JP6336696B2 - がんおよび自己免疫疾患の診断および治療に使用するためのモノクローナル抗体 - Google Patents
がんおよび自己免疫疾患の診断および治療に使用するためのモノクローナル抗体 Download PDFInfo
- Publication number
- JP6336696B2 JP6336696B2 JP2015521668A JP2015521668A JP6336696B2 JP 6336696 B2 JP6336696 B2 JP 6336696B2 JP 2015521668 A JP2015521668 A JP 2015521668A JP 2015521668 A JP2015521668 A JP 2015521668A JP 6336696 B2 JP6336696 B2 JP 6336696B2
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- cells
- hla
- tumor
- seq
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 147
- 238000011282 treatment Methods 0.000 title claims description 66
- 201000011510 cancer Diseases 0.000 title claims description 60
- 238000003745 diagnosis Methods 0.000 title description 20
- 208000023275 Autoimmune disease Diseases 0.000 title description 17
- 102000025850 HLA-A2 Antigen Human genes 0.000 claims description 154
- 108010074032 HLA-A2 Antigen Proteins 0.000 claims description 154
- 238000000034 method Methods 0.000 claims description 107
- 208000026310 Breast neoplasm Diseases 0.000 claims description 91
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 88
- 150000007523 nucleic acids Chemical class 0.000 claims description 56
- 230000014509 gene expression Effects 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 48
- 102000039446 nucleic acids Human genes 0.000 claims description 48
- 108020004707 nucleic acids Proteins 0.000 claims description 48
- 239000003814 drug Substances 0.000 claims description 39
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 239000003153 chemical reaction reagent Substances 0.000 claims description 34
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 31
- 208000032839 leukemia Diseases 0.000 claims description 27
- 229920001184 polypeptide Polymers 0.000 claims description 27
- 229940124597 therapeutic agent Drugs 0.000 claims description 24
- 230000001225 therapeutic effect Effects 0.000 claims description 24
- 102000004127 Cytokines Human genes 0.000 claims description 23
- 108090000695 Cytokines Proteins 0.000 claims description 23
- 238000002560 therapeutic procedure Methods 0.000 claims description 22
- 239000003053 toxin Substances 0.000 claims description 17
- 231100000765 toxin Toxicity 0.000 claims description 17
- 239000000556 agonist Substances 0.000 claims description 16
- 239000013604 expression vector Substances 0.000 claims description 16
- 238000001959 radiotherapy Methods 0.000 claims description 15
- 238000001356 surgical procedure Methods 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 12
- 230000005298 paramagnetic effect Effects 0.000 claims description 11
- 238000001415 gene therapy Methods 0.000 claims description 10
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims description 9
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims description 9
- 238000011319 anticancer therapy Methods 0.000 claims description 9
- 229940088597 hormone Drugs 0.000 claims description 9
- 239000005556 hormone Substances 0.000 claims description 9
- 238000013319 spin trapping Methods 0.000 claims description 9
- 238000002512 chemotherapy Methods 0.000 claims description 8
- 230000000139 costimulatory effect Effects 0.000 claims description 8
- 208000029742 colonic neoplasm Diseases 0.000 claims description 7
- 208000037819 metastatic cancer Diseases 0.000 claims description 7
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 7
- 206010025323 Lymphomas Diseases 0.000 claims description 6
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 6
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 6
- 201000003120 testicular cancer Diseases 0.000 claims description 6
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 5
- 238000001794 hormone therapy Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 206010061968 Gastric neoplasm Diseases 0.000 claims description 4
- 206010019695 Hepatic neoplasm Diseases 0.000 claims description 4
- 206010029098 Neoplasm skin Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 4
- 206010038111 Recurrent cancer Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 238000012258 culturing Methods 0.000 claims description 4
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 208000037841 lung tumor Diseases 0.000 claims description 4
- 208000025402 neoplasm of esophagus Diseases 0.000 claims description 4
- 208000025189 neoplasm of testis Diseases 0.000 claims description 4
- 208000014680 small intestine neoplasm Diseases 0.000 claims description 4
- 208000021550 spleen neoplasm Diseases 0.000 claims description 4
- 208000025421 tumor of uterus Diseases 0.000 claims description 4
- 206010046766 uterine cancer Diseases 0.000 claims description 4
- 208000024719 uterine cervix neoplasm Diseases 0.000 claims description 4
- 201000005787 hematologic cancer Diseases 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 description 343
- 108090000623 proteins and genes Proteins 0.000 description 104
- 206010006187 Breast cancer Diseases 0.000 description 93
- 108010028275 Leukocyte Elastase Proteins 0.000 description 90
- 102000016799 Leukocyte elastase Human genes 0.000 description 90
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 76
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 74
- 210000001519 tissue Anatomy 0.000 description 63
- 102000004169 proteins and genes Human genes 0.000 description 57
- 235000018102 proteins Nutrition 0.000 description 55
- 241000699670 Mus sp. Species 0.000 description 54
- 239000000427 antigen Substances 0.000 description 52
- 108091007433 antigens Proteins 0.000 description 51
- 102000036639 antigens Human genes 0.000 description 51
- 201000001441 melanoma Diseases 0.000 description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 45
- 230000027455 binding Effects 0.000 description 43
- 238000009739 binding Methods 0.000 description 42
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 40
- 201000010099 disease Diseases 0.000 description 39
- 102000011786 HLA-A Antigens Human genes 0.000 description 37
- 108010075704 HLA-A Antigens Proteins 0.000 description 37
- 238000002347 injection Methods 0.000 description 34
- 239000007924 injection Substances 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 33
- 239000013598 vector Substances 0.000 description 33
- 241000699666 Mus <mouse, genus> Species 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 26
- 210000001185 bone marrow Anatomy 0.000 description 26
- 230000000694 effects Effects 0.000 description 26
- 108020004414 DNA Proteins 0.000 description 25
- 229940024606 amino acid Drugs 0.000 description 24
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 24
- 108020004635 Complementary DNA Proteins 0.000 description 23
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 23
- 102000005962 receptors Human genes 0.000 description 23
- 108020003175 receptors Proteins 0.000 description 23
- 150000001413 amino acids Chemical class 0.000 description 22
- 238000010804 cDNA synthesis Methods 0.000 description 22
- 239000002299 complementary DNA Substances 0.000 description 21
- 230000001965 increasing effect Effects 0.000 description 21
- 238000010186 staining Methods 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 19
- 206010047115 Vasculitis Diseases 0.000 description 18
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 18
- 230000006870 function Effects 0.000 description 18
- 210000004408 hybridoma Anatomy 0.000 description 18
- 230000001404 mediated effect Effects 0.000 description 18
- 201000006417 multiple sclerosis Diseases 0.000 description 18
- -1 radioisotope Substances 0.000 description 18
- 208000024891 symptom Diseases 0.000 description 18
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 description 17
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 description 17
- 238000002965 ELISA Methods 0.000 description 17
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 description 17
- 230000000295 complement effect Effects 0.000 description 17
- 238000000684 flow cytometry Methods 0.000 description 17
- 238000009169 immunotherapy Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 208000011231 Crohn disease Diseases 0.000 description 16
- 108010002352 Interleukin-1 Proteins 0.000 description 16
- 108700012359 toxins Proteins 0.000 description 16
- 102000000589 Interleukin-1 Human genes 0.000 description 15
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 15
- 210000001744 T-lymphocyte Anatomy 0.000 description 15
- 239000002246 antineoplastic agent Substances 0.000 description 15
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 239000013641 positive control Substances 0.000 description 15
- 239000000523 sample Substances 0.000 description 15
- 230000003013 cytotoxicity Effects 0.000 description 14
- 231100000135 cytotoxicity Toxicity 0.000 description 14
- 230000028993 immune response Effects 0.000 description 14
- 230000002147 killing effect Effects 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 238000011579 SCID mouse model Methods 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 210000004072 lung Anatomy 0.000 description 13
- 210000000440 neutrophil Anatomy 0.000 description 13
- 101000742121 Arabidopsis thaliana Pathogenesis-related protein 1 Proteins 0.000 description 12
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 12
- 101000742139 Cucumis melo Pathogenesis-related protein Proteins 0.000 description 12
- 102000002689 Toll-like receptor Human genes 0.000 description 12
- 108020000411 Toll-like receptor Proteins 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 230000003902 lesion Effects 0.000 description 12
- 210000004698 lymphocyte Anatomy 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000000178 monomer Substances 0.000 description 12
- 239000013642 negative control Substances 0.000 description 12
- 238000006467 substitution reaction Methods 0.000 description 12
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 11
- 201000004681 Psoriasis Diseases 0.000 description 11
- 241000700605 Viruses Species 0.000 description 11
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 11
- 229940127089 cytotoxic agent Drugs 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 239000000499 gel Substances 0.000 description 11
- 150000002500 ions Chemical class 0.000 description 11
- 210000000265 leukocyte Anatomy 0.000 description 11
- 210000003622 mature neutrocyte Anatomy 0.000 description 11
- 210000005259 peripheral blood Anatomy 0.000 description 11
- 239000011886 peripheral blood Substances 0.000 description 11
- 238000003752 polymerase chain reaction Methods 0.000 description 11
- 210000003491 skin Anatomy 0.000 description 11
- 238000002054 transplantation Methods 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 10
- 230000002159 abnormal effect Effects 0.000 description 10
- 238000001574 biopsy Methods 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 230000008685 targeting Effects 0.000 description 10
- 230000009261 transgenic effect Effects 0.000 description 10
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 9
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 9
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 9
- 125000000539 amino acid group Chemical group 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 210000003719 b-lymphocyte Anatomy 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 238000002648 combination therapy Methods 0.000 description 9
- 238000002784 cytotoxicity assay Methods 0.000 description 9
- 239000000032 diagnostic agent Substances 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 239000003550 marker Substances 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 9
- 230000003612 virological effect Effects 0.000 description 9
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 8
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 8
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 8
- 208000003456 Juvenile Arthritis Diseases 0.000 description 8
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 8
- 102000035195 Peptidases Human genes 0.000 description 8
- 108091005804 Peptidases Proteins 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 238000010162 Tukey test Methods 0.000 description 8
- 102100040247 Tumor necrosis factor Human genes 0.000 description 8
- 238000000540 analysis of variance Methods 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 230000009089 cytolysis Effects 0.000 description 8
- 231100000263 cytotoxicity test Toxicity 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 229940039227 diagnostic agent Drugs 0.000 description 8
- 239000000975 dye Substances 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 8
- 238000000370 laser capture micro-dissection Methods 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000002271 resection Methods 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 210000000952 spleen Anatomy 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 239000013603 viral vector Substances 0.000 description 8
- 108091026890 Coding region Proteins 0.000 description 7
- 241000701022 Cytomegalovirus Species 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 108700020796 Oncogene Proteins 0.000 description 7
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 210000002798 bone marrow cell Anatomy 0.000 description 7
- 210000000481 breast Anatomy 0.000 description 7
- 230000004663 cell proliferation Effects 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 239000003431 cross linking reagent Substances 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 210000004700 fetal blood Anatomy 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 7
- 210000000987 immune system Anatomy 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 210000004969 inflammatory cell Anatomy 0.000 description 7
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 238000002595 magnetic resonance imaging Methods 0.000 description 7
- 230000010412 perfusion Effects 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 235000019833 protease Nutrition 0.000 description 7
- 230000001177 retroviral effect Effects 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 7
- 230000001052 transient effect Effects 0.000 description 7
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 239000011534 wash buffer Substances 0.000 description 7
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 108700028369 Alleles Proteins 0.000 description 6
- 241000283707 Capra Species 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 6
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 6
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- 102000013760 Microphthalmia-Associated Transcription Factor Human genes 0.000 description 6
- 108010050345 Microphthalmia-Associated Transcription Factor Proteins 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 6
- 206010037660 Pyrexia Diseases 0.000 description 6
- 239000012980 RPMI-1640 medium Substances 0.000 description 6
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 6
- 206010003246 arthritis Diseases 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 208000019069 chronic childhood arthritis Diseases 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 238000004624 confocal microscopy Methods 0.000 description 6
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 6
- 210000003714 granulocyte Anatomy 0.000 description 6
- 206010020718 hyperplasia Diseases 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000000411 inducer Substances 0.000 description 6
- 230000008595 infiltration Effects 0.000 description 6
- 238000001764 infiltration Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 208000025113 myeloid leukemia Diseases 0.000 description 6
- 238000004806 packaging method and process Methods 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- 241000701161 unidentified adenovirus Species 0.000 description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 5
- 102100022749 Aminopeptidase N Human genes 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 5
- 239000004971 Cross linker Substances 0.000 description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 5
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- 241000713666 Lentivirus Species 0.000 description 5
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 5
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 5
- 206010033661 Pancytopenia Diseases 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 208000021386 Sjogren Syndrome Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 description 5
- 239000002260 anti-inflammatory agent Substances 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 238000010226 confocal imaging Methods 0.000 description 5
- 229960004397 cyclophosphamide Drugs 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 5
- 210000003128 head Anatomy 0.000 description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
- 230000036039 immunity Effects 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 230000001613 neoplastic effect Effects 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 208000033808 peripheral neuropathy Diseases 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 241001430294 unidentified retrovirus Species 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 239000012130 whole-cell lysate Substances 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 4
- 241000945470 Arcturus Species 0.000 description 4
- 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 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 4
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001007 Interleukin-8 Proteins 0.000 description 4
- 102000004890 Interleukin-8 Human genes 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- 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 4
- DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 239000004472 Lysine Substances 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 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
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 208000001647 Renal Insufficiency Diseases 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 230000009471 action Effects 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 230000000735 allogeneic effect Effects 0.000 description 4
- 238000012197 amplification kit Methods 0.000 description 4
- 238000009175 antibody therapy Methods 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 4
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 210000003855 cell nucleus Anatomy 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 239000003246 corticosteroid Substances 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 238000012137 double-staining Methods 0.000 description 4
- 102000015694 estrogen receptors Human genes 0.000 description 4
- 108010038795 estrogen receptors Proteins 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 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 4
- 230000004927 fusion Effects 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 230000002390 hyperplastic effect Effects 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 210000001503 joint Anatomy 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 210000003712 lysosome Anatomy 0.000 description 4
- 230000001868 lysosomic effect Effects 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 201000000050 myeloid neoplasm Diseases 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 239000013610 patient sample Substances 0.000 description 4
- 229940023041 peptide vaccine Drugs 0.000 description 4
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 4
- 229960004618 prednisone Drugs 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 108091008146 restriction endonucleases Proteins 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 238000011870 unpaired t-test Methods 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 3
- 101000797614 Arabidopsis thaliana Protein MEI2-like 5 Proteins 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 3
- 208000032544 Cicatrix Diseases 0.000 description 3
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- 206010058314 Dysplasia Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010014950 Eosinophilia Diseases 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 108010058597 HLA-DR Antigens Proteins 0.000 description 3
