CA2556632C - Egf receptor epitope peptides and uses thereof - Google Patents
Egf receptor epitope peptides and uses thereof Download PDFInfo
- Publication number
- CA2556632C CA2556632C CA2556632A CA2556632A CA2556632C CA 2556632 C CA2556632 C CA 2556632C CA 2556632 A CA2556632 A CA 2556632A CA 2556632 A CA2556632 A CA 2556632A CA 2556632 C CA2556632 C CA 2556632C
- Authority
- CA
- Canada
- Prior art keywords
- egfr
- receptor
- binding
- mab
- antibodies
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 263
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 100
- 108060006698 EGF receptor Proteins 0.000 title description 457
- 102000001301 EGF receptor Human genes 0.000 title description 439
- 102000005962 receptors Human genes 0.000 claims abstract description 275
- 108020003175 receptors Proteins 0.000 claims abstract description 275
- 238000000034 method Methods 0.000 claims abstract description 107
- 230000027455 binding Effects 0.000 claims description 242
- 239000012634 fragment Substances 0.000 claims description 89
- 230000035772 mutation Effects 0.000 claims description 59
- 150000001413 amino acids Chemical class 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 52
- 230000002163 immunogen Effects 0.000 claims description 35
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 29
- 239000002671 adjuvant Substances 0.000 claims description 28
- 238000006467 substitution reaction Methods 0.000 claims description 21
- 230000002159 abnormal effect Effects 0.000 claims description 17
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 14
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 8
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 8
- 238000012216 screening Methods 0.000 claims description 7
- 238000000338 in vitro Methods 0.000 claims description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims 2
- 102220625006 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1_E10A_mutation Human genes 0.000 claims 1
- 102220470231 Charged multivesicular body protein 5_D11A_mutation Human genes 0.000 claims 1
- 102220473072 Chemerin-like receptor 2_R14Q_mutation Human genes 0.000 claims 1
- 102220509819 General transcription factor II-I_K15E_mutation Human genes 0.000 claims 1
- 102220470369 Thymosin beta-10_K15A_mutation Human genes 0.000 claims 1
- 102220293323 rs1191543342 Human genes 0.000 claims 1
- 102200006537 rs121913529 Human genes 0.000 claims 1
- 102220006559 rs137853934 Human genes 0.000 claims 1
- 102220243686 rs1555618729 Human genes 0.000 claims 1
- 102220024746 rs199473444 Human genes 0.000 claims 1
- 102220102016 rs746768839 Human genes 0.000 claims 1
- 102200127696 rs869025583 Human genes 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 118
- 201000011510 cancer Diseases 0.000 abstract description 63
- 108010009202 Growth Factor Receptors Proteins 0.000 abstract description 47
- 102000009465 Growth Factor Receptors Human genes 0.000 abstract description 46
- 230000000259 anti-tumor effect Effects 0.000 abstract description 32
- 238000011282 treatment Methods 0.000 abstract description 29
- 230000028993 immune response Effects 0.000 abstract description 23
- 230000004936 stimulating effect Effects 0.000 abstract description 8
- 230000001093 anti-cancer Effects 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 253
- 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 139
- 101800003838 Epidermal growth factor Proteins 0.000 description 135
- 229940116977 epidermal growth factor Drugs 0.000 description 135
- 102400001368 Epidermal growth factor Human genes 0.000 description 132
- 239000003446 ligand Substances 0.000 description 120
- 108090000623 proteins and genes Proteins 0.000 description 78
- 230000014509 gene expression Effects 0.000 description 60
- 230000000694 effects Effects 0.000 description 59
- 102100032768 Complement receptor type 2 Human genes 0.000 description 56
- 235000001014 amino acid Nutrition 0.000 description 56
- 102000004169 proteins and genes Human genes 0.000 description 56
- 230000004913 activation Effects 0.000 description 53
- 229940024606 amino acid Drugs 0.000 description 53
- 235000018102 proteins Nutrition 0.000 description 52
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 48
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 48
- 239000000539 dimer Substances 0.000 description 47
- 239000000427 antigen Substances 0.000 description 42
- 230000003993 interaction Effects 0.000 description 42
- 108091007433 antigens Proteins 0.000 description 40
- 102000036639 antigens Human genes 0.000 description 40
- 238000006471 dimerization reaction Methods 0.000 description 40
- 108020004414 DNA Proteins 0.000 description 36
- 108091028043 Nucleic acid sequence Proteins 0.000 description 35
- 230000009257 reactivity Effects 0.000 description 30
- 238000002474 experimental method Methods 0.000 description 28
- 108091000080 Phosphotransferase Proteins 0.000 description 27
- 102000020233 phosphotransferase Human genes 0.000 description 27
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 26
- 230000001965 increasing effect Effects 0.000 description 26
- 238000013507 mapping Methods 0.000 description 26
- 229920001184 polypeptide Polymers 0.000 description 26
- 206010018338 Glioma Diseases 0.000 description 25
- 239000003795 chemical substances by application Substances 0.000 description 25
- 235000018417 cysteine Nutrition 0.000 description 25
- 230000011664 signaling Effects 0.000 description 25
- 230000001225 therapeutic effect Effects 0.000 description 25
- 230000001419 dependent effect Effects 0.000 description 24
- 229960005486 vaccine Drugs 0.000 description 24
- 239000013598 vector Substances 0.000 description 24
- 208000032612 Glial tumor Diseases 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 23
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 22
- 230000004044 response Effects 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 239000000872 buffer Substances 0.000 description 21
- 108020001756 ligand binding domains Proteins 0.000 description 21
- 239000013612 plasmid Substances 0.000 description 21
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 20
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 20
- 239000002246 antineoplastic agent Substances 0.000 description 20
- 230000006870 function Effects 0.000 description 20
- 238000006366 phosphorylation reaction Methods 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 101150039808 Egfr gene Proteins 0.000 description 18
- 238000003556 assay Methods 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 239000000178 monomer Substances 0.000 description 18
- 230000026731 phosphorylation Effects 0.000 description 18
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 16
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 16
- 108091026890 Coding region Proteins 0.000 description 15
- 102000053602 DNA Human genes 0.000 description 15
- 210000004408 hybridoma Anatomy 0.000 description 15
- 239000012528 membrane Substances 0.000 description 15
- 238000011533 pre-incubation Methods 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 208000026310 Breast neoplasm Diseases 0.000 description 14
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 14
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 14
- 230000001413 cellular effect Effects 0.000 description 14
- 208000014829 head and neck neoplasm Diseases 0.000 description 14
- 208000023958 prostate neoplasm Diseases 0.000 description 14
- -1 Q or N X14 is R Inorganic materials 0.000 description 13
- 125000000539 amino acid group Chemical group 0.000 description 13
- 238000013459 approach Methods 0.000 description 13
- 201000010536 head and neck cancer Diseases 0.000 description 13
- 239000000523 sample Substances 0.000 description 13
- 206010006187 Breast cancer Diseases 0.000 description 12
- 108020004705 Codon Proteins 0.000 description 12
- 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 12
- 102000043136 MAP kinase family Human genes 0.000 description 12
- 108091054455 MAP kinase family Proteins 0.000 description 12
- 238000010790 dilution Methods 0.000 description 12
- 239000012895 dilution Substances 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 210000003739 neck Anatomy 0.000 description 12
- 230000002018 overexpression Effects 0.000 description 12
- 238000013391 scatchard analysis Methods 0.000 description 12
- 238000002741 site-directed mutagenesis Methods 0.000 description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 108020004511 Recombinant DNA Proteins 0.000 description 11
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 11
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 11
- 230000003053 immunization Effects 0.000 description 11
- 229940121354 immunomodulator Drugs 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 238000002823 phage display Methods 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 230000008685 targeting Effects 0.000 description 11
- 206010005003 Bladder cancer Diseases 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 108060003951 Immunoglobulin Proteins 0.000 description 10
- 206010023825 Laryngeal cancer Diseases 0.000 description 10
- 206010033128 Ovarian cancer Diseases 0.000 description 10
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 10
- 235000004279 alanine Nutrition 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 229960004316 cisplatin Drugs 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 102000018358 immunoglobulin Human genes 0.000 description 10
- 239000002955 immunomodulating agent Substances 0.000 description 10
- 206010023841 laryngeal neoplasm Diseases 0.000 description 10
- 201000005202 lung cancer Diseases 0.000 description 10
- 208000020816 lung neoplasm Diseases 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 102000039446 nucleic acids Human genes 0.000 description 10
- 108020004707 nucleic acids Proteins 0.000 description 10
- 150000007523 nucleic acids Chemical class 0.000 description 10
- 201000005112 urinary bladder cancer Diseases 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 9
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 9
- 206010023856 Laryngeal squamous cell carcinoma Diseases 0.000 description 9
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 9
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 9
- 206010061535 Ovarian neoplasm Diseases 0.000 description 9
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 9
- 238000012867 alanine scanning Methods 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 229940127089 cytotoxic agent Drugs 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 238000003119 immunoblot Methods 0.000 description 9
- 230000002584 immunomodulator Effects 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 229910052698 phosphorus Inorganic materials 0.000 description 9
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 210000005253 yeast cell Anatomy 0.000 description 9
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000003321 amplification Effects 0.000 description 8
- 210000000481 breast Anatomy 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 238000010348 incorporation Methods 0.000 description 8
- 238000002372 labelling Methods 0.000 description 8
- 238000003199 nucleic acid amplification method Methods 0.000 description 8
- 238000006384 oligomerization reaction Methods 0.000 description 8
- BQVCCPGCDUSGOE-UHFFFAOYSA-N phenylarsine oxide Chemical compound O=[As]C1=CC=CC=C1 BQVCCPGCDUSGOE-UHFFFAOYSA-N 0.000 description 8
- 238000002708 random mutagenesis Methods 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 7
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 108091034117 Oligonucleotide Proteins 0.000 description 7
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 108700021358 erbB-1 Genes Proteins 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 238000009396 hybridization Methods 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000002285 radioactive effect Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 102000003390 tumor necrosis factor Human genes 0.000 description 7
- 231100000588 tumorigenic Toxicity 0.000 description 7
- 230000000381 tumorigenic effect Effects 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- OOIBFPKQHULHSQ-UHFFFAOYSA-N (3-hydroxy-1-adamantyl) 2-methylprop-2-enoate Chemical compound C1C(C2)CC3CC2(O)CC1(OC(=O)C(=C)C)C3 OOIBFPKQHULHSQ-UHFFFAOYSA-N 0.000 description 6
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 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 6
- 241001465754 Metazoa Species 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- 235000003704 aspartic acid Nutrition 0.000 description 6
- 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 6
- 210000004899 c-terminal region Anatomy 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 210000004443 dendritic cell Anatomy 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 230000003463 hyperproliferative effect Effects 0.000 description 6
- 238000002649 immunization Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 230000002269 spontaneous effect Effects 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 210000003932 urinary bladder Anatomy 0.000 description 6
- 238000002255 vaccination Methods 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 230000006820 DNA synthesis Effects 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 5
- 241000287828 Gallus gallus Species 0.000 description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 5
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 5
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 5
- 230000001594 aberrant effect Effects 0.000 description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 230000002860 competitive effect Effects 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 210000003527 eukaryotic cell Anatomy 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 229960002949 fluorouracil Drugs 0.000 description 5
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 5
- 229960002584 gefitinib Drugs 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 238000002703 mutagenesis Methods 0.000 description 5
- 231100000350 mutagenesis Toxicity 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 5
- 229960001972 panitumumab Drugs 0.000 description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 230000001131 transforming effect Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 5
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 5
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 230000004544 DNA amplification Effects 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 239000002033 PVDF binder Substances 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 239000006180 TBST buffer Substances 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 235000009582 asparagine Nutrition 0.000 description 4
- 229960001230 asparagine Drugs 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 238000002405 diagnostic procedure Methods 0.000 description 4
- 229960004679 doxorubicin Drugs 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 229930182817 methionine Natural products 0.000 description 4
- 239000006151 minimal media Substances 0.000 description 4
- 230000002297 mitogenic effect Effects 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- GFNNBHLJANVSQV-UHFFFAOYSA-N tyrphostin AG 1478 Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1 GFNNBHLJANVSQV-UHFFFAOYSA-N 0.000 description 4
- 230000003313 weakening effect Effects 0.000 description 4
- YDFAYDGRSWSLCT-UHFFFAOYSA-N 1-[4-[2-[4-(2,5-dioxo-3-sulfopyrrolidin-1-yl)oxy-4-oxobutanoyl]oxyethoxy]-4-oxobutanoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCC(=O)OCCOC(=O)CCC(=O)ON1C(=O)C(S(O)(=O)=O)CC1=O YDFAYDGRSWSLCT-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010032595 Antibody Binding Sites Proteins 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 3
- 239000004971 Cross linker Substances 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 230000005778 DNA damage Effects 0.000 description 3
- 231100000277 DNA damage Toxicity 0.000 description 3
- 239000012623 DNA damaging agent Substances 0.000 description 3
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 3
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102000018997 Growth Hormone Human genes 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 108010002386 Interleukin-3 Proteins 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- 108010033276 Peptide Fragments Proteins 0.000 description 3
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 3
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 3
- 108010008038 Synthetic Vaccines Proteins 0.000 description 3
- 230000024932 T cell mediated immunity Effects 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 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 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000002927 anti-mitotic effect Effects 0.000 description 3
- 230000005875 antibody response Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229940022399 cancer vaccine Drugs 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 229940044683 chemotherapy drug Drugs 0.000 description 3
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000007783 downstream signaling Effects 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 108010087914 epidermal growth factor receptor VIII Proteins 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 239000000122 growth hormone Substances 0.000 description 3
- 210000004524 haematopoietic cell Anatomy 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 102000045108 human EGFR Human genes 0.000 description 3
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 229940047122 interleukins Drugs 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 208000037841 lung tumor Diseases 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 230000008747 mitogenic response Effects 0.000 description 3
- 238000003032 molecular docking Methods 0.000 description 3
- 239000003068 molecular probe Substances 0.000 description 3
- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 238000002818 protein evolution Methods 0.000 description 3
- 230000002797 proteolythic effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229930182490 saponin Natural products 0.000 description 3
- 235000017709 saponins Nutrition 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- 241001515965 unidentified phage Species 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 2
- NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 206010057248 Cell death Diseases 0.000 description 2
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 2
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 241000282552 Chlorocebus aethiops Species 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- 101150029707 ERBB2 gene Proteins 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 241000724791 Filamentous phage Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 108010051696 Growth Hormone Proteins 0.000 description 2
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 2
- 101000619805 Homo sapiens Peroxiredoxin-5, mitochondrial Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-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
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 2
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000057297 Pepsin A Human genes 0.000 description 2
- 108090000284 Pepsin A Proteins 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 102100022078 Peroxiredoxin-5, mitochondrial Human genes 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 108091027981 Response element Proteins 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 108091006629 SLC13A2 Proteins 0.000 description 2
- 241000219287 Saponaria Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 101150109894 TGFA gene Proteins 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000012452 Xenomouse strains Methods 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 230000006023 anti-tumor response Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 229940125683 antiemetic agent Drugs 0.000 description 2
- 239000003080 antimitotic agent Substances 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 230000001908 autoinhibitory effect Effects 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 229920001222 biopolymer Polymers 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000004227 calcium gluconate Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 239000013553 cell monolayer Substances 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229960003067 cystine Drugs 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000004925 denaturation Methods 0.000 description 2
- 230000036425 denaturation Effects 0.000 description 2
- 229940029030 dendritic cell vaccine Drugs 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 229960001433 erlotinib Drugs 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 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 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 239000011544 gradient gel Substances 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000008863 intramolecular interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 2
- 229960000991 ketoprofen Drugs 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 229960002247 lomustine Drugs 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 208000025440 neoplasm of neck Diseases 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000007899 nucleic acid hybridization Methods 0.000 description 2
- 229940023146 nucleic acid vaccine Drugs 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 229940127240 opiate Drugs 0.000 description 2
- 239000006179 pH buffering agent Substances 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 229940111202 pepsin Drugs 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 229960000624 procarbazine Drugs 0.000 description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 2
- 238000000163 radioactive labelling Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 239000012723 sample buffer Substances 0.000 description 2
- 150000007949 saponins Chemical class 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000007781 signaling event Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000034005 thiol-disulfide exchange Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- PJOHVEQSYPOERL-SHEAVXILSA-N (e)-n-[(4r,4as,7ar,12br)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a-yl]-3-(4-methylphenyl)prop-2-enamide Chemical compound C1=CC(C)=CC=C1\C=C\C(=O)N[C@]1(CCC(=O)[C@@H]2O3)[C@H]4CC5=CC=C(O)C3=C5[C@]12CCN4CC1CC1 PJOHVEQSYPOERL-SHEAVXILSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- FJQZXCPWAGYPSD-UHFFFAOYSA-N 1,3,4,6-tetrachloro-3a,6a-diphenylimidazo[4,5-d]imidazole-2,5-dione Chemical compound ClN1C(=O)N(Cl)C2(C=3C=CC=CC=3)N(Cl)C(=O)N(Cl)C12C1=CC=CC=C1 FJQZXCPWAGYPSD-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
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- YVOOPGWEIRIUOX-UHFFFAOYSA-N 2-azanyl-3-sulfanyl-propanoic acid Chemical compound SCC(N)C(O)=O.SCC(N)C(O)=O YVOOPGWEIRIUOX-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical group O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-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
- 101150096316 5 gene Proteins 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101100163869 Arabidopsis thaliana AS1 gene Proteins 0.000 description 1
- 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000711895 Bovine orthopneumovirus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 241000219193 Brassicaceae Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 102000018361 Contactin Human genes 0.000 description 1
- 108060003955 Contactin Proteins 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 230000004543 DNA replication Effects 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
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 239000012983 Dulbecco’s minimal essential medium Substances 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 230000037057 G1 phase arrest Effects 0.000 description 1
- 241000272496 Galliformes Species 0.000 description 1
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 238000012450 HuMAb Mouse Methods 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 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
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 150000008575 L-amino acids Chemical group 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 102000046795 Mitogen-Activated Protein Kinase 3 Human genes 0.000 description 1
- 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 241001092142 Molina Species 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 101100118551 Mus musculus Egfr gene Proteins 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 101710149086 Nuclease S1 Proteins 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 101150012394 PHO5 gene Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
- 241001222774 Salmonella enterica subsp. enterica serovar Minnesota Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010068542 Somatotropin Receptors Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000187747 Streptomyces Species 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
- 108020005038 Terminator Codon Proteins 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- 102000008236 Toll-Like Receptor 7 Human genes 0.000 description 1
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 108010046334 Urease Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003127 anti-melanomic effect Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical group N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- JPIYZTWMUGTEHX-UHFFFAOYSA-N auramine O free base Chemical compound C1=CC(N(C)C)=CC=C1C(=N)C1=CC=C(N(C)C)C=C1 JPIYZTWMUGTEHX-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- 244000309466 calf Species 0.000 description 1
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
- 229930195731 calicheamicin Natural products 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 108010079058 casein hydrolysate Proteins 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000002113 chemopreventative effect Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008876 conformational transition Effects 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 229940104302 cytosine Drugs 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
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000012407 engineering method Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 201000003911 head and neck carcinoma Diseases 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000001894 hemadsorption Effects 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 229960003685 imatinib mesylate Drugs 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- 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 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 239000012642 immune effector Substances 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000017555 immunoglobulin mediated immune response Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 208000033353 latent tuberculosis infection Diseases 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 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 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 229950008001 matuzumab Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(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](CC=1C=CC(O)=CC=1)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](CCCCN)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)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)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=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 239000011022 opal Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000447 polyanionic polymer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012910 preclinical development Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 229940030749 prostate cancer vaccine Drugs 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 229940051022 radioimmunoconjugate Drugs 0.000 description 1
- 238000011363 radioimmunotherapy Methods 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 229940126583 recombinant protein vaccine Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009703 regulation of cell differentiation Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 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
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000001913 submandibular gland Anatomy 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229910052713 technetium Inorganic materials 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 150000003626 triacylglycerols Chemical class 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
- 239000013638 trimer Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 230000001875 tumorinhibitory effect Effects 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000005924 vaccine-induced immune response Effects 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54660204P | 2004-02-20 | 2004-02-20 | |
| US60/546,602 | 2004-02-20 | ||
| US58462304P | 2004-07-01 | 2004-07-01 | |
| US60/584,623 | 2004-07-01 | ||
| PCT/US2005/005155 WO2005081854A2 (en) | 2004-02-20 | 2005-02-18 | Egf receptor epitope peptides and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2556632A1 CA2556632A1 (en) | 2005-09-09 |
| CA2556632C true CA2556632C (en) | 2016-10-11 |
Family
ID=34915579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2556632A Expired - Lifetime CA2556632C (en) | 2004-02-20 | 2005-02-18 | Egf receptor epitope peptides and uses thereof |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7767792B2 (enExample) |
| EP (2) | EP2514763A1 (enExample) |
| JP (2) | JP2008501308A (enExample) |
| KR (2) | KR101280267B1 (enExample) |
| AU (2) | AU2005216082B8 (enExample) |
| CA (1) | CA2556632C (enExample) |
| ES (1) | ES2536974T3 (enExample) |
| WO (1) | WO2005081854A2 (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1392359E (pt) * | 2001-05-11 | 2010-01-27 | Ludwig Inst For Cancer Res Ltd | Proteínas de ligação específica e suas utilizações |
| US20100056762A1 (en) * | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| DE60237282D1 (de) * | 2001-06-28 | 2010-09-23 | Domantis Ltd | Doppelspezifischer ligand und dessen verwendung |
| 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 |
| DK1517921T3 (da) * | 2002-06-28 | 2006-10-09 | Domantis Ltd | Immunglobulin-enkeltvariable antigen-bindende domæner og dobbeltspecifikke konstruktioner deraf |
| US9321832B2 (en) * | 2002-06-28 | 2016-04-26 | Domantis Limited | Ligand |
| CA2511910A1 (en) * | 2002-12-27 | 2004-07-15 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
| US7767792B2 (en) | 2004-02-20 | 2010-08-03 | Ludwig Institute For Cancer Research Ltd. | Antibodies to EGF receptor epitope peptides |
| US20070009972A1 (en) * | 2005-02-16 | 2007-01-11 | Ginger Chao | Epidermal growth factor receptor polypeptides and antibodies |
| CN104857500A (zh) * | 2005-11-02 | 2015-08-26 | 杜克大学 | 同时的化学疗法和免疫疗法 |
| KR20080077238A (ko) * | 2005-12-01 | 2008-08-21 | 도만티스 리미티드 | 인터루킨 1 수용체 타입 1에 결합하는 비경쟁적 도메인항체 포맷 |
| CA2647671A1 (en) * | 2006-03-31 | 2007-11-01 | Massachusetts Institute Of Technology | Treatment of tumors expressing mutant egf receptors |
| EP2068929A4 (en) * | 2006-09-15 | 2010-04-28 | Life Science Pharmaceuticals | METHOD OF DETECTING AND TREATING SKIN DISORDERS |
| WO2008091701A2 (en) * | 2007-01-25 | 2008-07-31 | Dana-Farber Cancer Institute | Use of anti-egfr antibodies in treatment of egfr mutant mediated disease |
| JP2010520748A (ja) | 2007-02-20 | 2010-06-17 | アナプティスバイオ インコーポレイティッド | 体細胞超変異系 |
| CA2680854C (en) | 2007-03-15 | 2017-02-14 | Ludwig Institute For Cancer Research | Treatment method using egfr antibodies and src inhibitors and related formulations |
| USRE47534E1 (en) * | 2007-04-23 | 2019-07-23 | Ramot At Tel Aviv University Ltd. | System, method and a computer readable medium for providing an output image |
| BRPI0812398A2 (pt) | 2007-06-06 | 2019-09-24 | Domantis Ltd | domínio variável simples de imunoglobulina anti-vegf, antagonista anti-vegf, domínio variável simples de imunoglobulina resistente à protease, uso do antagonista vegf, método para a dispensação oral ou dispensação de um medicamento ao trato gi de um paciente ou ao pulmão ou tecido pulmonar ou olho de um paciente, dispositivo de dispensação pulmonar, formulação oral, ligando específico duplo, ácido nucleico isolado ou recombinante, vetor, célula hospedeira, método para produzir polipeptídeo, composição farmacêutica, polipeptídeo, e, proteína de fusão |
| MX2010001757A (es) * | 2007-08-14 | 2010-09-14 | Ludwig Inst Cancer Res | Anticuerpo monoclonal 175 que activa el receptor egf y derivados y usos del mismo. |
| WO2009023266A1 (en) * | 2007-08-14 | 2009-02-19 | Ludwig Institute For Cancer Research | Generation of antibodies to cell-surface receptors and cancer-associated proteins including egfr family members |
| EP3492488A1 (en) | 2007-08-22 | 2019-06-05 | The Regents of The University of California | Activatable binding polypeptides and methods of identification and use thereof |
| DE112008003232T5 (de) | 2007-11-30 | 2011-02-24 | Glaxo Group Limited, Greenford | Antigen-Bindungskonstrukte |
| WO2009149094A2 (en) * | 2008-06-02 | 2009-12-10 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Cytotoxic t cell defined egfr peptide and an optimized derivative peptide |
| JP2010006705A (ja) * | 2008-06-13 | 2010-01-14 | Atlas Antibodies Ab | Ｈｅｒ２サブセット |
| WO2009155381A1 (en) * | 2008-06-18 | 2009-12-23 | Abbott Laboratories | P/gf-1 companion diagnostic methods and products |
| US20100004306A1 (en) * | 2008-06-18 | 2010-01-07 | Abbott Laboratories | PIGF-1 Assay and kits and components thereof |
| US8741287B2 (en) * | 2008-06-18 | 2014-06-03 | Abbott Laboratories | PlGF-1 assay and kits and components thereof |
| US8895702B2 (en) | 2008-12-08 | 2014-11-25 | City Of Hope | Development of masked therapeutic antibodies to limit off-target effects; application to anti-EGFR antibodies |
| EP2356131A4 (en) * | 2008-12-08 | 2012-09-12 | Tegopharm Corp | MASKING LIGANDS FOR REVERSIBLE INHIBITION OF VERSATILE COMPOUNDS |
| WO2010081173A2 (en) | 2009-01-12 | 2010-07-15 | Cytomx Therapeutics, Llc | Modified antibody compositions, methods of making and using thereof |
| AU2010215761B2 (en) * | 2009-02-23 | 2017-04-06 | Cytomx Therapeutics, Inc | Proproteins and methods of use thereof |
| JP5680087B2 (ja) * | 2009-09-22 | 2015-03-04 | シャンハイ・イージェー・バイオテクノロジー・カンパニー、リミテッドＳｈａｎｇｈａｉ Ｙｉｊｉｅ Ｂｉｏｔｅｃｈｎｏｌｏｇｙ Ｃｏ．，Ｌｔｄ | 特異的結合タンパク質およびその使用 |
| CN102127147B (zh) * | 2010-01-20 | 2014-07-02 | 上海市肿瘤研究所 | 表皮生长因子受体模拟表位肽及其应用 |
| CN103539840B (zh) * | 2010-01-20 | 2015-04-01 | 上海市肿瘤研究所 | 表皮生长因子受体模拟表位肽及其应用 |
| JP2013534515A (ja) | 2010-06-01 | 2013-09-05 | モナシュ ユニバーシティ | プロセシングされていない受容体型チロシンキナーゼｃ−ＭＥＴに対する抗体 |
| WO2012024659A2 (en) | 2010-08-20 | 2012-02-23 | Massachusetts Institute Of Technology | Antibody-based constructs directed against tyrosine kinase receptors |
| TWI582112B (zh) | 2011-04-21 | 2017-05-11 | 西雅圖遺傳學公司 | 新穎結合劑－藥物接合物（ＡＤＣｓ）及其用途（二） |
| EP2832363B1 (en) * | 2012-03-27 | 2018-09-19 | Green Cross Corporation | Epitopes of epidermal growth factor receptor surface antigen and use thereof |
| JP6103832B2 (ja) | 2012-06-25 | 2017-03-29 | Hoya株式会社 | Ｅｇｆｒ結合性ペプチド |
| JP6721507B2 (ja) | 2013-12-23 | 2020-07-15 | バイエル・ファルマ・アクティエンゲゼルシャフト | Ｋｓｐ阻害剤との抗体薬物複合体（ａｄｃ） |
| KR102399005B1 (ko) | 2014-03-11 | 2022-05-17 | 리제너론 파마슈티칼스 인코포레이티드 | 항-egfrviii 항체 및 그것의 용도 |
| CN110845616A (zh) | 2014-03-21 | 2020-02-28 | 艾伯维公司 | 抗-egfr抗体及抗体药物偶联物 |
| US20190099475A1 (en) | 2015-04-08 | 2019-04-04 | Nantomics, Llc | Cancer neoepitopes |
| WO2016172722A1 (en) | 2015-04-23 | 2016-10-27 | Nantomics, Llc | Cancer neoepitopes |
| SG10201908685QA (en) | 2015-06-22 | 2019-10-30 | Bayer Pharma AG | Antibody drug conjugates (adcs) and antibody prodrug conjugates (apdcs) with enzymatically cleavable groups |
| WO2017060322A2 (en) | 2015-10-10 | 2017-04-13 | Bayer Pharma Aktiengesellschaft | Ptefb-inhibitor-adc |
| JP2018532736A (ja) | 2015-10-12 | 2018-11-08 | ナントミクス，エルエルシー | チェックポイント阻害物質への感受性を予測するｍｓｉおよびネオエピトープの探索のための系、組成物、および方法 |
| AU2017236431A1 (en) | 2016-03-24 | 2018-09-27 | Bayer Pharma Aktiengesellschaft | Prodrugs of cytotoxic active agents having enzymatically cleavable groups |
| CA3027445A1 (en) | 2016-06-15 | 2017-12-21 | Bayer Pharma Aktiengesellschaft | Specific antibody-drug-conjugates (adcs) with ksp inhibitors and anti-cd123-antibodies |
| EP3558386A1 (de) | 2016-12-21 | 2019-10-30 | Bayer Aktiengesellschaft | Prodrugs von cytotoxischen wirkstoffen mit enzymatisch spaltbaren gruppen |
| WO2018114804A1 (de) | 2016-12-21 | 2018-06-28 | Bayer Pharma Aktiengesellschaft | Spezifische antikörper-wirkstoff-konjugate (adcs) mit ksp-inhibitoren |
| MX2019007641A (es) | 2016-12-21 | 2019-09-09 | Bayer Pharma AG | Conjugados de ligando-farmaco (adcs) con grupos escindibles enzimaticamente. |
| US11459391B2 (en) | 2019-02-26 | 2022-10-04 | Janssen Biotech, Inc. | Combination therapies and patient stratification with bispecific anti-EGFR/c-Met antibodies |
| JP7727549B2 (ja) * | 2019-03-22 | 2025-08-21 | セルティス・セラピューティクス・ピーティーワイ・リミテッド | 抗ｈｅｒ２結合分子 |
| JOP20210304A1 (ar) | 2019-05-14 | 2023-01-30 | Janssen Biotech Inc | علاجات مركبة باستخدام الأجسام المضادة ثنائية النوعية المضادة لمستقبل عامل نمو البشرة (EGFR)/ مستقبل عامل نمو خلايا الكبد (c-Met) ومثبطات كيناز التيروسين الخاصة بمستقبل عامل نمو البشرة (EGFR) من الجيل الثالث |
| JOP20220184A1 (ar) | 2020-02-12 | 2023-01-30 | Janssen Biotech Inc | علاج مصابي السرطان ممن لديهم طفرات تخطي c-Met إكسون14 |
| CN111647074B (zh) * | 2020-06-01 | 2023-12-19 | 皖南医学院 | 一种her3二聚化界面抗原肽、重组抗原肽、编码基因及其应用 |
| AR124681A1 (es) | 2021-01-20 | 2023-04-26 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
| JP2024527235A (ja) | 2021-06-22 | 2024-07-24 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 抗ＥＧＦＲｖＩＩＩ抗体薬物コンジュゲート及びその使用 |
Family Cites Families (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE31006E (en) | 1968-09-24 | 1982-08-03 | Akzona Incorporated | Process for the demonstration and determination of reaction components having specific binding affinity for each other |
| US3654090A (en) | 1968-09-24 | 1972-04-04 | Organon | Method for the determination of antigens and antibodies |
| NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
| US4016043A (en) | 1975-09-04 | 1977-04-05 | Akzona Incorporated | Enzymatic immunological method for the determination of antigens and antibodies |
| US4491632A (en) | 1979-10-22 | 1985-01-01 | The Massachusetts General Hospital | Process for producing antibodies to hepatitis virus and cell lines therefor |
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4342566A (en) | 1980-02-22 | 1982-08-03 | Scripps Clinic & Research Foundation | Solid phase anti-C3 assay for detection of immune complexes |
| DE3167442D1 (en) | 1980-07-07 | 1985-01-10 | Nat Res Dev | Improvements in or relating to cell lines |
| US4341761A (en) | 1980-07-25 | 1982-07-27 | E. I. Du Pont De Nemours And Company | Antibodies to immunogenic peptides and their use to purify human fibroblast interferon |
| US4466917A (en) | 1981-02-12 | 1984-08-21 | New York University | Malaria vaccine |
| US4493890A (en) | 1981-03-23 | 1985-01-15 | Miles Laboratories, Inc. | Activated apoglucose oxidase and its use in specific binding assays |
| US4451570A (en) | 1981-03-26 | 1984-05-29 | The Regents Of The University Of California | Immunoglobulin-secreting human hybridomas from a cultured human lymphoblastoid cell line |
| US4596792A (en) | 1981-09-04 | 1986-06-24 | The Regents Of The University Of California | Safe vaccine for hepatitis containing polymerized serum albumin |
| US4399121A (en) | 1981-11-04 | 1983-08-16 | Miles Laboratories, Inc. | Iodothyronine immunogens and antibodies |
| US4427783A (en) | 1981-12-14 | 1984-01-24 | Hoffmann-La Roche Inc. | Immunoassay of thymosin α1 |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4493795A (en) | 1983-10-17 | 1985-01-15 | Syntex (U.S.A.) Inc. | Synthetic peptide sequences useful in biological and pharmaceutical applications and methods of manufacture |
| US4943533A (en) * | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
| US4599230A (en) | 1984-03-09 | 1986-07-08 | Scripps Clinic And Research Foundation | Synthetic hepatitis B virus vaccine including both T cell and B cell determinants |
| US4599231A (en) | 1984-03-09 | 1986-07-08 | Scripps Clinic And Research Foundation | Synthetic hepatitis B virus vaccine including both T cell and B cell determinants |
| US4601903A (en) | 1985-05-01 | 1986-07-22 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine against Neisseria meningitidis Group B serotype 2 invasive disease |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US5071773A (en) | 1986-10-24 | 1991-12-10 | The Salk Institute For Biological Studies | Hormone receptor-related bioassays |
| US4981784A (en) | 1987-12-02 | 1991-01-01 | The Salk Institute For Biological Studies | Retinoic acid receptor method |
| JP3040121B2 (ja) * | 1988-01-12 | 2000-05-08 | ジェネンテク，インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
| AU4128089A (en) * | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| AU633867B2 (en) | 1989-02-02 | 1993-02-11 | Eli Lilly And Company | Delivery of cytotoxic agents |
| ATE135373T1 (de) | 1989-09-08 | 1996-03-15 | Univ Johns Hopkins | Modifikationen der struktur des egf-rezeptor-gens in menschlichen glioma |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5459061A (en) * | 1990-01-26 | 1995-10-17 | W. Alton Jones Cell Science Center, Inc. | Hybridomas producing monoclonal antibodies which specifically bind to continuous epitope on the human EGF receptor and compete with EGF for binding to the EGF receptor |
| AU7774391A (en) | 1990-04-20 | 1991-11-11 | Ludwig Institute For Cancer Research | Aberrant, epidermal growth factor receptor dna, rna and protein forms and method |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| AU649275B2 (en) | 1990-11-06 | 1994-05-19 | Bristol-Myers Squibb Company | Prodrugs for beta-lactamase and uses thereof |
| US5795965A (en) * | 1991-04-25 | 1998-08-18 | Chugai Seiyaku Kabushiki Kaisha | Reshaped human to human interleukin-6 receptor |
| US6797492B2 (en) | 1991-05-17 | 2004-09-28 | Merck & Co., Inc. | Method for reducing the immunogenicity of antibody variable domains |
| WO1994001137A1 (en) | 1992-07-06 | 1994-01-20 | Hybritech Incorporated | Method for delivery of cytotoxic agents and components thereof |
| EP0672142B1 (en) | 1992-12-04 | 2001-02-28 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
| US5922545A (en) | 1993-10-29 | 1999-07-13 | Affymax Technologies N.V. | In vitro peptide and antibody display libraries |
| US6111166A (en) | 1994-09-19 | 2000-08-29 | Medarex, Incorporated | Transgenic mice expressing human Fcα and β receptors |
| DE69532767T2 (de) | 1994-11-28 | 2004-08-12 | Thomas Jefferson University | Peptid umfassend eine Sequenz aus einer Fusionsverbindungsstelle in einem mutierten EGF-Rezeptor vom Typ III |
| UA56132C2 (uk) | 1995-04-25 | 2003-05-15 | Смітклайн Бічем Байолоджікалс С.А. | Композиція вакцини (варіанти), спосіб стабілізації qs21 відносно гідролізу (варіанти), спосіб приготування композиції вакцини |
| US5708156A (en) * | 1996-05-31 | 1998-01-13 | Ilekis; John V. | Epidermal growth factor receptor-like gene product and its uses |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| US5942602A (en) * | 1997-02-13 | 1999-08-24 | Schering Aktiengessellschaft | Growth factor receptor antibodies |
| DK1226177T3 (da) * | 1999-10-29 | 2008-10-06 | Genentech Inc | Antistofsammensætninger mod anti-prostata stamcelle-antigen (PSCA) og anvendelser deraf |
| MXPA02007190A (es) * | 2000-01-25 | 2003-02-12 | Genentech Inc | Proteina relacionada a liv-1, polinucleotidos que codifican para la misma y uso de la misma para el tratamiento de cancer. |
| WO2002011677A2 (en) | 2000-08-09 | 2002-02-14 | Imclone Systems Incorporated | Treatment of hyperproliferative diseases with epidermal growth factor receptor antagonists |
| PT1392359E (pt) | 2001-05-11 | 2010-01-27 | Ludwig Inst For Cancer Res Ltd | Proteínas de ligação específica e suas utilizações |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| CZ200438A3 (cs) * | 2001-06-13 | 2004-06-16 | Genmab A/S | Název neuveden |
| WO2003014159A1 (en) * | 2001-08-03 | 2003-02-20 | Commonwealth Scientific And Industrial Research Organisation | Methods of screening based on the egf receptor crystal structure |
| AU2003236346A1 (en) * | 2002-04-11 | 2003-10-20 | Fuso Pharmaceutical Industries, Ltd. | Monoclonal antibody neutralizing megsin |
| US7767792B2 (en) * | 2004-02-20 | 2010-08-03 | Ludwig Institute For Cancer Research Ltd. | Antibodies to EGF receptor epitope peptides |
| EP2592155B2 (en) * | 2004-06-04 | 2019-09-11 | Genentech, Inc. | EGFR mutations |
| AU2005314127A1 (en) * | 2004-12-07 | 2006-06-15 | Genentech, Inc. | Selecting patients for therapy with a HER inhibitor |
| EP2068929A4 (en) | 2006-09-15 | 2010-04-28 | Life Science Pharmaceuticals | METHOD OF DETECTING AND TREATING SKIN DISORDERS |
| WO2008091701A2 (en) | 2007-01-25 | 2008-07-31 | Dana-Farber Cancer Institute | Use of anti-egfr antibodies in treatment of egfr mutant mediated disease |
| CA2680854C (en) * | 2007-03-15 | 2017-02-14 | Ludwig Institute For Cancer Research | Treatment method using egfr antibodies and src inhibitors and related formulations |
| MX2010001757A (es) | 2007-08-14 | 2010-09-14 | Ludwig Inst Cancer Res | Anticuerpo monoclonal 175 que activa el receptor egf y derivados y usos del mismo. |
| US20110076232A1 (en) | 2009-09-29 | 2011-03-31 | Ludwig Institute For Cancer Research | Specific binding proteins and uses thereof |
| US9209965B2 (en) | 2014-01-14 | 2015-12-08 | Microsemi Semiconductor Ulc | Network interface with clock recovery module on line card |
-
2005
- 2005-02-17 US US11/060,646 patent/US7767792B2/en active Active
- 2005-02-18 WO PCT/US2005/005155 patent/WO2005081854A2/en not_active Ceased
- 2005-02-18 EP EP12164335A patent/EP2514763A1/en not_active Withdrawn
- 2005-02-18 KR KR1020067019405A patent/KR101280267B1/ko not_active Expired - Lifetime
- 2005-02-18 JP JP2006554221A patent/JP2008501308A/ja active Pending
- 2005-02-18 ES ES05723258.9T patent/ES2536974T3/es not_active Expired - Lifetime
- 2005-02-18 KR KR1020127010335A patent/KR101270443B1/ko not_active Expired - Lifetime
- 2005-02-18 AU AU2005216082A patent/AU2005216082B8/en not_active Expired
- 2005-02-18 EP EP05723258.9A patent/EP1722808B1/en not_active Expired - Lifetime
- 2005-02-18 CA CA2556632A patent/CA2556632C/en not_active Expired - Lifetime
-
2010
- 2010-01-29 US US12/657,919 patent/US8652473B2/en not_active Expired - Lifetime
- 2010-09-20 AU AU2010224335A patent/AU2010224335B2/en not_active Expired
-
2011
- 2011-12-15 JP JP2011274098A patent/JP6045147B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| KR20070031871A (ko) | 2007-03-20 |
| JP6045147B2 (ja) | 2016-12-14 |
| CA2556632A1 (en) | 2005-09-09 |
| AU2005216082B8 (en) | 2010-11-18 |
| US20050255555A1 (en) | 2005-11-17 |
| EP1722808A2 (en) | 2006-11-22 |
| KR101270443B1 (ko) | 2013-05-31 |
| EP2514763A1 (en) | 2012-10-24 |
| US7767792B2 (en) | 2010-08-03 |
| AU2010224335A1 (en) | 2010-10-14 |
| JP2008501308A (ja) | 2008-01-24 |
| EP1722808B1 (en) | 2015-04-08 |
| KR20120050530A (ko) | 2012-05-18 |
| US8652473B2 (en) | 2014-02-18 |
| WO2005081854A2 (en) | 2005-09-09 |
| AU2010224335B2 (en) | 2012-04-05 |
| KR101280267B1 (ko) | 2013-07-15 |
| AU2005216082A1 (en) | 2005-09-09 |
| ES2536974T3 (es) | 2015-06-01 |
| AU2005216082B2 (en) | 2010-10-14 |
| EP1722808A4 (en) | 2009-08-19 |
| JP2012102109A (ja) | 2012-05-31 |
| US20100322937A1 (en) | 2010-12-23 |
| WO2005081854A3 (en) | 2006-01-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2556632C (en) | Egf receptor epitope peptides and uses thereof | |
| JP7494245B2 (ja) | Ｃｄ４７及びｅｇｆｒの二重標的化による癌治療 | |
| CA2696360C (en) | Monoclonal antibody targeting the egfr receptor and uses thereof | |
| US20250059256A1 (en) | Her-1, her-3 and igf-1r compositions and uses thereof | |
| PT1735348E (pt) | Anticorpo anti-receptor do factor de crescimento humano | |
| WO2009023266A1 (en) | Generation of antibodies to cell-surface receptors and cancer-associated proteins including egfr family members | |
| US20240383998A1 (en) | Asymmetric antibody with improved cytotoxicity against cancer cells | |
| AU2008287335B8 (en) | Monoclonal antibody 175 targeting the EGF receptor and derivatives and uses thereof | |
| HK1141033B (en) | Monoclonal antibody 175 targeting the egf receptor and derivatives and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |