JP6235085B2 - 高静水圧によって死滅させた腫瘍細胞および樹状細胞を用いた活性細胞癌免疫療法のための手段および方法 - Google Patents
高静水圧によって死滅させた腫瘍細胞および樹状細胞を用いた活性細胞癌免疫療法のための手段および方法 Download PDFInfo
- Publication number
- JP6235085B2 JP6235085B2 JP2016153454A JP2016153454A JP6235085B2 JP 6235085 B2 JP6235085 B2 JP 6235085B2 JP 2016153454 A JP2016153454 A JP 2016153454A JP 2016153454 A JP2016153454 A JP 2016153454A JP 6235085 B2 JP6235085 B2 JP 6235085B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- tumor
- tumor cells
- induced
- dendritic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 210000004881 tumor cell Anatomy 0.000 title claims description 201
- 210000004443 dendritic cell Anatomy 0.000 title claims description 177
- 210000004027 cell Anatomy 0.000 title claims description 102
- 238000009931 pascalization Methods 0.000 title claims description 70
- 238000000034 method Methods 0.000 title claims description 33
- 238000009169 immunotherapy Methods 0.000 title claims description 12
- 201000009030 Carcinoma Diseases 0.000 title 1
- 206010028980 Neoplasm Diseases 0.000 claims description 86
- 238000011282 treatment Methods 0.000 claims description 52
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 34
- 206010060862 Prostate cancer Diseases 0.000 claims description 33
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- 230000030833 cell death Effects 0.000 claims description 24
- 201000011510 cancer Diseases 0.000 claims description 21
- 210000003289 regulatory T cell Anatomy 0.000 claims description 19
- 230000028993 immune response Effects 0.000 claims description 18
- 230000006698 induction Effects 0.000 claims description 14
- 210000000265 leukocyte Anatomy 0.000 claims description 13
- 108090000549 Calreticulin Proteins 0.000 claims description 11
- 206010033128 Ovarian cancer Diseases 0.000 claims description 11
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 11
- 210000001616 monocyte Anatomy 0.000 claims description 11
- 239000003550 marker Substances 0.000 claims description 8
- 206010057249 Phagocytosis Diseases 0.000 claims description 7
- 230000008782 phagocytosis Effects 0.000 claims description 7
- 101100016370 Danio rerio hsp90a.1 gene Proteins 0.000 claims description 6
- 101100285708 Dictyostelium discoideum hspD gene Proteins 0.000 claims description 6
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 claims description 6
- 101150031823 HSP70 gene Proteins 0.000 claims description 6
- 101100071627 Schizosaccharomyces pombe (strain 972 / ATCC 24843) swo1 gene Proteins 0.000 claims description 6
- 239000000427 antigen Substances 0.000 claims description 6
- 102000036639 antigens Human genes 0.000 claims description 6
- 108091007433 antigens Proteins 0.000 claims description 6
- 101150052825 dnaK gene Proteins 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000002706 hydrostatic effect Effects 0.000 claims description 5
- 230000001939 inductive effect Effects 0.000 claims description 5
- 208000010658 metastatic prostate carcinoma Diseases 0.000 claims description 5
- 239000005556 hormone Substances 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 3
- 210000002865 immune cell Anatomy 0.000 claims 2
- 101100339431 Arabidopsis thaliana HMGB2 gene Proteins 0.000 claims 1
- 102100029968 Calreticulin Human genes 0.000 claims 1
- 108700010013 HMGB1 Proteins 0.000 claims 1
- 101150021904 HMGB1 gene Proteins 0.000 claims 1
- 102100037907 High mobility group protein B1 Human genes 0.000 claims 1
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 28
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 28
- 230000004083 survival effect Effects 0.000 description 21
- 230000006907 apoptotic process Effects 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 16
- 238000002255 vaccination Methods 0.000 description 16
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 14
- 239000002953 phosphate buffered saline Substances 0.000 description 14
- 238000002619 cancer immunotherapy Methods 0.000 description 13
- 239000002158 endotoxin Substances 0.000 description 13
- 229920006008 lipopolysaccharide Polymers 0.000 description 13
- 230000035800 maturation Effects 0.000 description 13
- 230000002163 immunogen Effects 0.000 description 12
- 230000037449 immunogenic cell death Effects 0.000 description 12
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 12
- 238000002512 chemotherapy Methods 0.000 description 11
- 102000004082 Calreticulin Human genes 0.000 description 10
- 230000001640 apoptogenic effect Effects 0.000 description 10
- 210000000612 antigen-presenting cell Anatomy 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 230000017074 necrotic cell death Effects 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 229960005486 vaccine Drugs 0.000 description 8
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 7
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 7
- 206010028851 Necrosis Diseases 0.000 description 7
- 229940045799 anthracyclines and related substance Drugs 0.000 description 7
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 6
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 6
- 102100037850 Interferon gamma Human genes 0.000 description 6
- 108010074328 Interferon-gamma Proteins 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 6
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000001959 radiotherapy Methods 0.000 description 6