- 102000006354 HLA-DR Antigens Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 3
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 3
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 102000013462 Interleukin-12 Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 3
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 3
- 102100038225 Lysosome-associated membrane glycoprotein 2 Human genes 0.000 description 3
- 101710116771 Lysosome-associated membrane glycoprotein 2 Proteins 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- 102000003896 Myeloperoxidases Human genes 0.000 description 3
- 108090000235 Myeloperoxidases Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 3
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 3
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 3
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 3
- 238000002123 RNA extraction Methods 0.000 description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
- 208000009527 Refractory anemia Diseases 0.000 description 3
- 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- 108010039491 Ricin Proteins 0.000 description 3
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 3
- 238000012300 Sequence Analysis Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 3
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
- 238000009534 blood test Methods 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 238000010322 bone marrow transplantation Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 210000003679 cervix uteri Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940044683 chemotherapy drug Drugs 0.000 description 3
- 210000000038 chest Anatomy 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000012325 curative resection Methods 0.000 description 3
- 238000004163 cytometry Methods 0.000 description 3
- 208000024389 cytopenia Diseases 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000003238 esophagus Anatomy 0.000 description 3
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 3
- 229960005542 ethidium bromide Drugs 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 210000004602 germ cell Anatomy 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 208000024908 graft versus host disease Diseases 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 230000002489 hematologic effect Effects 0.000 description 3
- 230000003053 immunization Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 230000003308 immunostimulating effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000007972 injectable composition Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000002601 intratumoral effect Effects 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 238000009533 lab test Methods 0.000 description 3
- 210000002429 large intestine Anatomy 0.000 description 3
- 201000002364 leukopenia Diseases 0.000 description 3
- 231100001022 leukopenia Toxicity 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000002751 lymph Anatomy 0.000 description 3
- 230000002132 lysosomal effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical class NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000000386 microscopy Methods 0.000 description 3
- 102000035118 modified proteins Human genes 0.000 description 3
- 108091005573 modified proteins Proteins 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 210000003739 neck Anatomy 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 210000000019 nipple aspirate fluid Anatomy 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 102000013415 peroxidase activity proteins Human genes 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 3
- 230000008488 polyadenylation Effects 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 150000003141 primary amines Chemical group 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 102000016914 ras Proteins Human genes 0.000 description 3
- 108010014186 ras Proteins Proteins 0.000 description 3
- 208000013718 rectal benign neoplasm Diseases 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 231100000241 scar Toxicity 0.000 description 3
- 230000037387 scars Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- 238000011477 surgical intervention Methods 0.000 description 3
- 210000001550 testis Anatomy 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- 238000002255 vaccination Methods 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- 229960003048 vinblastine Drugs 0.000 description 3
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical group C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 2
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 206010068051 Chimerism Diseases 0.000 description 2
- 108010049048 Cholera Toxin Proteins 0.000 description 2
- 102000009016 Cholera Toxin Human genes 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 2
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 2
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 2
- 102000018251 Hypoxanthine Phosphoribosyltransferase Human genes 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 108010079944 Interferon-alpha2b Proteins 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 108090000177 Interleukin-11 Proteins 0.000 description 2
- 102000003815 Interleukin-11 Human genes 0.000 description 2
- 102100030703 Interleukin-22 Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 102000005727 Mammaglobin A Human genes 0.000 description 2
- 108010031030 Mammaglobin A Proteins 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- 206010028570 Myelopathy Diseases 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
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- 241001028048 Nicola Species 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 241001452677 Ogataea methanolica Species 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 101710160107 Outer membrane protein A Proteins 0.000 description 2
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 2
- 102100039467 P3 protein Human genes 0.000 description 2
- 101710117080 P3 protein Proteins 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 108010081690 Pertussis Toxin Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 229940079156 Proteasome inhibitor Drugs 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- 108700020978 Proto-Oncogene Proteins 0.000 description 2
- 102000052575 Proto-Oncogene Human genes 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 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 2
- 239000013543 active substance Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940124650 anti-cancer therapies Drugs 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 230000000719 anti-leukaemic effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 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
- 229960002170 azathioprine Drugs 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000001815 biotherapy Methods 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 229960002092 busulfan Drugs 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 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 2
- 229940127093 camptothecin Drugs 0.000 description 2
- 210000001736 capillary Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 238000010370 cell cloning Methods 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- 229960004630 chlorambucil Drugs 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 2
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 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 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000003979 eosinophil Anatomy 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
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000015220 hamburgers Nutrition 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000011132 hemopoiesis Effects 0.000 description 2
- 229940022353 herceptin Drugs 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- 239000012216 imaging agent Substances 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 239000012642 immune effector Substances 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 229940124589 immunosuppressive drug Drugs 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 208000018937 joint inflammation Diseases 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- 229960004963 mesalazine Drugs 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 206010063344 microscopic polyangiitis Diseases 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 230000004001 molecular interaction Effects 0.000 description 2
- 210000003007 myelin sheath Anatomy 0.000 description 2
- BNWJOHGLIBDBOB-UHFFFAOYSA-N myristicin Chemical compound COC1=CC(CC=C)=CC2=C1OCO2 BNWJOHGLIBDBOB-UHFFFAOYSA-N 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 229940086322 navelbine Drugs 0.000 description 2
- 208000004235 neutropenia Diseases 0.000 description 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 2
- 210000001331 nose Anatomy 0.000 description 2
- 238000012758 nuclear staining Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 210000003463 organelle Anatomy 0.000 description 2
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 2
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 210000002741 palatine tonsil Anatomy 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 238000002823 phage display Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 2
- 201000006292 polyarteritis nodosa Diseases 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000001855 preneoplastic effect Effects 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
- 229960000624 procarbazine Drugs 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 208000023958 prostate neoplasm Diseases 0.000 description 2
- 239000003207 proteasome inhibitor Substances 0.000 description 2
- 229960000856 protein c Drugs 0.000 description 2
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 230000003439 radiotherapeutic effect Effects 0.000 description 2
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 2
- 229960004622 raloxifene Drugs 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 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 2
- 210000003079 salivary gland Anatomy 0.000 description 2
- 238000009094 second-line therapy Methods 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 201000009890 sinusitis Diseases 0.000 description 2
- 235000020183 skimmed milk Nutrition 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 210000004988 splenocyte Anatomy 0.000 description 2
- 238000011301 standard therapy Methods 0.000 description 2
- 238000011272 standard treatment Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 201000004595 synovitis Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960001967 tacrolimus Drugs 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 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 2
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000007306 turnover Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 210000005166 vasculature Anatomy 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
- 229960004528 vincristine Drugs 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
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- XAXNKAGAUFXFDO-JVJDXIHNSA-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-chlorophenyl)prop-2-enamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)NC(=O)\C=C\C=2C=CC(Cl)=CC=2)CC1)O)CC1CC1 XAXNKAGAUFXFDO-JVJDXIHNSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- WUAPFZMCVAUBPE-NJFSPNSNSA-N 188Re Chemical compound [188Re] WUAPFZMCVAUBPE-NJFSPNSNSA-N 0.000 description 1
- 108020004463 18S ribosomal RNA Proteins 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- MEOVPKDOYAIVHZ-UHFFFAOYSA-N 2-chloro-1-(1-methylpyrrol-2-yl)ethanol Chemical compound CN1C=CC=C1C(O)CCl MEOVPKDOYAIVHZ-UHFFFAOYSA-N 0.000 description 1
- 108020005096 28S Ribosomal RNA Proteins 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
- IDLISIVVYLGCKO-UHFFFAOYSA-N 6-carboxy-4',5'-dichloro-2',7'-dimethoxyfluorescein Chemical compound O1C(=O)C2=CC=C(C(O)=O)C=C2C21C1=CC(OC)=C(O)C(Cl)=C1OC1=C2C=C(OC)C(O)=C1Cl IDLISIVVYLGCKO-UHFFFAOYSA-N 0.000 description 1
- BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 101150111160 ALA1 gene Proteins 0.000 description 1
- 101150118692 ALS5 gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 208000022316 Arachnoid cyst Diseases 0.000 description 1
- 206010003101 Arnold-Chiari Malformation Diseases 0.000 description 1
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 102100027314 Beta-2-microglobulin Human genes 0.000 description 1
- 108030001720 Bontoxilysin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 241001598984 Bromius obscurus Species 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 102100036846 C-C motif chemokine 21 Human genes 0.000 description 1
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 108010062802 CD66 antigens Proteins 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- 108090000426 Caspase-1 Proteins 0.000 description 1
- 231100000023 Cell-mediated cytotoxicity Toxicity 0.000 description 1
- 206010057250 Cell-mediated cytotoxicity Diseases 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 229940123150 Chelating agent Drugs 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 208000015321 Chiari malformation Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 229910052692 Dysprosium Inorganic materials 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- 102100026560 Filamin-C Human genes 0.000 description 1
- 101710091745 Filamin-C Proteins 0.000 description 1
- 108010040721 Flagellin Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010001515 Galectin 4 Proteins 0.000 description 1
- 102100039556 Galectin-4 Human genes 0.000 description 1
- GYHNNYVSQQEPJS-OIOBTWANSA-N Gallium-67 Chemical compound [67Ga] GYHNNYVSQQEPJS-OIOBTWANSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 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 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000000616 Hemoptysis Diseases 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000713085 Homo sapiens C-C motif chemokine 21 Proteins 0.000 description 1
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 1
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 1
- 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 1
- 101001034314 Homo sapiens Lactadherin Proteins 0.000 description 1
- 101000621344 Homo sapiens Protein Wnt-2 Proteins 0.000 description 1
- 101000653679 Homo sapiens Translationally-controlled tumor protein Proteins 0.000 description 1
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 1
- 102100040018 Interferon alpha-2 Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 101800003050 Interleukin-16 Proteins 0.000 description 1
- 102000049772 Interleukin-16 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 102000003810 Interleukin-18 Human genes 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 102100039879 Interleukin-19 Human genes 0.000 description 1
- 108050009288 Interleukin-19 Proteins 0.000 description 1
- 108010065637 Interleukin-23 Proteins 0.000 description 1
- 102000013264 Interleukin-23 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 208000008081 Intestinal Fistula Diseases 0.000 description 1
- 206010022678 Intestinal infections Diseases 0.000 description 1
- 206010022699 Intestinal stenosis Diseases 0.000 description 1
- ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 102100039648 Lactadherin Human genes 0.000 description 1
- 102100038609 Lactoperoxidase Human genes 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 102000002297 Laminin Receptors Human genes 0.000 description 1
- 108010000851 Laminin Receptors Proteins 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 102100032352 Leukemia inhibitory factor Human genes 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 102100033486 Lymphocyte antigen 75 Human genes 0.000 description 1
- 101710157884 Lymphocyte antigen 75 Proteins 0.000 description 1
- 102100026894 Lymphotoxin-beta Human genes 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- 239000012515 MabSelect SuRe Substances 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical compound [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 101710169959 Membrane protein 2 Proteins 0.000 description 1
- 208000009795 Microphthalmos Diseases 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 206010073148 Multiple endocrine neoplasia type 2A Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000985214 Mus musculus 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- 241000187482 Mycobacterium avium subsp. paratuberculosis Species 0.000 description 1
- 241000186366 Mycobacterium bovis Species 0.000 description 1
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 208000000592 Nasal Polyps Diseases 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- AWZJFZMWSUBJAJ-UHFFFAOYSA-N OG-514 dye Chemical compound OC(=O)CSC1=C(F)C(F)=C(C(O)=O)C(C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)=C1F AWZJFZMWSUBJAJ-UHFFFAOYSA-N 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 102100025386 Oxidized low-density lipoprotein receptor 1 Human genes 0.000 description 1
- 101710199789 Oxidized low-density lipoprotein receptor 1 Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102100022427 Plasmalemma vesicle-associated protein Human genes 0.000 description 1
- 101710193105 Plasmalemma vesicle-associated protein Proteins 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000034943 Primary Sjögren syndrome Diseases 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 102100025803 Progesterone receptor Human genes 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 102100038358 Prostate-specific antigen Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102100022805 Protein Wnt-2 Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 208000037323 Rare tumor Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 208000033501 Refractory anemia with excess blasts Diseases 0.000 description 1
- 241001068295 Replication defective viruses Species 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 229910052772 Samarium Inorganic materials 0.000 description 1
- 102400000827 Saposin-D Human genes 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 108010032838 Sialoglycoproteins Proteins 0.000 description 1
- 102000007365 Sialoglycoproteins Human genes 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000710960 Sindbis virus Species 0.000 description 1
- 206010040744 Sinus headache Diseases 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 101100177443 Spinacia oleracea HEMB gene Proteins 0.000 description 1
- 206010041591 Spinal osteoarthritis Diseases 0.000 description 1
- 208000035286 Spontaneous Remission Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 102100029887 Translationally-controlled tumor protein Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 108010091356 Tumor Protein p73 Proteins 0.000 description 1
- 102000018252 Tumor Protein p73 Human genes 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 101710145727 Viral Fc-gamma receptor-like protein UL119 Proteins 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- 108010027570 Xanthine phosphoribosyltransferase Proteins 0.000 description 1
- 229910052769 Ytterbium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 1
- 244000126002 Ziziphus vulgaris Species 0.000 description 1
- 235000008529 Ziziphus vulgaris Nutrition 0.000 description 1
- PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 201000011186 acute T cell leukemia Diseases 0.000 description 1
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000003314 affinity selection Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003092 anti-cytokine Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 238000011091 antibody purification Methods 0.000 description 1
- 238000011230 antibody-based therapy Methods 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 230000005744 arteriovenous malformation Effects 0.000 description 1
- RYXHOMYVWAEKHL-OUBTZVSYSA-N astatine-211 Chemical compound [211At] RYXHOMYVWAEKHL-OUBTZVSYSA-N 0.000 description 1
- 230000006470 autoimmune attack Effects 0.000 description 1
- WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 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 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000000746 body region Anatomy 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 238000009583 bone marrow aspiration Methods 0.000 description 1
- 229940053031 botulinum toxin Drugs 0.000 description 1
- 238000013276 bronchoscopy Methods 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 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
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008568 cell cell communication Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000005890 cell-mediated cytotoxicity Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000004640 cellular pathway Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 208000036319 cervical spondylosis Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- BFGKITSFLPAWGI-UHFFFAOYSA-N chromium(3+) Chemical compound [Cr+3] BFGKITSFLPAWGI-UHFFFAOYSA-N 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000012321 colectomy Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- RYGMFSIKBFXOCR-AKLPVKDBSA-N copper-67 Chemical compound [67Cu] RYGMFSIKBFXOCR-AKLPVKDBSA-N 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000002681 cryosurgery Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000030381 cutaneous melanoma Diseases 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000002559 cytogenic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 108010017271 denileukin diftitox Proteins 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- HQWKKEIVHQXCPI-UHFFFAOYSA-L disodium;phthalate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C([O-])=O HQWKKEIVHQXCPI-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- BJDWURMSYDDCRX-UHFFFAOYSA-N ethoxycarbonyl ethyl carbonate;hydrate Chemical compound O.CCOC(=O)OC(=O)OCC BJDWURMSYDDCRX-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
- 238000011156 evaluation Methods 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000002270 exclusion chromatography Methods 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 229960004887 ferric hydroxide Drugs 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000004905 finger nail Anatomy 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 210000000285 follicular dendritic cell Anatomy 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 108700004026 gag Genes Proteins 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 210000001280 germinal center Anatomy 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- CBMIPXHVOVTTTL-UHFFFAOYSA-N gold(3+) Chemical compound [Au+3] CBMIPXHVOVTTTL-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 208000006750 hematuria Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 208000008675 hereditary spastic paraplegia Diseases 0.000 description 1
- SCKNFLZJSOHWIV-UHFFFAOYSA-N holmium(3+) Chemical compound [Ho+3] SCKNFLZJSOHWIV-UHFFFAOYSA-N 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 102000056982 human CD33 Human genes 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000002169 hydrotherapy Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000003463 hyperproliferative effect Effects 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
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000001571 immunoadjuvant effect Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 238000011575 immunodeficient mouse model Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 108090000681 interleukin 20 Proteins 0.000 description 1
- 102000004114 interleukin 20 Human genes 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 108010074109 interleukin-22 Proteins 0.000 description 1
- 108090000237 interleukin-24 Proteins 0.000 description 1
- 102000003898 interleukin-24 Human genes 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000004673 intestinal mucosal barrier function Effects 0.000 description 1
- 230000008316 intracellular mechanism Effects 0.000 description 1
- 102000027411 intracellular receptors Human genes 0.000 description 1
- 108091008582 intracellular receptors Proteins 0.000 description 1
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- IEECXTSVVFWGSE-UHFFFAOYSA-M iron(3+);oxygen(2-);hydroxide Chemical compound [OH-].[O-2].[Fe+3] IEECXTSVVFWGSE-UHFFFAOYSA-M 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 238000011862 kidney biopsy Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- CZMAIROVPAYCMU-UHFFFAOYSA-N lanthanum(3+) Chemical compound [La+3] CZMAIROVPAYCMU-UHFFFAOYSA-N 0.000 description 1
- 238000002430 laser surgery Methods 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 210000004324 lymphatic system Anatomy 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
- 239000006296 mab medium Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 201000010893 malignant breast melanoma Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012913 medium supplement Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 238000001531 micro-dissection Methods 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 201000010478 microphthalmia Diseases 0.000 description 1
- 208000011873 mild conjunctivitis Diseases 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 206010051747 multiple endocrine neoplasia Diseases 0.000 description 1
- 238000012314 multivariate regression analysis Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 208000016586 myelodysplastic syndrome with excess blasts Diseases 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 230000027498 negative regulation of mitosis Effects 0.000 description 1
- QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 description 1
- 230000009707 neogenesis Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 208000002040 neurosyphilis Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000008689 nuclear function Effects 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 229940100027 ontak Drugs 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 210000004789 organ system Anatomy 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
- 230000008520 organization Effects 0.000 description 1
- 238000011499 palliative surgery Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- IZRPKIZLIFYYKR-UHFFFAOYSA-N phenyltoloxamine Chemical compound CN(C)CCOC1=CC=CC=C1CC1=CC=CC=C1 IZRPKIZLIFYYKR-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- BLFWHYXWBKKRHI-JYBILGDPSA-N plap Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](N)CCC(O)=O BLFWHYXWBKKRHI-JYBILGDPSA-N 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000011045 prefiltration Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 239000013608 rAAV vector Substances 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 1
- 229950010550 resiquimod Drugs 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- WUAPFZMCVAUBPE-IGMARMGPSA-N rhenium-186 Chemical compound [186Re] WUAPFZMCVAUBPE-IGMARMGPSA-N 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 239000012146 running buffer Substances 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 125000005630 sialyl group Chemical group 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- HBMJWWWQQXIZIP-UHFFFAOYSA-N silicon carbide Chemical compound [Si+]#[C-] HBMJWWWQQXIZIP-UHFFFAOYSA-N 0.000 description 1
- 229910010271 silicon carbide Inorganic materials 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 108700021652 sis Genes Proteins 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 201000003708 skin melanoma Diseases 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 208000005801 spondylosis Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 101150047061 tag-72 gene Proteins 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 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
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 210000004906 toe nail Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 238000013414 tumor xenograft model Methods 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6871—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting an enzyme
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0058—Antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3061—Blood cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
- G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/71—Decreased effector function due to an Fc-modification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96433—Serine endopeptidases (3.4.21)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Hospice & Palliative Care (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
Description
本願は、2012年7月10日に出願された米国仮特許出願第61/669,967号、および2012年9月19日に出願された米国仮特許出願第61/702,916号の利益を主張し、双方の出願の全体の内容は、本明細書中に参考として援用される。
本発明は、国立がん研究所/国立衛生研究所によって授与されたP50CA100632の下、政府の支援を受けてなされた。政府は、本発明について一定の権利を有する。
本発明は、一般に、がんおよび免疫療法の分野に関する。より具体的には、それは、がんおよび自己免疫疾患の処置および予防のための免疫診断抗体および免疫治療抗体に関する。
免疫系は、長い間、がんの制御に関連するとされてきたが、ヒトがんにおける特異的かつ有効な免疫応答の証拠を欠いていた。慢性骨髄性白血病(CML)では、同種骨髄移植(BMT)またはインターフェロン−α2b(IFN−α2b)療法により完全寛解がもたらされるが、疾病制御の機構は知られておらず、それには、免疫抗白血病応答が関与し得る。
本発明の実施形態において、例えば以下の項目が提供される。
(項目1)
HLA−A2受容体に結合されるとVLQELNVTV(配列番号45)に結合する単離および精製された抗体であって、配列番号3、4および5を含む重鎖CDRと、配列番号8、9および10を含む軽鎖CDRとを有する、単離および精製された抗体。
(項目2)
マウス抗体である、項目1に記載の抗体。
(項目3)
一本鎖抗体または二重特異性抗体である、項目1に記載の抗体。
(項目4)
非抗体ペプチドまたはポリペプチドセグメントに融合されている、項目1に記載の抗体。
(項目5)
診断試薬に連結されている、項目1に記載の抗体。
(項目6)
前記診断試薬が、フルオロフォア、発色団、色素、放射性同位体、化学発光分子、常磁性イオンまたはスピントラッピング試薬である、項目5に記載の抗体。
(項目7)
治療試薬に連結されている、項目1に記載の抗体。
(項目8)
前記治療試薬が、サイトカイン、化学療法薬、放射線療法薬、ホルモン、抗体Fc断片、TLRアゴニスト、CpG含有分子または免疫共刺激分子である、項目7に記載の抗体。
(項目9)
ヒト化抗体である、項目1に記載の抗体。
(項目10)
前記ヒト化抗体が、配列番号38および36または配列番号40および36ならびに配列番号40および42の軽鎖/重鎖配列を有する、項目1に記載の抗体。
(項目11)
配列番号8、9および10によってコードされる軽鎖CDRをコードする、核酸。
(項目12)
配列番号7または配列番号12をコードする、項目11に記載の核酸。
(項目13)
配列番号23または配列番号25をコードする、項目11に記載の核酸。
(項目14)
前記軽鎖CDRをコードする前記核酸の5’側に位置するプロモーター配列をさらに含む、項目11に記載の核酸。
(項目15)
前記プロモーターが真核細胞内で活性である、項目14に記載の核酸。
(項目16)
前記プロモーターが原核細胞内で活性である、項目14に記載の核酸。
(項目17)
複製可能なベクター内に配置されている、項目11に記載の核酸。
(項目18)
前記複製可能なベクターが非ウイルスベクターである、項目17に記載の核酸。
(項目19)
前記複製可能なベクターがウイルスベクターである、項目17に記載の核酸。
(項目20)
前記CDRコードセグメント間に位置するリンカーコードセグメントをさらに含む、項目11に記載の核酸。
(項目21)
前記リンカーコードセグメントの1つ以上が、ヘリックス−ターン−ヘリックスモチーフをコードする、項目20に記載の核酸。
(項目22)
配列番号3、4および5の配列を含むCDRを含む重鎖コードセグメントを含み、配列番号8、9および10の配列を含むCDRを含む軽鎖コードセグメントを含む、人工抗体。
(項目23)
前記CDRが合成リンカーによって連結されている、項目22に記載の人工抗体。
(項目24)
前記重鎖が非抗体ペプチドまたはポリペプチドセグメントに融合されている、項目22に記載の人工抗体。
(項目25)
診断試薬に連結されている、項目22に記載の人工抗体。
(項目26)
前記診断試薬が、フルオロフォア、発色団、色素、放射性同位体、化学発光分子、常磁性イオンまたはスピントラッピング試薬である、項目25に記載の人工抗体。
(項目27)
治療試薬に連結されている、項目22に記載の人工抗体。
(項目28)
前記治療試薬が、サイトカイン、毒素、化学療法薬、放射線療法薬、ホルモン、抗体Fc断片、好中球エラスターゼ、プロテイナーゼ3、TLRアゴニスト、CpG含有分子または免疫共刺激分子である、項目27に記載の人工抗体。
(項目29)
前記軽鎖が配列番号7、配列番号12、配列番号23もしくは配列番号25を含み、および/または前記重鎖が配列番号36もしくは配列番号42を含む、項目22に記載の人工抗体。
(項目30)
抗体を作製する方法であって、(a)(i)配列番号3、4および5に示されるCDRを含む重鎖をコードする核酸配列、および(ii)配列番号8、9および10に示されるCDRを含む軽鎖をコードする核酸配列を宿主細胞に導入すること;ならびに(b)該軽鎖および重鎖の発現を支援する条件下で該宿主細胞を培養することを含む、方法。
(項目31)
前記抗体を単離することをさらに含む、項目30に記載の方法。
(項目32)
前記抗体を診断剤または治療剤に連結する工程をさらに含む、項目31に記載の方法。
(項目33)
異常細胞を含有すると疑われるサンプル中の異常細胞を検出する方法であって、該サンプルと、項目1に記載の抗体または項目22に記載の人工抗体とを接触させることを含む、方法。
(項目34)
前記抗体または人工抗体が診断剤にコンジュゲートされている、項目33に記載の方法。
(項目35)
前記診断剤が、フルオロフォア、発色団、色素、放射性同位体、化学発光分子、常磁性イオンまたはスピントラッピング試薬である、項目34に記載の方法。
(項目36)
二次結合剤を使用して、前記抗体または人工抗体を検出する、項目33に記載の方法。
(項目37)
前記二次結合剤が抗Fc受容体抗体である、項目36に記載の方法。
(項目38)
前記サンプルが、(a)頭頸部、脳、食道、乳房、肺、肝臓、脾臓、胃、小腸、大腸、直腸、卵巣、子宮、子宮頸部、前立腺、睾丸もしくは皮膚組織由来の腫瘍組織、または(b)体液、例えば血液、リンパ液、尿、骨髄穿刺液もしくは乳頭吸引液である、項目33に記載の方法。
(項目39)
前記サンプルが切除腫瘍床に由来する、項目33に記載の方法。
(項目40)
検出の存在、非存在または程度に基づいて処置決定をすることをさらに含む、項目33に記載の方法。
(項目41)
前記処置決定が、PR−1ベースのペプチドワクチンで前記被験体を処置することを含む、項目40に記載の方法。
(項目42)
原発性がん細胞、転移性がん細胞または骨髄異形成細胞を検出する、項目33に記載の方法。
(項目43)
がんを有する被験体を処置する方法であって、項目1に記載の抗体または項目22に記載の人工抗体を該被験体に投与することを含む、方法。
(項目44)
前記抗体または人工抗体が治療剤にコンジュゲートされている、項目43に記載の方法。
(項目45)
前記がんが固形腫瘍である、項目43に記載の方法。
(項目46)
前記固形腫瘍が、頭頸部腫瘍、脳腫瘍、食道腫瘍、乳房腫瘍、肺腫瘍、肝臓腫瘍、脾臓腫瘍および胃腫瘍、小腸腫瘍、大腸腫瘍、直腸腫瘍、卵巣腫瘍、子宮腫瘍、子宮頸部腫瘍、前立腺腫瘍、睾丸腫瘍または皮膚腫瘍である、項目45に記載の方法。
(項目47)
前記がんが血液がんである、項目43に記載の方法。
(項目48)
前記血液腫瘍が白血病またはリンパ腫である、項目47に記載の方法。
(項目49)
前記治療剤が、サイトカイン、毒素、化学療法薬、放射線療法薬、ホルモン、抗体Fc断片、TLRアゴニスト、CpG含有分子または免疫共刺激分子である、項目44に記載の方法。
(項目50)
第2の抗がん療法を前記被験体に提供することをさらに含む、項目43に記載の方法。
(項目51)
前記第2の抗がん療法が、遺伝子治療、化学療法、放射線療法、ホルモン療法、毒素療法または手術である、項目50に記載の方法。
(項目52)
前記抗体または人工抗体を前記被験体に複数回投与する、項目43に記載の方法。
(項目53)
前記がんが、再発性がんまたは転移性がんである、項目43に記載の方法。
(項目54)
自己免疫疾患を有する被験体を処置する方法であって、項目1に記載の抗体または項目22に記載の人工抗体を前記被験体に投与することを含む、方法。
(項目55)
前記自己免疫疾患が、ウェゲナー肉芽腫症、チャーグ‐ストラウス症候群または全身性小血管血管炎である、項目54に記載の方法。
(項目56)
前記抗体または人工抗体が治療剤にコンジュゲートされている、項目54に記載の方法。
(項目57)
前記治療剤が、毒素またはアポトーシス誘導剤である、項目56に記載の方法。
(項目58)
第2の抗自己免疫療法を前記被験体に提供することをさらに含む、項目54に記載の方法。
(項目59)
前記第2の抗自己免疫療法が抗炎症剤である、項目58に記載の方法。
(項目60)
前記抗体を前記被験体に複数回投与する、項目54に記載の方法。
(項目61)
HLA−A2がん細胞の補体媒介性細胞傷害を誘導する方法であって、該がん細胞と、項目1に記載の抗体または項目22に記載の人工抗体とを接触させることを含む、方法。
PR−1自己ペプチド(VLQELNVTV;配列番号45)は、白血病細胞膜で発現されるHLA−A*0201においてCD8+細胞傷害性Tリンパ球(CTL)によって認識されることが示されており、PR1特異的CTLは骨髄性白血病細胞を特異的に溶解するが、正常骨髄細胞を溶解しない。AML、CMLおよびMDSを有するHLA−A2+患者にPR1ペプチドをワクチン接種することにより、患者の58%でPR−1−CTL免疫が誘導され、患者66人中13人(20%)で客観的臨床応答が誘導された。これらの結果は有望であるが、高全身腫瘍組織量は依然として、ワクチン接種の成功を妨げる障害である。
語句「単離された」または「生物学的に純粋な」は、材料であって、その天然の状態で見出されるとおり該材料に通常付随する成分を、実質的にまたは本質的に含まない材料を指す。したがって、本発明によって単離されたペプチドは、好ましくは、そのインサイチュ環境でペプチドと通常会合した材料を含まない。
A.PR−1
PR−1自己ペプチド(VLQELNVTV;配列番号45)は、その両方が白血病で異常発現しているプロテイナーゼ3(P3)および好中球エラスターゼ(NE)に由来する。それは、白血病細胞膜で発現されるHLA−A*0201においてCD8+細胞傷害性Tリンパ球(CTL)によって認識されることが示されている。PR1特異的CTLは、骨髄性白血病(急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)および骨髄異形成症候群(MDS)を含む)細胞を特異的に溶解するが、正常骨髄細胞を溶解しない。以前に、本発明者らは、モンタニドISA−51中のPR−1ペプチドおよびGM−CSFにより、AML、CMLおよびMDSを有するHLA−A2+患者をPR−1ワクチン接種することにより、患者の58%でPR−1−CTL免疫が誘導され、患者66人中13人(20%)で客観的臨床応答が誘導されたことを示した。
ヒト白血球抗原系(HLA)は、ヒトにおける主要組織適合性複合体(MHC)の名称である。この超遺伝子座(superlocus)は、ヒトにおける免疫系機能に関係する多数の遺伝子を含有する。この遺伝子群は第6染色体上に存在し、細胞表面抗原提示タンパク質および多くの他の遺伝子をコードする。特定の遺伝子によってコードされるこれらのタンパク質は、臓器移植における因子として歴史的に発見された結果、抗原としても公知である。主要HLA抗原は、免疫機能に必須の因子である。様々なクラスが様々な機能を有する。
本発明は、HLA−A2提示との関連では、PR1に結合する抗体の生成および使用に関する。抗体は、特定の標的または一連の抗原性で関係する標的に「特異的に結合」することができる。本明細書で使用される場合、抗体は、抗体の可変領域に対する結合に基づいて、抗原性で区別可能な分子と識別される場合に、抗原に「特異的に結合」することができるといわれる。このような相互作用は、化合物のクラスが関与する非特異的結合とは対照的に、化学構造とは無関係である(例えば、ニトロセルロースに対するタンパク質の結合など)。特に、本発明の抗体は、近縁分子にさえ結合不可能であるか、または実質的に結合不可能であるように、「高度に特異的な結合」を示し得る。
以下は、改変されたタンパク質を作製するための、タンパク質のアミノ酸の変更に基づいた考察である。このような変化の作製では、アミノ酸のハイドロパシーインデックスを考慮することができる。タンパク質上の相互作用的生物学的機能の付与におけるアミノ酸のハイドロパシーインデックスの重要性は当技術分野で一般に理解されている(Kyte and Doolittle,1982)。アミノ酸の相対ハイドロパシー性が、得られたタンパク質の二次構造に寄与すること、言い換えると、タンパク質の他の分子(例えば、酵素、基質、受容体、DNA、抗体、および抗原など)との相互作用を定義することが認められている。
一本鎖可変断片(scFv)は、免疫グロブリンの重鎖および軽鎖の可変領域が短い(通常は、セリン、グリシン)リンカーによって共に連結された融合物である。定常領域の除去およびリンカーペプチドの導入にもかかわらず、このキメラ分子は、元の免疫グロブリンの特異性を保持する。右の画像は、この改変が通例として特異性を変化させない仕組みを示している。歴史的には、単一ペプチドとして抗原結合ドメインを発現させるのに非常に便利なファージディスプレイを容易にするために、これらの分子が作られた。あるいは、ハイブリドーマ由来のサブクローニングされた重鎖および軽鎖から、scFvを直接作り得る。一本鎖可変断片は、完全抗体分子で見出される定常Fc領域を欠くので、共通の結合部位(例えば、プロテインA/G)を抗体の精製に使用する。プロテインLはカッパ軽鎖の可変領域と相互作用するので、多くの場合、プロテインLを使用してこれらの断片を精製/固定化し得る。
表3−ヘテロ二官能性架橋リンカー
特定の実施形態では、本発明の抗体を精製することができる。本明細書で使用される場合、用語「精製された」は、他の成分から単離可能であり、このタンパク質をその天然に得ることができる状態と比較して任意の程度で精製される組成物を指すことを意図する。したがって、精製されたタンパク質はまた、それが天然に存在し得る環境から遊離されたタンパク質を指す。用語「実質的に精製された」を使用する場合、この用語は、タンパク質またはペプチドが組成物の主成分を形成する(例えば、組成物中のタンパク質の約50%、約60%、約70%、約80%、約90%、約95%以上を構成する)組成物を指す。
一実施形態では、本発明の抗体は、疾患の診断および治療で使用するための様々な試薬に連結され得る。様々な周知の化学反応および作用物質(これらのいくつかは、本文書の他の場所に記載される)を使用して、連結を実施し得る。
多くの診断剤/イメージング剤が、それらをタンパク質(抗体を含む)に結合するための方法と同様に当技術分野で公知である(例えば、米国特許第5,021,236号;米国特許第4,938,948号;および米国特許第4,472,509号(これらはそれぞれ、参照により本明細書に組み込まれる)を参照のこと)。使用されるイメージング部分は、常磁性イオン、放射性同位体、蛍光色素、NMRで検出可能な物質およびX線イメージング剤であり得る。
本発明の抗体に連結される多種多様な治療剤。例えば、上で議論した放射性同位体は、診断関連では有用だが、治療剤(therapeuticc agents)としても使用され得る。化学療薬もまた抗体にコンジュゲートされ得、それらとしては、シスプラチン(CDDP)、カルボプラチン、プロカルバジン、メクロレタミン、シクロホスファミド、カンプトテシン、イホスファミド、メルファラン、クロラムブシル、ブスルファン、ニトロソ尿素、ダクチノマイシン、ダウノルビシン、ドキソルビシン、ブレオマイシン、プリカマイシン(plicomycin)、マイトマイシン、エトポシド(VP16)、タモキシフェン、ラロキシフェン、エストロゲン受容体結合剤、タキソール、ゲムシタビン(gemcitabien)、ナベルビン、ファルネシルタンパク質トランスフェラーゼ阻害剤、トランスプラチナ、5−フルオロウラシル、ビンクリスチン、ビンブラスチンおよびメトトレキサートが挙げられる。
A.抗体をコードする核酸
本発明の一態様では、抗体の重鎖および軽鎖、可変ドメインおよび定常ドメインの様々な部分をコードする核酸が提供される。核酸セグメントは、ゲノムDNA、相補DNA(cDNA)、または合成DNAに由来し得る。発現ベクターへの組み込みが望ましい場合、核酸は、天然のイントロンまたは別の遺伝子由来のイントロンならびに他の非コード(例えば、調節)領域およびコード領域(例えば、リンカー)も含み得る。本明細書で使用される場合、用語「cDNA」は、テンプレートとして伝令RNA(mRNA)を使用して調製したDNAを指すことを意図する。ゲノムDNAまたはゲノムの非プロセシングまたは部分プロセシングRNAテンプレートから重合したDNAと対照的なcDNAを使用することの利点は、cDNAは主に対応するタンパク質のコード配列を含むという点である。
表4−コドン表
原核生物および/または真核生物ベースの系を使用して、核酸配列またはその同族(cognate)ポリペプチド、タンパク質、およびペプチドを産生することができる。本発明は、PR−1/HLA−A2に結合する抗体を産生するためのこのような発現系の使用を意図する。強力な発現技術1つは、昆虫細胞/バキュロウイルス系を使用する。米国特許第5,871,986号および米国特許第4,879,236号(両方とも参照により本明細書に組み込まれる)などに記載され、例えば、INVITROGEN(登録商標)のMaxBac2.0(登録商標)およびCLONTECH(登録商標)のBACPACK(商標)BACULOVIRUS EXPRESSION SYSTEMという名称で購入することができる昆虫細胞/バキュロウイルス系は、異種核酸セグメントからタンパク質を高レベルで発現することができる。
発現ベクターを細胞に導入することができる多数の方法が存在する。ウイルスは、核酸によってコードされるタンパク質産物を発現させるための強力なツールを提供する。したがって、本発明の特定の実施形態では、発現ベクターは、ウイルスまたはウイルスゲノム由来の操作ベクターを含む。受容体媒介エンドサイトーシスを介して細胞に侵入し、宿主細胞ゲノムに組み込まれ、ウイルス遺伝子を安定かつ有効に発現する特定のウイルスの能力のために、ウイルスは外来遺伝子を哺乳動物細胞に導入するための魅力的な候補となっている(Ridgeway,1988;Nicolas and Rubenstein,1988;Baichwal and Sugden,1986;Temin,1986)。遺伝子ベクターとして使用された最初のウイルスは、DNAウイルス(パポバウイルス(サルウイルス40、ウシ乳頭腫ウイルス、およびポリオーマ)(Ridgeway,1988;Baichwal and Sugden,1986)およびアデノウイルス(Ridgeway,1988;Baichwal and Sugden,1986)が含まれる)であった。
本発明の組成物を発現させるための適切な非ウイルス核酸送達方法は、本明細書に記載されているか当業者公知であるとおり、核酸(例えば、DNA)をオルガネラ、細胞、組織、または生物に導入することができる事実上任意の方法が含まれると考えられる。このような方法としては、注射(米国特許第5,994,624号、米国特許第5,981,274号、米国特許第5,945,100号、米国特許第5,780,448号、米国特許第5,736,524号、米国特許第5,702,932号、米国特許第5,656,610号、米国特許第5,589,466号、および米国特許第5,580,859号(それぞれ参照により本明細書に組み込まれる))(微量注入((Harland and Weintraub,1985;米国特許第5,789,215号(参照により本明細書に組み込まれる))が含まれる);エレクトロポレーション(米国特許第5,384,253号(参照により本明細書に組み込まれる));リン酸カルシウム沈殿(Graham and Van Der Eb,1973;Chen and Okayama,1987;Rippeら、1990);DEAE−デキストラン使用後のポリエチレングリコールの使用(Gopal,1985);直接音波負荷(direct sonic loading)(Fechheimerら、1987);リポソーム媒介トランスフェクション(Nicolau and Sene,1982;Fraleyら、1979;Nicolauら、1987;Wongら、1980;Kanedaら、1989;Katoら、1991);微粒子銃(PCT出願第WO94/09699号およびPCT出願第WO95/06128号;米国特許第5,610,042号;米国特許第5,322,783号、米国特許第5,563,055号、米国特許第5,550,318号、米国特許第5,538,877号、および米国特許第5,538,880号(それぞれ参照により本明細書に組み込まれる);炭化ケイ素繊維との撹拌(Kaepplerら、1990;米国特許第5,302,523号および米国特許第5,464,765号(それぞれ参照により本明細書に組み込まれる);またはプロトプラストのPEG媒介トランスフェクション(Omirullehら、1993;米国特許第4,684,611号および米国特許第4,952,500号(それぞれ参照により本明細書に組み込まれる);乾燥/阻害媒介DNA取り込み(Potrykusら、1985)などによるDNAの直接送達が挙げられるが、これらに限定されない。これらなどの技術の適用によって、オルガネラ(複数可)、細胞(複数可)、組織(複数可)、または生物(複数可)を、安定または一過性に形質転換することができる。
本発明の一実施形態では、白血病(例えば、AML、CML、MDS)および骨髄異形成障害などのがんを診断する方法が提供される。骨髄異形成(MDS)は、骨髄が正常に機能せず、不十分な数の正常血液細胞を産生する障害群を指す。MDSは、赤血球、血小板および白血球を含む任意の、そして時にはすべての種類の血液細胞の産生に影響を与える(血球減少症)。小児骨髄異形成の約50%は、5種類のMDSに分類され得る:不応性貧血、環状鉄芽球を伴う不応性貧血、過剰芽球を伴う不応性貧血、形質転換で過剰芽球を伴う不応性貧血、および慢性骨髄単球性白血病。典型的には、残りの50%は孤立性か、または複合血球減少症、例えば貧血、白血球減少症および/もしくは血小板減少症(低血小板数)を呈する。MDSは慢性だが、患者の約30パーセントでは進行して急性骨髄性白血病(AML)になる。
診断試薬の投与は当技術分野で周知であり、達成すべき診断に応じて変化する。例えば、1つ以上の別個の腫瘍塊をイメージングしようとする場合、局所(local)投与または局所(regional)投与(例えば、腫瘍血管系、局所リンパ系または局所動脈もしくは静脈)が利用され得る(my be utilized)。あるいは、局所にまたは全身に診断試薬を提供し得る。四肢全体もしくは生物のイメージングを望む場合、公知の特定の腫瘍塊が同定された場合、または転移が疑われる場合、これが選択の経路であり得る。
本発明による医薬品の1つの送達方法は全身性である。しかしながら、あるいは、米国特許第5,543,158号;米国特許第5,641,515号、および米国特許第5,399,363号(それぞれ、その全体が参照により本明細書に明確に組み込まれる)に記載されているように、本明細書に開示される医薬組成物を、非経口、静脈内、皮内、筋肉内、経皮、またはさらに腹腔内に投与することができる。
A.がんおよび過形成/異形成/新形成疾患
本発明の抗体を、がんを含む過形成/異形成/新形成疾患/状態を処置する方法で使用することができる。本発明のペプチドを使用して処置することを意図する疾患/状態の種類として、AML、MDS、およびCMLならびに骨髄異形成などの白血病が挙げられるが、これらに限定されない。他の種類のがんとして、肺がん、頭頸部がん、乳がん、膵臓がん、前立腺がん、腎臓がん、骨がん、精巣がん、子宮頸がん、消化管がん、リンパ腫、肺の前新形成病変、結腸がん、黒色腫、膀胱がん、および任意の他の新形成疾患を挙げることができる。
第2の抗がん剤を含める場合、併用療法を使用することが有利な場合もある。「抗がん」剤は、例えば、がん細胞の死滅化、がん細胞のアポトーシスの誘導、がん細胞の成長速度の減少、転移の発生率または数の減少、腫瘍サイズの減少、腫瘍成長の阻害、腫瘍もしくはがん細胞への血液供給の減少、がん細胞もしくは腫瘍に対する免疫応答の促進、がん進行の防止もしくは阻害、またはがんを有する被験体の寿命の延長によって、被験体のがんに負の影響を与えることができる。抗がん剤としては、生物学的薬剤(生物療法)、化学療法薬、および放射線療法薬が挙げられる。より一般に、本発明による治療と共に、これらの他の組成物を、細胞の死滅化または細胞増殖の阻害に有効な組み合わせた量で提供することになる。この方法は、細胞と両方の薬剤とを同時に接触させることを含み得る。細胞と、両薬剤を含む単一の組成物もしくは薬理学的製剤とを接触させること、または細胞と、2つの異なる組成物もしくは製剤とを同時に接触させることによってこれを行うことができる。
A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B
B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A
B/A/B/A B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A
がん療法には、化学物質および照射ベースの処置の両方を使用した様々な併用療法も含まれる。併用化学療法薬としては、例えば、シスプラチン(CDDP)、カルボプラチン、プロカルバジン、メクロレタミン、シクロホスファミド、カンプトテシン、イホスファミド、メルファラン、クロラムブシル、ブスルファン、ニトロソ尿素、ダクチノマイシン、ダウノルビシン、ドキソルビシン、ブレオマイシン、プリコマイシン(plicomycin)、マイトマイシン、エトポシド(VP16)、タモキシフェン、ラロキシフェン、エストロゲン受容体結合剤、タキソール、ゲムシタビン(gemcitabien)、ナベルビン、ファルネシル−タンパク質トランスフェラーゼ阻害剤、トランスプラチナ、5−フルオロウラシル、ビンクリスチン、ビンブラスチン、およびメトトレキセート、テモゾロミド(Temazolomide)(DTICの水性形態)、または上記の任意の類似体もしくは誘導バリアントが挙げられる。化学療法と生物学的療法との組み合わせは、生化学療法として公知である。本発明は、がんの処置もしくは予防に関して、用いられ得るかまたは当技術分野で公知の任意の化学療法薬を意図する。
DNA損傷を引き起こし、かつ広範に使用されている他の因子としては、γ線、X線、および/または腫瘍細胞への放射性同位体の定方向送達として一般的に知られているものが挙げられる。マイクロ波およびUV照射などの他の形態のDNA損傷因子も意図される。すべてのこれらの因子は、DNA、DNAの前駆体、DNAの複製および修復、および染色体のアセンブリおよび維持に対して広範な損傷を与える可能性が最も高い。X線の線量範囲は、長期間(3〜4週間)のための50〜200レントゲンの日線量から2000〜6000レントゲンの単回線量の範囲である。放射性同位体の照射線量範囲は、広範に変化し、同位体の半減期、放出した照射の強度および型、ならびに新形成細胞による取り込みに依存する。
一般に、免疫療法は、がん細胞を標的として破壊するための免疫エフェクター細胞および分子の使用に依存する。免疫エフェクターは、例えば、腫瘍細胞の表面上の一部のマーカーに特異的な抗体であり得る。抗体は単独で治療エフェクターとして役立ち得るか、または細胞の死滅を実質的にもたらす他の細胞を動員し得る。抗体は薬物または毒素(化学療法薬、放射性核種、リシンA鎖、コレラ毒素、百日咳毒素など)にコンジュゲートすることもできるし、単にターゲティング剤として機能することもできる。あるいは、エフェクターは、直接または間接的に腫瘍細胞標的と相互作用する表面分子を有するリンパ球であり得る。様々なエフェクター細胞には、細胞傷害性T細胞およびNK細胞が含まれる。治療方法の組み合わせ(すなわち、直接細胞傷害活性およびホルチリン(Fortilin)の阻害または減少)により、がん処置において治療上の利益が得られることになる。
さらに別の実施形態では、二次処置は、腫瘍関連HLA拘束性ペプチドの投与前、投与後、または投与と同時に治療ポリヌクレオチドを投与する遺伝子治療である。以下の遺伝子産物の1つをコードする第2のベクターと併せた腫瘍関連HLA拘束性ペプチドをコードするベクターの送達により、標的組織に対して複合的な抗過剰増殖効果が得られる。あるいは、両遺伝子をコードする単一のベクターを使用することができる。様々なタンパク質が本発明に包含され、これらのいくつかを以下に記載する。本発明と組み合わせたいくつかの形態の遺伝子治療のためにターゲティングすることができる様々な遺伝子が当業者に公知であり、がんに関与する任意の遺伝子を含み得る。
がんを有するヒトの約60%がいくつかの種類の手術を受け、それらとしては、予防的手術、診断または病期分類のための手術、治癒切除、および姑息的手術が挙げられる。治癒切除は、本発明の処置、化学療法、放射線療法、ホルモン療法、遺伝子治療、免疫療法、および/または代替療法などの他の療法と併せて使用することができるがん処置である。
本発明はまた、本発明の抗体を使用する自己免疫疾患の処置を意図する。PR1は、骨髄系の自己タンパク質に由来する。ウェゲナー肉芽腫症では、PR1を含有するプロテイナーゼ3(Pr3)が自己免疫攻撃の標的である。小血管血管炎では、ミエロペルオキシダーゼ(MPO)が標的抗原であり(Franssenら、1996;Brouwerら、1994;Molldremら、1996)、これらの疾患を有する患者において、T細胞免疫および抗体免疫の両方の証拠がある。ウェゲナー肉芽腫症は、Pr3に対する特異性を有する細胞質抗好中球細胞質抗体(cANCA)の産生を伴うが(Molldremら、1997)、顕微鏡的多発血管炎およびチャーグ−ストラウス症候群は、MPOに対する特異性を有する核周囲ANCA(pANCA)を伴う(Molldremら、1999;Savageら、1999)。このように、PR1の免疫細胞認識を阻害することは、自己免疫疾患の治療法となり得る。
血管炎は、血管壁の炎症によって引き起こされる過程であり、様々な障害をもたらす。血管炎に関する認められている分類システムは登場していないが、関与する血管のサイズまたは種類によって大血管血管炎、中血管血管炎または小血管血管炎と分類され得る。小血管血管炎は、動脈(すなわち、細動脈、細静脈および毛細血管)よりも小さな血管に影響を与える血管炎と定義される;しかしながら、小血管血管炎には、中サイズの動脈も関与し得る。抗好中球細胞質抗体(ANCA)関連血管炎は、小血管血管炎の最も一般的な原因であり、顕微鏡的多発血管炎、ウェゲナー肉芽腫症、チャーグ−ストラウス症候群および特定種の薬物誘発性血管炎が挙げられる。
クローン病の症候には、腸の炎症、ならびに腸狭窄およびフィステルの発症が含まれ;これらの症候はニューロパチーを伴うことが多い。典型的には、5−アミノサリチル酸類(例えば、メサラミン)またはコルチコステロイドのような抗炎症薬が処方されるが、常に有効という訳ではない(V.A.Botomanら、1998に概説されている)。シクロスポリンによる免疫抑制は、コルチコステロイドに抵抗性または不耐性の患者にとって有益であることがある(Brynskovら、1989)。
RAの正確な病因は依然として不明であるが、自己免疫的な側面を有することが明らかである。滑膜線維芽細胞の増殖および関節端の関節表面へのそれらの付着を含む、関節疾患の最初の兆候は、滑膜表層に出現する(Lipsky,1998)。その後、マクロファージ、T細胞、および他の炎症細胞が関節へと動員され、そこで、それらは、骨および軟骨の破壊をもたらす慢性後遺症に寄与するサイトカインのインターロイキン−1(IL−1)、ならびに炎症において役割を果たす腫瘍壊死因子(TNF−α)を含む、多数のメディエーターを産生する(Dinarello,1998;Burger&Dayer,1995;van den Berg,2001)。血漿中のIL−1の濃度は、健常個体よりRAを有する患者において有意に高く、注目すべきことに、血漿IL−1レベルがRA疾患の活動性と相関する(Eastgateら、1988)。さらに、滑液IL−1レベルは、RAの様々なX線写真の特色および組織学的特色と相関する(Kahleら、1992;Rooneyら、1990)。
全身性エリテマトーデス(SLE)は、組織損傷をもたらす自己抗体および免疫複合体の組織内の沈着を特徴とする自己免疫リウマチ性疾患である(Kotzin,19966)。MSおよび1型糖尿病のような自己免疫疾患とは対照的に、SLEには、潜在的に、複数の臓器系が直接関与しており、その臨床徴候は多様で可変性である(Kotzin&O’Dell,1995により概説されている)。例えば、主として皮疹および関節痛を示し、自然緩解を明らかに示し、薬物治療をほとんど必要としなくてもよい患者も存在する。スペクトルのもう一端には、高用量のステロイド、およびシクロホスファミドのような細胞傷害性薬物による治療を必要とする重度かつ進行性の腎臓障害を明らかに示す患者がいる(Kotzin,1996)。
小児における最も有病率の高い関節炎の型を表す用語である若年性関節リウマチ(JRA)とは、慢性炎症および滑膜の肥厚を特徴とする疾病ファミリーに適用される。この用語は、欧州において、若年性慢性関節炎および/または若年性特発性関節炎と称される疾病のファミリーとオーバーラップするが、完全には同義ではない。
原発性シェーグレン症候群(SS)は、中年の女性に主に影響を与えるが(男女比1:9)、小児を含むすべての年齢において認めることができる、慢性の、進行の遅い、全身性の自己免疫疾患である(Jonssonら、2002)。それは、CD4+リンパ球、CD8+リンパ球、およびB細胞を含む単核細胞が浸潤する、外分泌腺のリンパ球浸潤および破壊を特徴とする(Jonssonら、2002)。さらに、腺外(全身性)徴候が、患者の3分の1に認められる(Jonssonら、2001)。
乾癬は、米国の人口の2〜2.6%または580〜750万人に影響を与えている鱗屑および炎症の慢性皮膚疾患である。この疾患は、すべての年齢群において起こるが、主として成人に影響を与える。それは男女にほぼ等しく現れる。皮膚細胞が、皮膚表面下の起源から急速に生じ、それが成熟する機会を得る前に表面に積み重なる場合に、乾癬が起こる。通常、(代謝回転とも呼ばれる)この移動には、約1ヵ月かかるが、乾癬においては、わずか数日でそれが起こり得る。典型的な型では、乾癬は、銀色の鱗屑により覆われた厚い赤色の(炎症を起こした)皮膚の斑をもたらす。プラークと称されることもある、これらの斑は、通常、痒みまたは痛みを伴う。それらは、肘、膝、脚の他の部分、頭皮、下背部、顔面、手掌、および足の裏に起こることが最も多いが、身体上のいかなる場所の皮膚にも起こり得る。この疾患は、指の爪、足の爪、ならびに性器および口内の軟部組織にも影響を与えることがある。影響を受けた関節の周囲の皮膚に亀裂が入ることは珍しくないが、乾癬を有するおよそ100万人が、関節炎の症候を生ずる関節の炎症を経験する。この状態は、乾癬性関節炎と称される。
多発性硬化症(MS)は、毎年米国だけで数十万人、そして世界中では数百万人を苦しめている深刻な健康問題であり続けている。それは、中枢神経系(脳および脊髄)の最も一般的な疾患の1つである。MSは、脱髄またはミエリン鞘の消失に関連する炎症状態である。ミエリンは神経を絶縁する脂肪物質であり、神経がある地点から別の地点にインパルスを伝達することを可能にする絶縁体として作用する。MSでは、ミエリンの消失は、神経が電気インパルスを脳にまたは脳から伝導する能力の崩壊を伴い、これが様々なMS症候、例えば視力、筋協調、強度、感覚、発話および嚥下、膀胱の制御、性的能力ならびに認知機能の障害をもたらす。ミエリンが消失したプラークまたは病変は、硬化した瘢痕様領域のように見える。これらの瘢痕は脳および脊髄の様々な領域に様々な時点で現れるので、用語「多発性」硬化症は、文字通り多くの瘢痕を意味する。
上記免疫障害のための併用療法も意図される。このような治療法としては、抗炎症薬および免疫抑制剤などの標準的な治療法を本発明の治療方法と併用するものが挙げられよう。このような標準的な治療法は、被験体において疾患を引き起こす免疫細胞に負の影響を与えることができるか、またはこのような疾患の症候を緩和することになる。この方法は、細胞または被験体と両薬剤とを同時に接触させることを含み得る。これは、両薬剤を含む単一の組成物もしくは薬理学的製剤を用いて、または2つの別個の組成物もしくは製剤を同時に用いて達成され得る。あるいは、抗体療法は、数分間〜数週間の範囲の間隔で他の薬剤処置に先行してもよいし、またはその後に続いてもよい。
A/B/A B/A/B B/B/A A/A/B A/B/B B/A/A A/B/B/B B/A/B/B
B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A
B/A/B/A B/A/A/B A/A/A/B B/A/A/A A/B/A/A A/A/B/A
以下の実施例は、本発明の好ましい実施形態を実証するために含まれる。当業者であれば、以下の実施例に開示される技術が、本発明の実施において十分に機能することが本発明者によって発見された技術の代表的なものであり、その実施のための好ましい様式を構成すると見なし得ると認識するはずである。しかしながら、当業者であれば、本開示を考慮して、本発明の精神および範囲を逸脱することなく、開示される特定の実施形態において多くの変更を行うことができ、依然として同様または類似の結果が得られることを認識するはずである。
実施例1:方法
実施例2:結果
表5
実施例3:方法
実施例4:結果
表6−LCMおよび共焦点顕微鏡検査に使用した乳房腫瘍組織および黒色腫腫瘍組織の病理学的特徴
以下の参考文献は、参考文献が本明細書に示されたものを補足する例示的手順または他の詳細を提供する範囲で、特に参照により本明細書に組み込まれる。
Claims (22)
- HLA−A2受容体に結合したVLQELNVTV(配列番号45)に結合するヒト化抗体であって、該抗体は、それぞれ配列番号3、60および5により示されるアミノ酸配列からなるCDRを含む重鎖可変領域、ならびにそれぞれ配列番号8、9および10により示されるアミノ酸配列からなるCDRを含む軽鎖可変領域を含む、ヒト化抗体。
- 前記抗体は、配列番号16により示されるアミノ酸配列からなる重鎖可変領域、および配列番号19または20により示されるアミノ酸配列からなる軽鎖可変領域を含む、請求項1に記載の抗体。
- 前記抗体は、配列番号16により示されるアミノ酸配列からなる重鎖可変領域、およびヒトガンマ−1重鎖定常領域である重鎖定常領域を含む重鎖、ならびに配列番号19により示されるアミノ酸配列からなる軽鎖可変領域、およびヒトカッパ軽鎖定常領域である軽鎖定常領域を含む軽鎖を含む、請求項2に記載の抗体。
- 前記抗体は、配列番号16により示されるアミノ酸配列からなる重鎖可変領域、およびヒトガンマ−1重鎖定常領域である重鎖定常領域を含む重鎖、ならびに配列番号20により示されるアミノ酸配列からなる軽鎖可変領域、およびヒトカッパ軽鎖定常領域である軽鎖定常領域を含む軽鎖を含む、請求項2に記載の抗体。
- 前記抗体は、単離および精製されたものである、請求項1〜4のいずれか一項に記載の抗体。
- 前記抗体は、非抗体ペプチドまたはポリペプチドセグメントに融合されている、請求項1〜5のいずれか一項に記載の抗体。
- 前記抗体は、フルオロフォア、発色団、色素、放射性同位体、化学発光分子、常磁性イオンおよびスピントラッピング試薬からなる群から選択される診断試薬に連結されているか、または前記抗体は、サイトカイン、化学療法薬、放射線療法薬、ホルモン、抗体Fc断片、TLRアゴニスト、CpG含有分子および免疫共刺激分子からなる群から選択される治療試薬に連結されている、請求項1〜6のいずれか一項に記載の抗体。
- 請求項1または2に記載の抗体の軽鎖可変領域をコードする核酸、および請求項1または2に記載の抗体の重鎖可変領域をコードする核酸を含む発現ベクター。
- 請求項2に記載の抗体の重鎖可変領域をコードする核酸および請求項2に記載の抗体の軽鎖可変領域をコードする核酸が導入されている、宿主細胞。
- 請求項3に記載の抗体の重鎖をコードする核酸および請求項3に記載の抗体の軽鎖可変領域をコードする核酸が導入されている、宿主細胞。
- HLA−A2受容体に結合したVLQELNVTV(配列番号45)に結合するヒト化抗体の発現を支援する条件下で、請求項9に記載の宿主細胞を培養することを含む、ヒト化抗体を産生する方法。
- HLA−A2受容体に結合したVLQELNVTV(配列番号45)に結合するヒト化抗体の発現を支援する条件下で、請求項10に記載の宿主細胞を培養することを含む、ヒト化抗体を産生する方法。
- HLA−A2受容体に結合したVLQELNVTV(配列番号45)に結合する、請求項11に記載の方法により産生されたヒト化抗体。
- HLA−A2受容体に結合したVLQELNVTV(配列番号45)に結合する、請求項12に記載の方法により産生されたヒト化抗体。
- 前記抗体は、フルオロフォア、発色団、色素、放射性同位体、化学発光分子、常磁性イオンおよびスピントラッピング試薬からなる群から選択される診断試薬に連結されているか、または該抗体は、サイトカイン、化学療法薬、放射線療法薬、ホルモン、抗体Fc断片、TLRアゴニスト、CpG含有分子および免疫共刺激分子からなる群から選択される治療試薬に連結されている、請求項13または14に記載の抗体。
- 請求項1〜7または13〜15のいずれか一項に記載の抗体を含む、医薬組成物。
- 前記組成物は、がんの処置のためのものである、請求項16に記載の医薬組成物。
- 前記がんは、頭頸部腫瘍、脳腫瘍、食道腫瘍、乳房腫瘍、肺腫瘍、肝臓腫瘍、脾臓腫瘍、胃腫瘍、小腸腫瘍、大腸腫瘍、直腸腫瘍、卵巣腫瘍、子宮腫瘍、子宮頸部腫瘍、前立腺腫瘍、睾丸腫瘍および皮膚腫瘍からなる群から選択される固形腫瘍であるか、または該がんは、白血病およびリンパ腫からなる群から選択される血液がんである、請求項17に記載の医薬組成物。
- 前記がんが、再発性がんまたは転移性がんである、請求項17または18に記載の医薬組成物。
- 前記組成物は、前記第2の抗がん療法と組み合わせて投与されることを特徴とする、請求項19に記載の組成物。
- 前記第2の抗がん療法が、遺伝子治療、化学療法、放射線療法、ホルモン療法、毒素療法または手術である、請求項20に記載の組成物。
- 前記組成物は、前記被験体に複数回投与されることを特徴とする、請求項21に記載の組成物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261669967P | 2012-07-10 | 2012-07-10 | |
US61/669,967 | 2012-07-10 | ||
US201261702916P | 2012-09-19 | 2012-09-19 | |
US61/702,916 | 2012-09-19 | ||
PCT/US2013/049368 WO2014011489A2 (en) | 2012-07-10 | 2013-07-03 | Monoclonal antibodies for use in diagnosis and therapy of cancers and automimmune disease |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2015530359A JP2015530359A (ja) | 2015-10-15 |
JP2015530359A5 JP2015530359A5 (ja) | 2016-08-25 |
JP6336696B2 true JP6336696B2 (ja) | 2018-06-06 |
Family
ID=49916655
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015521668A Active JP6336696B2 (ja) | 2012-07-10 | 2013-07-03 | がんおよび自己免疫疾患の診断および治療に使用するためのモノクローナル抗体 |
Country Status (26)
Country | Link |
---|---|
US (2) | US9926380B2 (ja) |
EP (2) | EP2872174A2 (ja) |
JP (1) | JP6336696B2 (ja) |
KR (1) | KR102049222B1 (ja) |
CN (1) | CN104540522B (ja) |
AU (1) | AU2013288982B2 (ja) |
CA (1) | CA2883056C (ja) |
CY (1) | CY1121743T1 (ja) |
DK (1) | DK3088421T3 (ja) |
EA (1) | EA034033B1 (ja) |
ES (1) | ES2720291T3 (ja) |
HK (1) | HK1208168A1 (ja) |
HR (1) | HRP20190939T1 (ja) |
HU (1) | HUE043443T2 (ja) |
IL (1) | IL236664B (ja) |
IN (1) | IN2015DN00263A (ja) |
LT (1) | LT3088421T (ja) |
MX (1) | MX360984B (ja) |
PH (1) | PH12015500074B1 (ja) |
PL (1) | PL3088421T3 (ja) |
PT (1) | PT3088421T (ja) |
RS (1) | RS58755B1 (ja) |
SI (1) | SI3088421T1 (ja) |
UA (1) | UA114108C2 (ja) |
WO (1) | WO2014011489A2 (ja) |
ZA (1) | ZA201500247B (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN116656605A (zh) * | 2014-04-16 | 2023-08-29 | 朱诺治疗有限公司 | 用于扩增细胞群的方法、试剂盒及装置 |
NL2014935B1 (en) | 2015-06-08 | 2017-02-03 | Applied Immune Tech Ltd | T cell receptor like antibodies having fine specificity. |
MA45488A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés, kits et appareil de culture de cellules |
MA45489A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés de culture de cellules, kits et appareil associés |
RU2021134624A (ru) | 2015-10-22 | 2022-03-15 | Джуно Терапьютикс Гмбх | Способы, наборы, средства и устройства для трансдукции |
MA44334A (fr) | 2015-10-29 | 2018-09-05 | Novartis Ag | Conjugués d'anticorps comprenant un agoniste du récepteur de type toll |
WO2018009916A1 (en) | 2016-07-07 | 2018-01-11 | The Board Of Trustees Of The Leland Stanford Junior University | Antibody adjuvant conjugates |
CA3060526A1 (en) | 2017-04-27 | 2018-11-01 | Juno Therapeutics Gmbh | Oligomeric particle reagents and methods of use thereof |
AU2017418590A1 (en) | 2017-06-14 | 2020-01-16 | Adicet Therapeutics, Inc. | Antibodies capable of binding HLA-A2/TyrD in an HLA restricted manner and uses thereof |
CN108611322B (zh) * | 2018-05-09 | 2020-02-11 | 邹畅 | 乳腺癌循环肿瘤细胞系ctc-3、培养基及ctc-3的建立方法和应用 |
JP2022525594A (ja) | 2019-03-15 | 2022-05-18 | ボルト バイオセラピューティクス、インコーポレーテッド | Her2を標的とする免疫結合体 |
US20230192824A1 (en) * | 2020-04-02 | 2023-06-22 | United States Of America As Represented By The Secretary Of The Navy | Antigen Binding Proteins to Class 5 ETEC Adhesins |
CA3227281A1 (en) * | 2021-07-26 | 2023-02-02 | Michael H. Cardone | Methods and compositions related to mcl-1 and bim heterodimer antibodies |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4680338A (en) | 1985-10-17 | 1987-07-14 | Immunomedics, Inc. | Bifunctional linker |
US4843092A (en) | 1986-04-25 | 1989-06-27 | Hitoshi Shichi | Immunosuppressive agent |
US5824311A (en) | 1987-11-30 | 1998-10-20 | Trustees Of The University Of Pennsylvania | Treatment of tumors with monoclonal antibodies against oncogene antigens |
US5141648A (en) | 1987-12-02 | 1992-08-25 | Neorx Corporation | Methods for isolating compounds using cleavable linker bound matrices |
US5563250A (en) | 1987-12-02 | 1996-10-08 | Neorx Corporation | Cleavable conjugates for the delivery and release of agents in native form |
US5443826A (en) | 1988-08-02 | 1995-08-22 | Borody; Thomas J. | Treatment of gastro-intestinal disorders with a fecal composition or a composition of bacteroides and E. Coli |
FR2658197B1 (fr) | 1990-02-14 | 1992-05-22 | Inst Nat Sante Rech Med | Anticorps monoclonaux restreints reconnaissant un peptide associe a un antigene du complexe majeur d'histocompatibilite - applications au diagnostic et au traitement. |
WO1994012520A1 (en) | 1992-11-20 | 1994-06-09 | Enzon, Inc. | Linker for linked fusion polypeptides |
US5846945A (en) | 1993-02-16 | 1998-12-08 | Onyx Pharmaceuticals, Inc. | Cytopathic viruses for therapy and prophylaxis of neoplasia |
US5801005A (en) | 1993-03-17 | 1998-09-01 | University Of Washington | Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated |
US6491916B1 (en) | 1994-06-01 | 2002-12-10 | Tolerance Therapeutics, Inc. | Methods and materials for modulation of the immunosuppresive activity and toxicity of monoclonal antibodies |
US7074904B2 (en) | 1994-07-29 | 2006-07-11 | Altor Bioscience Corporation | MHC complexes and uses thereof |
US5599795A (en) | 1994-08-19 | 1997-02-04 | Mccann; Michael | Method for treatment of idiopathic inflammatory bowel disease (IIBD) |
GB9506466D0 (en) | 1994-08-26 | 1995-05-17 | Prolifix Ltd | Cell cycle regulated repressor and dna element |
US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
WO1996040662A2 (en) | 1995-06-07 | 1996-12-19 | Cellpro, Incorporated | Aminooxy-containing linker compounds and their application in conjugates |
US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
US5739169A (en) | 1996-05-31 | 1998-04-14 | Procept, Incorporated | Aromatic compounds for inhibiting immune response |
US5846225A (en) | 1997-02-19 | 1998-12-08 | Cornell Research Foundation, Inc. | Gene transfer therapy delivery device and method |
US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
US6534633B1 (en) | 1998-10-21 | 2003-03-18 | Altor Bioscience Corporation | Polyspecific binding molecules and uses thereof |
CN1692124B (zh) | 2001-06-05 | 2012-05-30 | 阿尔特生物科学公司 | 与p53结合的T细胞受体分子以及其用途 |
IL159682A0 (en) | 2001-07-02 | 2004-06-20 | Aimsco Ltd | Use of polyclonal anti-hiv goat serum as a therapeutic agent |
US6992176B2 (en) | 2002-02-13 | 2006-01-31 | Technion Research & Development Foundation Ltd. | Antibody having a T-cell receptor-like specificity, yet higher affinity, and the use of same in the detection and treatment of cancer, viral infection and autoimmune disease |
EP1561759B9 (en) | 2002-10-11 | 2009-08-26 | Chugai Seiyaku Kabushiki Kaisha | Cell death-inducing agent |
WO2004065418A1 (ja) * | 2003-01-20 | 2004-08-05 | Chugai Seiyaku Kabushiki Kaisha | 抗pci中和抗体 |
FR2858235B1 (fr) | 2003-07-31 | 2006-02-17 | Lab Francais Du Fractionnement | Utilisation d'anticorps optimises en adcc pour traiter les patients faibles repondeurs |
JP4767016B2 (ja) | 2003-12-12 | 2011-09-07 | 中外製薬株式会社 | 細胞死誘導剤 |
EP1773383B1 (en) | 2004-05-27 | 2012-09-12 | Jon A. Weidanz | Antibodies as t cell receptor mimics, methods of production and uses thereof |
US20090042285A1 (en) | 2004-05-27 | 2009-02-12 | Weidanz Jon A | Antibodies at T cell receptor mimics, methods of production and uses thereof |
US20090233318A1 (en) | 2004-12-28 | 2009-09-17 | Weidanz Jon A | Methods of assaying vaccine potency |
US20090304679A1 (en) | 2004-05-27 | 2009-12-10 | Weidanz Jon A | Antibodies as T cell receptor mimics, methods of production and uses thereof |
US20060045884A1 (en) | 2004-08-26 | 2006-03-02 | Board Of Regents | Vaccines for autoimmune and infectious disease |
US20060045881A1 (en) | 2004-08-26 | 2006-03-02 | Board Of Regents, The University Of Texas System | Anti-cancer vaccines |
EP2824183B1 (en) * | 2005-04-08 | 2020-07-29 | Chugai Seiyaku Kabushiki Kaisha | Methods for producing bispecific antibodies |
EP1927367A4 (en) | 2005-05-18 | 2009-08-12 | Univ Tokushima | NOVEL PHARMACEUTICAL AGENT BASED ON AN ANTI-HLA ANTIBODY |
EP1933864A4 (en) | 2005-09-07 | 2009-12-16 | Receptor Logic Ltd | ANTIBODIES AS T-CELL RECEPTOR MIMICS, METHOD OF MANUFACTURE AND ITS USES |
CA2657385A1 (en) | 2006-07-13 | 2008-01-17 | Naoki Kimura | Cell death inducer |
CL2008000719A1 (es) | 2007-03-12 | 2008-09-05 | Univ Tokushima Chugai Seiyaku | Agente terapeutico para cancer resistente a agentes quimioterapeuticos que comprende un anticuerpo que reconoce hla de clase i como ingrediente activo; composicion farmaceutica que comprende dicho anticuerpo; y metodo para tratar cancer resistente a |
WO2009073163A1 (en) * | 2007-12-03 | 2009-06-11 | American Type Culture Collection (Atcc) | Avian influenza antibodies, compositions, and methods thereof |
WO2010065962A2 (en) * | 2008-12-05 | 2010-06-10 | The Board Of Regents Of The University Of Texas System | Monoclonal antibodies for use in diagnosis and therapy of cancers and autoimmune disease |
TW201118166A (en) | 2009-09-24 | 2011-06-01 | Chugai Pharmaceutical Co Ltd | HLA class I-recognizing antibodies |
-
2013
- 2013-03-07 UA UAA201501025A patent/UA114108C2/uk unknown
- 2013-07-03 LT LTEP16152641.3T patent/LT3088421T/lt unknown
- 2013-07-03 MX MX2015000450A patent/MX360984B/es active IP Right Grant
- 2013-07-03 JP JP2015521668A patent/JP6336696B2/ja active Active
- 2013-07-03 DK DK16152641.3T patent/DK3088421T3/da active
- 2013-07-03 ES ES16152641T patent/ES2720291T3/es active Active
- 2013-07-03 SI SI201331371T patent/SI3088421T1/sl unknown
- 2013-07-03 EP EP13816335.7A patent/EP2872174A2/en not_active Withdrawn
- 2013-07-03 CA CA2883056A patent/CA2883056C/en active Active
- 2013-07-03 EP EP16152641.3A patent/EP3088421B1/en active Active
- 2013-07-03 AU AU2013288982A patent/AU2013288982B2/en active Active
- 2013-07-03 WO PCT/US2013/049368 patent/WO2014011489A2/en active Application Filing
- 2013-07-03 CN CN201380042522.1A patent/CN104540522B/zh active Active
- 2013-07-03 PT PT16152641T patent/PT3088421T/pt unknown
- 2013-07-03 IN IN263DEN2015 patent/IN2015DN00263A/en unknown
- 2013-07-03 KR KR1020157003610A patent/KR102049222B1/ko active IP Right Grant
- 2013-07-03 HU HUE16152641A patent/HUE043443T2/hu unknown
- 2013-07-03 EA EA201590187A patent/EA034033B1/ru not_active IP Right Cessation
- 2013-07-03 RS RS20190609A patent/RS58755B1/sr unknown
- 2013-07-03 PL PL16152641T patent/PL3088421T3/pl unknown
- 2013-07-03 US US14/413,833 patent/US9926380B2/en active Active
-
2015
- 2015-01-11 IL IL236664A patent/IL236664B/en active IP Right Grant
- 2015-01-12 PH PH12015500074A patent/PH12015500074B1/en unknown
- 2015-01-14 ZA ZA2015/00247A patent/ZA201500247B/en unknown
- 2015-09-10 HK HK15108802.4A patent/HK1208168A1/xx unknown
-
2018
- 2018-02-13 US US15/895,782 patent/US11192958B2/en active Active
-
2019
- 2019-05-07 CY CY20191100490T patent/CY1121743T1/el unknown
- 2019-05-21 HR HRP20190939TT patent/HRP20190939T1/hr unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6336696B2 (ja) | がんおよび自己免疫疾患の診断および治療に使用するためのモノクローナル抗体 | |
US11155632B2 (en) | Anti-CD47 monoclonal antibody and use thereof | |
US10308721B2 (en) | Anti-DLL3 antibodies and drug conjugates for use in melanoma | |
CN107683289B (zh) | IL13Rα2结合剂和其在癌症治疗中的用途 | |
JP7070932B2 (ja) | Baff-r標的化キメラ抗原受容体修飾t細胞及びその使用 | |
TW201639887A (zh) | 抗-dll3嵌合抗原受體及其使用方法 | |
AU2013203506A1 (en) | Novel modulators and methods of use | |
WO2020114479A1 (zh) | 多特异性蛋白分子 | |
WO2022068810A1 (zh) | 抗Claudin18.2和CD3的双特异性抗体以及其用途 | |
WO2015095766A2 (en) | Novel anti-lingo1 antibodies and methods of use | |
CN114641310A (zh) | 治疗癌症和其他疾病的靶向α3β1整合素 | |
JP2022508309A (ja) | 抗ヒトtim-3モノクローナル抗体およびその応用 | |
WO2020108636A1 (zh) | 全人抗gitr抗体及其制备方法 | |
US20110293620A1 (en) | Monoclonal Antibodies For Use In Diagnosis and Therapy of Cancers and Autoimmune Disease | |
JP2021506260A (ja) | 抗cct5結合分子およびその使用方法 | |
TWI837517B (zh) | 抗claudin 18.2和cd3的雙特異性抗體以及其用途 | |
US20220089727A1 (en) | Anti-CD47 monoclonal antibody and use thereof | |
US12006356B2 (en) | Anti-CCT5 binding molecules and chimeric antigen receptors comprising the same | |
MOLLDREM et al. | Patent 2883056 Summary | |
TW202340240A (zh) | 多特異性抗體及其藥物用途 | |
CN113368232A (zh) | 多特异性抗原结合蛋白及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160704 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160704 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170501 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170728 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171127 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180226 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180326 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180409 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180503 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6336696 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |