 claims description 27
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 26
- 108010074328 Interferon-gamma Proteins 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 22
- 102000013462 Interleukin-12 Human genes 0.000 claims description 21
- 108010065805 Interleukin-12 Proteins 0.000 claims description 21
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 20
- 230000002601 intratumoral effect Effects 0.000 claims description 20
- 102100037850 Interferon gamma Human genes 0.000 claims description 19
- 230000000638 stimulation Effects 0.000 claims description 18
- 102000003777 Interleukin-1 beta Human genes 0.000 claims description 16
- 108090000193 Interleukin-1 beta Proteins 0.000 claims description 16
- 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 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 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 claims description 6
- 102000008070 Interferon-gamma Human genes 0.000 claims description 4
- 229960003130 interferon gamma Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 159000000000 sodium salts Chemical class 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 102000006992 Interferon-alpha Human genes 0.000 claims description 3
- 108010047761 Interferon-alpha Proteins 0.000 claims description 3
- 102000000589 Interleukin-1 Human genes 0.000 claims description 3
- 108010002352 Interleukin-1 Proteins 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 230000035800 maturation Effects 0.000 description 41
- 210000000822 natural killer cell Anatomy 0.000 description 34
- 238000004519 manufacturing process Methods 0.000 description 32
- 210000001744 T-lymphocyte Anatomy 0.000 description 28
- 102000036639 antigens Human genes 0.000 description 26
- 108091007433 antigens Proteins 0.000 description 26
- 239000000427 antigen Substances 0.000 description 25
- 241001465754 Metazoa Species 0.000 description 23
- 230000000735 allogeneic effect Effects 0.000 description 20
- 102000002689 Toll-like receptor Human genes 0.000 description 19
- 108020000411 Toll-like receptor Proteins 0.000 description 19
- 239000006228 supernatant Substances 0.000 description 19
- 229940117681 interleukin-12 Drugs 0.000 description 17
- 238000000034 method Methods 0.000 description 17
- 230000001617 migratory effect Effects 0.000 description 17
- 210000001616 monocyte Anatomy 0.000 description 16
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 15
- 108010014231 Chemokine CXCL9 Proteins 0.000 description 15
- 238000003501 co-culture Methods 0.000 description 15
- 102000019034 Chemokines Human genes 0.000 description 14
- 108010012236 Chemokines Proteins 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- 239000003446 ligand Substances 0.000 description 13
- 102000004127 Cytokines Human genes 0.000 description 12
- 108090000695 Cytokines Proteins 0.000 description 12
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 230000003213 activating effect Effects 0.000 description 11
- 210000002540 macrophage Anatomy 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 102000004388 Interleukin-4 Human genes 0.000 description 10
- 108090000978 Interleukin-4 Proteins 0.000 description 10
- 239000002671 adjuvant Substances 0.000 description 10
- 230000007115 recruitment Effects 0.000 description 10
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 9
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 9
- 108010055166 Chemokine CCL5 Proteins 0.000 description 8
- 230000000981 bystander Effects 0.000 description 8
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 7
- 101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 229950010550 resiquimod Drugs 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 231100000617 superantigen Toxicity 0.000 description 6
- 230000002459 sustained effect Effects 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 4
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 4
- 102100025136 Macrosialin Human genes 0.000 description 4
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 4
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 4
- 230000001464 adherent effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000009977 dual effect Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000003071 memory t lymphocyte Anatomy 0.000 description 4
- 208000011581 secondary neoplasm Diseases 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108010029697 CD40 Ligand Proteins 0.000 description 3
- 102100032937 CD40 ligand Human genes 0.000 description 3
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 3
- 102000008230 Toll-like receptor 3 Human genes 0.000 description 3
- 108010060885 Toll-like receptor 3 Proteins 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 238000002619 cancer immunotherapy Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 238000007489 histopathology method Methods 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000019734 interleukin-12 production Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000037452 priming Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 102100031092 C-C motif chemokine 3 Human genes 0.000 description 2
- 101710155856 C-C motif chemokine 3 Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 2
- 206010015548 Euthanasia Diseases 0.000 description 2
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 230000006043 T cell recruitment Effects 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 101710101607 Toxic shock syndrome toxin-1 Proteins 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960002986 dinoprostone Drugs 0.000 description 2
- 231100000655 enterotoxin Toxicity 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000009434 installation Methods 0.000 description 2
- 201000002313 intestinal cancer Diseases 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000005212 secondary lymphoid organ Anatomy 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 101150004010 CXCR3 gene Proteins 0.000 description 1
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 1
- 101100454808 Caenorhabditis elegans lgg-2 gene Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 230000006051 NK cell activation Effects 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 230000006044 T cell activation Effects 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
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 1
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010044250 Toxic shock syndrome staphylococcal Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 102000046157 human CSF2 Human genes 0.000 description 1
- 102000055229 human IL4 Human genes 0.000 description 1
- 230000037417 hyperactivation Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035802 rapid maturation Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- CBHOWTTXCQAOID-UHFFFAOYSA-L sodium ethane formaldehyde mercury(2+) molecular iodine 2-sulfidobenzoate Chemical class [Na+].[Hg++].C[CH2-].II.C=O.[O-]C(=O)c1ccccc1[S-] CBHOWTTXCQAOID-UHFFFAOYSA-L 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 208000017756 staphylococcal toxic-shock syndrome Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 230000024664 tolerance induction Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4648—Bacterial antigens
- A61K39/464821—Staphylococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by the route of administration
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Cell Biology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Developmental Biology & Embryology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Claims (8)
1. Proinflammatorisk dendritisk celle (DC), som et blevet stimuleret til modning ex vivo ved behandling med stofferne polyinosin-polycytidylsyre-natriumsalt (poly-I:C), resiquimod (R848) og interferon gamma (IFN-γ), men ikke med prostaglandin E2 (PGE2), til anvendelse i behandling af cancer i et individ andet end kilden til den proinflammatoriske modne DC, hvor anvendelsen er intratumoral indsprøjtning.
2. Den proinflammatoriske modne DC til anvendelse ifølge krav 1, hvilken derudover er blevet stimuleret med mindst et af stofferne valgt fra gruppen bestående af interferon α (IFN-α), interleukin 1, beta (IL-1 β) og tumornekrosefaktor α (TNF-α).
3. Den proinflammatoriske modne DC til anvendelse ifølge kravene 1 eller 2, som producerer mindst 25 000 pg IL-12/ml_/106 celler, mindst 100 000 pg CXCL9/ml_/106 celler, og mindst 40 000 pg CCL3/ml_/106 celler i løbet af 24 timer efter tilbagetrækning af stimuli.
4. Den proinflammatoriske modne DC til anvendelse ifølge et hvilket som helst af kravene 1 til 3, som yderligere producerer mindst 2 000 pg TNF-a/mL/106 celler og mindst 500 pg IL-1 β/mL/lO6 celler i løbet af 24 timer efter tilbagetrækning af stimuli.
5. Den proinflammatoriske modne DC til anvendelse ifølge et hvilket som helst af kravene 1 til 4, hvor canceren er valgt fra gruppen bestående af: brystkræft, prostatakræft, nyrekræft, tarmkræft, ondartede gliomer, osteosarkom, ondartet melanom, kræft i bugspytkirtel, ondartede lymfomer og s pise rørs kræft.
6. Farmaceutisk sammensætning omfattende modne proinflammatoriske dendritiske celler ifølge et hvilket som helst af kravene 1 til 5 og farmaceutisk acceptable excipiens(er), til anvendelse i behandling af cancer i et individ forskelligt fra kilden til den proinflammatoriske modne DC, hvor anvendelsen er intratumoral indsprøjtning.
7. Den farmaceutiske sammensætning til anvendelse ifølge krav 6, yderligere omfattende perifert blod mononukleære celler.
8. Den farmaceutiske sammensætning til anvendelse ifølge krav 7, hvor de perifert blod mononukleære celler er opnået fra en person forskellig fra patienten.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30315310P | 2010-02-10 | 2010-02-10 | |
SE1050133 | 2010-02-10 | ||
PCT/EP2011/051952 WO2011098516A1 (en) | 2010-02-10 | 2011-02-10 | Improved composition for inhibiting tumor cell proliferation |
Publications (1)
Publication Number | Publication Date |
---|---|
DK2534242T3 true DK2534242T3 (da) | 2016-07-18 |
Family
ID=43903832
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DK11702471.1T DK2534242T3 (da) | 2010-02-10 | 2011-02-10 | Forbedret sammensætning til inhibition af tumorcelleproliferation |
Country Status (13)
Country | Link |
---|---|
US (1) | US9034317B2 (da) |
EP (1) | EP2534242B1 (da) |
JP (1) | JP5855018B2 (da) |
KR (1) | KR101770785B1 (da) |
CN (1) | CN102782123B (da) |
BR (1) | BR112012019267B1 (da) |
DK (1) | DK2534242T3 (da) |
ES (1) | ES2581277T3 (da) |
HU (1) | HUE028352T2 (da) |
PL (1) | PL2534242T3 (da) |
RU (1) | RU2565542C2 (da) |
SI (1) | SI2534242T1 (da) |
WO (1) | WO2011098516A1 (da) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK2788474T3 (da) * | 2012-12-18 | 2015-09-28 | Immunicum Ab | Co-differentiering af monocytter fra allogen donorer |
AU2016259020B2 (en) * | 2015-05-07 | 2021-12-09 | Baylor College Of Medicine | Dendritic cell immunotherapy |
CN105695403A (zh) * | 2015-12-31 | 2016-06-22 | 深圳市中美康士生物科技有限公司 | 一种杀伤性免疫细胞的培养方法及其应用 |
CN105462926A (zh) * | 2015-12-31 | 2016-04-06 | 深圳市中美康士生物科技有限公司 | 一种免疫细胞瘤苗的制备方法及其应用 |
CN107574149B (zh) * | 2016-07-05 | 2022-02-18 | 上海细胞治疗研究院 | 一种树突状细胞的促成熟方法及其用途 |
CN106085960A (zh) * | 2016-07-28 | 2016-11-09 | 广州赛莱拉干细胞科技股份有限公司 | 一种培养dc细胞的培养基及培养方法 |
EP3516045A1 (en) | 2016-09-23 | 2019-07-31 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Methods of preparing an isolated population of dendritic cells and methods of treating cancer using same |
GB201711379D0 (en) * | 2017-07-14 | 2017-08-30 | Univ Cape Town | Maturation of dendritic cells |
ES2769128T3 (es) * | 2017-09-20 | 2020-06-24 | Immunicum Ab | Células dendríticas alogénicas mejoradas para uso en el tratamiento de cáncer |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040214783A1 (en) * | 2002-05-08 | 2004-10-28 | Terman David S. | Compositions and methods for treatment of neoplastic disease |
PT1567155E (pt) * | 2002-12-06 | 2011-01-28 | Northwest Biotherapeutics Inc | Administração de células dendríticas parcialmente amadurecidas in vitro para o tratamento de tumores |
EP1840206A1 (en) * | 2006-03-28 | 2007-10-03 | Gsf-Forschungszentrum Für Umwelt Und Gesundheit, Gmbh | Compositions for the preparation of mature dendritic cells |
WO2008110569A1 (en) * | 2007-03-12 | 2008-09-18 | Bioneer A/S | Method for determination of immunomodulatory effect |
KR101655487B1 (ko) | 2007-10-08 | 2016-09-08 | 인트렉손 코포레이션 | 가공된 수지상 세포 및 암의 치료를 위한 이의 용도 |
WO2010065876A2 (en) * | 2008-12-06 | 2010-06-10 | The Board Of Regents Of The University Of Texas System | Methods and compositions related to th-1 dendritic cells |
CN101481677B (zh) * | 2009-01-22 | 2011-12-14 | 复旦大学附属华山医院 | 体外刺激树突状细胞成熟的方法 |
-
2011
- 2011-02-10 EP EP11702471.1A patent/EP2534242B1/en active Active
- 2011-02-10 JP JP2012552394A patent/JP5855018B2/ja not_active Expired - Fee Related
- 2011-02-10 PL PL11702471.1T patent/PL2534242T3/pl unknown
- 2011-02-10 CN CN201180008012.3A patent/CN102782123B/zh not_active Expired - Fee Related
- 2011-02-10 DK DK11702471.1T patent/DK2534242T3/da active
- 2011-02-10 HU HUE11702471A patent/HUE028352T2/en unknown
- 2011-02-10 US US13/522,741 patent/US9034317B2/en active Active
- 2011-02-10 RU RU2012137173/10A patent/RU2565542C2/ru active
- 2011-02-10 ES ES11702471.1T patent/ES2581277T3/es active Active
- 2011-02-10 SI SI201130868A patent/SI2534242T1/sl unknown
- 2011-02-10 WO PCT/EP2011/051952 patent/WO2011098516A1/en active Application Filing
- 2011-02-10 KR KR1020127021390A patent/KR101770785B1/ko active IP Right Grant
- 2011-02-10 BR BR112012019267-1A patent/BR112012019267B1/pt active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
EP2534242B1 (en) | 2016-04-20 |
BR112012019267A2 (pt) | 2020-10-06 |
US20120328662A1 (en) | 2012-12-27 |
PL2534242T3 (pl) | 2016-11-30 |
KR101770785B1 (ko) | 2017-08-23 |
RU2012137173A (ru) | 2014-03-20 |
RU2565542C2 (ru) | 2015-10-20 |
CN102782123A (zh) | 2012-11-14 |
JP5855018B2 (ja) | 2016-02-09 |
EP2534242A1 (en) | 2012-12-19 |
CN102782123B (zh) | 2016-05-11 |
WO2011098516A1 (en) | 2011-08-18 |
BR112012019267B1 (pt) | 2022-03-03 |
ES2581277T3 (es) | 2016-09-05 |
HUE028352T2 (en) | 2016-12-28 |
SI2534242T1 (sl) | 2016-08-31 |
KR20120114358A (ko) | 2012-10-16 |
US9034317B2 (en) | 2015-05-19 |
JP2013519363A (ja) | 2013-05-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DK2534242T3 (da) | Forbedret sammensætning til inhibition af tumorcelleproliferation | |
Xu et al. | Nanovaccine based on a protein-delivering dendrimer for effective antigen cross-presentation and cancer immunotherapy | |
Liau et al. | Treatment of intracranial gliomas with bone marrow—derived dendritic cells pulsed with tumor antigens | |
KR20120093978A (ko) | 항원 특이적 t 세포의 증식 방법 | |
EP3460052B1 (en) | Improved allogeneic dendritic cells for use in cancer treatment | |
KR20140043340A (ko) | T 세포의 프라이밍을 위한 방법 | |
AU2008265911A1 (en) | Use of TLR agonists and/or type 1 interferons to alleviate toxicity of TNF-R agonist therapeutic regimens | |
WO2018137643A1 (zh) | 溶瘤病毒作为用于治疗肿瘤和/或癌症的免疫刺激剂的应用 | |
JP2018535191A (ja) | 樹状細胞を産生するための組成物及び方法 | |
Shi et al. | Sequential administration of GM-CSF and IL-2 surface-modified MB49 cells vaccines against the metastatic bladder cancer | |
O'Neill et al. | Immunotherapeutic potential of dendritic cells generated in long term stroma-dependent cultures | |
ES2927913B2 (es) | Composición que comprende una combinación de las furanocumarinas psoraleno y angelicina y su uso en terapia | |
JP7146732B2 (ja) | 宿主抗原提示並びに宿主抗腫瘍及び抗病原体免疫を最適化するためのプラットフォーム及び方法 | |
US10716810B2 (en) | Canine autologous immunotherapy using dendritic cell induced cancer killing immunocytes | |
WO2016135286A1 (en) | Method for stimulating dendritic cells (dcs) | |
Ishii et al. | Application of NKT Cells in Immunotherapy | |
WO2013040027A1 (en) | Reprogramming immune environment in breast cancer via dendritic cells | |
AU2008280436A1 (en) | Compositions and methods for generating an immune response in a subject |