JP6441320B2 - がん治療のための予測的バイオマーカー - Google Patents
がん治療のための予測的バイオマーカー Download PDFInfo
- Publication number
- JP6441320B2 JP6441320B2 JP2016515715A JP2016515715A JP6441320B2 JP 6441320 B2 JP6441320 B2 JP 6441320B2 JP 2016515715 A JP2016515715 A JP 2016515715A JP 2016515715 A JP2016515715 A JP 2016515715A JP 6441320 B2 JP6441320 B2 JP 6441320B2
- Authority
- JP
- Japan
- Prior art keywords
- tlr
- agonist
- treatment
- cells
- dna
- 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.)
- Expired - Fee Related
Links
- 238000011282 treatment Methods 0.000 title claims description 39
- 206010028980 Neoplasm Diseases 0.000 title claims description 25
- 201000011510 cancer Diseases 0.000 title claims description 16
- 239000000092 prognostic biomarker Substances 0.000 title description 4
- 239000000556 agonist Substances 0.000 claims description 30
- 210000000581 natural killer T-cell Anatomy 0.000 claims description 30
- 210000004027 cell Anatomy 0.000 claims description 28
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims description 12
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims description 12
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical group O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 12
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 102100025137 Early activation antigen CD69 Human genes 0.000 claims description 8
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 7
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 claims description 6
- CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 229960005486 vaccine Drugs 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000002773 nucleotide Substances 0.000 claims description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 4
- 230000000977 initiatory effect Effects 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 150000004705 aldimines Chemical class 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 235000014633 carbohydrates Nutrition 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 238000009093 first-line therapy Methods 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 239000002082 metal nanoparticle Substances 0.000 claims description 2
- 239000002923 metal particle Substances 0.000 claims description 2
- 239000000693 micelle Substances 0.000 claims description 2
- 238000012544 monitoring process Methods 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 239000007790 solid phase Substances 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 9
- 239000004480 active ingredient Substances 0.000 claims 1
- 108020004414 DNA Proteins 0.000 description 46
- 239000000090 biomarker Substances 0.000 description 34
- 239000000902 placebo Substances 0.000 description 12
- 229940068196 placebo Drugs 0.000 description 12
- 230000004913 activation Effects 0.000 description 11
- 102000053602 DNA Human genes 0.000 description 10
- 210000003719 b-lymphocyte Anatomy 0.000 description 8
- 210000000987 immune system Anatomy 0.000 description 8
- 210000005087 mononuclear cell Anatomy 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 230000028993 immune response Effects 0.000 description 7
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 7
- 239000000427 antigen Substances 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 230000003308 immunostimulating effect Effects 0.000 description 6
- 206010061309 Neoplasm progression Diseases 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000005751 tumor progression Effects 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 102000002689 Toll-like receptor Human genes 0.000 description 4
- 108020000411 Toll-like receptor Proteins 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 3
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 3
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 230000005934 immune activation Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 2
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 238000011238 DNA vaccination Methods 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- 101100269308 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PFS1 gene Proteins 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 2
- 208000026872 Addison Disease Diseases 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101100273742 Mus musculus Cd69 gene Proteins 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- -1 TLR-3 Proteins 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000000837 carbohydrate group Chemical group 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 238000007418 data mining Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 238000013394 immunophenotyping Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 238000010801 machine learning Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
-
- 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
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
-
- 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
-
- 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
- C12N2310/17—Immunomodulatory nucleic acids
-
- 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
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N2333/7051—T-cell receptor (TcR)-CD3 complex
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2469/00—Immunoassays for the detection of microorganisms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Physiology (AREA)
- Plant Pathology (AREA)
- Mycology (AREA)
Description
Claims (14)
- 治療の開始に先立ってCD3+ CD56+ CD69+活性化ナチュラルキラーT(NKT)細胞の頻度を決定することにより、がんに冒された患者がTLR−9アゴニストによる治療に応答するであろうかまたは応答するかを予測またはモニターする方法であって、前記頻度が、全NKT細胞集団のCD3+ CD56+ CD69+活性化NKT細胞の頻度であり、前記TLR−9アゴニストが、少なくとも1つの配列モチーフN1N2CGN3N4を含むDNAコンストラクトであり、ここでN1N2およびN3N4はA、C、TおよびGの任意の組合せであり、Cはデオキシシチジンであり、Gはデオキシグアノシンであり、Aはデオキシアデノシンであり、Tはデオキシチミジンであり、前記DNAコンストラクトは、共有結合的に閉じた部分的に自己相補的なものであり、二本鎖ステム及び一本鎖末端ループを備え、前記一本鎖末端ループは、前記配列モチーフN1N2CGN3N4を少なくとも1つ備えている、前記方法。
- TLR−9アゴニストによる治療の応答者が、全NKT細胞集団のCD3+ CD56+ CD69+活性化NKT細胞の少なくとも3%の頻度を有する、請求項1に記載の方法。
- 先立って非DNA薬物による導入療法が行われた、請求項1または2に記載の方法。
- 前記TLR−9アゴニストがMGN1703である、請求項1から3のいずれか一項に記載の方法。
- TLR−9アゴニストを有効成分として含有する、全ナチュラルキラーT(NKT)細胞集団のCD3+ CD56+ CD69+活性化NKT細胞のレベルが治療の開始に先立って上昇している患者のがん治療に用いる組成物であって、前記TLR−9アゴニストが、少なくとも1つの配列モチーフN1N2CGN3N4を含むDNAコンストラクトを少なくとも含んでなり、ここでN1N2およびN3N4はA、C、TおよびGの任意の組合せであり、Cはデオキシシチジンであり、Gはデオキシグアノシンであり、Aはデオキシアデノシンであり、Tはデオキシチミジンであり、前記DNAコンストラクトは、共有結合的に閉じた部分的に自己相補的なものであり、二本鎖ステム及び一本鎖末端ループを備え、前記一本鎖末端ループは、前記配列モチーフN1N2CGN3N4を少なくとも1つ備えている、前記組成物。
- N1N2がGT、GG、GA、ATまたはAAを含む群から選択される要素であり、N3N4がCTまたはTTを含む群から選択される要素である、請求項5に記載の組成物。
- 前記TLR−9アゴニストが少なくとも1つのL−DNAヌクレオチドを含む、請求項5または6に記載の組成物。
- 前記TLR−9アゴニストがMGN1703である、請求項5または6に記載の組成物。
- 前記TLR−9アゴニストの少なくとも1つのヌクレオチドが、カルボキシル、アミン、アミド、アルジミン、ケタール、アセタール、エステル、エーテル、ジスルフィド、チオールおよびアルデヒド基を含む群から選択される官能基により修飾されている、請求項5から8のいずれか一項に記載の組成物。
- 前記DNAコンストラクトが、ペプチド、タンパク質、炭水化物、抗体、脂質、ミセル、ベシクル、合成分子、ポリマー、マイクロプロジェクタイル、金属粒子、ナノ粒子または固相を含む群から選択される化合物に連結している、請求項5から9のいずれか一項に記載の組成物。
- 前記DNAコンストラクトが医薬組成物の一部である、請求項5から10のいずれか一項に記載の組成物。
- 前記医薬組成物がワクチンである、請求項11に記載の組成物。
- 全ナチュラルキラーT(NKT)細胞集団のCD3+ CD56+ CD69+活性化NKT細胞の頻度を検出および定量するための蛍光標識抗体を含む、がんに冒された患者がTLR−9アゴニストによる治療に応答するであろうかまたは応答するかを治療の開始に先立って予測またはモニターするためのキットであって、前記TLR−9アゴニストが、少なくとも1つの配列モチーフN1N2CGN3N4を含むDNAコンストラクトであり、ここでN1N2およびN3N4はA、C、TおよびGの任意の組合せであり、Cはデオキシシチジンであり、Gはデオキシグアノシンであり、Aはデオキシアデノシンであり、Tはデオキシチミジンであり、前記DNAコンストラクトは、共有結合的に閉じた部分的に自己相補的なものであり、二本鎖ステム及び一本鎖末端ループを備え、前記一本鎖末端ループは、前記配列モチーフN1N2CGN3N4を少なくとも1つ備えている、前記キット。
- 前記TLR−9アゴニストがMGN1703である、請求項13に記載のキット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB1309657.3 | 2013-05-30 | ||
GB1309657.3A GB2514591A (en) | 2013-05-30 | 2013-05-30 | Predictive biomarker for cancer therapy |
PCT/EP2014/059995 WO2014191222A1 (en) | 2013-05-30 | 2014-05-15 | Predictive biomarker for cancer therapy |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016526164A JP2016526164A (ja) | 2016-09-01 |
JP6441320B2 true JP6441320B2 (ja) | 2018-12-19 |
Family
ID=48805478
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016515715A Expired - Fee Related JP6441320B2 (ja) | 2013-05-30 | 2014-05-15 | がん治療のための予測的バイオマーカー |
Country Status (18)
Country | Link |
---|---|
US (1) | US10006032B2 (ja) |
EP (1) | EP3004875B1 (ja) |
JP (1) | JP6441320B2 (ja) |
KR (1) | KR101937442B1 (ja) |
CN (2) | CN105247365B (ja) |
AU (1) | AU2014273400B2 (ja) |
BR (1) | BR112015029852A2 (ja) |
CA (1) | CA2907980A1 (ja) |
DK (1) | DK3004875T3 (ja) |
ES (1) | ES2795929T3 (ja) |
GB (1) | GB2514591A (ja) |
HK (1) | HK1216779A1 (ja) |
IL (1) | IL242551A (ja) |
MX (1) | MX365512B (ja) |
PL (1) | PL3004875T3 (ja) |
RU (1) | RU2672358C2 (ja) |
WO (1) | WO2014191222A1 (ja) |
ZA (1) | ZA201506813B (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3508198A1 (en) | 2014-06-04 | 2019-07-10 | Exicure, Inc. | Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications |
LU92821B1 (en) | 2015-09-09 | 2017-03-20 | Mologen Ag | Combination comprising immunostimulatory oligonucleotides |
GB2542425A (en) | 2015-09-21 | 2017-03-22 | Mologen Ag | Means for the treatment of HIV |
US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
EP3392345A1 (en) | 2017-04-22 | 2018-10-24 | Mologen AG | Biomarker for small cell lung cancer therapy |
US11433131B2 (en) | 2017-05-11 | 2022-09-06 | Northwestern University | Adoptive cell therapy using spherical nucleic acids (SNAs) |
US20210155933A1 (en) * | 2017-08-31 | 2021-05-27 | Gilead Sciences, Inc. | Tlr-9 agonists for modulation of tumor microenvironment |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0314682D0 (en) * | 2003-06-24 | 2003-07-30 | Isis Innovation | Materials and methods relating to the modulation of T cell response to soluble antigen |
WO2006015560A1 (de) | 2004-08-09 | 2006-02-16 | Mologen Ag | Immunmodulierendes mittel in verbindung mit chemotherapeutischen massnahmen |
AU2006289514A1 (en) | 2005-09-08 | 2007-03-15 | Mologen Ag | Functional in vitro immunoassay |
CN101610671A (zh) * | 2006-12-12 | 2009-12-23 | 艾德拉药物股份有限公司 | 合成的tlr9激动剂 |
EP2112930B1 (en) * | 2007-02-21 | 2017-01-11 | Vaccinex, Inc. | Modulation of nkt cell activity with antigen-loaded cdid molecules |
CN101878311A (zh) * | 2007-08-01 | 2010-11-03 | 艾德拉药物股份有限公司 | Tlr9的新型合成性激动剂 |
MX2010001785A (es) * | 2007-08-15 | 2010-03-10 | Idera Pharmaceuticals Inc | Moduladores de receptores tipo larga distancia. |
MX2010005104A (es) * | 2007-11-09 | 2010-08-04 | Peregrine Pharmaceuticals Inc | Composiciones de anticuerpo anti-factor de crecimiento endotelial vascular y metodos. |
EP2073009A1 (en) * | 2007-12-19 | 2009-06-24 | Cell Med Research GMBH | Method for T, NK and NKT cells |
EP2711021B1 (en) | 2008-05-02 | 2016-03-09 | BliNK Therapeutics Limited | Products and methods for stimulating an immune response |
WO2009138494A2 (en) * | 2008-05-15 | 2009-11-19 | Ablynx N.V. | Amino acid sequences directed against toll-like receptors and polypeptides comprising the same for the treatment of diseases related to toll-like receptors |
GB0820698D0 (en) * | 2008-11-12 | 2008-12-17 | Ludwig Inst Cancer Res | Uses of immunomodulators |
WO2010136569A1 (en) * | 2009-05-29 | 2010-12-02 | F. Hoffmann-La Roche Ag | Modulators for her2 signaling in her2 expressing patients with gastric cancer |
CA2817891C (en) * | 2010-11-19 | 2021-10-12 | Idera Pharmaceuticals, Inc. | Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response |
GB201021867D0 (en) * | 2010-12-23 | 2011-02-02 | Mologen Ag | Non-coding immunomodulatory DNA construct |
SG10201606788VA (en) * | 2011-08-16 | 2016-09-29 | Morphosys Ag | Combination therapy with an anti - cd19 antibody and a purine analog |
EP2682750A1 (en) * | 2012-07-02 | 2014-01-08 | Sotio a.s. | In vitro method for the diagnosis and surveillance of cancer |
-
2013
- 2013-05-30 GB GB1309657.3A patent/GB2514591A/en not_active Withdrawn
-
2014
- 2014-05-15 WO PCT/EP2014/059995 patent/WO2014191222A1/en active Application Filing
- 2014-05-15 KR KR1020157029934A patent/KR101937442B1/ko active IP Right Grant
- 2014-05-15 CN CN201480024805.8A patent/CN105247365B/zh not_active Expired - Fee Related
- 2014-05-15 CA CA2907980A patent/CA2907980A1/en not_active Abandoned
- 2014-05-15 EP EP14725114.4A patent/EP3004875B1/en active Active
- 2014-05-15 CN CN201910417409.6A patent/CN110201156A/zh active Pending
- 2014-05-15 MX MX2015016305A patent/MX365512B/es active IP Right Grant
- 2014-05-15 AU AU2014273400A patent/AU2014273400B2/en not_active Ceased
- 2014-05-15 RU RU2015150739A patent/RU2672358C2/ru not_active Application Discontinuation
- 2014-05-15 US US14/891,869 patent/US10006032B2/en active Active
- 2014-05-15 BR BR112015029852A patent/BR112015029852A2/pt not_active Application Discontinuation
- 2014-05-15 JP JP2016515715A patent/JP6441320B2/ja not_active Expired - Fee Related
- 2014-05-15 PL PL14725114T patent/PL3004875T3/pl unknown
- 2014-05-15 ES ES14725114T patent/ES2795929T3/es active Active
- 2014-05-15 DK DK14725114.4T patent/DK3004875T3/da active
-
2015
- 2015-09-15 ZA ZA2015/06813A patent/ZA201506813B/en unknown
- 2015-11-11 IL IL242551A patent/IL242551A/en active IP Right Grant
-
2016
- 2016-04-20 HK HK16104519.6A patent/HK1216779A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
EP3004875B1 (en) | 2020-03-04 |
ES2795929T3 (es) | 2020-11-25 |
RU2672358C2 (ru) | 2018-11-14 |
RU2015150739A (ru) | 2017-07-06 |
KR101937442B1 (ko) | 2019-01-11 |
JP2016526164A (ja) | 2016-09-01 |
BR112015029852A2 (pt) | 2017-07-25 |
IL242551A (en) | 2017-07-31 |
AU2014273400B2 (en) | 2017-02-23 |
CN110201156A (zh) | 2019-09-06 |
WO2014191222A1 (en) | 2014-12-04 |
GB2514591A (en) | 2014-12-03 |
KR20150129860A (ko) | 2015-11-20 |
HK1216779A1 (zh) | 2016-12-02 |
US10006032B2 (en) | 2018-06-26 |
EP3004875A1 (en) | 2016-04-13 |
CN105247365B (zh) | 2019-06-18 |
CN105247365A (zh) | 2016-01-13 |
ZA201506813B (en) | 2017-01-25 |
PL3004875T3 (pl) | 2020-11-16 |
MX365512B (es) | 2019-06-05 |
GB201309657D0 (en) | 2013-07-17 |
DK3004875T3 (da) | 2020-06-08 |
US20160115479A1 (en) | 2016-04-28 |
CA2907980A1 (en) | 2014-12-04 |
AU2014273400A1 (en) | 2015-10-08 |
MX2015016305A (es) | 2016-03-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6441320B2 (ja) | がん治療のための予測的バイオマーカー | |
JP6247253B2 (ja) | 白血病幹細胞マーカー | |
RU2724370C2 (ru) | Предсказание иммуногенности т-клеточных эпитопов | |
Pashenkov et al. | Phase II trial of a toll-like receptor 9–activating oligonucleotide in patients with metastatic melanoma | |
Fűri et al. | Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: clinico-pathogenic aspects | |
Bienkowska et al. | Cancer-associated fibroblasts in oral cancer: a current perspective on function and potential for therapeutic targeting | |
WO2006054129A1 (en) | Improved treatment of cancer by double-stranded rna | |
Belmont et al. | Expression of TLR9 in tumor‐infiltrating mononuclear cells enhances angiogenesis and is associated with a worse survival in lung cancer | |
JP2020517665A (ja) | 小細胞肺がん治療のためのバイオマーカー | |
US20210155933A1 (en) | Tlr-9 agonists for modulation of tumor microenvironment | |
Tanegashima et al. | CXCL14 acts as a specific carrier of CpG DNA into dendritic cells and activates Toll-like receptor 9-mediated adaptive immunity | |
Wang et al. | HMGB1-containing nucleosome mediates chemotherapy-induced metastasis of human lung cancer | |
CN117757931A (zh) | 选择新表位作为具有增强效力的用于治疗的疾病特异性靶标 | |
ES2728998T3 (es) | Nuevo antígeno de cáncer EEF2 | |
Avci‐Adali et al. | In vitro test system for evaluation of immune activation potential of new single‐stranded DNA‐based therapeutics | |
KR102565608B1 (ko) | 전립선암 진단용 마커 | |
RU2782336C2 (ru) | Способы прогнозирования применимости белков или белковых фрагментов для иммунотерапии | |
JP2024513960A (ja) | Folr2+マクロファージおよび抗腫瘍免疫 | |
JP2023539332A (ja) | 個別化された免疫原性組成物及びその製造方法及びその使用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20161222 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170117 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170327 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170718 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171129 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180223 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180427 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180528 |
|
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: 20181023 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181121 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6441320 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
LAPS | Cancellation because of no payment of annual fees |