- 102000004388 Interleukin-4 Human genes 0.000 description 5
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 229960003668 docetaxel Drugs 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 244000052769 pathogen Species 0.000 description 5
- 230000001717 pathogenic effect Effects 0.000 description 5
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 4
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 4
- 108010050904 Interferons Proteins 0.000 description 4
- 102000014150 Interferons Human genes 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000005975 antitumor immune response Effects 0.000 description 4
- 238000009566 cancer vaccine Methods 0.000 description 4
- 229940022399 cancer vaccine Drugs 0.000 description 4
- 230000000139 costimulatory effect Effects 0.000 description 4
- 238000005138 cryopreservation Methods 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000037455 tumor specific immune response Effects 0.000 description 4
- 102000004121 Annexin A5 Human genes 0.000 description 3
- 108090000672 Annexin A5 Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102000006354 HLA-DR Antigens Human genes 0.000 description 3
- 108010058597 HLA-DR Antigens Proteins 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000000432 density-gradient centrifugation Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 229940028885 interleukin-4 Drugs 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 230000000242 pagocytic effect Effects 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 238000011471 prostatectomy Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 102100035793 CD83 antigen Human genes 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 2
- 102000008228 Toll-like receptor 2 Human genes 0.000 description 2
- 108010060888 Toll-like receptor 2 Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 238000011342 chemoimmunotherapy Methods 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012894 fetal calf serum Substances 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
- 238000003306 harvesting Methods 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 231100000619 immunotoxicology Toxicity 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 102000007863 pattern recognition receptors Human genes 0.000 description 2
- 108010089193 pattern recognition receptors Proteins 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 101710116895 DNA-binding protein H-NS Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 101710113864 Heat shock protein 90 Proteins 0.000 description 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 1
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
- 108010009489 Lysosomal-Associated Membrane Protein 3 Proteins 0.000 description 1
- 102100038213 Lysosome-associated membrane glycoprotein 3 Human genes 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000035992 Postmortem Changes Diseases 0.000 description 1
- 101710132617 Protein B1 Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101710170630 Ribonucleoside-diphosphate reductase 1 subunit alpha Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000037453 T cell priming Effects 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000009643 clonogenic assay Methods 0.000 description 1
- 231100000096 clonogenic assay Toxicity 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000001159 endocytotic effect Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000036252 glycation Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 208000018821 hormone-resistant prostate carcinoma Diseases 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000005061 intracellular organelle Anatomy 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 230000004987 nonapoptotic effect Effects 0.000 description 1
- 239000011824 nuclear material Substances 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- 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
- A61K2039/5152—Tumor 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
- A61K2039/51—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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Medicinal Chemistry (AREA)
- Mycology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161504387P | 2011-07-05 | 2011-07-05 | |
| US61/504,387 | 2011-07-05 | ||
| EP11172622.0 | 2011-07-05 | ||
| EP11172622A EP2543386A1 (en) | 2011-07-05 | 2011-07-05 | Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014517778A Division JP5986196B2 (ja) | 2011-07-05 | 2012-07-04 | 高静水圧によって死滅させた腫瘍細胞および樹状細胞を用いた活性細胞癌免疫療法のための手段および方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017025066A JP2017025066A (ja) | 2017-02-02 |
| JP6235085B2 true JP6235085B2 (ja) | 2017-11-22 |
Family
ID=50023029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016153454A Active JP6235085B2 (ja) | 2011-07-05 | 2016-08-04 | 高静水圧によって死滅させた腫瘍細胞および樹状細胞を用いた活性細胞癌免疫療法のための手段および方法 |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JP6235085B2 (hr) |
| CL (1) | CL2013003282A1 (hr) |
| CY (1) | CY1115803T1 (hr) |
| HR (1) | HRP20141230T1 (hr) |
| IL (2) | IL229702A (hr) |
| MX (1) | MX2013013243A (hr) |
| ZA (1) | ZA201307886B (hr) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10526573B2 (en) | 2014-11-14 | 2020-01-07 | Massachusetts Institute Of Technology | Disruption and field enabled delivery of compounds and compositions into cells |
| US10696944B2 (en) | 2011-10-17 | 2020-06-30 | Massachusetts Institute Of Technology | Intracellular delivery |
| US10870112B2 (en) | 2013-08-16 | 2020-12-22 | Massachusetts Institute Of Technology | Selective delivery of material to cells |
| US11111472B2 (en) | 2014-10-31 | 2021-09-07 | Massachusetts Institute Of Technology | Delivery of biomolecules to immune cells |
| US11125739B2 (en) | 2015-01-12 | 2021-09-21 | Massachusetts Institute Of Technology | Gene editing through microfluidic delivery |
| US11299698B2 (en) | 2015-07-09 | 2022-04-12 | Massachusetts Institute Of Technology | Delivery of materials to anucleate cells |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2872199A (en) * | 1998-02-20 | 1999-09-06 | Rockefeller University, The | Apoptotic cell-mediated antigen presentation to dendritic cells |
| WO2006095330A2 (en) * | 2005-03-10 | 2006-09-14 | Yeda Research And Development Co. Ltd. | Methods and immunogenic cell preparations for treating antigen-associated diseases |
-
2012
- 2012-07-04 MX MX2013013243A patent/MX2013013243A/es active IP Right Grant
-
2013
- 2013-10-22 ZA ZA2013/07886A patent/ZA201307886B/en unknown
- 2013-11-14 CL CL2013003282A patent/CL2013003282A1/es unknown
- 2013-11-28 IL IL229702A patent/IL229702A/en active IP Right Grant
-
2014
- 2014-12-05 CY CY20141101015T patent/CY1115803T1/el unknown
- 2014-12-17 HR HRP20141230AT patent/HRP20141230T1/hr unknown
-
2016
- 2016-08-04 JP JP2016153454A patent/JP6235085B2/ja active Active
- 2016-09-12 IL IL24778116A patent/IL247781B/en active IP Right Grant
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10696944B2 (en) | 2011-10-17 | 2020-06-30 | Massachusetts Institute Of Technology | Intracellular delivery |
| US10870112B2 (en) | 2013-08-16 | 2020-12-22 | Massachusetts Institute Of Technology | Selective delivery of material to cells |
| US11806714B2 (en) | 2013-08-16 | 2023-11-07 | Massachusetts Institute Of Technology | Selective delivery of material to cells |
| US11111472B2 (en) | 2014-10-31 | 2021-09-07 | Massachusetts Institute Of Technology | Delivery of biomolecules to immune cells |
| US10526573B2 (en) | 2014-11-14 | 2020-01-07 | Massachusetts Institute Of Technology | Disruption and field enabled delivery of compounds and compositions into cells |
| US11125739B2 (en) | 2015-01-12 | 2021-09-21 | Massachusetts Institute Of Technology | Gene editing through microfluidic delivery |
| US11299698B2 (en) | 2015-07-09 | 2022-04-12 | Massachusetts Institute Of Technology | Delivery of materials to anucleate cells |
Also Published As
| Publication number | Publication date |
|---|---|
| IL229702A0 (en) | 2014-01-30 |
| IL229702A (en) | 2016-09-29 |
| JP2017025066A (ja) | 2017-02-02 |
| IL247781A0 (en) | 2016-11-30 |
| CY1115803T1 (el) | 2017-01-25 |
| CL2013003282A1 (es) | 2014-10-10 |
| ZA201307886B (en) | 2015-03-25 |
| IL247781B (en) | 2019-11-28 |
| HRP20141230T1 (hr) | 2015-02-13 |
| MX2013013243A (es) | 2014-05-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5986196B2 (ja) | 高静水圧によって死滅させた腫瘍細胞および樹状細胞を用いた活性細胞癌免疫療法のための手段および方法 | |
| JP6235085B2 (ja) | 高静水圧によって死滅させた腫瘍細胞および樹状細胞を用いた活性細胞癌免疫療法のための手段および方法 | |
| US10918704B2 (en) | Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure and dendritic cells | |
| AU2012280322A1 (en) | Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure and dendritic cells | |
| JP6134763B2 (ja) | ＧＭ−ＣＳＦ及びインターフェロンαを用いて生成され、且つ熱処理され死滅したがん細胞を取り込んだ樹状細胞 | |
| EP2787005A1 (en) | Targeted cancer immune therapy | |
| Su et al. | Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models | |
| JP2021533798A (ja) | エクソソームに基づく抗腫瘍ワクチン | |
| JP2006518219A (ja) | 電気穿孔法による細胞への抗原の負荷方法 | |
| Shan et al. | Cytokine-induced killer cells co-cultured with dendritic cells loaded with the protein lysate produced by radiofrequency ablation induce a specific antitumor response | |
| Graf et al. | Tumor infiltration by myeloid suppressor cells in response to T cell activation in rat gliomas | |
| Santin et al. | Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer | |
| WO2011060205A1 (en) | Methods, compositions, and assays for determining the effect of an immune cell on a cell from an infectious or neoplastic disease | |
| Xie et al. | Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced apoptotic tumor cells on tumor cell antigens in mouse bladder cancer | |
| US10716810B2 (en) | Canine autologous immunotherapy using dendritic cell induced cancer killing immunocytes | |
| NZ618000B2 (en) | Means and methods for active cellular immunotherapy of cancer by using tumor cells killed by high hydrostatic pressure and dendritic cells | |
| Jæhger | Preclinical Evaluation of Novel Drug Delivery Platforms for the Improvement of Adoptive T cell Therapy | |
| Park et al. | Active immunization using dendritic cells mixed with tumor cells inhibits the growth of lymphomas. | |
| Jacobs | Towards immunotherapy in pediatric cancer patients. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170502 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170711 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20171003 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20171025 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6235085 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |