JP2018529320A - 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ - Google Patents
前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ Download PDFInfo
- Publication number
- JP2018529320A JP2018529320A JP2018505723A JP2018505723A JP2018529320A JP 2018529320 A JP2018529320 A JP 2018529320A JP 2018505723 A JP2018505723 A JP 2018505723A JP 2018505723 A JP2018505723 A JP 2018505723A JP 2018529320 A JP2018529320 A JP 2018529320A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- cancer
- cell
- seq
- cells
- 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.)
- Granted
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 668
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 292
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 284
- 208000000236 Prostatic Neoplasms Diseases 0.000 title claims description 83
- 206010060862 Prostate cancer Diseases 0.000 title claims description 82
- 238000009169 immunotherapy Methods 0.000 title abstract description 16
- 210000004027 cell Anatomy 0.000 claims abstract description 217
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 136
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 131
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims abstract description 113
- 108091008874 T cell receptors Proteins 0.000 claims abstract description 112
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 claims abstract description 105
- 108700018351 Major Histocompatibility Complex Proteins 0.000 claims abstract description 104
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 71
- 230000027455 binding Effects 0.000 claims abstract description 65
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 57
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 52
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 52
- 238000000338 in vitro Methods 0.000 claims abstract description 49
- 229960005486 vaccine Drugs 0.000 claims abstract description 35
- 210000001519 tissue Anatomy 0.000 claims description 170
- 238000000034 method Methods 0.000 claims description 107
- 201000011510 cancer Diseases 0.000 claims description 102
- 108091007433 antigens Proteins 0.000 claims description 97
- 102000036639 antigens Human genes 0.000 claims description 97
- 239000000427 antigen Substances 0.000 claims description 96
- 230000014509 gene expression Effects 0.000 claims description 78
- 241000282414 Homo sapiens Species 0.000 claims description 66
- 229920001184 polypeptide Polymers 0.000 claims description 58
- 150000001413 amino acids Chemical class 0.000 claims description 54
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 36
- 239000013604 expression vector Substances 0.000 claims description 34
- 108091054437 MHC class I family Proteins 0.000 claims description 32
- 230000005847 immunogenicity Effects 0.000 claims description 30
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 25
- 208000026310 Breast neoplasm Diseases 0.000 claims description 24
- 102000043129 MHC class I family Human genes 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 206010006187 Breast cancer Diseases 0.000 claims description 23
- 230000006870 function Effects 0.000 claims description 22
- 239000003446 ligand Substances 0.000 claims description 22
- 108091054438 MHC class II family Proteins 0.000 claims description 20
- 206010009944 Colon cancer Diseases 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 108091023037 Aptamer Proteins 0.000 claims description 18
- 230000005867 T cell response Effects 0.000 claims description 17
- 230000035772 mutation Effects 0.000 claims description 17
- 238000001727 in vivo Methods 0.000 claims description 16
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 15
- 201000005202 lung cancer Diseases 0.000 claims description 15
- 208000020816 lung neoplasm Diseases 0.000 claims description 15
- 238000001514 detection method Methods 0.000 claims description 14
- 201000007270 liver cancer Diseases 0.000 claims description 13
- 208000014018 liver neoplasm Diseases 0.000 claims description 13
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 13
- 230000002018 overexpression Effects 0.000 claims description 13
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 12
- 210000004443 dendritic cell Anatomy 0.000 claims description 12
- 239000012636 effector Substances 0.000 claims description 12
- 206010033128 Ovarian cancer Diseases 0.000 claims description 11
- 238000004949 mass spectrometry Methods 0.000 claims description 11
- 201000001441 melanoma Diseases 0.000 claims description 11
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 10
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 10
- 108020001507 fusion proteins Proteins 0.000 claims description 10
- 102000037865 fusion proteins Human genes 0.000 claims description 10
- 238000010186 staining Methods 0.000 claims description 10
- 206010005003 Bladder cancer Diseases 0.000 claims description 9
- 102000004127 Cytokines Human genes 0.000 claims description 9
- 108090000695 Cytokines Proteins 0.000 claims description 9
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 claims description 9
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 9
- 206010038389 Renal cancer Diseases 0.000 claims description 9
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 9
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 9
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 claims description 9
- 201000010982 kidney cancer Diseases 0.000 claims description 9
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 9
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 9
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 9
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 8
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 8
- 238000003556 assay Methods 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 8
- 238000010195 expression analysis Methods 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 8
- 201000002528 pancreatic cancer Diseases 0.000 claims description 8
- 206010046766 uterine cancer Diseases 0.000 claims description 8
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 7
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 7
- 102000006354 HLA-DR Antigens Human genes 0.000 claims description 7
- 108010058597 HLA-DR Antigens Proteins 0.000 claims description 7
- 208000002030 Merkel cell carcinoma Diseases 0.000 claims description 7
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 7
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- 238000003745 diagnosis Methods 0.000 claims description 7
- 201000004101 esophageal cancer Diseases 0.000 claims description 7
- 201000010175 gallbladder cancer Diseases 0.000 claims description 7
- 206010017758 gastric cancer Diseases 0.000 claims description 7
- 230000003308 immunostimulating effect Effects 0.000 claims description 7
- 201000011549 stomach cancer Diseases 0.000 claims description 7
- 239000003053 toxin Substances 0.000 claims description 7
- 231100000765 toxin Toxicity 0.000 claims description 7
- 108700012359 toxins Proteins 0.000 claims description 7
- 206010004593 Bile duct cancer Diseases 0.000 claims description 6
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 6
- 238000012258 culturing Methods 0.000 claims description 6
- 230000004927 fusion Effects 0.000 claims description 6
- 239000012931 lyophilized formulation Substances 0.000 claims description 6
- 230000003211 malignant effect Effects 0.000 claims description 6
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 claims description 5
- 108010028930 invariant chain Proteins 0.000 claims description 5
- 230000002147 killing effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 238000012163 sequencing technique Methods 0.000 claims description 5
- 229940022399 cancer vaccine Drugs 0.000 claims description 4
- 238000002659 cell therapy Methods 0.000 claims description 4
- 239000001963 growth medium Substances 0.000 claims description 4
- 238000002493 microarray Methods 0.000 claims description 4
- 230000006698 induction Effects 0.000 claims description 3
- 229920002477 rna polymer Polymers 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 210000000822 natural killer cell Anatomy 0.000 claims description 2
- 238000012070 whole genome sequencing analysis Methods 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims 2
- 238000011510 Elispot assay Methods 0.000 claims 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 claims 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 claims 1
- 230000005934 immune activation Effects 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 230000003278 mimic effect Effects 0.000 claims 1
- 229940038309 personalized vaccine Drugs 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 36
- 238000002619 cancer immunotherapy Methods 0.000 abstract description 9
- 230000005975 antitumor immune response Effects 0.000 abstract description 5
- 239000008186 active pharmaceutical agent Substances 0.000 abstract description 3
- 235000018102 proteins Nutrition 0.000 description 64
- 239000000523 sample Substances 0.000 description 62
- 235000001014 amino acid Nutrition 0.000 description 55
- 229940024606 amino acid Drugs 0.000 description 53
- 108020004414 DNA Proteins 0.000 description 47
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 37
- 108010075704 HLA-A Antigens Proteins 0.000 description 37
- 210000002307 prostate Anatomy 0.000 description 36
- 239000013598 vector Substances 0.000 description 32
- 239000012634 fragment Substances 0.000 description 29
- 210000004881 tumor cell Anatomy 0.000 description 23
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 22
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 22
- 238000002955 isolation Methods 0.000 description 22
- -1 9-fluorenylmethyloxycarbonyl (Fmoc) group Chemical group 0.000 description 21
- 125000000539 amino acid group Chemical group 0.000 description 21
- 238000006467 substitution reaction Methods 0.000 description 21
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 20
- 239000002671 adjuvant Substances 0.000 description 20
- 230000028993 immune response Effects 0.000 description 20
- 210000002784 stomach Anatomy 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 238000011002 quantification Methods 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- 102000040430 polynucleotide Human genes 0.000 description 17
- 108091033319 polynucleotide Proteins 0.000 description 17
- 239000002157 polynucleotide Substances 0.000 description 17
- 238000002648 combination therapy Methods 0.000 description 16
- 230000000875 corresponding effect Effects 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- 230000001105 regulatory effect Effects 0.000 description 15
- 230000000638 stimulation Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 210000003734 kidney Anatomy 0.000 description 14
- 210000004698 lymphocyte Anatomy 0.000 description 14
- 230000004048 modification Effects 0.000 description 14
- 238000012986 modification Methods 0.000 description 14
- 102000043131 MHC class II family Human genes 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 238000013459 approach Methods 0.000 description 13
- 210000001072 colon Anatomy 0.000 description 13
- 238000011161 development Methods 0.000 description 13
- 230000018109 developmental process Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
- 208000023958 prostate neoplasm Diseases 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 12
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 12
- 210000004072 lung Anatomy 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 210000003491 skin Anatomy 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 11
- 210000001367 artery Anatomy 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 210000004556 brain Anatomy 0.000 description 11
- 210000000481 breast Anatomy 0.000 description 11
- 210000004899 c-terminal region Anatomy 0.000 description 11
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 11
- 210000002216 heart Anatomy 0.000 description 11
- 210000000496 pancreas Anatomy 0.000 description 11
- 210000000952 spleen Anatomy 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- 210000004291 uterus Anatomy 0.000 description 11
- 102100028163 ATP-binding cassette sub-family C member 4 Human genes 0.000 description 10
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 10
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 10
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 10
- 101000986629 Homo sapiens ATP-binding cassette sub-family C member 4 Proteins 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 108010038807 Oligopeptides Proteins 0.000 description 10
- 102000015636 Oligopeptides Human genes 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000000090 biomarker Substances 0.000 description 10
- 210000000987 immune system Anatomy 0.000 description 10
- 210000000265 leukocyte Anatomy 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 210000001541 thymus gland Anatomy 0.000 description 10
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 9
- 108700028369 Alleles Proteins 0.000 description 9
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 210000003238 esophagus Anatomy 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000002163 immunogen Effects 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000010647 peptide synthesis reaction Methods 0.000 description 9
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 9
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 9
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 210000002443 helper t lymphocyte Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000000178 monomer Substances 0.000 description 8
- 210000000664 rectum Anatomy 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 210000002027 skeletal muscle Anatomy 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 210000001550 testis Anatomy 0.000 description 8
- 210000003932 urinary bladder Anatomy 0.000 description 8
- 102000053602 DNA Human genes 0.000 description 7
- 102100036912 Desmin Human genes 0.000 description 7
- 108010044052 Desmin Proteins 0.000 description 7
- 241000238631 Hexapoda Species 0.000 description 7
- 102100032832 Integrin alpha-7 Human genes 0.000 description 7
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 7
- 108010063045 Lactoferrin Proteins 0.000 description 7
- 102000012174 Lactotransferrin Human genes 0.000 description 7
- 102100040349 Peptidyl-prolyl cis-trans isomerase FKBP10 Human genes 0.000 description 7
- 101710111764 Peptidyl-prolyl cis-trans isomerase FKBP10 Proteins 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 230000000890 antigenic effect Effects 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 210000005045 desmin Anatomy 0.000 description 7
- 210000001165 lymph node Anatomy 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 210000001672 ovary Anatomy 0.000 description 7
- 210000002826 placenta Anatomy 0.000 description 7
- 210000003079 salivary gland Anatomy 0.000 description 7
- 208000000587 small cell lung carcinoma Diseases 0.000 description 7
- 210000000813 small intestine Anatomy 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000007790 solid phase Substances 0.000 description 7
- 210000001685 thyroid gland Anatomy 0.000 description 7
- 210000003437 trachea Anatomy 0.000 description 7
- 210000003462 vein Anatomy 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 6
- 241000701022 Cytomegalovirus Species 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 102100036367 Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A Human genes 0.000 description 6
- 102000011852 GATA2 Transcription Factor Human genes 0.000 description 6
- 108010075641 GATA2 Transcription Factor Proteins 0.000 description 6
- 101001072029 Homo sapiens Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A Proteins 0.000 description 6
- 101000745406 Homo sapiens Ketimine reductase mu-crystallin Proteins 0.000 description 6
- 101000616881 Homo sapiens MANSC domain-containing protein 1 Proteins 0.000 description 6
- 101000662909 Homo sapiens T cell receptor beta constant 1 Proteins 0.000 description 6
- 101000662902 Homo sapiens T cell receptor beta constant 2 Proteins 0.000 description 6
- 101000818517 Homo sapiens Zinc-alpha-2-glycoprotein Proteins 0.000 description 6
- 206010062767 Hypophysitis Diseases 0.000 description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
- 102100039386 Ketimine reductase mu-crystallin Human genes 0.000 description 6
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
- 102100021835 MANSC domain-containing protein 1 Human genes 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- 102100037272 T cell receptor beta constant 1 Human genes 0.000 description 6
- 102100037298 T cell receptor beta constant 2 Human genes 0.000 description 6
- 102000003610 TRPM8 Human genes 0.000 description 6
- 101150111302 Trpm8 gene Proteins 0.000 description 6
- 102100021144 Zinc-alpha-2-glycoprotein Human genes 0.000 description 6
- 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 6
- 230000004913 activation Effects 0.000 description 6
- 210000000577 adipose tissue Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 235000018417 cysteine Nutrition 0.000 description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
- 210000001198 duodenum Anatomy 0.000 description 6
- 210000000232 gallbladder Anatomy 0.000 description 6
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 230000001613 neoplastic effect Effects 0.000 description 6
- 210000000578 peripheral nerve Anatomy 0.000 description 6
- 210000004303 peritoneum Anatomy 0.000 description 6
- 238000002823 phage display Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 210000003635 pituitary gland Anatomy 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 210000004224 pleura Anatomy 0.000 description 6
- 239000002516 radical scavenger Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 229950010550 resiquimod Drugs 0.000 description 6
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 210000000626 ureter Anatomy 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 101001091376 Homo sapiens Kallikrein-4 Proteins 0.000 description 5
- 101000721757 Homo sapiens Olfactory receptor 51E2 Proteins 0.000 description 5
- 101000620559 Homo sapiens Ras-related protein Rab-3B Proteins 0.000 description 5
- 101000662997 Homo sapiens TRAF2 and NCK-interacting protein kinase Proteins 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 102100034872 Kallikrein-4 Human genes 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 5
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 102100025128 Olfactory receptor 51E2 Human genes 0.000 description 5
- 108700020796 Oncogene Proteins 0.000 description 5
- 102100022306 Ras-related protein Rab-3B Human genes 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102100037671 TRAF2 and NCK-interacting protein kinase Human genes 0.000 description 5
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 5
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 5
- 102100029637 Tryptase beta-2 Human genes 0.000 description 5
- 210000004100 adrenal gland Anatomy 0.000 description 5
- 239000003098 androgen Substances 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 229960002685 biotin Drugs 0.000 description 5
- 235000020958 biotin Nutrition 0.000 description 5
- 239000011616 biotin Substances 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 229960004397 cyclophosphamide Drugs 0.000 description 5
- 230000034994 death Effects 0.000 description 5
- 231100000517 death Toxicity 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 229940029030 dendritic cell vaccine Drugs 0.000 description 5
- 238000013467 fragmentation Methods 0.000 description 5
- 238000006062 fragmentation reaction Methods 0.000 description 5
- 210000004602 germ cell Anatomy 0.000 description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 5
- 239000005556 hormone Substances 0.000 description 5
- 229940088597 hormone Drugs 0.000 description 5
- 229960002751 imiquimod Drugs 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 108010092830 integrin alpha7beta1 Proteins 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 239000000439 tumor marker Substances 0.000 description 5
- 238000002255 vaccination Methods 0.000 description 5
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 102100028622 Brefeldin A-inhibited guanine nucleotide-exchange protein 3 Human genes 0.000 description 4
- 108010078791 Carrier Proteins Proteins 0.000 description 4
- 102100034497 Cip1-interacting zinc finger protein Human genes 0.000 description 4
- 229910020366 ClO 4 Inorganic materials 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000710327 Homo sapiens Cip1-interacting zinc finger protein Proteins 0.000 description 4
- 101000628535 Homo sapiens Metalloreductase STEAP2 Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102000006992 Interferon-alpha Human genes 0.000 description 4
- 108010047761 Interferon-alpha Proteins 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 4
- 102100026711 Metalloreductase STEAP2 Human genes 0.000 description 4
- 102100028194 Mitogen-activated protein kinase kinase kinase kinase 4 Human genes 0.000 description 4
- 101710144518 Mitogen-activated protein kinase kinase kinase kinase 4 Proteins 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 108010004729 Phycoerythrin Proteins 0.000 description 4
- 108010054050 Plectin Proteins 0.000 description 4
- 102000056300 Plectins Human genes 0.000 description 4
- 102100038358 Prostate-specific antigen Human genes 0.000 description 4
- 108020004511 Recombinant DNA Proteins 0.000 description 4
- 208000006265 Renal cell carcinoma Diseases 0.000 description 4
- 208000000453 Skin Neoplasms Diseases 0.000 description 4
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 4
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 4
- 102100029639 Tryptase alpha/beta-1 Human genes 0.000 description 4
- 230000000735 allogeneic effect Effects 0.000 description 4
- 150000001408 amides Chemical group 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 238000011088 calibration curve Methods 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000006058 immune tolerance Effects 0.000 description 4
- 239000002955 immunomodulating agent Substances 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 229940023041 peptide vaccine Drugs 0.000 description 4
- 230000001817 pituitary effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
- 102100031621 Cysteine and glycine-rich protein 2 Human genes 0.000 description 3
- 101710185482 Cysteine and glycine-rich protein 2 Proteins 0.000 description 3
- 101001006786 Dictyostelium discoideum Kinesin-related protein 7 Proteins 0.000 description 3
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 101000695868 Homo sapiens Brefeldin A-inhibited guanine nucleotide-exchange protein 3 Proteins 0.000 description 3
- 101001006787 Homo sapiens Kinesin-like protein KIF7 Proteins 0.000 description 3
- 101001124900 Homo sapiens PR domain zinc finger protein 8 Proteins 0.000 description 3
- 101000640289 Homo sapiens Synemin Proteins 0.000 description 3
- 101000844217 Homo sapiens Thioredoxin domain-containing protein 16 Proteins 0.000 description 3
- 101000795074 Homo sapiens Tryptase alpha/beta-1 Proteins 0.000 description 3
- 101000776450 Homo sapiens Uncharacterized protein C6orf132 Proteins 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 102100027929 Kinesin-like protein KIF7 Human genes 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 102100040274 Leucine-zipper-like transcriptional regulator 1 Human genes 0.000 description 3
- 101710138656 Leucine-zipper-like transcriptional regulator 1 Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 102100029128 PR domain zinc finger protein 8 Human genes 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108010090804 Streptavidin Proteins 0.000 description 3
- 102100033920 Synemin Human genes 0.000 description 3
- 102100032034 Thioredoxin domain-containing protein 16 Human genes 0.000 description 3
- 102000002689 Toll-like receptor Human genes 0.000 description 3
- 108020000411 Toll-like receptor Proteins 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
- 102100031217 Uncharacterized protein C6orf132 Human genes 0.000 description 3
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 3
- 231100000504 carcinogenesis Toxicity 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000000139 costimulatory effect Effects 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 230000002584 immunomodulator Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 210000002752 melanocyte Anatomy 0.000 description 3
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 108700002563 poly ICLC Proteins 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000037452 priming Effects 0.000 description 3
- 238000011471 prostatectomy Methods 0.000 description 3
- 230000009145 protein modification Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 108091008146 restriction endonucleases Proteins 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 201000000849 skin cancer Diseases 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- VUCNQOPCYRJCGQ-UHFFFAOYSA-N 2-[4-(hydroxymethyl)phenoxy]acetic acid Chemical class OCC1=CC=C(OCC(O)=O)C=C1 VUCNQOPCYRJCGQ-UHFFFAOYSA-N 0.000 description 2
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 2
- JVJFIQYAHPMBBX-UHFFFAOYSA-N 4-hydroxynonenal Chemical compound CCCCCC(O)C=CC=O JVJFIQYAHPMBBX-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 102100027705 Astrotactin-2 Human genes 0.000 description 2
- 101710120650 Astrotactin-2 Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 2
- 210000003359 CD4-positive helper T lymphocyte Anatomy 0.000 description 2
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- 102000036364 Cullin Ring E3 Ligases Human genes 0.000 description 2
- 108091007045 Cullin Ring E3 Ligases Proteins 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010040721 Flagellin Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 229940032072 GVAX vaccine Drugs 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 description 2
- 102100028971 HLA class I histocompatibility antigen, C alpha chain Human genes 0.000 description 2
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 2
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 2
- 108010058607 HLA-B Antigens Proteins 0.000 description 2
- 108010052199 HLA-C Antigens Proteins 0.000 description 2
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 2
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 2
- 102100030332 Homeobox protein Mohawk Human genes 0.000 description 2
- 101000990997 Homo sapiens Homeobox protein Mohawk Proteins 0.000 description 2
- 101000605528 Homo sapiens Kallikrein-2 Proteins 0.000 description 2
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 2
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 2
- 101001047102 Homo sapiens Potassium voltage-gated channel subfamily G member 1 Proteins 0.000 description 2
- 101000768466 Homo sapiens Protein unc-13 homolog B Proteins 0.000 description 2
- 101000798076 Homo sapiens T cell receptor delta constant Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 2
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 102000000704 Interleukin-7 Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 102100038356 Kallikrein-2 Human genes 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 2
- 108010010995 MART-1 Antigen Proteins 0.000 description 2
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- AIJULSRZWUXGPQ-UHFFFAOYSA-N Methylglyoxal Chemical compound CC(=O)C=O AIJULSRZWUXGPQ-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 108010088373 Neurofilament Proteins Proteins 0.000 description 2
- 102000008763 Neurofilament Proteins Human genes 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 2
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 102100022783 Potassium voltage-gated channel subfamily G member 1 Human genes 0.000 description 2
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 102100027897 Protein unc-13 homolog B Human genes 0.000 description 2
- 108010026552 Proteome Proteins 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 241000713880 Spleen focus-forming virus Species 0.000 description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 230000037453 T cell priming Effects 0.000 description 2
- 102100032272 T cell receptor delta constant Human genes 0.000 description 2
- 108700042076 T-Cell Receptor alpha Genes Proteins 0.000 description 2
- 108700042077 T-Cell Receptor beta Genes Proteins 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 108060005989 Tryptase Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 2
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 102100021365 Zinc finger protein 426 Human genes 0.000 description 2
- 101710145258 Zinc finger protein 426 Proteins 0.000 description 2
- GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 2
- 229960000853 abiraterone Drugs 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 239000008364 bulk solution Substances 0.000 description 2
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
- LYQFWZFBNBDLEO-UHFFFAOYSA-M caesium bromide Chemical compound [Br-].[Cs+] LYQFWZFBNBDLEO-UHFFFAOYSA-M 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 230000021235 carbamoylation Effects 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 229940030156 cell vaccine Drugs 0.000 description 2
- 230000021617 central nervous system development Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229940047120 colony stimulating factors Drugs 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 230000004041 dendritic cell maturation Effects 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- OQALFHMKVSJFRR-UHFFFAOYSA-N dityrosine Chemical compound OC(=O)C(N)CC1=CC=C(O)C(C=2C(=CC=C(CC(N)C(O)=O)C=2)O)=C1 OQALFHMKVSJFRR-UHFFFAOYSA-N 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000012520 frozen sample Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000003500 gene array Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 2
- 229920000140 heteropolymer Polymers 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 229940124452 immunizing agent Drugs 0.000 description 2
- 230000002998 immunogenetic effect Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000008676 import Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 108010024084 integrin alpha7 Proteins 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 108010074108 interleukin-21 Proteins 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229960004942 lenalidomide Drugs 0.000 description 2
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- ZCQGVFNHUATAJY-UHFFFAOYSA-N methyl 2-[methyl(prop-2-enoyl)amino]acetate Chemical compound COC(=O)CN(C)C(=O)C=C ZCQGVFNHUATAJY-UHFFFAOYSA-N 0.000 description 2
- 239000011325 microbead Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 2
- 210000005044 neurofilament Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 230000000683 nonmetastatic effect Effects 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 150000003254 radicals Chemical group 0.000 description 2
- HCWPIIXVSYCSAN-OIOBTWANSA-N radium-223 Chemical compound [223Ra] HCWPIIXVSYCSAN-OIOBTWANSA-N 0.000 description 2
- 229960005562 radium-223 Drugs 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 208000019465 refractory cytopenia of childhood Diseases 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 2
- 229960003310 sildenafil Drugs 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 208000000649 small cell carcinoma Diseases 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000006104 solid solution Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229960001796 sunitinib Drugs 0.000 description 2
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 230000002381 testicular Effects 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 108010060175 trypsinogen activation peptide Proteins 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000000277 virosome Substances 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 description 1
- DMQYDVBIPXAAJA-VHXPQNKSSA-N (3z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)-(5-methyl-1h-imidazol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1CN(CC)CCC1NC1=CC=C(NC(=O)\C2=C(/C=3NC=C(C)N=3)C=3C=C(F)C=CC=3)C2=C1 DMQYDVBIPXAAJA-VHXPQNKSSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- 101150028074 2 gene Proteins 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- KFDPCYZHENQOBV-UHFFFAOYSA-N 2-(bromomethyl)-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1CBr KFDPCYZHENQOBV-UHFFFAOYSA-N 0.000 description 1
- IOJUJUOXKXMJNF-UHFFFAOYSA-N 2-acetyloxybenzoic acid [3-(nitrooxymethyl)phenyl] ester Chemical compound CC(=O)OC1=CC=CC=C1C(=O)OC1=CC=CC(CO[N+]([O-])=O)=C1 IOJUJUOXKXMJNF-UHFFFAOYSA-N 0.000 description 1
- IZQAUUVBKYXMET-UHFFFAOYSA-N 2-bromoethanamine Chemical compound NCCBr IZQAUUVBKYXMET-UHFFFAOYSA-N 0.000 description 1
- JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- SEBPXHSZHLFWRL-UHFFFAOYSA-N 3,4-dihydro-2,2,5,7,8-pentamethyl-2h-1-benzopyran-6-ol Chemical compound O1C(C)(C)CCC2=C1C(C)=C(C)C(O)=C2C SEBPXHSZHLFWRL-UHFFFAOYSA-N 0.000 description 1
- HXHAJRMTJXHJJZ-UHFFFAOYSA-N 3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-(4-pyrrolidin-1-ylbutylcarbamoylamino)-1,2-thiazole-4-carboxamide Chemical compound S1N=C(OCC=2C(=CC(Br)=CC=2F)F)C(C(=O)N)=C1NC(=O)NCCCCN1CCCC1 HXHAJRMTJXHJJZ-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
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- QHRCVGXBBIRPTE-UHFFFAOYSA-N 5-ethyl-4-(4-methoxyphenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC(OC)=CC=2)=C1CC QHRCVGXBBIRPTE-UHFFFAOYSA-N 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010049777 Ankyrins Proteins 0.000 description 1
- 102000008102 Ankyrins Human genes 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- BXTVQNYQYUTQAZ-UHFFFAOYSA-N BNPS-skatole Chemical compound N=1C2=CC=CC=C2C(C)(Br)C=1SC1=CC=CC=C1[N+]([O-])=O BXTVQNYQYUTQAZ-UHFFFAOYSA-N 0.000 description 1
- 241001289141 Babr Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 108020004513 Bacterial RNA Proteins 0.000 description 1
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 229920002498 Beta-glucan Polymers 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 101710100909 Brefeldin A-inhibited guanine nucleotide-exchange protein 3 Proteins 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 101000709520 Chlamydia trachomatis serovar L2 (strain 434/Bu / ATCC VR-902B) Atypical response regulator protein ChxR Proteins 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 108010072732 Core Binding Factors Proteins 0.000 description 1
- 102000006990 Core Binding Factors Human genes 0.000 description 1
- 102100037313 Core-binding factor subunit beta Human genes 0.000 description 1
- 101710145030 Core-binding factor subunit beta Proteins 0.000 description 1
- 241000723655 Cowpea mosaic virus Species 0.000 description 1
- 108091029523 CpG island Proteins 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- 102100033270 Cyclin-dependent kinase inhibitor 1 Human genes 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- YVGGHNCTFXOJCH-UHFFFAOYSA-N DDT Chemical compound C1=CC(Cl)=CC=C1C(C(Cl)(Cl)Cl)C1=CC=C(Cl)C=C1 YVGGHNCTFXOJCH-UHFFFAOYSA-N 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 108091008102 DNA aptamers Proteins 0.000 description 1
- 238000007399 DNA isolation Methods 0.000 description 1
- 238000013382 DNA quantification Methods 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 102100040278 E3 ubiquitin-protein ligase RNF19A Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 102100030013 Endoribonuclease Human genes 0.000 description 1
- 101710199605 Endoribonuclease Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 101150008284 FKBP10 gene Proteins 0.000 description 1
- 240000008168 Ficus benjamina Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 208000032320 Germ cell tumor of testis Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102000001398 Granzyme Human genes 0.000 description 1
- 101150009006 HIS3 gene Proteins 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 108010036115 Histone Methyltransferases Proteins 0.000 description 1
- 102000011787 Histone Methyltransferases Human genes 0.000 description 1
- 102100028092 Homeobox protein Nkx-3.1 Human genes 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000922020 Homo sapiens Cysteine and glycine-rich protein 1 Proteins 0.000 description 1
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 1
- 101000578249 Homo sapiens Homeobox protein Nkx-3.1 Proteins 0.000 description 1
- 101000608935 Homo sapiens Leukosialin Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 101001019104 Homo sapiens Mediator of RNA polymerase II transcription subunit 14 Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101001091365 Homo sapiens Plasma kallikrein Proteins 0.000 description 1
- 101000952113 Homo sapiens Probable ATP-dependent RNA helicase DDX5 Proteins 0.000 description 1
- 101000605534 Homo sapiens Prostate-specific antigen Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000669460 Homo sapiens Toll-like receptor 5 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 101000777646 Homo sapiens Uncharacterized protein encoded by LINC01587 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 1
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 1
- 102000012355 Integrin beta1 Human genes 0.000 description 1
- 108010022222 Integrin beta1 Proteins 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
- 102100026720 Interferon beta Human genes 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 102100030703 Interleukin-22 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 201000008645 Joubert syndrome Diseases 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100039564 Leukosialin Human genes 0.000 description 1
- 229910018119 Li 3 PO 4 Inorganic materials 0.000 description 1
- 229910013684 LiClO 4 Inorganic materials 0.000 description 1
- 229910013553 LiNO Inorganic materials 0.000 description 1
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000057 Mannan Polymers 0.000 description 1
- 102100025169 Max-binding protein MNT Human genes 0.000 description 1
- 206010027452 Metastases to bone Diseases 0.000 description 1
- 206010050513 Metastatic renal cell carcinoma Diseases 0.000 description 1
- 102000002151 Microfilament Proteins Human genes 0.000 description 1
- 108010040897 Microfilament Proteins Proteins 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 102100028192 Mitogen-activated protein kinase kinase kinase kinase 2 Human genes 0.000 description 1
- 101710144533 Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 1
- 108010006519 Molecular Chaperones Proteins 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100096028 Mus musculus Smok1 gene Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- GUVMFDICMFQHSZ-UHFFFAOYSA-N N-(1-aminoethenyl)-1-[4-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[hydroxy-[[3-[hydroxy-[[3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[5-(4-amino-2-oxopyrimidin-1-yl)-2-[[hydroxy-[2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylimidazole-4-carboxamide Chemical compound CC1=C(C(=O)NC(N)=C)N=CN1C1OC(COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)CO)C(OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)O)C1 GUVMFDICMFQHSZ-UHFFFAOYSA-N 0.000 description 1
- LPPJGTSPIBSYQO-YLNOTJRMSA-N N-Acetyl-S-(1,2-dichlorovinyl)-cysteine Chemical compound CC(=O)N[C@H](C(O)=O)CS\C(Cl)=C/Cl LPPJGTSPIBSYQO-YLNOTJRMSA-N 0.000 description 1
- VIHYIVKEECZGOU-UHFFFAOYSA-N N-acetylimidazole Chemical compound CC(=O)N1C=CN=C1 VIHYIVKEECZGOU-UHFFFAOYSA-N 0.000 description 1
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010029098 Neoplasm skin Diseases 0.000 description 1
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
- 102000012547 Olfactory receptors Human genes 0.000 description 1
- 108050002069 Olfactory receptors Proteins 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108700006640 OspA Proteins 0.000 description 1
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
- 239000012648 POLY-ICLC Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000030412 Plakin Human genes 0.000 description 1
- 108091000120 Plakin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102100037434 Probable ATP-dependent RNA helicase DDX5 Human genes 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- 101710171947 Putative thioredoxin 2 Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 101100394989 Rhodopseudomonas palustris (strain ATCC BAA-98 / CGA009) hisI gene Proteins 0.000 description 1
- 238000010847 SEQUEST Methods 0.000 description 1
- 108091006552 SLC30A4 Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 108010002687 Survivin Proteins 0.000 description 1
- 102100035603 Synaptopodin-2 Human genes 0.000 description 1
- 101710122802 Synaptopodin-2 Proteins 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
- 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 239000012163 TRI reagent Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- NYTOUQBROMCLBJ-UHFFFAOYSA-N Tetranitromethane Chemical compound [O-][N+](=O)C([N+]([O-])=O)([N+]([O-])=O)[N+]([O-])=O NYTOUQBROMCLBJ-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102100039357 Toll-like receptor 5 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 102100034030 Transient receptor potential cation channel subfamily M member 8 Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 102000001400 Tryptase Human genes 0.000 description 1
- 101710134953 Tryptase beta-2 Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 102100031590 Uncharacterized protein encoded by LINC01587 Human genes 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046799 Uterine leiomyosarcoma Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 108700020467 WT1 Proteins 0.000 description 1
- 101150084041 WT1 gene Proteins 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 101001062349 Xenopus tropicalis Forkhead box protein A1 Proteins 0.000 description 1
- 101710185494 Zinc finger protein Proteins 0.000 description 1
- 102100023597 Zinc finger protein 816 Human genes 0.000 description 1
- 102100026641 Zinc transporter 4 Human genes 0.000 description 1
- 102100023144 Zinc transporter ZIP6 Human genes 0.000 description 1
- 101710097851 Zinc transporter ZIP6 Proteins 0.000 description 1
- 108091006550 Zinc transporters Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 238000011467 adoptive cell therapy Methods 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 208000037842 advanced-stage tumor Diseases 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940060265 aldara Drugs 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 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
- 238000009167 androgen deprivation therapy Methods 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 1
- 230000008349 antigen-specific humoral response Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- VGPYEHKOIGNJKV-UHFFFAOYSA-N asulam Chemical compound COC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 VGPYEHKOIGNJKV-UHFFFAOYSA-N 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 238000005422 blasting Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 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
- 230000005907 cancer growth Effects 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000002327 cardiovascular agent Substances 0.000 description 1
- 229940125692 cardiovascular agent Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000010094 cellular senescence Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000002230 centromere Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- QUPYHCHUQVNFJW-UHFFFAOYSA-M cesium;thiocyanate Chemical compound [Cs+].[S-]C#N QUPYHCHUQVNFJW-UHFFFAOYSA-M 0.000 description 1
- 230000002925 chemical effect Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 230000006328 chemical modification of amino acids Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 239000001752 chlorophylls and chlorophyllins Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- 230000021953 cytokinesis Effects 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 108010017271 denileukin diftitox Proteins 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 125000004989 dicarbonyl group Chemical group 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000006334 disulfide bridging Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 229940056913 eftilagimod alfa Drugs 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000001437 electrospray ionisation time-of-flight quadrupole detection Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000008622 extracellular signaling Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000002594 fluoroscopy Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 238000003208 gene overexpression Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 230000000091 immunopotentiator Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 210000003963 intermediate filament Anatomy 0.000 description 1
- 238000010813 internal standard method Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 108010057670 laminin 1 Proteins 0.000 description 1
- 229910052747 lanthanoid Inorganic materials 0.000 description 1
- 150000002602 lanthanoids Chemical class 0.000 description 1
- 125000001909 leucine group Chemical class [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000007477 logistic regression Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000010453 lymph node cancer Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 108010051618 macrophage stimulatory lipopeptide 2 Proteins 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 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
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 150000002730 mercury Chemical class 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229940035036 multi-peptide vaccine Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 210000003365 myofibril Anatomy 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 201000008026 nephroblastoma Diseases 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- 230000017511 neuron migration Effects 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- VXAPDXVBDZRZKP-UHFFFAOYSA-N nitric acid phosphoric acid Chemical compound O[N+]([O-])=O.OP(O)(O)=O VXAPDXVBDZRZKP-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 231100001221 nontumorigenic Toxicity 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229940100027 ontak Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction 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
- 208000003154 papilloma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000000863 peptide conjugate Substances 0.000 description 1
- 230000016446 peptide cross-linking Effects 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 229940125667 peptide vaccine candidate Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical group OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229940115270 poly iclc Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229940021993 prophylactic vaccine Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 210000000064 prostate epithelial cell Anatomy 0.000 description 1
- 201000002709 prostate leiomyosarcoma Diseases 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 230000016434 protein splicing Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 229940034080 provenge Drugs 0.000 description 1
- 229940076788 pyruvate Drugs 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000004161 regulation of exocytosis Effects 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 230000025488 response to cold Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000004621 scanning probe microscopy Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 229940074386 skatole Drugs 0.000 description 1
- 210000002356 skeleton Anatomy 0.000 description 1
- 208000020352 skin basal cell carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000008410 smoothened signaling pathway Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
- PUZPDOWCWNUUKD-ULWFUOSBSA-M sodium;fluorine-18(1-) Chemical compound [18F-].[Na+] PUZPDOWCWNUUKD-ULWFUOSBSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960000835 tadalafil Drugs 0.000 description 1
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 1
- 108010010186 talactoferrin alfa Proteins 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- 208000002918 testicular germ cell tumor Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 208000013076 thyroid tumor Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 108091006107 transcriptional repressors Proteins 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 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
- 239000012588 trypsin Substances 0.000 description 1
- 239000000107 tumor biomarker Substances 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 210000005043 type IV intermediate filament Anatomy 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 210000001644 umbilical artery Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 239000012646 vaccine adjuvant Substances 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 229960002381 vardenafil Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
- 230000002034 xenobiotic effect Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- 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
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino 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
- 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
- C12N15/115—Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0639—Dendritic cells, e.g. Langherhans cells in the epidermis
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6445—Kallikreins (3.4.21.34; 3.4.21.35)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- 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
- G01N33/57407—Specifically defined cancers
-
- 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
- G01N33/5748—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving oncogenic proteins
-
- 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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6848—Methods of protein analysis involving mass spectrometry
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
- A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- 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
- C12N2310/16—Aptamers
-
- 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
- C12N2510/00—Genetically modified 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
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/106—Plasmid DNA for vertebrates
- C12N2800/107—Plasmid DNA for vertebrates for mammalian
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/16—Primer sets for multiplex assays
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2570/00—Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes
-
- 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)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Urology & Nephrology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Plant Pathology (AREA)
Abstract
Description
a)がん精巣抗原:T細胞によって認識され得る初めて同定されたTAAはこのクラスに属し、元々はがん精巣(CT)抗原と称されたが、それは、そのメンバーが組織学的に異なるヒト腫瘍において発現し、正常組織では精巣の精母細胞/精原細胞のみに存在し、時として胎盤に存在するためであった。精巣の細胞は、クラスIおよびII HLA分子を発現しないので、これらの抗原は正常組織のT細胞によって認識され得ず、したがって免疫学的に腫瘍特異的と見なされる。CT抗原の周知の例は、MAGEファミリーメンバーおよびNY−ESO−1である。
b)分化抗原:これらのTAAは、腫瘍と、それから腫瘍が生じる正常組織との間で共有される。既知の分化抗原のほとんどは、黒色腫および正常メラノサイトに見いだされる。これらのメラノサイト系関連タンパク質の多くは、メラニン生合成に関与し、したがって腫瘍特異的でないが、それでもなおがん免疫療法のために広く利用されている。例としては、黒色腫に対するチロシナーゼとMelan−A/MART−1、または前立腺がんに対するPSAが挙げられるが、これに限定されるものではない。
c)過剰発現TAA:広範に発現されるTAAをエンコードする遺伝子は、組織学的に異なる型の腫瘍において検出され、多数の正常組織においても概してより低い発現レベルで検出されている。正常組織によってプロセスされて潜在的に提示さるエピトープの多くは、T細胞認識の閾値レベル未満であり得る一方で、腫瘍細胞におけるそれらの過剰発現は、以前確立された免疫寛容を破壊することにより、抗がん応答を始動し得る。このクラスのTAAの顕著な例は、Her−2/neu、サバイビン、テロメラーゼまたはWT1である。
d)腫瘍特異的抗原:これらのユニークなTAAは、正常な遺伝子(β−カテニン、CDK4など)の変異から生じる。これらの分子変化のいくつかは、腫瘍性形質転換および/または進行に関連している。腫瘍特異的抗原は、通常、正常組織に対する自己免疫反応のリスクなしに、強力な免疫応答を誘導できる。他方、これらのTAAは、ほとんどの場合、その上でそれらが同定されたまさにその腫瘍のみと関係があり、通常は、多くの個々の腫瘍間で共有されない。腫瘍特異的(関連)イソ型を有するタンパク質では、ペプチドの腫瘍特異性(または関連性)はまた、ペプチドが腫瘍(関連)エクソンに由来する場合に生じてもよい。
e)異常な翻訳後修飾から生じるTAA:このようなTAAは、特異的でなく腫瘍において過剰発現もされないタンパク質から生じてもよいが、それでもなお、腫瘍において主に活性である翻訳後プロセスによって腫瘍関連になる。このクラスの例は、腫瘍にMUC1のような新規エピトープをもたらす改変グリコシル化パターン、または腫瘍特異的であってもなくてもよい分解中のタンパク質スプライシングのような事象から生じる。
f)オンコウイルスタンパク質:これらのTAAはウイルスタンパク質であり、それらは発がん過程において重要な役割を果たしてもよく、外来性である(ヒト由来でない)ため、それらはT細胞応答を誘起し得る。このようなタンパク質の例は、子宮頸がんにおいて発現されるヒト乳頭腫16型ウイルスタンパク質E6およびE7である。
マイトジェン−活性化タンパク質キナーゼキナーゼキナーゼキナーゼ4(MAP4K4)MAP4K4は、セリン/スレオニンタンパク質キナーゼファミリーのメンバーであり、TNF−αシグナル伝達経路を媒介する(RefSeq,2002)。MAP4K4は、前立腺がんの侵襲性のバイオマーカーとして示唆されている(Rizzardi et al.,2014)。
RAB3B、メンバーRAS発がん遺伝子ファミリー(RAB3B)−RAB3Bは、開口分泌の調節に関与するとされている低分子量GTP結合タンパク質である(Rotondo et al.,2009)。RAB3Bは前立腺がん患者において過剰発現され、AR、FoxA1、およびNKX3−1に加えて、RAB3Bが前立腺がん進行の重要な調節因子であることが示唆される(Tan et al.,2012)。
TRAF2およびNCK相互作用キナーゼ(TNIK)−TNIKは胚中心キナーゼであり、アクチン細胞骨格の調節に潜在的に関与する(Fu et al.,1999)。TNIKは、Wnt標的遺伝子の不可欠かつ特異的なアクチベーターである。TNIKは、TRAF6依存性のJNKおよびNF−κBシグナル伝達の中心的存在、およびヒトB細胞におけるシグナルの活性化および変換のトランスデューサとして記載されている(Shkoda et al.,2012)。ホルモン受容体陰性乳がんでは、TNIKは、成長および増殖に影響を及ぼす潜在的ながん遺伝子として同定された(Jiao et al.,2013)。
トリプターゼα/β1(TPSAB1)、トリプターゼβ2(TPSB2)−TPSAB1およびTPSB2は、どちらも主に肥満細胞によって発現されるセリンプロテアーゼである。腫瘍組織におけるトリプターゼ陽性肥満細胞の存在は、黒色腫、子宮内膜がん、乳がん、胃がんおよび結腸直腸がんをはじめとする、いくつかのがん型における血管新生と相関する(Ammendola et al.,2014)。
同一性百分率=100[1−(C/R)]
式中、Cは、参照配列と比較される配列との間のアライメント長にわたる、参照配列と比較配列の間の差異の数であり、
(i)比較配列中に対応する整列塩基またはアミノ酸を有しない、参照配列中の各塩基またはアミノ酸、および
(ii)参照配列中の各ギャップ、および
(iii)比較配列中の整列塩基またはアミノ酸と異なる、参照配列中の各整列塩基またはアミノ酸が差異を構成して、
(iiii)アライメントは、整合配列の1位から開始しなくてはならず;
Rは、比較配列とのアライメント長にわたる参照配列中の塩基またはアミノ酸の数であり、参照配列中に生じる任意のギャップもまた、塩基またはアミノ酸として数えられる。
(a)溶液中のまたは凍結乾燥形態の上述の医薬組成物を含有する容器;
(b)任意選択的に、凍結乾燥製剤のための希釈剤または再構成溶液を含有する第2の容器;および
(c)任意選択的に、(i)溶液の使用、または(ii)凍結乾燥製剤の再構成および/または使用のための取扱説明書
を含んでなるキットをさらに目的とする。
1.腫瘍性物質からのHLAリガンドを質量分析法によって同定した
2.ゲノム規模メッセンジャーリボ核酸(mRNA)発現解析を使用して、一連の正常器官および組織と比較して悪性組織(前立腺がん)中の遺伝子過剰発現を同定した
3.同定されたHLAリガンドを遺伝子発現データと比較した。好ましくは、ステップ2で検出されたような選択的に発現されまたは過剰発現される遺伝子によってコードされる、腫瘍組織上で過剰提示されまたは選択的に提示されるペプチドが、多重ペプチドワクチンのための適切なTUMAP候補と見なされた。
4.同定されたペプチドのTUMAPとしての妥当性を支持する追加的な証拠を同定するために、文献調査を実施した
5.mRNAレベルでの過剰発現の関連性をステップ3からの選択されたTUMAPの腫瘍組織上における再検出と、健常組織における検出の欠如(またはまれな)検出によって確認した。
6.選択されたペプチドによる生体内T細胞応答の誘導が可能かどうかを評価するために、健常ドナーならびに前立腺がん患者からのヒトT細胞を使用して、生体外免疫原性アッセイを実施した。
細胞表面に提示される腫瘍関連ペプチドの同定および定量化
組織サンプル
患者の前立腺腫瘍組織は、Asterand(Detroit,USA and Royston,Herts,UK);BioServe(Beltsville,MD,USA);Geneticist Inc.(Glendale,CA,USA);Indivumed GmbH(Hamburg,Germany);Saint Savas Hospital,Athens,Greece,University Hospital of Tubingenから入手された。正常組織は、Asterand(Detroit,USA and Royston,Herts,UK);Bio−Options Inc,CA,USA;BioServe,Beltsville,MD,USA;Capital BioScience Inc,Rockville,MD,USA;Geneticist Inc.,Glendale,CA,USA;University Hospital of Geneva;University Hospital of Heidelberg;Kyoto Prefectural University of Medicine(KPUM);Osaka City University(OCU);University Hospital Munich;ProteoGenex Inc.,Culver City,CA,USA;Tissue Solutions Ltd.,Glasgow,United Kingdom;University Hospital of Tubingenから入手された。全ての患者の告知に基づく同意書は、外科手術または検死解剖前に得られた。組織は切除の直後に衝撃凍結されて、TUMAPの単離まで−70℃未満で保存された。
衝撃凍結組織サンプルからのHLAペプチド貯留は、わずかに修正されたプロトコル(Falk et al.,1991;Seeger et al.,1999)に従って、HLA−A*02−特異的抗体BB7.2、HLA−A、−B、−C特異的抗体W6/32、CNBr活性化セファロース、酸処理、および限外濾過を使用して、免疫沈殿によって固形組織から得られた。
得られたHLAペプチド貯留は、逆相クロマトグラフィー(nanoAcquity UPL C system、Waters)によってそれらの疎水性に従って分離し、ESI源を装着したLTQ−velosおよびfusion hybrid質量分光計(ThermoElectron)内で溶出ペプチドを分析した。ペプチド貯留は、毎分400nLの流速を適用して、1.7μm C18逆相材料(Waters)で充填された分析用融合シリカマイクロキャピラリーカラム(75μm内径×250mm)上に直接挿入した。引き続いて、毎分300nLの流速で10%から33%へのBの二段階180分間二成分勾配を用いて、ペプチドを分離した。勾配は、溶媒A(水中の0.1%ギ酸)および溶媒B(アセトニトリル中の0.1%ギ酸)から構成された。nanoESI源への導入には、金被覆ガラス毛管(PicoTip,New Objective)を使用した。LTQ−Orbitrap質量分光計は、TOP5ストラテジーを使用してデータ依存モードで操作した。手短に述べると、Orbitrap(R=30000)内の高質量精度の完全スキャンでスキャンサイクルを開始し、これもまたOrbitrap(R=7500)内の5種の最も豊富な前駆イオンのMS/MSスキャンがそれに続き、以前選択されたイオンは動的に排除された。タンデム質量スペクトルは、SEQUESTおよび追加的な手動調節によって解釈した。同定されたペプチド配列は、生成された天然ペプチド断片化パターンと、配列が同一の合成参照ペプチドの断片化パターンとの比較によって確認した。
本発明のペプチドをコードする遺伝子発現プロファイリング
正常細胞と比較した腫瘍細胞上のペプチドの過剰提示または特異的提示は、免疫療法におけるその有用性にとって十分であり、いくつかのペプチドは、それらの起源タンパク質が正常組織にもまた存在するにもかかわらず、腫瘍特異的である。それでもなお、mRNA発現プロファイリングは、免疫療法のためのペプチド標的の選択において、安全性のレベルを高めることができる。特に、アフィニティ成熟TCRなどの安全性リスクが高い治療の選択肢では、理想的な標的ペプチドは、腫瘍に特有で正常組織上には見いだされないタンパク質に由来する。
外科的に除去された組織標本は、告知に基づく同意書が各患者から入手された後に、上述の通り提供された(実施例1を参照されたい)。腫瘍組織標本を手術直後にスナップ凍結し、その後、液体窒素下で乳鉢と乳棒を用いて均質化した。TRI試薬(Ambion,Darmstadt,Germany)を使用して、これらのサンプルから全RNAを調製し、RNeasy(QIAGEN,Hilden,Germany)による精製がそれに続き;どちらの方法も製造業者のプロトコルに従って実施した。
全ての腫瘍および正常組織RNAサンプルの遺伝子発現解析は、Affymetrix Human Genome(HG)U133AまたはHG−U133 Plus 2.0オリゴヌクレオチドマイクロアレイ(Affymetrix,Santa Clara,CA,USA)によって実施した。全てのステップは、Affymetrixマニュアルに従って実施した。簡単に述べると、マニュアルに記載されるようにして、SuperScript RTII(Invitrogen)およびオリゴdT−T7プライマー(MWG Biotech,Ebersberg,Germany)を使用して、5〜8μgの全RNAから二本鎖cDNAを合成した。生体外転写は、U133AアレイのためのBioArray High Yield RNA Transcript Labelling Kit(ENZO Diagnostics,Inc.,Farmingdale,NY,USA)を用いて、またはU133 Plus 2.0のためのGeneChip IVT Labelling Kit(Affymetrix)を用いて実施し、cRNA断片化、ハイブリダイゼーション、そしてストレプトアビジン−フィコエリトリンとビオチン化抗ストレプトアビジン抗体(Molecular Probes,Leiden,Netherlands)とを用いた染色がそれに続いた。Agilent 2500A GeneArray Scanner(U133A)またはAffymetrix Gene−Chip Scanner 3000(U133 Plus 2.0)で画像をスキャンして、全てのパラメータについてデフォルト設定を使用して、GCOSソフトウェア(Affymetrix)によってデータを解析した。正規化のために、Affymetrixによって提供される100個のハウスキーピング遺伝子を使用した。ソフトウェアによって与えられるシグナルlog比から、相対的発現値を計算し、正常な腎臓サンプルを自由裁量で1.0に設定した。前立腺がんにおいて高度に過剰発現され、または排他的に発現される、本発明の起源遺伝子の例示的発現プロファイルが、図2A〜Eに示される。さらなる例示的遺伝子の発現スコアは、表14に示される。
MHCクラスI提示ペプチドの生体外免疫原性
本発明のTUMAPの免疫原性に関する情報を得るために、本発明者らは、ペプチド/MHC複合体および抗CD28抗体を負荷した人工抗原提示細胞(aAPC)によるCD8+T細胞の反復刺激に基づく、生体外T細胞プライミングアッセイを用いて研究を実施した。このようにして、本発明者らは、いくつかの選択されたTUMAPについて、本発明のHLA−A*0201拘束性およびHLA−A*24拘束性TUMAPに対する免疫原性を示し得て、これらのペプチドが、それに対するCD8前駆体T細胞がヒトに存在する、T細胞エピトープであることが実証された(表15A+B)。
ペプチドMHC複合体(pMHC)および抗CD28抗体を負荷した、人工抗原提示細胞による生体外刺激を実施するために、本発明者らは、最初に、告知に基づく同意後に、University clinics Mannheim,Germanyから得られた健常ドナーのCD8ミクロビーズ(Miltenyi Biotec,Bergisch−Gladbach,Germany)を使用した正の選択を通じて、新鮮HLA−A*02白血球除去生成物からCD8+T細胞を単離した。
HLAクラスIペプチドを試験するために、ペプチド特異的T細胞株の生成によって生体外免疫原性が実証され得た。本発明の2種のペプチドの、TUMAP特異的多量体染色後の例示的フローサイトメトリー結果は、対応する陰性対照と共に図3に示される。本発明からの5種のペプチドの結果は、表15Aに要約される。本発明からの6種のペプチドのさらなる結果は、表15Bに要約される。
出願人によって実施された本発明のペプチドの生体外免疫原性実験の例示的結果。<20 % = +; 20 % - 49 % = ++; 50 % - 69 %= +++; >= 70 % = ++++
出願人によって実施された本発明のペプチドの生体外免疫原性実験の例示的結果。<20 % = +; 20 % - 49 % = ++; 50 % - 69 %= +++; >= 70 % = ++++
ペプチドの合成
Fmocストラテジーを使用した標準的な十分に確立された固相ペプチド合成を使用して、全てのペプチドを合成した。個々のペプチドのアイデンティティーおよび純度は、質量分析および分析用RP−HPLCによって判定された。ペプチドは、純度>50%の白色から灰白色の凍結乾燥物(トリフルオロ酢酸塩)として得られた。全てのTUMAPは、好ましくはトリフルオロ酢酸塩または酢酸塩として投与され、その他の塩形態もまた可能である。
MHC結合アッセイ
本発明によるT細胞ベースの治療法のための候補ペプチドを、それらのMHC結合能力(親和性)についてさらに試験した。個々のペプチド−MHC複合体は、UVリガンド交換によって生成され、UV感受性ペプチドはUV照射に際して切断されて、分析される目的ペプチドで交換された。ペプチド受容性MHC分子と効果的に結合して安定化し得るペプチド候補のみが、MHC複合体の分離を防止する。交換反応の収率を判定するために、安定化MHC複合体の軽鎖(β2m)の検出に基づくELISAを実施した。アッセイは、Rodenko et al.(Rodenko et al.,2006)に一般的に記載されるようにして実施した。
HLAクラスI拘束性ペプチドとHLA-A*24との結合は、ペプチド交換収率によって評価された: >10% = +; >20% = ++; >50 = +++; > 75% = ++++
HLAクラスI拘束性ペプチドとHLA-A*02との結合は、ペプチド交換収率によって評価された: >10% = +; >20% = ++; >50 = +++; > 75% = ++++
細胞表面に提示される腫瘍関連ペプチドの絶対定量化
抗体および/またはTCRなどのバインダーの生成は、骨の折れる工程であり、いくつかの選択された標的に対してのみ実施されてもよい。腫瘍関連および特異的ペプチドの場合、選択基準としては、提示の排他性および細胞表面に提示されるペプチドの密度が挙げられるが、これに限定されない。本明細書に記載されるようなペプチドの単離および相対定量化に加えて、本発明者らは、記載されるように、細胞当たりの絶対ペプチドコピー数を分析した。固形腫瘍サンプル中の細胞当たりのTUMAPコピーの定量化は、単離されたTUMAPの絶対定量化、TUMAP単離の効率、および分析される組織サンプルの細胞計数を必要とする。
質量分析によるペプチドの正確な定量化のために、内標準法を使用して各ペプチドの検量線を作成した。内標準は各ペプチドの二重同位体標識変異体であり、すなわち、2つの同位体標識アミノ酸がTUMAP合成に含まれた。それは、腫瘍関連ペプチドとはその質量異なるのみであるが、他の物理化学的性質に差異を示さない(Anderson et al.,2012)。内標準を各MSサンプルに添加して、全てのMSシグナルを内標準のMSシグナルに対して正規化し、MS実験間の潜在的な技術的変動を平準化した。
あらゆるタンパク質精製処理と同様に、組織サンプルからのタンパク質の単離には、目的タンパク質のいくらかの損失が伴う。TUMAP単離の効率を判定するために、絶対定量化のために選択された全てのTUMAPについて、ペプチド/MHC複合体を生成した。添加されたものを天然ペプチド/MHC複合体から識別できるように、TUMAPの単一同位体標識バージョンが使用され、すなわち、1つの同位体標識アミノ酸がTUMAP合成に含まれた。これらの複合体は、新鮮に調製された組織溶解産物に、すなわち、TUMAP単離手順の可能な限り早い時点で添加され、次に、以下の親和性精製において、天然ペプチド/MHC複合体のように捕捉された。したがって単一標識TUMAPの回収率を測定することで、個々の天然TUMAPの単離効率に関する結論が可能になる。
絶対ペプチド定量化に供した組織サンプルの細胞数を測定するために、本発明者らは、DNA含量分析を適用した。この方法は、異なる起点の幅広いサンプルに、最も重要なことには、冷凍サンプルに適用できる(Alcoser et al.,2011;Forsey and Chaudhuri,2009;Silva et al.,2013)。ペプチド単離プロトコル中に、組織サンプルを均質溶解産物に処理して、それから小さな溶解産物アリコートを取り出す。アリコートを3つに分割し、それからDNAを単離する(QiaAmp DNA Mini Kit,Qiagen,Hilden,Germany)。蛍光ベースのDNA定量化アッセイ(Qubit dsDNA HS Assay Kit,Life Technologies,Darmstadt,Germany)を使用して、少なくとも2つの反復試験において、各DNA単離からの全DNA含有量を定量化する。
前述の実験のデータを用いて、本発明者らは、サンプルの全ペプチド量を総細胞数で除算して、それに続いて単離効率により除算することで、細胞当たりのTUMAPコピー数を算出した。選択されたペプチドの細胞コピー数は、表17に示される。
Adachi, H. et al., Oncogene 23 (2004): 3495-3500
Allison, J. P. et al., Science 270 (1995): 932-933
American Cancer Society, (2015), www.cancer.org
Ammendola, M. et al., Biomed.Res.Int. 2014 (2014): 154702
Andersen, R. S. et al., Nat.Protoc. 7 (2012): 891-902
Andres, S. A. et al., BMC.Cancer 13 (2013): 326
Appay, V. et al., Eur.J Immunol. 36 (2006): 1805-1814
Arentz, G. et al., Clin Proteomics. 8 (2011): 16
Banchereau, J. et al., Cell 106 (2001): 271-274
Bausch, D. et al., Clin Cancer Res. 17 (2011): 302-309
Beatty, G. et al., J Immunol 166 (2001): 2276-2282
Beggs, J. D., Nature 275 (1978): 104-109
Benjamini, Y. et al., Journal of the Royal Statistical Society.Series B (Methodological), Vol.57 (1995): 289-300
Bhosle, R. C. et al., Biochem.Biophys.Res.Commun. 346 (2006): 768-777
Bouameur, J. E. et al., J Invest Dermatol. 134 (2014): 885-894
Boulter, J. M. et al., Protein Eng 16 (2003): 707-711
Braumuller, H. et al., Nature (2013)
Bresnick, E. H. et al., Nucleic Acids Res. 40 (2012): 5819-5831
Brossart, P. et al., Blood 90 (1997): 1594-1599
Bruckdorfer, T. et al., Curr.Pharm.Biotechnol. 5 (2004): 29-43
Card, K. F. et al., Cancer Immunol.Immunother. 53 (2004): 345-357
Chanock, S. J. et al., Hum.Immunol. 65 (2004): 1211-1223
Chen, L. et al., Med.Oncol 30 (2013): 498
Chong, I. W. et al., Oncol Rep. 16 (2006): 981-988
Clemen, C. S. et al., Acta Neuropathol. 129 (2015): 297-315
Cohen, C. J. et al., J Mol.Recognit. 16 (2003a): 324-332
Cohen, C. J. et al., J Immunol. 170 (2003b): 4349-4361
Cohen, S. N. et al., Proc.Natl.Acad.Sci.U.S.A 69 (1972): 2110-2114
Coligan, J. E. et al., Current Protocols in Protein Science (1995)
Colombetti, S. et al., J Immunol. 176 (2006): 2730-2738
Davidson, B. et al., Hum.Pathol. 45 (2014): 691-700
Deng, M. et al., Oncogene 32 (2013): 4273-4283
Dengjel, J. et al., Clin Cancer Res 12 (2006): 4163-4170
Denkberg, G. et al., J Immunol. 171 (2003): 2197-2207
Dubrowinskaja, N. et al., Cancer Med. (2014)
Falk, K. et al., Nature 351 (1991): 290-296
Faucz, F. R. et al., J Clin Endocrinol.Metab 96 (2011): E135-E140
Fawcett, L. et al., Proc.Natl.Acad.Sci.U.S.A 97 (2000): 3702-3707
Fong, L. et al., Proc.Natl.Acad.Sci.U.S.A 98 (2001): 8809-8814
Forti, S. et al., Breast Cancer Res Treat. 73 (2002): 245-256
Frattini, V. et al., Nat Genet. 45 (2013): 1141-1149
Fu, C. A. et al., J Biol.Chem. 274 (1999): 30729-30737
Gabrilovich, D. I. et al., Nat.Med 2 (1996): 1096-1103
Gattinoni, L. et al., Nat.Rev.Immunol. 6 (2006): 383-393
Gnjatic, S. et al., Proc Natl.Acad.Sci.U.S.A 100 (2003): 8862-8867
Godkin, A. et al., Int.Immunol 9 (1997): 905-911
Graddis, T. J. et al., Int.J Clin Exp.Pathol. 4 (2011): 295-306
Green, M. R. et al., Molecular Cloning, A Laboratory Manual 4th (2012)
Greene, M. H. et al., Endocr.Relat Cancer 17 (2010): R109-R121
Greenfield, E. A., Antibodies: A Laboratory Manual 2nd (2014)
Grunewald, T. G. et al., Biol.Cell 104 (2012): 641-657
Gutman, G. A. et al., Pharmacol.Rev. 57 (2005): 473-508
Haferlach, C. et al., Haematologica 96 (2011): 829-836
Hale, L. P. et al., Clinical Cancer Research 7 (2001): 846-853
Hallen, A. et al., J Neurochem. 118 (2011): 379-387
Halpain, S. et al., Genome Biol. 7 (2006): 224
Hanahan, D. et al., Cell 100 (2000): 57-70
Hassan, M. I. et al., Mol Cancer Res 6 (2008): 892-906
Higgins, G. et al., Proc.Natl.Acad.Sci.U.S.A 109 (2012): E3128-E3135
Ho, L. L. et al., Prostate 68 (2008): 1421-1429
Horvath, A. et al., Curr.Opin.Endocrinol.Diabetes Obes. 15 (2008): 227-233
Hu, J. C. et al., Gene 251 (2000): 1-8
Hwang, M. L. et al., J Immunol. 179 (2007): 5829-5838
Hyodo, T. et al., J Biol.Chem. 287 (2012): 25019-25029
Ito, S. et al., Head Neck 32 (2010a): 96-103
Ito, Y. et al., Proc.Natl.Acad.Sci.U.S.A 107 (2010b): 10538-10542
Jiao, X. et al., BMC.Genomics 14 (2013): 165
Jin, Y. et al., Proc.Natl.Acad.Sci.U.S.A 110 (2013): E2572-E2581
Jung, G. et al., Proc Natl Acad Sci U S A 84 (1987): 4611-4615
Kai, F. et al., Oncotarget. 6 (2015): 11162-11174
Kandimalla, R. et al., Eur.Urol. 61 (2012): 1245-1256
Katada, K. et al., J Proteomics. 75 (2012): 1803-1815
Katoh, Y. et al., Cancer Biol.Ther. 4 (2005): 1050-1054
Kibbe, A. H., Handbook of Pharmaceutical Excipients rd (2000)
Kibel, A. S. et al., Int.J Cancer 109 (2004): 668-672
Kinameri, E. et al., PLoS.ONE. 3 (2008): e3859
Klejnot, M. et al., Acta Crystallogr.D.Biol.Crystallogr. 68 (2012): 154-159
Krieg, A. M., Nat.Rev.Drug Discov. 5 (2006): 471-484
Lapointe, J. et al., Proc.Natl.Acad.Sci.U.S.A 101 (2004): 811-816
Laviolette, L. A. et al., Int.J Cancer 135 (2014): 1072-1084
Lee, K. Y. et al., J Med. 35 (2004): 141-149
Li, Y. W. et al., PLoS.ONE. 9 (2014): e87505
Li, Z. J. et al., Development 139 (2012): 4152-4161
Liddy, N. et al., Nat.Med. 18 (2012): 980-987
Liu, P. et al., Science 261 (1993): 1041-1044
Liu, Y. H. et al., Biochem.Biophys.Res Commun. 404 (2011): 488-493
Ljunggren, H. G. et al., J Exp.Med 162 (1985): 1745-1759
Longenecker, B. M. et al., Ann N.Y.Acad.Sci. 690 (1993): 276-291
Lue, H. W. et al., PLoS.ONE. 6 (2011): e27720
Lukas, T. J. et al., Proc.Natl.Acad.Sci.U.S.A 78 (1981): 2791-2795
Lundblad, R. L., Chemical Reagents for Protein Modification 3rd (2004)
Ma, Y. et al., Mol Cell Proteomics. 8 (2009): 1878-1890
Malinowska, K. et al., Prostate 69 (2009): 1109-1118
Matsumoto, F. et al., Hum.Pathol. 37 (2006): 1592-1600
Matsuoka, R. et al., Am.J Med.Genet. 46 (1993): 61-67
Meziere, C. et al., J Immunol 159 (1997): 3230-3237
Midorikawa, Y. et al., Jpn.J Cancer Res. 93 (2002): 636-643
Montani, M. et al., Virchows Arch. 462 (2013): 437-443
Morgan, R. A. et al., Science 314 (2006): 126-129
Mori, M. et al., Transplantation 64 (1997): 1017-1027
Mortara, L. et al., Clin Cancer Res. 12 (2006): 3435-3443
Mueller, L. N. et al., J Proteome.Res. 7 (2008): 51-61
Mueller, L. N. et al., Proteomics. 7 (2007): 3470-3480
Mumberg, D. et al., Proc.Natl.Acad.Sci.U.S.A 96 (1999): 8633-8638
Nicke, B. et al., Mol.Cell 20 (2005): 673-685
Nishibe, R. et al., FEBS Lett. 587 (2013): 1529-1535
Nishidate, T. et al., Int.J Oncol 25 (2004): 797-819
Noetzel, E. et al., Oncogene 29 (2010): 4814-4825
Olesen, S. H. et al., Mol Cell Proteomics. 4 (2005): 534-544
Peters, I. et al., Target Oncol (2014)
Petrella, B. L. et al., Cancer Lett. 325 (2012): 220-226
Pinheiro, J. et al., nlme: Linear and Nonlinear Mixed Effects Models (http://CRAN.R-project.org/packe=nlme) (2015)
Plebanski, M. et al., Eur.J Immunol 25 (1995): 1783-1787
Porta, C. et al., Virology 202 (1994): 949-955
Prevarskaya, N. et al., Biochim.Biophys.Acta 1772 (2007): 937-946
Quinn, D. I. et al., Urol.Oncol 33 (2015): 245-260
Quinn, M. C. et al., Int.J Oncol 42 (2013): 912-920
Rae, J. M. et al., Prostate 66 (2006): 886-894
Rammensee, H. G. et al., Immunogenetics 50 (1999): 213-219
RefSeq, The NCBI handbook [Internet], Chapter 18, (2002), http://www.ncbi.nlm.nih.gov/books/NBK21091/
Rini, B. I. et al., Cancer 107 (2006): 67-74
Rizzardi, A. E. et al., BMC.Cancer 14 (2014): 244
Rock, K. L. et al., Science 249 (1990): 918-921
Rotondo, F. et al., Appl.Immunohistochem.Mol.Morphol. 17 (2009): 185-188
Russel, F. G. et al., Trends Pharmacol.Sci. 29 (2008): 200-207
S3-Leitlinie Prostatakarzinom, 043/022OL, (2014)
Saiki, R. K. et al., Science 239 (1988): 487-491
Sakai, T. et al., J Pharmacol.Sci. 98 (2005): 41-48
Schmitt, M. et al., Radiol.Oncol. 47 (2013): 319-329
Seeger, F. H. et al., Immunogenetics 49 (1999): 571-576
SEER Stat facts, (2014), http://seer.cancer.gov/
Severi, G. et al., Cancer Med. 3 (2014): 1266-1274
Shaheduzzaman, S. et al., Cancer Biol.Ther 6 (2007): 1088-1095
Sherman, F. et al., Laboratory Course Manual for Methods in Yeast Genetics (1986)
Shkoda, A. et al., PLoS.Biol. 10 (2012): e1001376
Singh-Jasuja, H. et al., Cancer Immunol.Immunother. 53 (2004): 187-195
Small, E. J. et al., J Clin Oncol. 24 (2006): 3089-3094
Sturm, M. et al., BMC.Bioinformatics. 9 (2008): 163
Sudhof, T. C., Neuron 75 (2012): 11-25
Sun, Z. et al., J Proteome.Res 13 (2014): 1593-1601
Tan, L. Z. et al., Am.J Pathol. 183 (2013): 831-840
Tan, P. Y. et al., Mol.Cell Biol. 32 (2012): 399-414
Teufel, R. et al., Cell Mol.Life Sci. 62 (2005): 1755-1762
Tran, E. et al., Science 344 (2014): 641-645
Tsavaler, L. et al., Cancer Research 61 (2001): 3760-3769
UniProt, (2015), http://www.uniprot.org/
Walter, S. et al., J.Immunol. 171 (2003): 4974-4978
Walter, S. et al., Nat Med. 18 (2012): 1254-1261
Wang, J. et al., Arch.Pharm.Res 34 (2011): 987-995
Wang, L. et al., Cancer Research 70 (2010): 5818-5828
Wang, R. J. et al., Asian Pac.J Cancer Prev. 15 (2014): 7223-7228
Wang, Y. et al., Hum.Mol.Genet. 21 (2012): 569-576
Wang, Z. et al., Med.Oncol 32 (2015): 87
Ward, P. P. et al., Cell Mol Life Sci. 62 (2005): 2540-2548
Weng, J. et al., Int.J Cancer 113 (2005): 811-818
Westdorp, H. et al., Front Immunol. 5 (2014): 191
Whiteland, H. et al., Clin Exp.Metastasis 31 (2014): 909-920
Willcox, B. E. et al., Protein Sci. 8 (1999): 2418-2423
Willoughby, V. et al., Appl.Immunohistochem.Mol.Morphol. 16 (2008): 344-348
Wilson, P. M. et al., J Neurosci. 30 (2010): 8529-8540
World Cancer Report, (2014)
Wu, J. P. et al., Asian J Androl 16 (2014): 710-714
Yamamoto, G. L. et al., J Med.Genet. 52 (2015): 413-421
Yang, Z. et al., J Virol. 81 (2007): 6294-6306
Ye, Q. et al., PLoS.ONE. 9 (2014): e103298
Yin, J. et al., Mol.Med.Rep. 8 (2013): 1630-1634
Yu, Y. P. et al., Urology 68 (2006): 578-582
Zaremba, S. et al., Cancer Res. 57 (1997): 4570-4577
Zhang, G. et al., Oncol Rep. (2014)
Zhao, X. et al., Onco.Targets.Ther 7 (2014): 343-351
Claims (39)
- 配列番号1〜配列番号48、および配列番号1〜配列番号48と少なくとも88%相同的なその変異配列の群から選択されるアミノ酸配列を含んでなるペプチドおよびその薬学的に許容可能な塩であって;前記変異体が、主要組織適合性複合体(MHC)分子と結合し、および/またはT細胞を前記変異体ペプチドと交差反応させ;前記ペプチドが完全長ポリペプチドでない、ペプチド。
- MHCクラスIまたはII分子に結合する能力を有し、前記MHCに結合すると、CD4および/またはCD8T細胞によって認識されることができるようになる、請求項1に記載のペプチド。
- そのアミノ酸配列が、配列番号1〜配列番号48のいずれか1つに記載の一続きのアミノ酸を含んでなる、請求項1または2に記載のペプチドまたはその変異体。
- 前記ペプチドまたはその変異体が、8〜100、好ましくは8〜30、より好ましくは8〜16のアミノ酸の全長を有し、最も好ましくは前記ペプチドが、配列番号1〜配列番号48のいずれかに記載のアミノ酸配列からなり、またはそれから本質的になる、請求項1〜3のいずれか一項に記載のペプチドまたはその変異体。
- 前記ペプチドが、修飾され、および/または非ペプチド結合を含む、請求項1〜4のいずれか一項に記載のペプチドまたはその変異体。
- 前記ペプチドが、特にHLA−DR抗原関連不変鎖(Ii)のN末端アミノ酸を含んでなる融合タンパク質の一部である、請求項1〜5のいずれか一項に記載のペプチドまたはその変異体。
- 請求項1〜6のいずれか一項に記載のペプチドまたはその変異体をエンコードする核酸であって、任意選択的に異種プロモーター配列と結合する、核酸。
- 請求項7に記載の核酸を発現する能力がある、発現ベクター。
- 請求項1〜6のいずれか一項に記載のペプチド、請求項7に記載の核酸または請求項8に記載の発現ベクターを含んでなり、好ましくは樹状細胞などの抗原提示細胞である、組換え宿主細胞。
- 医療において使用するための、請求項1〜6のいずれか一項に記載のペプチドまたはその変異体、請求項7に記載の核酸、請求項8に記載の発現ベクター、または請求項9に記載の宿主細胞。
- 請求項1〜6のいずれか一項に記載のペプチドを提示する、または請求項7に記載の核酸を発現する、または請求項8に記載の発現ベクターを有する、請求項9に記載の宿主細胞を培養するステップと、前記ペプチドまたはその変異体を前記宿主細胞またはその培養液から単離するステップとを含んでなる、請求項1〜6のいずれか一項に記載のペプチドまたはその変異体を製造する方法。
- T細胞を、適切な抗原提示細胞の表面に、または抗原提示細胞を模倣する人工コンストラクトの表面に発現される抗原負荷ヒトクラスIまたはII MHC分子に、前記T細胞を抗原特異的様式で活性化するのに十分な時間にわたり、生体外で接触させるステップを含んでなり、前記抗原が、請求項1〜4のいずれか一項に記載のペプチドである、活性化Tリンパ球を製造するインビトロ法。
- 請求項1〜4のいずれか一項に記載のアミノ酸配列を含んでなるポリペプチドを提示する細胞を選択的に認識する、請求項12に記載の方法によって製造される活性化Tリンパ球。
- 請求項13で定義される活性T細胞の有効数を患者に投与するステップを含んでなる、その標的細胞が、請求項1〜4のいずれか一項に記載のアミノ酸配列を含んでなるポリペプチドを提示する患者において、標的細胞を死滅させる方法。
- MHC分子と結合すると、好ましくは請求項1〜5のいずれか一項に記載のペプチドまたはその変異体である、請求項1〜5のいずれか一項に記載のペプチドまたはその変異体を特異的に認識する、特に可溶性または膜結合抗体である、抗体。
- がんの診断および/または治療において使用するための、またはがんに対する薬剤の製造において使用するための、請求項1〜6のいずれか一項に記載のペプチド、請求項7に記載の核酸、請求項8に記載の発現ベクター、請求項9に記載の細胞、請求項13に記載の活性化Tリンパ球または請求項15に記載の抗体の使用。
- がんが、ペプチド配列番号1〜配列番号48がそれに由来するタンパク質の過剰発現を示す、前立腺がん、膀胱がん、脳がん、乳がん、結腸直腸がん、食道がん、腎臓がん、肝臓がん、肺がん(NSCLC、SCLC)、卵巣がん、子宮がん、膵臓がん、胃がん、胆嚢がん、胆管がん、黒色腫、メルケル細胞がん、白血病(AML、CLL)およびその他の腫瘍の群から選択される、請求項16に記載の使用。
- (a)請求項1〜6のいずれか一項に記載のペプチド変異体、請求項7に記載の核酸、請求項8に記載の発現ベクター、請求項10に記載の細胞、請求項13に記載の活性化Tリンパ球、または請求項15に記載の抗体を含有する医薬組成物を溶液または凍結乾燥形態で含んでなる容器;
(b)任意選択的に、前記凍結乾燥製剤のための希釈剤または再構成溶液を含有する第2の容器;
(c)任意選択的に、配列番号1〜配列番号59からなる群から選択される少なくとももう1つのペプチド、および
(d)任意選択的に、(i)前記溶液の使用、または(ii)前記凍結乾燥製剤の再構成および/または使用のための取扱説明書を含んでなるキット。 - (iii)緩衝液、(iv)希釈剤、(v)フィルター、(vi)針、または(v)シリンジの1つまたは複数をさらに含んでなる、請求項18に記載のキット。
- 前記ペプチドが、配列番号1〜配列番号48からなる群から選択される、請求項18または19に記載のキット。
- a)前記個々の患者からの腫瘍サンプルによって提示される、腫瘍関連ペプチド(TUMAP)を同定するステップと;
b)a)で同定された前記ペプチドを、正常組織との比較で腫瘍における免疫原性および/または過剰提示について予備選別されたペプチド貯蔵庫と比較するステップと;
c)少なくとも1つのペプチドを、前記患者において同定されたTUMAPと一致する前記貯蔵庫から選択するステップと;
d)ステップc)に基づいて、個別化ワクチンまたは化合物ベースのまたは細胞療法を製造および/または処方するステップとを含んでなる、個々の患者のための化合物ベースのおよび/または細胞療法のための個別化抗がんワクチンを製造する方法。 - 前記TUMAPが、
a1)前記腫瘍サンプルからの発現データを前記腫瘍サンプルの組織型に対応する正常組織サンプルからの発現データと比較して、前記腫瘍サンプルにおいて過剰発現されまたは異常に発現されるタンパク質を同定するステップと;
a2)前記発現データを、前記腫瘍サンプル中のMHCクラスI/またはクラスII分子と結合しているMHCリガンドの配列と相関させて、前記腫瘍によって過剰発現されまたは異常に発現されるタンパク質に由来するMHCリガンドを同定するステップとによって同定される、請求項21に記載の方法。 - 結合ペプチドを前記腫瘍サンプルから単離されたMHC分子から溶出させて、前記溶出したリガンドを配列決定することで、MHCリガンドの配列が同定される、請求項21または22に記載の方法。
- 前記腫瘍サンプルの組織型に対応する前記正常組織が、前記同一患者から得られる、請求項21〜23のいずれか一項に記載の方法。
- 前記貯蔵庫に包含される前記ペプチドが、
aa.正常組織または組織群と比較して悪性組織で過剰発現される遺伝子を同定するステップを含んでなる、マイクロアレイまたは配列決定ベース発現プロファイリングなどの高度並列法によって、ゲノム規模メッセンジャーリボ核酸(mRNA)発現解析を実施するステップと;
ab.ステップaaで検出された、選択的に発現されまたは過剰発現される遺伝子によってコードされる、ペプチドを選択するステップと;
ac.健常ドナーまたは前記患者からのヒトT細胞を使用した生体外免疫原性アッセイを含んでなる、前記選択されたペプチドによる生体内T細胞応答の誘導を判定するステップ;または
ba.HLAリガンドを前記腫瘍サンプルから質量分析を使用して同定するステップと;
bb.正常組織または組織群と比較して悪性組織で過剰発現される遺伝子を同定するステップを含んでなる、マイクロアレイまたは配列決定ベース発現プロファイリングなどの高度並列法によって、ゲノム規模メッセンジャーリボ核酸(mRNA)発現解析を実施するステップと;
bc.前記同定されたHLAリガンドを前記遺伝子発現データと比較するステップと;
bd.ステップbcで検出された、選択的に発現されまたは過剰発現される遺伝子によってコードされる、ペプチドを選択するステップと;
be.ステップbdから選択されたTUMAPを腫瘍組織上で再検出し、健常組織上の検出欠如または希な検出が、mRNAレベルにおける過剰発現の関連性を裏付けるステップと;
bf.健常ドナーまたは前記患者からのヒトT細胞を使用した生体外免疫原性アッセイを含んでなる、前記選択されたペプチドによる生体内T細胞応答の誘導を判定するステップと
に基づいて同定される、請求項21〜24のいずれか一項に記載の方法。 - 前記貯蔵庫に包含される前記ペプチドの免疫原性が、生体外免疫原性アッセイ、個々のHLA結合についての患者免疫モニタリング、MHC多量体染色、ELISPOTアッセイおよび/または細胞内サイトカイン染色を含んでなる方法によって判定される、請求項21〜25のいずれか一項に記載の方法。
- 前記貯蔵庫が、配列番号1〜配列番号59からなる群から選択される複数のペプチドを含んでなる、請求項21〜26のいずれか一項に記載の方法。
- 前記個々の患者からの正常な対応する組織と比較して前記腫瘍サンプルに特有の少なくとも1つの変異を同定するステップと、前記ワクチンに包含するために、または細胞療法を作成するために、前記変異に関連があるペプチドを選択するステップとをさらに含んでなる、請求項21〜27のいずれか一項に記載の方法。
- 前記少なくとも1つの変異が、全ゲノム配列決定によって同定される、請求項28に記載の方法。
- T細胞受容体、好ましくは可溶性または膜結合T細胞受容体であって、HLAリガンドと反応性であり、前記リガンドが配列番号1〜配列番号48からなる群から選択されるアミノ酸配列と少なくとも75%の同一性を有する、T細胞受容体。
- 前記アミノ酸配列が、配列番号1〜配列番号48と少なくとも88%同一である、請求項30に記載のT細胞受容体。
- 前記アミノ酸配列が、配列番号1〜配列番号59のいずれかからなる、請求項30または31に記載のT細胞受容体。
- 前記T細胞受容体が可溶性分子として提供され、任意選択的に、免疫刺激ドメインまたは毒素などのさらなるエフェクター機能を保有する、請求項30〜32のいずれか一項に記載のT細胞受容体。
- 請求項30〜33のいずれか一項に記載のTCRをエンコードする核酸であって、任意選択的に異種プロモーター配列と結合する、核酸。
- 請求項34に記載の核酸を発現できる、発現ベクター。
- 請求項34に記載の核酸、または請求項15に記載の抗体をコードする核酸、または請求項35に記載の発現ベクターを含んでなる、好ましくはT細胞またはNK細胞である、宿主細胞。
- 請求項36に記載の宿主細胞を培養するステップと、前記T細胞受容体を前記宿主細胞および/またはその培養液から単離するステップとを含んでなる、請求項30〜33のいずれか一項に記載のT細胞受容体を製造する方法。
- a)配列番号1〜配列番号48からなる群から選択されるペプチド;
b)a)に記載のペプチドおよび/またはペプチドMHC複合体と反応性のT細胞受容体;
c)a)に記載のペプチドと、HLA−DR抗原関連不変鎖(Ii)のN末端のアミノ酸1〜80とを含んでなる融合タンパク質;
d)a)〜c)のいずれかをコードする核酸、または前記核酸を含んでなる発現ベクター;
e)d)の発現ベクターを含んでなる宿主細胞;
f)T細胞を、抗原特異的様式でT細胞を活性化するのに十分な時間にわたり、適切な抗原提示細胞の表面に発現されるa)に記載のペプチドと生体外で接触させるステップを含んでなる方法、ならびにこれらの活性化T細胞を自己または他の患者に移入する方法によって得られる、活性化Tリンパ球;
g)a)に記載のペプチドおよび/またはペプチド−MHC複合体および/またはa)に記載のペプチドを提示する細胞と反応性であり、例えば、免疫活性化ドメインまたは毒素との融合によって潜在的に修飾される、抗体、または可溶性T細胞受容体;
h)配列番号1〜配列番号48からなる群から選択されるペプチドを認識し、および/または配列番号1〜配列番号48からなる群から選択されるペプチドとMHC分子との複合体を認識する、アプタマー;
i)a)〜h)のいずれかに記載の結合または標識ペプチドまたはスキャフォールド
からなる群から選択される、少なくとも1つの活性成分と、薬学的に許容できる担体、および任意選択的に、薬学的に許容可能な賦形剤および/または安定剤とを含んでなる医薬組成物。 - 請求項1〜5のいずれか一項に記載のペプチドまたはその変異体、好ましくはMHC分子と結合している請求項1〜5のいずれか一項に記載のペプチドまたはその変異体を特異的に認識する、アプタマー。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562201289P | 2015-08-05 | 2015-08-05 | |
US62/201,289 | 2015-08-05 | ||
GB1513921.5 | 2015-08-06 | ||
GBGB1513921.5A GB201513921D0 (en) | 2015-08-05 | 2015-08-06 | Novel peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers |
PCT/EP2016/068727 WO2017021527A2 (en) | 2015-08-05 | 2016-08-05 | Novel peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020191407A Division JP7142957B2 (ja) | 2015-08-05 | 2020-11-18 | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018529320A true JP2018529320A (ja) | 2018-10-11 |
JP2018529320A5 JP2018529320A5 (ja) | 2019-09-12 |
JP6884752B2 JP6884752B2 (ja) | 2021-06-09 |
Family
ID=54200350
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018505723A Active JP6884752B2 (ja) | 2015-08-05 | 2016-08-05 | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ |
JP2020191407A Active JP7142957B2 (ja) | 2015-08-05 | 2020-11-18 | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ |
JP2022142129A Pending JP2022191218A (ja) | 2015-08-05 | 2022-09-07 | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020191407A Active JP7142957B2 (ja) | 2015-08-05 | 2020-11-18 | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ |
JP2022142129A Pending JP2022191218A (ja) | 2015-08-05 | 2022-09-07 | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ |
Country Status (35)
Country | Link |
---|---|
US (24) | US9908920B2 (ja) |
EP (4) | EP3854801A3 (ja) |
JP (3) | JP6884752B2 (ja) |
KR (1) | KR20180035845A (ja) |
CN (2) | CN107849107A (ja) |
AR (1) | AR105817A1 (ja) |
AU (8) | AU2016303021B2 (ja) |
BR (1) | BR112018001687A2 (ja) |
CA (3) | CA3110640A1 (ja) |
CL (7) | CL2018000324A1 (ja) |
CO (1) | CO2018002202A2 (ja) |
CR (6) | CR20200431A (ja) |
CY (1) | CY1123854T1 (ja) |
DK (1) | DK3331900T3 (ja) |
EA (1) | EA201890440A1 (ja) |
ES (1) | ES2862400T3 (ja) |
GB (1) | GB201513921D0 (ja) |
HR (1) | HRP20210709T8 (ja) |
HU (1) | HUE053657T2 (ja) |
IL (2) | IL310078A (ja) |
LT (1) | LT3331900T (ja) |
MA (4) | MA46022B1 (ja) |
MD (1) | MD3331900T2 (ja) |
MX (2) | MX2018001421A (ja) |
PE (1) | PE20180695A1 (ja) |
PH (1) | PH12018500189A1 (ja) |
PL (1) | PL3331900T3 (ja) |
PT (1) | PT3331900T (ja) |
RS (1) | RS61713B1 (ja) |
SG (1) | SG10202001660YA (ja) |
SI (1) | SI3331900T1 (ja) |
TW (2) | TWI829618B (ja) |
UA (1) | UA125816C2 (ja) |
WO (1) | WO2017021527A2 (ja) |
ZA (1) | ZA201800513B (ja) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2508923A (en) * | 2012-12-17 | 2014-06-18 | Bombardier Transp Gmbh | Inductive power transfer system having inductive sensing array |
IL300761A (en) | 2013-08-05 | 2023-04-01 | Immatics Biotechnologies Gmbh | Innovative immunotherapy against several tumors, such as lung cancer, including NSCLC |
GB201513921D0 (en) | 2015-08-05 | 2015-09-23 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers |
CA2994842A1 (en) | 2015-08-05 | 2017-02-09 | Eisai R&D Management Co., Ltd. | Chiral reagents for preparation of homogeneous oligomers |
EP4299136A3 (en) | 2015-12-16 | 2024-02-14 | Gritstone bio, Inc. | Neoantigen identification, manufacture, and use |
JP7075125B2 (ja) | 2016-05-25 | 2022-05-25 | イマティクス バイオテクノロジーズ ゲーエムベーハー | 標的としてのおよび胆嚢がんおよび胆管がんおよびその他のがんに対する免疫療法で使用するための新規ペプチド、ペプチド組み合わせ |
GB201609193D0 (en) | 2016-05-25 | 2016-07-06 | Immatics Biotechnologies Gmbh | Novel peptides, combination of peptides as targets for use in immunotherapy against gallbladder cancer and cholangiocarcinoma and other cancers |
KR102639592B1 (ko) | 2016-12-08 | 2024-02-21 | 이매틱스 바이오테크놀로지스 게엠베하 | 짝짓기가 향상된 t 세포 수용체 |
DE102016123893A1 (de) | 2016-12-08 | 2018-06-14 | Immatics Biotechnologies Gmbh | T-Zellrezeptoren mit verbesserter Bindung |
WO2018213467A1 (en) * | 2017-05-16 | 2018-11-22 | The Johns Hopkins University | Manabodies and methods of using |
HUE057110T2 (hu) | 2017-07-14 | 2022-04-28 | Immatics Biotechnologies Gmbh | Továbbfejlesztett kettõs specifitású polipeptid-molekula |
DE102017115966A1 (de) | 2017-07-14 | 2019-01-17 | Immatics Biotechnologies Gmbh | Polypeptidmolekül mit verbesserter zweifacher Spezifität |
AU2018348165A1 (en) | 2017-10-10 | 2020-05-21 | Gritstone Bio, Inc. | Neoantigen identification using hotspots |
EP3714275A4 (en) | 2017-11-22 | 2021-10-27 | Gritstone bio, Inc. | REDUCTION OF JUNCTION EPITOPIC PRESENTATION FOR NEOANTIGENS |
DE102017127984B4 (de) | 2017-11-27 | 2019-12-05 | Immatics US, Inc. | Verfahren für die Vermehrung und Aktivierung von γδ-T-Zellen |
CN111684062A (zh) | 2018-02-09 | 2020-09-18 | 伊玛提克斯美国公司 | 制造t细胞的方法 |
AU2019276577A1 (en) * | 2018-06-01 | 2021-01-14 | Geneoscopy, Inc. | Detection method |
US10925947B2 (en) | 2018-06-29 | 2021-02-23 | Immatics Biotechnologies Gmbh | A*03 restricted peptides for use in immunotherapy against cancers and related methods |
TW202019955A (zh) | 2018-07-31 | 2020-06-01 | 德商英麥提克生物技術股份有限公司 | B*07 限制肽和肽組合的抗癌免疫治療和相關方法 |
US11945850B2 (en) * | 2018-09-17 | 2024-04-02 | Immatics Biotechnologies Gmbh | B*44 restricted peptides for use in immunotherapy against cancers and related methods |
WO2020167894A1 (en) * | 2019-02-12 | 2020-08-20 | Vanderbilt University | Polypeptides for restoring endothelial function and methods of use thereof |
US20200297768A1 (en) | 2019-03-19 | 2020-09-24 | Immatics US, Inc. | Cd28 t cell cultures, compositions, and methods of using thereof |
US11975025B2 (en) | 2019-05-27 | 2024-05-07 | Immatics US, Inc. | Viral vectors and use thereof in adoptive cellular therapy |
US20210002610A1 (en) | 2019-06-06 | 2021-01-07 | Immatics US, Inc. | Methods for manufacturing t cells by direct sorting and compositions thereof |
US20210032370A1 (en) | 2019-08-02 | 2021-02-04 | Immatics Biotechnologies Gmbh | Recruiting agent further binding an mhc molecule |
KR20230012465A (ko) | 2020-02-24 | 2023-01-26 | 이매틱스 유에스 인코포레이티드 | 암 및 관련 악성 종양을 치료하기 위해 t 세포를 확장하는 방법 |
DE102020111571A1 (de) | 2020-03-11 | 2021-09-16 | Immatics US, Inc. | Wpre-mutantenkonstrukte, zusammensetzungen und zugehörige verfahren |
DE102020106710A1 (de) | 2020-03-11 | 2021-09-16 | Immatics US, Inc. | Wpre-mutantenkonstrukte, zusammensetzungen und zugehörige verfahren |
CA3173666A1 (en) * | 2020-04-14 | 2021-10-21 | Claude Perreault | Novel tumor-specific antigens for acute myeloid leukemia (aml) and uses thereof |
WO2022040631A1 (en) | 2020-08-21 | 2022-02-24 | Immatics US, Inc. | Methods for isolating cd8+ selected t cells |
EP4255474A1 (en) * | 2020-12-07 | 2023-10-11 | Iogenetics, LLC. | Personalized immunotherapies |
JP2024502034A (ja) | 2020-12-31 | 2024-01-17 | イマティクス ユーエス,アイエヌシー. | Cd8ポリペプチド、組成物、及びそれらの使用方法 |
CA3217739A1 (en) | 2021-05-05 | 2022-11-10 | Sebastian Bunk | Bma031 antigen binding polypeptides |
US20230024554A1 (en) | 2021-06-28 | 2023-01-26 | Immatics Biotechnologies Gmbh | Method of characterizing the binding characteristics between a peptide of interest and mhc molecules |
EP4113120A1 (en) | 2021-06-28 | 2023-01-04 | Immatics Biotechnologies GmbH | Method of characterizing the binding characteristics between a peptide of interest and mhc molecules |
CN113527435B (zh) * | 2021-07-14 | 2022-06-07 | 呈诺再生医学科技(珠海横琴新区)有限公司 | 对前列腺癌细胞特异性识别的新型多肽及其衍生物与应用 |
WO2023025851A1 (en) | 2021-08-24 | 2023-03-02 | Immatics US, Inc. | Selection of immune cells using peptide mhc complexes generated by conditional ligand exchange |
TW202332765A (zh) | 2021-09-20 | 2023-08-16 | 美商英麥提克斯股份有限公司 | 用於t細胞療法之t細胞群體的單核球耗盡 |
WO2023081925A1 (en) | 2021-11-08 | 2023-05-11 | Immatics Biotechnologies Gmbh | Adoptive cell therapy combination treatment and compositions thereof |
WO2023212697A1 (en) | 2022-04-28 | 2023-11-02 | Immatics US, Inc. | Membrane-bound il-15, cd8 polypeptides, cells, compositions, and methods of using thereof |
WO2023212655A1 (en) | 2022-04-28 | 2023-11-02 | Immatics US, Inc. | Il-12 polypeptides, il-15 polypeptides, il-18 polypeptides, cd8 polypeptides, compositions, and methods of using thereof |
WO2023212691A1 (en) | 2022-04-28 | 2023-11-02 | Immatics US, Inc. | DOMINANT NEGATIVE TGFβ RECEPTOR POLYPEPTIDES, CD8 POLYPEPTIDES, CELLS, COMPOSITIONS, AND METHODS OF USING THEREOF |
US20230355678A1 (en) | 2022-05-05 | 2023-11-09 | Immatics US, Inc. | Methods for improving t cell efficacy |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011119484A1 (en) * | 2010-03-23 | 2011-09-29 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
JP2012504393A (ja) * | 2008-10-01 | 2012-02-23 | イマティクス バイオテクノロジーズ ゲーエムベーハー | 神経細胞性脳腫瘍など数種の腫瘍に対する新規免疫療法 |
WO2013040142A2 (en) * | 2011-09-16 | 2013-03-21 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
JP2014502961A (ja) * | 2010-12-14 | 2014-02-06 | イマティクス バイオテクノロジーズ ゲーエムベーハー | 前立腺関連抗原分子由来hla結合ペプチドおよびその使用方法 |
Family Cites Families (78)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4440859A (en) | 1977-05-27 | 1984-04-03 | The Regents Of The University Of California | Method for producing recombinant bacterial plasmids containing the coding sequences of higher organisms |
US4704362A (en) | 1977-11-08 | 1987-11-03 | Genentech, Inc. | Recombinant cloning vehicle microbial polypeptide expression |
FI86437C (fi) | 1978-12-22 | 1992-08-25 | Biogen Inc | Foerfarande foer framstaellning av polypeptider med de antigena egenskaperna hos ett hepatitis b- virusantigen. |
US4530901A (en) | 1980-01-08 | 1985-07-23 | Biogen N.V. | Recombinant DNA molecules and their use in producing human interferon-like polypeptides |
US4342566A (en) | 1980-02-22 | 1982-08-03 | Scripps Clinic & Research Foundation | Solid phase anti-C3 assay for detection of immune complexes |
US4678751A (en) | 1981-09-25 | 1987-07-07 | Genentech, Inc. | Hybrid human leukocyte interferons |
US4766075A (en) | 1982-07-14 | 1988-08-23 | Genentech, Inc. | Human tissue plasminogen activator |
US4582800A (en) | 1982-07-12 | 1986-04-15 | Hoffmann-La Roche Inc. | Novel vectors and method for controlling interferon expression |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4757006A (en) | 1983-10-28 | 1988-07-12 | Genetics Institute, Inc. | Human factor VIII:C gene and recombinant methods for production |
US4677063A (en) | 1985-05-02 | 1987-06-30 | Cetus Corporation | Human tumor necrosis factor |
US4810648A (en) | 1986-01-08 | 1989-03-07 | Rhone Poulenc Agrochimie | Haloarylnitrile degrading gene, its use, and cells containing the gene |
US4897445A (en) | 1986-06-27 | 1990-01-30 | The Administrators Of The Tulane Educational Fund | Method for synthesizing a peptide containing a non-peptide bond |
US6037135A (en) * | 1992-08-07 | 2000-03-14 | Epimmune Inc. | Methods for making HLA binding peptides and their uses |
US9340577B2 (en) * | 1992-08-07 | 2016-05-17 | Epimmune Inc. | HLA binding motifs and peptides and their uses |
SG49008A1 (en) | 1993-03-05 | 1998-05-18 | Cytel Corp | Hla-a2.1 binding peptides and their uses |
ES2108460T3 (es) | 1993-06-03 | 1997-12-16 | Therapeutic Antibodies Inc | Fragmentos de anticuerpos en terapeutica. |
US20040157780A1 (en) * | 1993-11-29 | 2004-08-12 | Epimmune Inc. | CTL inducing peptides from c-erb2 (HER-2/neu) |
AUPM322393A0 (en) | 1993-12-24 | 1994-01-27 | Austin Research Institute, The | Mucin carbohydrate compounds and their use in immunotherapy |
US6824993B2 (en) * | 1995-06-06 | 2004-11-30 | Human Genome Sciences, Inc. | Antibodies that bind human prostate specific G-protein receptor HPRAJ70 |
JP4767371B2 (ja) | 1996-01-17 | 2011-09-07 | インペリアル・イノベイションズ・リミテッド | 細胞障害性tリンパ球(ctl)を用いた免疫療法 |
US5849589A (en) | 1996-03-11 | 1998-12-15 | Duke University | Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells |
AU4086397A (en) * | 1996-09-06 | 1998-03-26 | Centocor Inc. | Monoclonal antibodies specific for prostate specific antigen and methods of detecting prostate specific antigen |
US7008772B1 (en) * | 1997-02-25 | 2006-03-07 | Corixa Corporation | Compounds for immunodiagnosis of prostate cancer and methods for their use |
US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US20070020327A1 (en) * | 1998-11-10 | 2007-01-25 | John Fikes | Inducing cellular immune responses to prostate cancer antigens using peptide and nucleic acid compositions |
US7361338B2 (en) | 1999-10-05 | 2008-04-22 | Agensys, Inc. | Methods to inhibit growth of prostate cancer cells |
EP1220931A1 (en) * | 1999-10-07 | 2002-07-10 | Schering Aktiengesellschaft | Dna encoding prost 07 polypeptide |
WO2001034802A2 (en) * | 1999-11-12 | 2001-05-17 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
HUP0203968A3 (en) * | 2000-01-14 | 2004-09-28 | Corixa Corp Seattle | Compositions and methods for the therapy and diagnosis of prostate cancer |
AU2001233114A1 (en) * | 2000-02-04 | 2001-08-14 | Aeomica, Inc. | Methods and apparatus for predicting, confirming, and displaying functional information derived from genomic sequence |
US20030219806A1 (en) * | 2000-02-22 | 2003-11-27 | Millennium Pharmaceuticals, Inc. | Novel 18607, 15603, 69318, 12303, 48000, 52920, 5433, 38554, 57301, 58324, 55063, 52991, 59914, 59921 and 33751 molecules and uses therefor |
US20040191260A1 (en) | 2003-03-26 | 2004-09-30 | Technion Research & Development Foundation Ltd. | Compositions capable of specifically binding particular human antigen presenting molecule/pathogen-derived antigen complexes and uses thereof |
CA2403909A1 (en) * | 2000-03-27 | 2001-10-04 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
EP2316950A1 (en) | 2000-03-27 | 2011-05-04 | Technion Research and Development Foundation, Ltd. | Single chain class I major histo-compatibility complexes, constructs encoding same and methods of generating same |
CA2404541A1 (en) * | 2000-03-31 | 2001-10-11 | Curagen Corporation | G-protein coupled receptors and nucleic acids encoding same |
US7834146B2 (en) * | 2000-05-08 | 2010-11-16 | Monsanto Technology Llc | Recombinant polypeptides associated with plants |
EP2322228B1 (en) | 2000-06-05 | 2018-01-10 | Altor BioScience Corporation | T cell receptor fusion proteins and conjugates and methods of use thereof |
GB0015722D0 (en) * | 2000-06-27 | 2000-08-16 | Smithkline Beecham Sa | Vaccine |
US7199229B2 (en) * | 2000-08-11 | 2007-04-03 | Mount Sinai Hospital | Kallikrein gene |
EP1911461B1 (en) * | 2000-10-19 | 2011-12-07 | Epimmune Inc. | HLA class I and II binding peptides and their uses |
US7048931B1 (en) * | 2000-11-09 | 2006-05-23 | Corixa Corporation | Compositions and methods for the therapy and diagnosis of prostate cancer |
US7459539B2 (en) * | 2000-12-15 | 2008-12-02 | Agensys, Inc. | Antibody that binds zinc transporter protein 108P5H8 |
WO2002055557A2 (en) * | 2000-12-18 | 2002-07-18 | Curagen Corp | Human proteins and nucleic acids encoding same |
AUPR402201A0 (en) * | 2001-03-27 | 2001-04-26 | Queensland University Of Technology | Polynucleotides and polypeptides linked to cancer and/or benign tumours |
US20040142325A1 (en) * | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
US6992176B2 (en) | 2002-02-13 | 2006-01-31 | Technion Research & Development Foundation Ltd. | Antibody having a T-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease |
JP2005533486A (ja) | 2002-02-20 | 2005-11-10 | ダイアックス、コープ | Mhc−ペプチド複合体結合リガンド |
DE10215321A1 (de) * | 2002-04-02 | 2003-10-23 | Metagen Pharmaceuticals Gmbh | Trp-p8 Splice Varianten und regulatorische RNA |
US7569225B2 (en) * | 2002-08-12 | 2009-08-04 | The Council Of The Queensland Institute Of Medical Research | Immunogenic lipopeptides comprising T-helper and B-cell epitopes |
WO2004016643A2 (en) | 2002-08-16 | 2004-02-26 | Yeda Research And Development Co. Ltd. | Tumor associated antigen, peptides thereof, and use of same as anti-tumor vaccines |
AU2003271904B2 (en) | 2002-10-09 | 2009-03-05 | Adaptimmune Limited | Single chain recombinant T cell receptors |
PT1558643E (pt) | 2002-11-09 | 2009-08-24 | Immunocore Ltd | Apresentação de um receptor das células t |
GB0304068D0 (en) | 2003-02-22 | 2003-03-26 | Avidex Ltd | Substances |
GB0318096D0 (en) * | 2003-08-01 | 2003-09-03 | Queen Mary & Westfield College | Vaccine |
CA2598593A1 (en) * | 2005-02-28 | 2006-09-08 | Nycomed Gmbh | Method for identifying pde11 modulators |
EP1862804B1 (en) * | 2005-03-14 | 2010-05-05 | Link Genomics, Inc. | Method for diagnosis of prostate cancer |
EP1806358B1 (en) | 2005-09-05 | 2010-03-17 | Immatics Biotechnologies GmbH | Tumor-associated peptides binding promiscuously to human leukocyte antigen (HLA) class II molecules |
AU2006308863A1 (en) * | 2005-10-31 | 2007-05-10 | Janssen Pharmaceutica N.V. | A polypeptide complex of TRPM8 and calmodulin and its uses thereof |
US20130332133A1 (en) * | 2006-05-11 | 2013-12-12 | Ramot At Tel Aviv University Ltd. | Classification of Protein Sequences and Uses of Classified Proteins |
US20090263574A1 (en) | 2008-04-21 | 2009-10-22 | Quinn Daniel E | Method of restoring an article |
WO2009135019A2 (en) | 2008-05-01 | 2009-11-05 | Beth Israel Deaconess Medical Center | Methods and compositions for prostate cancer immunotherapy |
PL2119726T5 (pl) | 2008-05-14 | 2018-04-30 | Immatics Biotechnologies Gmbh | Nowe i silne peptydy MHC klasy II pochodzące z surwiwiny i neurokanu |
WO2010037395A2 (en) * | 2008-10-01 | 2010-04-08 | Dako Denmark A/S | Mhc multimers in cancer vaccines and immune monitoring |
GB201006360D0 (en) | 2010-04-16 | 2010-06-02 | Immatics Biotechnologies Gmbh | Method for differentially quantifying naturally processed HLA-restricted peptides for cancer, autoimmune and infectious diseases immunotherapy development |
EA029860B1 (ru) * | 2010-07-15 | 2018-05-31 | Олег Ильич ЭПШТЕЙН | Фармацевтическая композиция и способы лечения заболеваний мочеполовой системы |
US20120121592A1 (en) * | 2010-10-13 | 2012-05-17 | Baylor Research Institute | Targeting Antigens to Human Dendritic Cells Via DC-Asialoglycoprotein Receptor to Produce IL-10 Regulatory T-Cells |
CA2816225A1 (en) | 2010-10-26 | 2012-05-03 | Technion Research & Development Foundation Ltd. | Antibodies which bind soluble t-cell receptor ligands |
WO2013057586A1 (en) | 2011-10-19 | 2013-04-25 | Oslo Universitetssykehus Hf | Compositions and methods for producing soluble t - cell receptors |
WO2014047085A2 (en) | 2012-09-20 | 2014-03-27 | Rongfu Wang | Prostate-specific tumor antigen and uses thereof |
US20190292535A1 (en) | 2012-11-08 | 2019-09-26 | Roche Diagnostics Operations, Inc. | Nucleic acids encoding chimeric polypeptides for library screening |
EP2808392A1 (en) | 2013-05-28 | 2014-12-03 | Rheinische Friedrich-Wilhelms-Universität Bonn | Aptamers and use of the aptamers in the diagnosis and treatment of cancer |
TWI636065B (zh) | 2013-08-05 | 2018-09-21 | 伊瑪提克斯生物科技有限公司 | 新穎肽類,細胞及其用於治療多種腫瘤的用途,其製造方法及包含其等之醫藥組成物 |
GB201423361D0 (en) | 2014-12-30 | 2015-02-11 | Immatics Biotechnologies Gmbh | Method for the absolute Quantification of naturally processed HLA-Restricted cancer peptides |
US20180028627A1 (en) * | 2015-02-26 | 2018-02-01 | Bioventures, Llc | Treatment vaccine for prostate cancer |
JP7236216B2 (ja) * | 2015-04-23 | 2023-03-09 | ナントミクス,エルエルシー | がんのネオエピトープ |
GB201513921D0 (en) * | 2015-08-05 | 2015-09-23 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers |
EP3648791A1 (en) * | 2017-07-04 | 2020-05-13 | CureVac AG | Novel nucleic acid molecules |
-
2015
- 2015-08-06 GB GBGB1513921.5A patent/GB201513921D0/en not_active Ceased
-
2016
- 2016-08-04 AR ARP160102395A patent/AR105817A1/es unknown
- 2016-08-05 TW TW105124943A patent/TWI829618B/zh active
- 2016-08-05 IL IL310078A patent/IL310078A/en unknown
- 2016-08-05 MA MA46022A patent/MA46022B1/fr unknown
- 2016-08-05 CA CA3110640A patent/CA3110640A1/en active Pending
- 2016-08-05 WO PCT/EP2016/068727 patent/WO2017021527A2/en active Application Filing
- 2016-08-05 HU HUE16750766A patent/HUE053657T2/hu unknown
- 2016-08-05 TW TW109124889A patent/TW202106702A/zh unknown
- 2016-08-05 CA CA3110633A patent/CA3110633A1/en active Pending
- 2016-08-05 CN CN201680045204.4A patent/CN107849107A/zh active Pending
- 2016-08-05 PE PE2018000178A patent/PE20180695A1/es unknown
- 2016-08-05 DK DK16750766.4T patent/DK3331900T3/da active
- 2016-08-05 CA CA2994771A patent/CA2994771C/en active Active
- 2016-08-05 EP EP20216899.3A patent/EP3854801A3/en active Pending
- 2016-08-05 MA MA41879A patent/MA41879A1/fr unknown
- 2016-08-05 CR CR20200431A patent/CR20200431A/es unknown
- 2016-08-05 MX MX2018001421A patent/MX2018001421A/es unknown
- 2016-08-05 EP EP20216870.4A patent/EP3842446A1/en active Pending
- 2016-08-05 UA UAA201800448A patent/UA125816C2/uk unknown
- 2016-08-05 RS RS20210446A patent/RS61713B1/sr unknown
- 2016-08-05 ES ES16750766T patent/ES2862400T3/es active Active
- 2016-08-05 MA MA053452A patent/MA53452A/fr unknown
- 2016-08-05 CR CR20200433A patent/CR20200433A/es unknown
- 2016-08-05 US US15/229,970 patent/US9908920B2/en active Active
- 2016-08-05 CR CR20200432A patent/CR20200432A/es unknown
- 2016-08-05 JP JP2018505723A patent/JP6884752B2/ja active Active
- 2016-08-05 KR KR1020187005514A patent/KR20180035845A/ko not_active Application Discontinuation
- 2016-08-05 EA EA201890440A patent/EA201890440A1/ru unknown
- 2016-08-05 SG SG10202001660YA patent/SG10202001660YA/en unknown
- 2016-08-05 PL PL16750766T patent/PL3331900T3/pl unknown
- 2016-08-05 CR CR20200434A patent/CR20200434A/es unknown
- 2016-08-05 MA MA053680A patent/MA53680A/fr unknown
- 2016-08-05 CN CN202111376484.6A patent/CN114395013A/zh active Pending
- 2016-08-05 EP EP23216403.8A patent/EP4324472A2/en active Pending
- 2016-08-05 EP EP16750766.4A patent/EP3331900B1/en active Active
- 2016-08-05 LT LTEP16750766.4T patent/LT3331900T/lt unknown
- 2016-08-05 CR CR20180074A patent/CR20180074A/es unknown
- 2016-08-05 CR CR20200435A patent/CR20200435A/es unknown
- 2016-08-05 MD MDE20180586T patent/MD3331900T2/ro unknown
- 2016-08-05 SI SI201631144T patent/SI3331900T1/sl unknown
- 2016-08-05 BR BR112018001687-0A patent/BR112018001687A2/pt active Search and Examination
- 2016-08-05 AU AU2016303021A patent/AU2016303021B2/en active Active
- 2016-08-05 PT PT167507664T patent/PT3331900T/pt unknown
-
2017
- 2017-06-29 US US15/637,906 patent/US9993539B2/en active Active
- 2017-06-29 US US15/638,072 patent/US10155032B2/en active Active
- 2017-12-21 US US15/849,878 patent/US10500259B2/en active Active
-
2018
- 2018-01-24 ZA ZA2018/00513A patent/ZA201800513B/en unknown
- 2018-01-25 PH PH12018500189A patent/PH12018500189A1/en unknown
- 2018-02-01 MX MX2021015933A patent/MX2021015933A/es unknown
- 2018-02-04 IL IL257331A patent/IL257331A/en unknown
- 2018-02-05 CL CL2018000324A patent/CL2018000324A1/es unknown
- 2018-02-27 CO CONC2018/0002202A patent/CO2018002202A2/es unknown
- 2018-08-10 US US16/100,498 patent/US10383930B2/en active Active
- 2018-10-05 US US16/153,294 patent/US10238727B2/en active Active
- 2018-12-05 US US16/210,330 patent/US10376568B2/en active Active
-
2019
- 2019-04-16 US US16/385,225 patent/US10478480B2/en active Active
- 2019-04-16 US US16/385,221 patent/US10449238B2/en active Active
- 2019-07-10 US US16/507,375 patent/US10532091B1/en active Active
- 2019-08-27 US US16/552,873 patent/US10799569B2/en active Active
-
2020
- 2020-06-29 US US16/915,465 patent/US11058754B2/en active Active
- 2020-09-10 US US17/017,281 patent/US11065315B2/en active Active
- 2020-11-18 JP JP2020191407A patent/JP7142957B2/ja active Active
-
2021
- 2021-02-26 CY CY20211100164T patent/CY1123854T1/el unknown
- 2021-04-01 AU AU2021202059A patent/AU2021202059B2/en active Active
- 2021-04-01 AU AU2021202060A patent/AU2021202060B2/en active Active
- 2021-04-01 AU AU2021202057A patent/AU2021202057B2/en active Active
- 2021-04-01 AU AU2021202058A patent/AU2021202058B2/en active Active
- 2021-04-01 AU AU2021202056A patent/AU2021202056B2/en active Active
- 2021-05-06 HR HRP20210709TT patent/HRP20210709T8/hr unknown
- 2021-05-14 US US17/320,929 patent/US11786584B2/en active Active
- 2021-05-14 US US17/320,938 patent/US11826409B2/en active Active
- 2021-05-14 US US17/320,878 patent/US20210275653A1/en not_active Abandoned
- 2021-06-11 CL CL2021001545A patent/CL2021001545A1/es unknown
- 2021-06-11 CL CL2021001542A patent/CL2021001542A1/es unknown
- 2021-06-11 CL CL2021001543A patent/CL2021001543A1/es unknown
- 2021-06-11 CL CL2021001544A patent/CL2021001544A1/es unknown
- 2021-06-30 CL CL2021001744A patent/CL2021001744A1/es unknown
-
2022
- 2022-01-14 US US17/576,185 patent/US20220125902A1/en active Pending
- 2022-01-14 US US17/576,067 patent/US20220133870A1/en active Pending
- 2022-01-21 US US17/581,049 patent/US20220143162A1/en active Pending
- 2022-01-21 US US17/581,054 patent/US20220143163A1/en active Pending
- 2022-01-28 US US17/587,474 patent/US20220152171A1/en active Pending
- 2022-01-28 US US17/587,536 patent/US20220143164A1/en active Pending
- 2022-02-04 US US17/592,573 patent/US20220152175A1/en active Pending
- 2022-09-07 JP JP2022142129A patent/JP2022191218A/ja active Pending
- 2022-11-21 CL CL2022003264A patent/CL2022003264A1/es unknown
-
2023
- 2023-07-13 AU AU2023204661A patent/AU2023204661A1/en active Pending
- 2023-08-17 US US18/451,216 patent/US20240016908A1/en active Pending
- 2023-09-22 AU AU2023233214A patent/AU2023233214A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012504393A (ja) * | 2008-10-01 | 2012-02-23 | イマティクス バイオテクノロジーズ ゲーエムベーハー | 神経細胞性脳腫瘍など数種の腫瘍に対する新規免疫療法 |
WO2011119484A1 (en) * | 2010-03-23 | 2011-09-29 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
JP2014502961A (ja) * | 2010-12-14 | 2014-02-06 | イマティクス バイオテクノロジーズ ゲーエムベーハー | 前立腺関連抗原分子由来hla結合ペプチドおよびその使用方法 |
WO2013040142A2 (en) * | 2011-09-16 | 2013-03-21 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
Non-Patent Citations (1)
Title |
---|
PLOS ONE, 2012.09.20, VOL. 7, NO. 9, ARTICLE NO. E45756 (PP. 1-9), JPN6020031271, ISSN: 0004330404 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7142957B2 (ja) | 前立腺がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ | |
JP2018511321A (ja) | 腎細胞がん(rcc)およびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドとスキャフォールドの組み合わせ | |
JP2019502360A (ja) | Cllおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ | |
JP2018531581A (ja) | 上皮性卵巣がんおよびその他のがんに対する免疫療法において使用するための新規ペプチドおよびペプチドの組み合わせ | |
TW202415673A (zh) | 用於攝護腺癌和其他癌症免疫治療的新型肽和肽組合物 | |
EA041120B1 (ru) | Новые пептиды и комбинации пептидов для применения в иммунотерапии рака предстательной железы и других видов рака |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190731 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190731 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200825 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20201118 |
|
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: 20210414 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210512 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6884752 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |