JP7358047B2 - 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー - Google Patents
腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー Download PDFInfo
- Publication number
- JP7358047B2 JP7358047B2 JP2018560847A JP2018560847A JP7358047B2 JP 7358047 B2 JP7358047 B2 JP 7358047B2 JP 2018560847 A JP2018560847 A JP 2018560847A JP 2018560847 A JP2018560847 A JP 2018560847A JP 7358047 B2 JP7358047 B2 JP 7358047B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- tumor
- cell
- expression
- infiltrating
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims description 215
- 210000003289 regulatory T cell Anatomy 0.000 title claims description 160
- 230000002074 deregulated effect Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims description 61
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 59
- 206010009944 Colon cancer Diseases 0.000 claims description 58
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 55
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 54
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 41
- 101001051272 Homo sapiens Layilin Proteins 0.000 claims description 25
- 102100024621 Layilin Human genes 0.000 claims description 25
- 239000012472 biological sample Substances 0.000 claims description 11
- 238000000338 in vitro Methods 0.000 claims description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 238000010837 poor prognosis Methods 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 208000037819 metastatic cancer Diseases 0.000 claims description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 3
- 238000004393 prognosis Methods 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 description 137
- 230000014509 gene expression Effects 0.000 description 112
- 210000004027 cell Anatomy 0.000 description 109
- 239000003550 marker Substances 0.000 description 108
- 230000000694 effects Effects 0.000 description 61
- 102000004169 proteins and genes Human genes 0.000 description 48
- 238000011282 treatment Methods 0.000 description 43
- 102000040430 polynucleotide Human genes 0.000 description 39
- 108091033319 polynucleotide Proteins 0.000 description 39
- 239000002157 polynucleotide Substances 0.000 description 39
- 210000001519 tissue Anatomy 0.000 description 35
- 239000000203 mixture Substances 0.000 description 31
- 108090000765 processed proteins & peptides Proteins 0.000 description 30
- 230000006870 function Effects 0.000 description 27
- 239000000523 sample Substances 0.000 description 27
- 201000011510 cancer Diseases 0.000 description 26
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 24
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 24
- 238000003559 RNA-seq method Methods 0.000 description 24
- 239000012634 fragment Substances 0.000 description 24
- 230000001225 therapeutic effect Effects 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 23
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 22
- 102000004196 processed proteins & peptides Human genes 0.000 description 20
- 101001057135 Homo sapiens Melanoma-associated antigen H1 Proteins 0.000 description 19
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 19
- 102100027256 Melanoma-associated antigen H1 Human genes 0.000 description 19
- 108010029485 Protein Isoforms Proteins 0.000 description 19
- 102000001708 Protein Isoforms Human genes 0.000 description 19
- 229920001184 polypeptide Polymers 0.000 description 19
- 108020004999 messenger RNA Proteins 0.000 description 18
- 108020004414 DNA Proteins 0.000 description 17
- 239000008194 pharmaceutical composition Substances 0.000 description 17
- 239000013598 vector Substances 0.000 description 17
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 16
- 210000005259 peripheral blood Anatomy 0.000 description 16
- 239000011886 peripheral blood Substances 0.000 description 16
- 230000027455 binding Effects 0.000 description 15
- 230000009368 gene silencing by RNA Effects 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 239000003446 ligand Substances 0.000 description 14
- 239000002299 complementary DNA Substances 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- 108020004459 Small interfering RNA Proteins 0.000 description 12
- 108091007433 antigens Proteins 0.000 description 12
- 238000000684 flow cytometry Methods 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 12
- 239000000427 antigen Substances 0.000 description 11
- 102000036639 antigens Human genes 0.000 description 11
- 108091034117 Oligonucleotide Proteins 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 230000000692 anti-sense effect Effects 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 9
- 108020004707 nucleic acids Proteins 0.000 description 9
- 150000007523 nucleic acids Chemical class 0.000 description 9
- 238000003753 real-time PCR Methods 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 8
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 8
- -1 antisense constructs Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 238000012544 monitoring process Methods 0.000 description 8
- 239000002773 nucleotide Substances 0.000 description 8
- 125000003729 nucleotide group Chemical group 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 102100022970 Basic leucine zipper transcriptional factor ATF-like Human genes 0.000 description 7
- 101000903742 Homo sapiens Basic leucine zipper transcriptional factor ATF-like Proteins 0.000 description 7
- 108091030071 RNAI Proteins 0.000 description 7
- 210000000068 Th17 cell Anatomy 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- 230000002596 correlated effect Effects 0.000 description 7
- 239000012636 effector Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 6
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
- 125000000539 amino acid group Chemical group 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 238000010195 expression analysis Methods 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 210000004962 mammalian cell Anatomy 0.000 description 6
- 239000013615 primer Substances 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000011222 transcriptome analysis Methods 0.000 description 6
- 229960005486 vaccine Drugs 0.000 description 6
- 238000000585 Mann–Whitney U test Methods 0.000 description 5
- 108091027967 Small hairpin RNA Proteins 0.000 description 5
- 102000040945 Transcription factor Human genes 0.000 description 5
- 108091023040 Transcription factor Proteins 0.000 description 5
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 230000003915 cell function Effects 0.000 description 5
- 229940127089 cytotoxic agent Drugs 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- 108020005544 Antisense RNA Proteins 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- 101000835928 Homo sapiens Signal-regulatory protein gamma Proteins 0.000 description 4
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 4
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 102100025795 Signal-regulatory protein gamma Human genes 0.000 description 4
- 230000006052 T cell proliferation Effects 0.000 description 4
- 210000000447 Th1 cell Anatomy 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 208000009956 adenocarcinoma Diseases 0.000 description 4
- 210000004102 animal cell Anatomy 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 229940022399 cancer vaccine Drugs 0.000 description 4
- JGPOSNWWINVNFV-UHFFFAOYSA-N carboxyfluorescein diacetate succinimidyl ester Chemical compound C=1C(OC(=O)C)=CC=C2C=1OC1=CC(OC(C)=O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O JGPOSNWWINVNFV-UHFFFAOYSA-N 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000004186 co-expression Effects 0.000 description 4
- 239000003184 complementary RNA Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000000779 depleting effect Effects 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 210000003162 effector t lymphocyte Anatomy 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000000207 lymphocyte subset Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000004055 small Interfering RNA Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 description 3
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 3
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108010017411 Interleukin-21 Receptors Proteins 0.000 description 3
- 102100030699 Interleukin-21 receptor Human genes 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 3
- 238000000636 Northern blotting Methods 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 108010008038 Synthetic Vaccines Proteins 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 3
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 3
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 3
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003491 array Methods 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000002619 cancer immunotherapy Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000001613 neoplastic effect Effects 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 102000035160 transmembrane proteins Human genes 0.000 description 3
- 108091005703 transmembrane proteins Proteins 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- 108020004491 Antisense DNA Proteins 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 108010074708 B7-H1 Antigen Proteins 0.000 description 2
- 239000003298 DNA probe Substances 0.000 description 2
- 108700022150 Designed Ankyrin Repeat Proteins Proteins 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102100029283 Hepatocyte nuclear factor 3-alpha Human genes 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 2
- 101001062353 Homo sapiens Hepatocyte nuclear factor 3-alpha Proteins 0.000 description 2
- 101000821449 Homo sapiens Secreted and transmembrane protein 1 Proteins 0.000 description 2
- 101000738413 Homo sapiens T-cell surface glycoprotein CD3 gamma chain Proteins 0.000 description 2
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 2
- 238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 108020004518 RNA Probes Proteins 0.000 description 2
- 239000003391 RNA probe Substances 0.000 description 2
- 238000010240 RT-PCR analysis Methods 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 102100021853 Secreted and transmembrane protein 1 Human genes 0.000 description 2
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102100037911 T-cell surface glycoprotein CD3 gamma chain Human genes 0.000 description 2
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 239000003816 antisense DNA Substances 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 230000005975 antitumor immune response Effects 0.000 description 2
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 210000001723 extracellular space Anatomy 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 238000003633 gene expression assay Methods 0.000 description 2
- 230000004547 gene signature Effects 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000001325 log-rank test Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 238000010827 pathological analysis Methods 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000008823 permeabilization Effects 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000000513 principal component analysis Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- WPUZGNPQMIWOHE-UHFFFAOYSA-N 3',6'-diacetyloxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-carboxylic acid Chemical compound O1C(=O)C2=CC(C(O)=O)=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 WPUZGNPQMIWOHE-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 108010088547 ARNTL Transcription Factors Proteins 0.000 description 1
- 102100034613 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 101100301218 Arabidopsis thaliana RDR5 gene Proteins 0.000 description 1
- 102100021661 Aryl hydrocarbon receptor nuclear translocator-like protein 2 Human genes 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 108090000342 C-Type Lectins Proteins 0.000 description 1
- 102000003930 C-Type Lectins Human genes 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 102100025221 CD70 antigen Human genes 0.000 description 1
- 108091011896 CSF1 Proteins 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 101100463133 Caenorhabditis elegans pdl-1 gene Proteins 0.000 description 1
- 102100025926 Calmodulin-3 Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108010072135 Cell Adhesion Molecule-1 Proteins 0.000 description 1
- 102100024649 Cell adhesion molecule 1 Human genes 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102100039299 Cyclic AMP-responsive element-binding protein 3-like protein 2 Human genes 0.000 description 1
- 102000013698 Cyclin-Dependent Kinase 6 Human genes 0.000 description 1
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
- 102100039061 Cytokine receptor common subunit beta Human genes 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102100031512 Fc receptor-like protein 3 Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010008599 Forkhead Box Protein M1 Proteins 0.000 description 1
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 1
- 241000700662 Fowlpox virus Species 0.000 description 1
- 102100031351 Galectin-9 Human genes 0.000 description 1
- 101710121810 Galectin-9 Proteins 0.000 description 1
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 1
- 102100038104 Glycogen synthase kinase-3 beta Human genes 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 1
- 102100022846 Histone acetyltransferase KAT2B Human genes 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
- 101000933777 Homo sapiens Calmodulin-3 Proteins 0.000 description 1
- 101000745624 Homo sapiens Cyclic AMP-responsive element-binding protein 3-like protein 2 Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101000846910 Homo sapiens Fc receptor-like protein 3 Proteins 0.000 description 1
- 101001047006 Homo sapiens Histone acetyltransferase KAT2B Proteins 0.000 description 1
- 101000852964 Homo sapiens Interleukin-27 subunit beta Proteins 0.000 description 1
- 101000998139 Homo sapiens Interleukin-32 Proteins 0.000 description 1
- 101001018034 Homo sapiens Lymphocyte antigen 75 Proteins 0.000 description 1
- 101000573447 Homo sapiens Multiple inositol polyphosphate phosphatase 1 Proteins 0.000 description 1
- 101000979357 Homo sapiens NEDD4 family-interacting protein 2 Proteins 0.000 description 1
- 101000604469 Homo sapiens Netrin-G2 Proteins 0.000 description 1
- 101000822072 Homo sapiens Neuronal acetylcholine receptor subunit alpha-6 Proteins 0.000 description 1
- 101000588303 Homo sapiens Nuclear factor erythroid 2-related factor 3 Proteins 0.000 description 1
- 101000686034 Homo sapiens Nuclear receptor ROR-gamma Proteins 0.000 description 1
- 101000643424 Homo sapiens Protein phosphatase Slingshot homolog 1 Proteins 0.000 description 1
- 101000830689 Homo sapiens Protein tyrosine phosphatase type IVA 3 Proteins 0.000 description 1
- 101001019136 Homo sapiens Putative methyltransferase-like protein 7A Proteins 0.000 description 1
- 101000717450 Homo sapiens RCC1 and BTB domain-containing protein 1 Proteins 0.000 description 1
- 101000606506 Homo sapiens Receptor-type tyrosine-protein phosphatase eta Proteins 0.000 description 1
- 101001087372 Homo sapiens Securin Proteins 0.000 description 1
- 101000713602 Homo sapiens T-box transcription factor TBX21 Proteins 0.000 description 1
- 101000612997 Homo sapiens Tetraspanin-5 Proteins 0.000 description 1
- 101000666234 Homo sapiens Thyroid adenoma-associated protein Proteins 0.000 description 1
- 101001057127 Homo sapiens Transcription factor ETV7 Proteins 0.000 description 1
- 101000723938 Homo sapiens Transcription factor HIVEP3 Proteins 0.000 description 1
- 101000642514 Homo sapiens Transcription factor SOX-4 Proteins 0.000 description 1
- 101000652684 Homo sapiens Transcriptional adapter 3 Proteins 0.000 description 1
- 101000798700 Homo sapiens Transmembrane protease serine 3 Proteins 0.000 description 1
- 101000798702 Homo sapiens Transmembrane protease serine 4 Proteins 0.000 description 1
- 101000798696 Homo sapiens Transmembrane protease serine 6 Proteins 0.000 description 1
- 101000835787 Homo sapiens Tudor domain-containing protein 3 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000916547 Homo sapiens Zinc finger and BTB domain-containing protein 38 Proteins 0.000 description 1
- 101000760225 Homo sapiens Zinc finger protein 334 Proteins 0.000 description 1
- 108700020121 Human Immunodeficiency Virus-1 rev Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102100036712 Interleukin-27 subunit beta Human genes 0.000 description 1
- 102100033501 Interleukin-32 Human genes 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 240000004752 Laburnum anagyroides Species 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100033486 Lymphocyte antigen 75 Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 102100026284 Multiple inositol polyphosphate phosphatase 1 Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102100023052 NEDD4 family-interacting protein 2 Human genes 0.000 description 1
- 108010018525 NFATC Transcription Factors Proteins 0.000 description 1
- 102000002673 NFATC Transcription Factors Human genes 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 102100038699 Netrin-G2 Human genes 0.000 description 1
- 102100021518 Neuronal acetylcholine receptor subunit alpha-6 Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102100031700 Nuclear factor erythroid 2-related factor 3 Human genes 0.000 description 1
- 102100023421 Nuclear receptor ROR-gamma Human genes 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100024601 Protein tyrosine phosphatase type IVA 3 Human genes 0.000 description 1
- 102100034758 Putative methyltransferase-like protein 7A Human genes 0.000 description 1
- 102100020837 RCC1 and BTB domain-containing protein 1 Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 102100039808 Receptor-type tyrosine-protein phosphatase eta Human genes 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108090000829 Ribosome Inactivating Proteins Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 102100033004 Securin Human genes 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108020004688 Small Nuclear RNA Proteins 0.000 description 1
- 102000039471 Small Nuclear RNA Human genes 0.000 description 1
- 108091060271 Small temporal RNA Proteins 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 201000001322 T cell deficiency Diseases 0.000 description 1
- 102100036840 T-box transcription factor TBX21 Human genes 0.000 description 1
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 102100040872 Tetraspanin-5 Human genes 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102100038148 Thyroid adenoma-associated protein Human genes 0.000 description 1
- 102100027263 Transcription factor ETV7 Human genes 0.000 description 1
- 102100028336 Transcription factor HIVEP3 Human genes 0.000 description 1
- 102100036693 Transcription factor SOX-4 Human genes 0.000 description 1
- 102100030836 Transcriptional adapter 3 Human genes 0.000 description 1
- 102100032454 Transmembrane protease serine 3 Human genes 0.000 description 1
- 102100032452 Transmembrane protease serine 6 Human genes 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 102100026362 Tudor domain-containing protein 3 Human genes 0.000 description 1
- 108010091356 Tumor Protein p73 Proteins 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 102100030018 Tumor protein p73 Human genes 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 108010083162 Twist-Related Protein 1 Proteins 0.000 description 1
- 102100030398 Twist-related protein 1 Human genes 0.000 description 1
- 241001024096 Uleiota Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 102100028125 Zinc finger and BTB domain-containing protein 38 Human genes 0.000 description 1
- 102100024774 Zinc finger protein 334 Human genes 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000011224 anti-cancer immunotherapy Methods 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 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
- 210000000481 breast Anatomy 0.000 description 1
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000030570 cellular localization Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000010109 chemoembolization Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000011970 concomitant therapy Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000036576 dermal application Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000004049 epigenetic modification Effects 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 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 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000003731 gingival crevicular fluid Anatomy 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000012296 in situ hybridization assay Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 102000008640 interleukin-21 receptor activity proteins Human genes 0.000 description 1
- 108040002099 interleukin-21 receptor activity proteins Proteins 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010212 intracellular staining Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 208000030776 invasive breast carcinoma Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 230000007762 localization of cell Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000011227 neoadjuvant chemotherapy Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 1
- 238000011499 palliative surgery Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007030 peptide scission Effects 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002135 phase contrast microscopy Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920006149 polyester-amide block copolymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002987 primer (paints) Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 208000009305 pseudorabies Diseases 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011127 radiochemotherapy Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000003196 serial analysis of gene expression Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 238000007860 single-cell PCR Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 101150065190 term gene Proteins 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 229940126836 transmembrane protease serine 6 synthesis reducer Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- 229940030325 tumor cell vaccine Drugs 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000002476 tumorcidal effect Effects 0.000 description 1
- 238000010396 two-hybrid screening Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000007473 univariate analysis Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001238 wet grinding Methods 0.000 description 1
- 239000000080 wetting agent Substances 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- C12N5/0637—Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Microbiology (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Plant Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Virology (AREA)
- Developmental Biology & Embryology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2023096086A JP2023113918A (ja) | 2016-05-16 | 2023-06-12 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
| JP2025132766A JP2025172069A (ja) | 2016-05-16 | 2025-08-07 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16169791.7 | 2016-05-16 | ||
| EP16169791 | 2016-05-16 | ||
| EP16198724 | 2016-11-14 | ||
| EP16198724.3 | 2016-11-14 | ||
| PCT/EP2017/061642 WO2017198631A1 (en) | 2016-05-16 | 2017-05-15 | Markers selectively deregulated in tumor-infiltrating regulatory t cells |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023096086A Division JP2023113918A (ja) | 2016-05-16 | 2023-06-12 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019518452A JP2019518452A (ja) | 2019-07-04 |
| JP2019518452A5 JP2019518452A5 (enExample) | 2020-06-25 |
| JP7358047B2 true JP7358047B2 (ja) | 2023-10-10 |
Family
ID=58772864
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018560847A Active JP7358047B2 (ja) | 2016-05-16 | 2017-05-15 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
| JP2023096086A Pending JP2023113918A (ja) | 2016-05-16 | 2023-06-12 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
| JP2025132766A Pending JP2025172069A (ja) | 2016-05-16 | 2025-08-07 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023096086A Pending JP2023113918A (ja) | 2016-05-16 | 2023-06-12 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
| JP2025132766A Pending JP2025172069A (ja) | 2016-05-16 | 2025-08-07 | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US20190391152A1 (enExample) |
| EP (2) | EP3458473B8 (enExample) |
| JP (3) | JP7358047B2 (enExample) |
| KR (1) | KR102623927B1 (enExample) |
| CN (1) | CN109715653A (enExample) |
| AU (1) | AU2017266686B2 (enExample) |
| BR (1) | BR112018073414A2 (enExample) |
| CA (1) | CA3023980A1 (enExample) |
| ES (1) | ES2922525T3 (enExample) |
| MX (2) | MX395142B (enExample) |
| WO (1) | WO2017198631A1 (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3023980A1 (en) | 2016-05-16 | 2017-11-23 | Checkmab S.R.L. | Markers selectively deregulated in tumor-infiltrating regulatory t cells |
| EP3431105B1 (en) | 2017-03-29 | 2020-01-01 | Shionogi&Co., Ltd. | Medicinal composition for treating cancer |
| AU2019324170A1 (en) | 2018-08-23 | 2021-02-18 | Seagen, Inc. | Anti-TIGIT antibodies |
| KR20250154552A (ko) | 2018-09-27 | 2025-10-28 | 실리오 디벨럽먼트, 인크. | 마스킹된 사이토카인 폴리펩타이드 |
| IL263394A (en) * | 2018-11-29 | 2020-05-31 | Amit Ido | Methods of activating dysfunctional immune cells and treatment of cancer |
| TW202039575A (zh) | 2018-12-27 | 2020-11-01 | 日商鹽野義製藥股份有限公司 | 新穎之抗ｃｃｒ８抗體 |
| EP3921335A4 (en) * | 2019-02-08 | 2023-02-08 | The Regents Of The University Of California | COMPOSITIONS AND METHODS USING LAYILIN |
| CN110187107A (zh) * | 2019-04-26 | 2019-08-30 | 温州医科大学 | 一种基于肿瘤组织浸润免疫细胞特征建立的结直肠癌预后评估装置及方法 |
| EP4107283A1 (en) * | 2020-02-20 | 2022-12-28 | Institut Curie | Method for identifying functional disease-specific regulatory t cells |
| JP2023515981A (ja) * | 2020-02-26 | 2023-04-17 | ペーアーエム セラノスティクス ゲゼルシャフト ミット ベシュレンクテル ハフツング | ペプチジルグリシンαアミド化モノオキシゲナーゼ（ＰＡＭ）を決定する方法および診断目的でのその使用 |
| IL296913A (en) * | 2020-04-01 | 2022-12-01 | Xilio Dev Inc | Il-12 masked cytokines and their cleavage products |
| TW202216771A (zh) | 2020-06-26 | 2022-05-01 | 德商拜耳廠股份有限公司 | 用於治療應用之ccr8抗體 |
| CN113933508A (zh) * | 2020-07-13 | 2022-01-14 | 上海吉凯基因医学科技股份有限公司 | 人batf基因的用途及相关产品 |
| US12012441B2 (en) | 2020-10-26 | 2024-06-18 | Neptune Biosciences Llc | Engineered human IL-21 cytokines and methods for using the same |
| EP4251187A4 (en) | 2020-11-25 | 2025-09-10 | Xilio Dev Inc | TUMOR-SPECIFIC CLASSIBLE LINKERS |
| IL309856A (en) | 2021-07-14 | 2024-02-01 | Genentech Inc | Antibodies anti-C-C motif receptor 8 (CCR8) and methods of use |
| HUE069018T2 (hu) | 2021-07-27 | 2025-02-28 | Abbvie Inc | Anti-CCR8 antitestek |
| CN114381528B (zh) * | 2022-02-14 | 2024-06-28 | 天津市泌尿外科研究所 | Mettl7a基因及其表达产物在诊断和治疗肿瘤中的用途 |
| KR102492241B1 (ko) * | 2022-02-25 | 2023-01-30 | 전남대학교산학협력단 | Kitenin의 이량체 형성을 저해하는 펩타이드 및 이의 용도 |
| WO2024151091A1 (ko) * | 2023-01-11 | 2024-07-18 | 한국과학기술원 | 종양 내 treg의 바이오마커를 포함하는 진단용 조성물 및 약학 조성물 |
| CN116496417B (zh) * | 2023-06-27 | 2023-10-10 | 北京市肿瘤防治研究所 | 含有膜型il7的融合蛋白及t细胞 |
| CN117079710B (zh) * | 2023-08-18 | 2024-05-31 | 上海爱谱蒂康生物科技有限公司 | 生物标志物及其在预测和/或诊断utuc肌肉浸润中的应用 |
| CN117587014B (zh) * | 2023-11-24 | 2025-01-24 | 上海恩凯细胞技术有限公司 | 多功能基因修饰载体及其制备的多功能基因修饰免疫细胞和它们的应用 |
| WO2025113643A1 (en) | 2023-12-01 | 2025-06-05 | Gilead Sciences Inc. | Anti-fap-light fusion protein and use thereof |
| WO2025145207A1 (en) | 2023-12-29 | 2025-07-03 | Bristol-Myers Squibb Company | Combination therapy of kras inhibitor and treg-depleting agent |
| CN117625792B (zh) * | 2024-01-23 | 2024-04-16 | 杭州华得森生物技术有限公司 | 用于胃癌诊断和预后判断的生物标志物及其应用 |
| CN118064595B (zh) * | 2024-04-17 | 2024-08-02 | 中山大学附属第六医院 | 一种预测结直肠癌肝转移的生物标志物及其应用 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5075A (en) | 1847-04-17 | Improvement in cultivators | ||
| US109A (en) | 1836-12-15 | Erawijtg | ||
| US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
| US3832253A (en) | 1973-03-21 | 1974-08-27 | Baxter Laboratories Inc | Method of making an inflatable balloon catheter |
| US4667014A (en) | 1983-03-07 | 1987-05-19 | Syntex (U.S.A.) Inc. | Nonapeptide and decapeptide analogs of LHRH, useful as LHRH antagonists |
| US4452775A (en) | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
| CA1200416A (en) | 1983-05-13 | 1986-02-11 | Societe Des Produits Nestle S.A. | Food process |
| US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
| US4954617A (en) | 1986-07-07 | 1990-09-04 | Trustees Of Dartmouth College | Monoclonal antibodies to FC receptors for immunoglobulin G on human mononuclear phagocytes |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| JPH04167172A (ja) | 1990-10-31 | 1992-06-15 | Nec Corp | ベクトルプロセッサ |
| AU8669598A (en) * | 1997-07-29 | 1999-02-22 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Chemokine receptor ccr8 dna and uses thereof |
| EP1030865A2 (en) * | 1997-11-13 | 2000-08-30 | Schering Corporation | Th2 CELL DEPLETION; COMPOSITIONS; METHODS |
| EP2434282A3 (en) * | 2002-07-01 | 2012-08-22 | Tufts University | Methods and compositions for inhibition of multi-drug resistance by hyaluronan oligomers |
| WO2007044756A2 (en) * | 2005-10-11 | 2007-04-19 | Icos Corporation | Monoclonal antibodies recognizing human ccr8 |
| JP2008072939A (ja) * | 2006-09-21 | 2008-04-03 | Fujifilm Corp | 多発性骨髄腫の検出方法および抑制方法 |
| US20100292303A1 (en) * | 2007-07-20 | 2010-11-18 | Birrer Michael J | Gene expression profile for predicting ovarian cancer patient survival |
| WO2009100035A2 (en) * | 2008-02-01 | 2009-08-13 | Wyeth | Interleukin-21 (il-21) and il-21 receptor (il-21r) modulation of regulatory t cells and forkhead box p3 (foxp3) |
| WO2013131010A2 (en) * | 2012-03-02 | 2013-09-06 | Icahn School Of Medicine At Mount Sinai | Function of chemokine receptor ccr8 in melanoma metastasis |
| WO2015017537A2 (en) * | 2013-07-30 | 2015-02-05 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Colorectal cancer recurrence gene expression signature |
| CA3023980A1 (en) | 2016-05-16 | 2017-11-23 | Checkmab S.R.L. | Markers selectively deregulated in tumor-infiltrating regulatory t cells |
-
2017
- 2017-05-15 CA CA3023980A patent/CA3023980A1/en active Pending
- 2017-05-15 AU AU2017266686A patent/AU2017266686B2/en active Active
- 2017-05-15 MX MX2018013952A patent/MX395142B/es unknown
- 2017-05-15 KR KR1020187036507A patent/KR102623927B1/ko active Active
- 2017-05-15 JP JP2018560847A patent/JP7358047B2/ja active Active
- 2017-05-15 BR BR112018073414A patent/BR112018073414A2/pt unknown
- 2017-05-15 US US16/301,805 patent/US20190391152A1/en not_active Abandoned
- 2017-05-15 ES ES17725914T patent/ES2922525T3/es active Active
- 2017-05-15 WO PCT/EP2017/061642 patent/WO2017198631A1/en not_active Ceased
- 2017-05-15 EP EP17725914.0A patent/EP3458473B8/en active Active
- 2017-05-15 EP EP22159825.3A patent/EP4092045A1/en active Pending
- 2017-05-15 CN CN201780043484.XA patent/CN109715653A/zh active Pending
-
2018
- 2018-11-14 MX MX2022010703A patent/MX2022010703A/es unknown
-
2023
- 2023-04-05 US US18/295,965 patent/US12247982B2/en active Active
- 2023-06-12 JP JP2023096086A patent/JP2023113918A/ja active Pending
-
2025
- 2025-01-27 US US19/037,818 patent/US20250251401A1/en active Pending
- 2025-08-07 JP JP2025132766A patent/JP2025172069A/ja active Pending
Non-Patent Citations (4)
| Title |
|---|
| Cancer Immunol. Res.，2013年04月07日，Vol. 1, No. 1，pp. 32-42 |
| Human Immunology，2015年12月10日，Vol. 77，pp. 201-213 |
| International Immunology，2016年05月09日，Vol. 28, No. 8，pp. 401-409 |
| The Journal of Clinical Investigation，2013年06月03日，Vol. 123, No. 6 ，pp. 2447-2463 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3458473A1 (en) | 2019-03-27 |
| CA3023980A1 (en) | 2017-11-23 |
| JP2023113918A (ja) | 2023-08-16 |
| AU2017266686A1 (en) | 2019-01-03 |
| MX2018013952A (es) | 2019-06-24 |
| JP2019518452A (ja) | 2019-07-04 |
| US20190391152A1 (en) | 2019-12-26 |
| MX2022010703A (es) | 2022-09-27 |
| US12247982B2 (en) | 2025-03-11 |
| KR20190006009A (ko) | 2019-01-16 |
| EP3458473B1 (en) | 2022-04-13 |
| US20230375555A1 (en) | 2023-11-23 |
| MX395142B (es) | 2025-03-25 |
| AU2017266686B2 (en) | 2023-03-09 |
| EP3458473B8 (en) | 2022-08-17 |
| KR102623927B1 (ko) | 2024-01-12 |
| BR112018073414A2 (pt) | 2019-08-27 |
| CN109715653A (zh) | 2019-05-03 |
| US20250251401A1 (en) | 2025-08-07 |
| ES2922525T3 (es) | 2022-09-16 |
| JP2025172069A (ja) | 2025-11-20 |
| EP4092045A1 (en) | 2022-11-23 |
| WO2017198631A1 (en) | 2017-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7358047B2 (ja) | 腫瘍浸潤制御性ｔ細胞において選択的に脱制御されたマーカー | |
| AU2018284077B2 (en) | Systems and methods for identifying responders and non-responders to immune checkpoint blockade therapy | |
| Schlößer et al. | Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma | |
| EP3606518A1 (en) | Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer | |
| JP2018102299A (ja) | 膀胱癌の処置および診断のための方法および組成物 | |
| EP3553186A1 (en) | Method for the diagnosis, prognosis and treatment of prostate cancer metastasis | |
| US20210347847A1 (en) | Therapeutic targeting of malignant cells using tumor markers | |
| JP2014020930A (ja) | 膵癌診断及び治療効果予測判定バイオマーカー | |
| KR20220031069A (ko) | 항-종양 치료의 효과를 진단하기 위한 방법 | |
| EP4130747A1 (en) | Biomarker for cancer immunotherapy and use thereof | |
| CN114341172A (zh) | 医学和诊断学中的hla-h | |
| US20220348667A1 (en) | Specific ACKR2 Modulators for Use in Therapy | |
| KR102528973B1 (ko) | 면역항암요법에 대한 바이오마커 및 이의 용도 | |
| Losurdo | Molecular features of T lymphocytes in the immune response against breast cancer | |
| WO2024040148A1 (en) | Combination treatment for cancer | |
| WO2024218260A1 (en) | Detecting tumor-associated-macrophages in pancreatic cancer | |
| EP4605752A1 (en) | Cd207 dendritic cells as a biomarker for tumoural progression and therapeutic target | |
| CN117795341A (zh) | 使用cd-40激动剂治疗癌症的方法 | |
| KR20220044504A (ko) | 개인 hla 패턴의 결정, 예후인자로서의 용도, 표적 유전자 및 치료제 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181116 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200511 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200511 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210616 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210914 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210916 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211213 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220427 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220722 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220726 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221027 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20221031 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20230213 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230612 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20230731 |
|
| 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: 20230829 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230927 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7358047 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |