TWI485161B - 抗上皮細胞黏著分子（ＥｐＣＡＭ）抗體及其使用方法 - Google Patents
抗上皮細胞黏著分子（ＥｐＣＡＭ）抗體及其使用方法 Download PDFInfo
- Publication number
- TWI485161B TWI485161B TW102107344A TW102107344A TWI485161B TW I485161 B TWI485161 B TW I485161B TW 102107344 A TW102107344 A TW 102107344A TW 102107344 A TW102107344 A TW 102107344A TW I485161 B TWI485161 B TW I485161B
- Authority
- TW
- Taiwan
- Prior art keywords
- epcam
- antibody
- cells
- cell
- binding fragment
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 26
- 101150084967 EPCAM gene Proteins 0.000 title description 18
- 108010067225 Cell Adhesion Molecules Proteins 0.000 title description 2
- 102000008395 cell adhesion mediator activity proteins Human genes 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims description 248
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 171
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims description 170
- 206010028980 Neoplasm Diseases 0.000 claims description 113
- 230000027455 binding Effects 0.000 claims description 62
- 239000012634 fragment Substances 0.000 claims description 52
- 201000011510 cancer Diseases 0.000 claims description 45
- 239000000427 antigen Substances 0.000 claims description 39
- 108091007433 antigens Proteins 0.000 claims description 39
- 102000036639 antigens Human genes 0.000 claims description 39
- 206010009944 Colon cancer Diseases 0.000 claims description 19
- 150000001413 amino acids Chemical group 0.000 claims description 17
- 235000001014 amino acid Nutrition 0.000 claims description 14
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 claims description 12
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 12
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 12
- 206010061306 Nasopharyngeal cancer Diseases 0.000 claims description 9
- 238000000338 in vitro Methods 0.000 claims description 9
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 6
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 5
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 5
- 230000009870 specific binding Effects 0.000 claims description 5
- 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 claims description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 210000005102 tumor initiating cell Anatomy 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims 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 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000000717 tumor promoter Substances 0.000 claims description 2
- 230000001093 anti-cancer Effects 0.000 claims 1
- 241000282414 Homo sapiens Species 0.000 description 77
- 108090000623 proteins and genes Proteins 0.000 description 46
- 108020004414 DNA Proteins 0.000 description 40
- 238000004458 analytical method Methods 0.000 description 35
- 230000014509 gene expression Effects 0.000 description 35
- 238000001262 western blot Methods 0.000 description 22
- 230000008672 reprogramming Effects 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 21
- 238000011282 treatment Methods 0.000 description 20
- 210000004881 tumor cell Anatomy 0.000 description 19
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 18
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 18
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 18
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 18
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 108060003951 Immunoglobulin Proteins 0.000 description 16
- 101100118936 Xenopus laevis epabp-a gene Proteins 0.000 description 16
- 102000018358 immunoglobulin Human genes 0.000 description 16
- 238000002487 chromatin immunoprecipitation Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 14
- DWJXYEABWRJFSP-XOBRGWDASA-N DAPT Chemical compound N([C@@H](C)C(=O)N[C@H](C(=O)OC(C)(C)C)C=1C=CC=CC=1)C(=O)CC1=CC(F)=CC(F)=C1 DWJXYEABWRJFSP-XOBRGWDASA-N 0.000 description 13
- 238000011977 dual antiplatelet therapy Methods 0.000 description 13
- 108020004999 messenger RNA Proteins 0.000 description 13
- 238000011529 RT qPCR Methods 0.000 description 12
- 125000003275 alpha amino acid group Chemical group 0.000 description 12
- 208000029742 colonic neoplasm Diseases 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 108091027967 Small hairpin RNA Proteins 0.000 description 11
- 230000006907 apoptotic process Effects 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000000684 flow cytometry Methods 0.000 description 11
- 239000004055 small Interfering RNA Substances 0.000 description 11
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 230000000977 initiatory effect Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- -1 Nanog Proteins 0.000 description 9
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 9
- 238000003776 cleavage reaction Methods 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 102000012411 Intermediate Filament Proteins Human genes 0.000 description 8
- 108010061998 Intermediate Filament Proteins Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 241001529936 Murinae Species 0.000 description 7
- 239000012228 culture supernatant Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 7
- 210000002706 plastid Anatomy 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 230000005945 translocation Effects 0.000 description 7
- 102000000905 Cadherin Human genes 0.000 description 6
- 108050007957 Cadherin Proteins 0.000 description 6
- 208000005623 Carcinogenesis Diseases 0.000 description 6
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 230000001464 adherent effect Effects 0.000 description 6
- 230000033228 biological regulation Effects 0.000 description 6
- 230000036952 cancer formation Effects 0.000 description 6
- 231100000504 carcinogenesis Toxicity 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 238000002493 microarray Methods 0.000 description 6
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 6
- 210000004940 nucleus Anatomy 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108010040476 FITC-annexin A5 Proteins 0.000 description 5
- 241000237858 Gastropoda Species 0.000 description 5
- 101000687905 Homo sapiens Transcription factor SOX-2 Proteins 0.000 description 5
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000011579 SCID mouse model Methods 0.000 description 5
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 210000000805 cytoplasm Anatomy 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 210000002889 endothelial cell Anatomy 0.000 description 5
- 210000002919 epithelial cell Anatomy 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000004408 hybridoma Anatomy 0.000 description 5
- 238000001114 immunoprecipitation Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000002823 phage display Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 4
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 102100024270 Transcription factor SOX-2 Human genes 0.000 description 4
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 4
- 239000001099 ammonium carbonate Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 238000001378 electrochemiluminescence detection Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 238000010185 immunofluorescence analysis Methods 0.000 description 4
- 238000003125 immunofluorescent labeling Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 230000005740 tumor formation Effects 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 210000003606 umbilical vein Anatomy 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 102100033421 Keratin, type I cytoskeletal 18 Human genes 0.000 description 3
- 108010066327 Keratin-18 Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010061309 Neoplasm progression Diseases 0.000 description 3
- 102100035423 POU domain, class 5, transcription factor 1 Human genes 0.000 description 3
- 101710126211 POU domain, class 5, transcription factor 1 Proteins 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000003242 anti-anoikis Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000005757 colony formation Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- 239000003540 gamma secretase inhibitor Substances 0.000 description 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229960004768 irinotecan Drugs 0.000 description 3
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 3
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 3
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 230000005937 nuclear translocation Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000007026 protein scission Effects 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000005751 tumor progression Effects 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 108020004463 18S ribosomal RNA Proteins 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000001490 Dengue Diseases 0.000 description 2
- 206010012310 Dengue fever Diseases 0.000 description 2
- 229940125373 Gamma-Secretase Inhibitor Drugs 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 2
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 2
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102220467332 Protein BEX4_L94A_mutation Human genes 0.000 description 2
- 239000012083 RIPA buffer Substances 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 241000193996 Streptococcus pyogenes Species 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 206010064390 Tumour invasion Diseases 0.000 description 2
- 230000002424 anti-apoptotic effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000009400 cancer invasion Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 208000025729 dengue disease Diseases 0.000 description 2
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
- 235000008191 folinic acid Nutrition 0.000 description 2
- 239000011672 folinic acid Substances 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000010569 immunofluorescence imaging Methods 0.000 description 2
- 230000002998 immunogenetic effect Effects 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 2
- 229960001691 leucovorin Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 201000002740 oral squamous cell carcinoma Diseases 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 239000012130 whole-cell lysate Substances 0.000 description 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 1
- 108091007505 ADAM17 Proteins 0.000 description 1
- 102000043279 ADAM17 Human genes 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 1
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 1
- 208000002109 Argyria Diseases 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 102220527485 Calcium-activated potassium channel subunit beta-4_N90A_mutation Human genes 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 102220604032 Clathrin heavy chain 1_Q89A_mutation Human genes 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 238000001712 DNA sequencing Methods 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
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 241001649081 Dina Species 0.000 description 1
- 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102220498733 Interleukin-6 receptor subunit alpha_N55A_mutation Human genes 0.000 description 1
- 102220565489 Killer cell immunoglobulin-like receptor 2DL2_D96A_mutation Human genes 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 1
- 208000000592 Nasal Polyps Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010063493 Premature ageing Diseases 0.000 description 1
- 208000032038 Premature aging Diseases 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000012162 RNA isolation reagent Substances 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 102100038081 Signal transducer CD24 Human genes 0.000 description 1
- 101710085955 Structural protein 1 Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 102220512015 Synaptotagmin-7_Q54A_mutation Human genes 0.000 description 1
- RWQNBRDOKXIBIV-UHFFFAOYSA-N Thymine Natural products CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102100040396 Transcobalamin-1 Human genes 0.000 description 1
- 101710124861 Transcobalamin-1 Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 230000008003 autocrine effect Effects 0.000 description 1
- RIIWUGSYXOBDMC-UHFFFAOYSA-N benzene-1,2-diamine;hydron;dichloride Chemical compound Cl.Cl.NC1=CC=CC=C1N RIIWUGSYXOBDMC-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000010226 confocal imaging Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 210000000448 cultured tumor cell Anatomy 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 229940029030 dendritic cell vaccine Drugs 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 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
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- JYEFSHLLTQIXIO-SMNQTINBSA-N folfiri regimen Chemical compound FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 JYEFSHLLTQIXIO-SMNQTINBSA-N 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 102000045551 human EPCAM Human genes 0.000 description 1
- 102000054751 human RUNX1T1 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 210000005008 immunosuppressive cell Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 208000021601 lentivirus infection Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000012917 library technology Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004492 nuclear pore Anatomy 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000012342 propidium iodide staining Methods 0.000 description 1
- 102000034272 protein filaments Human genes 0.000 description 1
- 108091005974 protein filaments Proteins 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 102200062292 rs1114167623 Human genes 0.000 description 1
- 102220020162 rs397508045 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002447 tumor necrosis factor alpha converting enzyme inhibitor Substances 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—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
-
- 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
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Pathology (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Oncology (AREA)
- Food Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261606220P | 2012-03-02 | 2012-03-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201350507A TW201350507A (zh) | 2013-12-16 |
| TWI485161B true TWI485161B (zh) | 2015-05-21 |
Family
ID=49083343
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102107344A TWI485161B (zh) | 2012-03-02 | 2013-03-01 | 抗上皮細胞黏著分子（ＥｐＣＡＭ）抗體及其使用方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9187558B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2819695B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP6163502B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN104168916B (cg-RX-API-DMAC7.html) |
| TW (1) | TWI485161B (cg-RX-API-DMAC7.html) |
| WO (1) | WO2013131001A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2726870B1 (en) | 2011-06-29 | 2018-10-03 | Academia Sinica | The capture, purification and release of biological substance using a surface coating |
| EP3126814B1 (en) | 2014-04-01 | 2019-06-12 | Academia Sinica | Methods and systems for cancer diagnosis and prognosis |
| WO2017023704A1 (en) * | 2015-07-31 | 2017-02-09 | Sutro Biopharma, Inc. | ANTI-EpCAM ANTIBODIES, COMPOSITIONS COMPRISING ANTI-EpCAM ANTIBODIES AND METHODS OF MAKING AND USING ANTI-EpCAM ANTIBODIES |
| DK3377103T4 (en) * | 2015-11-19 | 2025-05-19 | Revitope Ltd | Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells |
| US10107726B2 (en) | 2016-03-16 | 2018-10-23 | Cellmax, Ltd. | Collection of suspended cells using a transferable membrane |
| CN110035768A (zh) | 2016-07-26 | 2019-07-19 | 泰莎治疗私人有限公司 | 嵌合抗原受体 |
| JP6433951B2 (ja) * | 2016-08-09 | 2018-12-05 | 東芝デジタルソリューションズ株式会社 | ネットワーク監視装置およびプログラム |
| US10787499B2 (en) | 2017-02-13 | 2020-09-29 | Regents Of The University Of Minnesota | EpCAM targeted polypeptides, conjugates thereof, and methods of use thereof |
| WO2020018964A1 (en) | 2018-07-20 | 2020-01-23 | Fred Hutchinson Cancer Research Center | Compositions and methods for controlled expression of antigen-specific receptors |
| WO2020051141A1 (en) * | 2018-09-04 | 2020-03-12 | Academia Sinica | A medium composition and method for culturing mesenchymal stem cells |
| CN113874400B (zh) * | 2019-03-11 | 2025-02-07 | 詹森生物科技公司 | 抗Vβ17/抗CD123双特异性抗体 |
| US11851499B2 (en) | 2019-06-11 | 2023-12-26 | Bioatla, Inc. | Conditionally active anti-EpCAM antibodies, antibody fragments, their immunoconjugates and uses thereof |
| TWI828951B (zh) * | 2019-11-14 | 2024-01-11 | 中央研究院 | 抗上皮細胞黏附分子抗體於癌症治療之用途 |
| CN110950959B (zh) * | 2020-02-25 | 2020-07-03 | 和铂医药(上海)有限责任公司 | 靶向EpCAM的抗体及其制备和应用 |
| CN112094350B (zh) * | 2020-06-01 | 2024-01-05 | 普众发现医药科技(上海)有限公司 | 可应用于肿瘤细胞捕获的小鼠抗细胞表面糖蛋白cd326的单克隆抗体 |
| EP4190808A4 (en) * | 2020-08-19 | 2024-07-31 | Suzhou Immunofoco Biotechnology Co., Ltd. | Humanized antibody, chimeric antigen receptor, nucleic acid, vector, cell and use |
| WO2022133110A1 (en) * | 2020-12-18 | 2022-06-23 | Bioardis, Llc | Epcam binding molecules and uses thereof |
| TWI754504B (zh) * | 2020-12-25 | 2022-02-01 | 龍華科技大學 | 棉花棒棒體之膠體檢測系統及其檢測方法 |
| AU2022297542A1 (en) * | 2021-06-25 | 2024-01-04 | Academia Sinica | Combined cancer therapy with an epithelial cell adhesion molecule (epcam) inhibitor and a hepatocyte growth factor receptor (hgfr) inhibitor |
| JP2024527524A (ja) * | 2021-06-25 | 2024-07-25 | アカデミア シニカ | 上皮細胞接着分子（ｅｐｃａｍ）阻害剤およびｗｎｔ阻害剤の併用癌治療法 |
| JP2023069350A (ja) * | 2021-11-05 | 2023-05-18 | シスメックス株式会社 | 抗体の製造方法及び抗体 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100092491A1 (en) * | 2007-04-04 | 2010-04-15 | Anna Anastasi | Anti-epcam antibody and uses thereof |
| TW201125583A (en) * | 2009-12-23 | 2011-08-01 | Bioalliance Cv | Anti-EpCAM antibodies that induce apoptosis of cancer cells and methods using same |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE200679T1 (de) | 1997-04-14 | 2001-05-15 | Micromet Ag | Neues verfahren zur herstellung von anti-humanen antigenrezeptoren und deren verwendungen |
| EP1242823B1 (en) * | 1999-12-27 | 2007-07-04 | Crucell Holland B.V. | Selecting library members capable of binding to epitopes |
| CA2446087C (en) * | 2001-05-03 | 2013-06-18 | Stephen D. Gillies | Recombinant tumor specific antibody and use thereof |
| US20100311954A1 (en) * | 2002-03-01 | 2010-12-09 | Xencor, Inc. | Optimized Proteins that Target Ep-CAM |
| US7696320B2 (en) * | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| WO2004106917A2 (de) * | 2003-06-02 | 2004-12-09 | Igeneon Krebs-Immuntherapie Forschungs- Und Entwicklungs-Ag | Verfahren zur selektion von epitopen zur immuntherapie |
| US20050180979A1 (en) * | 2004-02-13 | 2005-08-18 | Micromet Ag | Anti-EpCAM immunoglobulins |
| WO2007008943A2 (en) * | 2005-07-08 | 2007-01-18 | Xencor, Inc. | Optimized anti-ep-cam antibodies |
| US7521195B1 (en) * | 2005-07-21 | 2009-04-21 | Celera Corporation | Lung disease targets and uses thereof |
| JP2011193728A (ja) * | 2008-07-17 | 2011-10-06 | Murata Mfg Co Ltd | ＥｐＣＡＭに結合能を有するペプチド |
| GB0909904D0 (en) * | 2009-06-09 | 2009-07-22 | Affitech As | Product |
| CN102844443B (zh) * | 2009-09-21 | 2014-08-06 | 保罗·沃尔菲什 | 用于甲状腺癌诊断和治疗的方法和组合物 |
| EP2567235B1 (en) * | 2010-05-04 | 2017-08-30 | Paul Walfish | Method for the diagnosis of epithelial cancers by the detection of epicd polypeptide |
-
2013
- 2013-03-01 JP JP2014560096A patent/JP6163502B2/ja active Active
- 2013-03-01 EP EP13754991.1A patent/EP2819695B1/en active Active
- 2013-03-01 CN CN201380012187.0A patent/CN104168916B/zh active Active
- 2013-03-01 WO PCT/US2013/028667 patent/WO2013131001A1/en not_active Ceased
- 2013-03-01 TW TW102107344A patent/TWI485161B/zh active
- 2013-03-01 US US14/381,362 patent/US9187558B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100092491A1 (en) * | 2007-04-04 | 2010-04-15 | Anna Anastasi | Anti-epcam antibody and uses thereof |
| TW201125583A (en) * | 2009-12-23 | 2011-08-01 | Bioalliance Cv | Anti-EpCAM antibodies that induce apoptosis of cancer cells and methods using same |
Non-Patent Citations (1)
| Title |
|---|
| P Ruf et al, Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer, British Journal of Cancer (2007) 97, 315 – 321 * |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201350507A (zh) | 2013-12-16 |
| US20150017230A1 (en) | 2015-01-15 |
| WO2013131001A1 (en) | 2013-09-06 |
| JP6163502B2 (ja) | 2017-07-12 |
| EP2819695A4 (en) | 2016-01-20 |
| EP2819695B1 (en) | 2018-06-27 |
| US9187558B2 (en) | 2015-11-17 |
| JP2015517982A (ja) | 2015-06-25 |
| CN104168916A (zh) | 2014-11-26 |
| EP2819695A1 (en) | 2015-01-07 |
| CN104168916B (zh) | 2017-07-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI485161B (zh) | 抗上皮細胞黏著分子（ＥｐＣＡＭ）抗體及其使用方法 | |
| CA3027417C (en) | Anti-human trop-2 antibody having an antitumor activity in vivo | |
| US9670287B2 (en) | Anti-human TROP-2 antibody having anti-tumor activity in vivo | |
| KR102159773B1 (ko) | 글리피칸-3에 대한 고친화력 단클론 항체 및 이의 용도 | |
| EP2096122B1 (en) | Anti-human dlk-1 antibody showing anti-tumor activity in vivo | |
| US8017118B2 (en) | Anti-hDlk-1 antibody having an antitumor activity in vivo | |
| JPWO2014054820A1 (ja) | ｉｎｖｉｖｏで抗腫瘍活性を有する抗ヒトＤｌｋ−１抗体 | |
| HK1198042A (en) | Anti-human trop-2 antibody exhibiting antitumor activity in vivo | |
| HK1198042B (en) | Anti-human trop-2 antibody exhibiting antitumor activity in vivo | |
| NZ623464B2 (en) | Anti-human trop-2 antibody having an antitumor activity in vivo | |
| NZ716839A (en) | Anti-human trop-2 antibody having an antitumor activity in vivo | |
| NZ716839B2 (en) | Anti-human trop-2 antibody having an antitumor activity in vivo |