TWI491408B - 與淋巴細胞活化基因－３（ｌａｇ－３）結合之人抗體類及彼等之用途 - Google Patents

Info

Publication number

TWI491408B

TWI491408B TW098126950A TW98126950A TWI491408B TW I491408 B TWI491408 B TW I491408B TW 098126950 A TW098126950 A TW 098126950A TW 98126950 A TW98126950 A TW 98126950A TW I491408 B TWI491408 B TW I491408B

Authority

TW

Taiwan

Prior art keywords

antibody

lag

human

seq

variable region

Prior art date

2008-08-11

Links

• Espacenet
• Global Dossier
• Discuss

• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 title claims description 302
• 241000282414 Homo sapiens Species 0.000 title claims description 300
• 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 title claims description 204
• 101100510617 Caenorhabditis elegans sel-8 gene Proteins 0.000 title description 5
• 239000000427 antigen Substances 0.000 claims description 189
• 108091007433 antigens Proteins 0.000 claims description 188
• 102000036639 antigens Human genes 0.000 claims description 188
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 187
• 238000009739 binding Methods 0.000 claims description 177
• 230000027455 binding Effects 0.000 claims description 175
• 210000004027 cell Anatomy 0.000 claims description 138
• 238000000034 method Methods 0.000 claims description 110
• 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims description 78
• 229940045513 CTLA4 antagonist Drugs 0.000 claims description 61
• 210000001744 T-lymphocyte Anatomy 0.000 claims description 48
• 230000028993 immune response Effects 0.000 claims description 46
• 230000005867 T cell response Effects 0.000 claims description 36
• 239000000203 mixture Substances 0.000 claims description 33
• 230000014509 gene expression Effects 0.000 claims description 27
• 230000003308 immunostimulating effect Effects 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 22
• 238000000338 in vitro Methods 0.000 claims description 20
• 150000007523 nucleic acids Chemical class 0.000 claims description 19
• 238000004519 manufacturing process Methods 0.000 claims description 18
• 102000039446 nucleic acids Human genes 0.000 claims description 18
• 108020004707 nucleic acids Proteins 0.000 claims description 18
• 230000004936 stimulating effect Effects 0.000 claims description 15
• 239000013598 vector Substances 0.000 claims description 14
• 229940124597 therapeutic agent Drugs 0.000 claims description 10
• 229940127121 immunoconjugate Drugs 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• 208000036142 Viral infection Diseases 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 230000009385 viral infection Effects 0.000 claims description 6
• 230000004565 tumor cell growth Effects 0.000 claims description 5
• 108090000623 proteins and genes Proteins 0.000 description 128
• 206010028980 Neoplasm Diseases 0.000 description 123
• 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 106
• 210000004602 germ cell Anatomy 0.000 description 103
• 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 67
• 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 67
• 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 65
• 241000699670 Mus sp. Species 0.000 description 59
• 239000000047 product Substances 0.000 description 53
• 241000699666 Mus <mouse, genus> Species 0.000 description 47
• 102000004169 proteins and genes Human genes 0.000 description 42
• 235000018102 proteins Nutrition 0.000 description 40
• 238000011282 treatment Methods 0.000 description 38
• 108060003951 Immunoglobulin Proteins 0.000 description 36
• 102000018358 immunoglobulin Human genes 0.000 description 36
• 235000001014 amino acid Nutrition 0.000 description 34
• 108090000765 processed proteins & peptides Proteins 0.000 description 31
• 239000012634 fragment Substances 0.000 description 28
• 108020004414 DNA Proteins 0.000 description 25
• 239000002773 nucleotide Substances 0.000 description 24
• 125000003729 nucleotide group Chemical group 0.000 description 24
• 229940024606 amino acid Drugs 0.000 description 23
• 230000004048 modification Effects 0.000 description 23
• 238000012986 modification Methods 0.000 description 23
• 241000282693 Cercopithecidae Species 0.000 description 22
• 238000002474 experimental method Methods 0.000 description 22
• 238000006206 glycosylation reaction Methods 0.000 description 22
• 150000001413 amino acids Chemical class 0.000 description 21
• 201000011510 cancer Diseases 0.000 description 21
• 230000013595 glycosylation Effects 0.000 description 21
• 230000000694 effects Effects 0.000 description 20
• 210000004881 tumor cell Anatomy 0.000 description 20
• 101001137986 Mus musculus Lymphocyte activation gene 3 protein Proteins 0.000 description 19
• 125000000539 amino acid group Chemical group 0.000 description 19
• 230000035772 mutation Effects 0.000 description 19
• 210000001519 tissue Anatomy 0.000 description 19
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 18
• 210000004408 hybridoma Anatomy 0.000 description 18
• 102000008096 B7-H1 Antigen Human genes 0.000 description 17
• 108010074708 B7-H1 Antigen Proteins 0.000 description 17
• 102000008203 CTLA-4 Antigen Human genes 0.000 description 17
• 108010021064 CTLA-4 Antigen Proteins 0.000 description 17
• 108010002350 Interleukin-2 Proteins 0.000 description 17
• 102000000588 Interleukin-2 Human genes 0.000 description 17
• 239000002253 acid Substances 0.000 description 17
• 238000001727 in vivo Methods 0.000 description 17
• 230000004614 tumor growth Effects 0.000 description 17
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 16
• 239000013604 expression vector Substances 0.000 description 16
• 108020001507 fusion proteins Proteins 0.000 description 16
• 102000037865 fusion proteins Human genes 0.000 description 16
• 108091054438 MHC class II family Proteins 0.000 description 15
• 241000700605 Viruses Species 0.000 description 15
• 239000003795 chemical substances by application Substances 0.000 description 15
• 150000003431 steroids Chemical class 0.000 description 15
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 14
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 14
• 239000002299 complementary DNA Substances 0.000 description 14
• 230000006870 function Effects 0.000 description 14
• 238000002649 immunization Methods 0.000 description 14
• 241000894007 species Species 0.000 description 14
• 238000002965 ELISA Methods 0.000 description 13
• 230000003053 immunization Effects 0.000 description 13
• 230000001965 increasing effect Effects 0.000 description 13
• 230000005764 inhibitory process Effects 0.000 description 13
• 230000001817 pituitary effect Effects 0.000 description 13
• 238000006467 substitution reaction Methods 0.000 description 13
• 238000012360 testing method Methods 0.000 description 13
• 201000010099 disease Diseases 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
• 230000001225 therapeutic effect Effects 0.000 description 12
• 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 11
• 230000000903 blocking effect Effects 0.000 description 11
• 238000000684 flow cytometry Methods 0.000 description 11
• 208000015181 infectious disease Diseases 0.000 description 11
• 230000002401 inhibitory effect Effects 0.000 description 11
• 102000004196 processed proteins & peptides Human genes 0.000 description 11
• 230000004044 response Effects 0.000 description 11
• 229960005486 vaccine Drugs 0.000 description 11
• 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 10
• 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 10
• 238000003364 immunohistochemistry Methods 0.000 description 10
• 244000052769 pathogen Species 0.000 description 10
• 150000003839 salts Chemical class 0.000 description 10
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 9
• 230000004913 activation Effects 0.000 description 9
• 210000000612 antigen-presenting cell Anatomy 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 230000037396 body weight Effects 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 238000002648 combination therapy Methods 0.000 description 9
• 230000002163 immunogen Effects 0.000 description 9
• 239000008194 pharmaceutical composition Substances 0.000 description 9
• 238000000159 protein binding assay Methods 0.000 description 9
• 230000001105 regulatory effect Effects 0.000 description 9
• 238000009097 single-agent therapy Methods 0.000 description 9
• 102000004127 Cytokines Human genes 0.000 description 8
• 108090000695 Cytokines Proteins 0.000 description 8
• 238000012449 Kunming mouse Methods 0.000 description 8
• 101150000931 L6 gene Proteins 0.000 description 8
• 239000002202 Polyethylene glycol Substances 0.000 description 8
• 210000004443 dendritic cell Anatomy 0.000 description 8
• 230000003463 hyperproliferative effect Effects 0.000 description 8
• 230000036039 immunity Effects 0.000 description 8
• 229920001223 polyethylene glycol Polymers 0.000 description 8
• 230000009261 transgenic effect Effects 0.000 description 8
• VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 7
• -1 FR3 Proteins 0.000 description 7
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 7
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 7
• 241000282560 Macaca mulatta Species 0.000 description 7
• 108700019146 Transgenes Proteins 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 7
• 150000001875 compounds Chemical class 0.000 description 7
• 238000012217 deletion Methods 0.000 description 7
• 230000037430 deletion Effects 0.000 description 7
• 206010012601 diabetes mellitus Diseases 0.000 description 7
• 239000012636 effector Substances 0.000 description 7
• 230000012010 growth Effects 0.000 description 7
• 238000002513 implantation Methods 0.000 description 7
• 201000001441 melanoma Diseases 0.000 description 7
• 230000000717 retained effect Effects 0.000 description 7
• 230000000638 stimulation Effects 0.000 description 7
• 238000011830 transgenic mouse model Methods 0.000 description 7
• 238000002255 vaccination Methods 0.000 description 7
• 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 6
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 6
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 6
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 6
• SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical group C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 6
• 241000282567 Macaca fascicularis Species 0.000 description 6
• 108091028043 Nucleic acid sequence Proteins 0.000 description 6
• 108010076504 Protein Sorting Signals Proteins 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• 239000002671 adjuvant Substances 0.000 description 6
• 230000030741 antigen processing and presentation Effects 0.000 description 6
• 239000002246 antineoplastic agent Substances 0.000 description 6
• 150000001720 carbohydrates Chemical class 0.000 description 6
• 235000014633 carbohydrates Nutrition 0.000 description 6
• 230000030833 cell death Effects 0.000 description 6
• 230000001472 cytotoxic effect Effects 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 238000003780 insertion Methods 0.000 description 6
• 230000037431 insertion Effects 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
• 206010069754 Acquired gene mutation Diseases 0.000 description 5
• 102000001189 Cyclic Peptides Human genes 0.000 description 5
• 108010069514 Cyclic Peptides Proteins 0.000 description 5
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 5
• 102000043131 MHC class II family Human genes 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 241001529936 Murinae Species 0.000 description 5
• 206010035226 Plasma cell myeloma Diseases 0.000 description 5
• 230000006023 anti-tumor response Effects 0.000 description 5
• 230000006472 autoimmune response Effects 0.000 description 5
• 229960004436 budesonide Drugs 0.000 description 5
• 230000001413 cellular effect Effects 0.000 description 5
• 239000000562 conjugate Substances 0.000 description 5
• 231100000433 cytotoxic Toxicity 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 230000002708 enhancing effect Effects 0.000 description 5
• 230000004927 fusion Effects 0.000 description 5
• 239000003862 glucocorticoid Substances 0.000 description 5
• 239000005556 hormone Substances 0.000 description 5
• 229940088597 hormone Drugs 0.000 description 5
• 210000004698 lymphocyte Anatomy 0.000 description 5
• 230000007246 mechanism Effects 0.000 description 5
• 238000002703 mutagenesis Methods 0.000 description 5
• 231100000350 mutagenesis Toxicity 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 230000001717 pathogenic effect Effects 0.000 description 5
• 230000037361 pathway Effects 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 150000003873 salicylate salts Chemical class 0.000 description 5
• 238000002741 site-directed mutagenesis Methods 0.000 description 5
• 239000000243 solution Substances 0.000 description 5
• 230000037439 somatic mutation Effects 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 241000894006 Bacteria Species 0.000 description 4
• 238000012286 ELISA Assay Methods 0.000 description 4
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 4
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 4
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 4
• 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 4
• 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 4
• 241000725303 Human immunodeficiency virus Species 0.000 description 4
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 4
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
• 241000699660 Mus musculus Species 0.000 description 4
• 108020004511 Recombinant DNA Proteins 0.000 description 4
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-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
• 230000002776 aggregation Effects 0.000 description 4
• 238000004220 aggregation Methods 0.000 description 4
• 239000000611 antibody drug conjugate Substances 0.000 description 4
• 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
• 229940049595 antibody-drug conjugate Drugs 0.000 description 4
• 230000000295 complement effect Effects 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 102000048776 human CD274 Human genes 0.000 description 4
• 102000043321 human CTLA4 Human genes 0.000 description 4
• 102000048362 human PDCD1 Human genes 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 238000001990 intravenous administration Methods 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• 238000002823 phage display Methods 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 230000000392 somatic effect Effects 0.000 description 4
• 210000000952 spleen Anatomy 0.000 description 4
• 238000001890 transfection Methods 0.000 description 4
• 239000004474 valine Substances 0.000 description 4
• LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 3
• 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 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 208000037259 Amyloid Plaque Diseases 0.000 description 3
• 241000283690 Bos taurus Species 0.000 description 3
• 241000283707 Capra Species 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 208000035473 Communicable disease Diseases 0.000 description 3
• SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
• 102000053602 DNA Human genes 0.000 description 3
• 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 3
• PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 3
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
• 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 3
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
• 108010073807 IgG Receptors Proteins 0.000 description 3
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
• 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
• 102000000440 Melanoma-associated antigen Human genes 0.000 description 3
• 108050008953 Melanoma-associated antigen Proteins 0.000 description 3
• 239000004698 Polyethylene Substances 0.000 description 3
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 108010088160 Staphylococcal Protein A Proteins 0.000 description 3
• 230000006044 T cell activation Effects 0.000 description 3
• 108010022394 Threonine synthase Proteins 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 102000012086 alpha-L-Fucosidase Human genes 0.000 description 3
• 108010061314 alpha-L-Fucosidase Proteins 0.000 description 3
• 230000001093 anti-cancer Effects 0.000 description 3
• 230000000259 anti-tumor effect Effects 0.000 description 3
• 230000005875 antibody response Effects 0.000 description 3
• 230000001363 autoimmune Effects 0.000 description 3
• 210000003719 b-lymphocyte Anatomy 0.000 description 3
• 230000008827 biological function Effects 0.000 description 3
• 239000006285 cell suspension Substances 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 238000006243 chemical reaction Methods 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 238000010367 cloning Methods 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 230000009260 cross reactivity Effects 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 102000004419 dihydrofolate reductase Human genes 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 229960004679 doxorubicin Drugs 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 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 3
• 208000006454 hepatitis Diseases 0.000 description 3
• 231100000283 hepatitis Toxicity 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 230000001900 immune effect Effects 0.000 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 230000001506 immunosuppresive effect Effects 0.000 description 3
• 238000009169 immunotherapy Methods 0.000 description 3
• 230000002458 infectious effect Effects 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 210000003563 lymphoid tissue Anatomy 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 238000002844 melting Methods 0.000 description 3
• 230000008018 melting Effects 0.000 description 3
• KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 3
• 229960004963 mesalazine Drugs 0.000 description 3
• 238000012737 microarray-based gene expression Methods 0.000 description 3
• 238000001823 molecular biology technique Methods 0.000 description 3
• 238000012243 multiplex automated genomic engineering Methods 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 230000006320 pegylation Effects 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 229920001184 polypeptide Polymers 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 230000005855 radiation Effects 0.000 description 3
• 238000003259 recombinant expression Methods 0.000 description 3
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 3
• 229960001860 salicylate Drugs 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 238000012216 screening Methods 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 210000002966 serum Anatomy 0.000 description 3
• 238000010186 staining Methods 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 239000003053 toxin Substances 0.000 description 3
• 231100000765 toxin Toxicity 0.000 description 3
• 108700012359 toxins Proteins 0.000 description 3
• 238000013518 transcription Methods 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 238000013519 translation Methods 0.000 description 3
• 238000011269 treatment regimen Methods 0.000 description 3
• 108700026220 vif Genes Proteins 0.000 description 3
• 230000003612 virological effect Effects 0.000 description 3
• 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 2
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• 108010011485 Aspartame Proteins 0.000 description 2
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 2
• 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 108091026890 Coding region Proteins 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• 206010012735 Diarrhoea Diseases 0.000 description 2
• 241000196324 Embryophyta Species 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• 108010021472 Fc gamma receptor IIB Proteins 0.000 description 2
• 108010087819 Fc receptors Proteins 0.000 description 2
• 102000009109 Fc receptors Human genes 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• 201000008808 Fibrosarcoma Diseases 0.000 description 2
• 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 2
• 108010019236 Fucosyltransferases Proteins 0.000 description 2
• 241000967808 Garra Species 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
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 2
• 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
• 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
• 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 2
• 101001094545 Homo sapiens Retrotransposon-like protein 1 Proteins 0.000 description 2
• 238000012450 HuMAb Mouse Methods 0.000 description 2
• 241000701806 Human papillomavirus Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
• 102000009490 IgG Receptors Human genes 0.000 description 2
• 102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 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
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• 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 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• 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 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 102000017578 LAG3 Human genes 0.000 description 2
• 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 2
• 108010071463 Melanoma-Specific Antigens Proteins 0.000 description 2
• 102000007557 Melanoma-Specific Antigens Human genes 0.000 description 2
• 102000018697 Membrane Proteins Human genes 0.000 description 2
• 108010052285 Membrane Proteins Proteins 0.000 description 2
• 101001043827 Mus musculus Interleukin-2 Proteins 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 238000012408 PCR amplification Methods 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• 238000011579 SCID mouse model Methods 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 230000006052 T cell proliferation Effects 0.000 description 2
• 206010042971 T-cell lymphoma Diseases 0.000 description 2
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 2
• 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 2
• 102000003425 Tyrosinase Human genes 0.000 description 2
• 108060008724 Tyrosinase Proteins 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 239000004037 angiogenesis inhibitor Substances 0.000 description 2
• 229940121369 angiogenesis inhibitor Drugs 0.000 description 2
• 230000009830 antibody antigen interaction Effects 0.000 description 2
• 230000000890 antigenic effect Effects 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
• 239000000605 aspartame Substances 0.000 description 2
• 229960003438 aspartame Drugs 0.000 description 2
• 235000010357 aspartame Nutrition 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 238000010322 bone marrow transplantation Methods 0.000 description 2
• AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
• 238000009566 cancer vaccine Methods 0.000 description 2
• 229940022399 cancer vaccine Drugs 0.000 description 2
• 238000005251 capillar electrophoresis Methods 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 230000000973 chemotherapeutic effect Effects 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 238000009104 chemotherapy regimen Methods 0.000 description 2
• 210000000349 chromosome Anatomy 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
• 238000011260 co-administration Methods 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 206010009887 colitis Diseases 0.000 description 2
• 230000004540 complement-dependent cytotoxicity Effects 0.000 description 2
• 239000013068 control sample Substances 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 230000000139 costimulatory effect Effects 0.000 description 2
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
• 231100000599 cytotoxic agent Toxicity 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 230000005860 defense response to virus Effects 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 238000010494 dissociation reaction Methods 0.000 description 2
• 230000005593 dissociations Effects 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 229940002671 entocort Drugs 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• 230000033581 fucosylation Effects 0.000 description 2
• 238000002825 functional assay Methods 0.000 description 2
• 101150023212 fut8 gene Proteins 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 238000009396 hybridization Methods 0.000 description 2
• 208000009326 ileitis Diseases 0.000 description 2
• 210000003405 ileum Anatomy 0.000 description 2
• 210000002865 immune cell Anatomy 0.000 description 2
• 230000037451 immune surveillance Effects 0.000 description 2
• 230000005847 immunogenicity Effects 0.000 description 2
• 229940072221 immunoglobulins Drugs 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 230000002779 inactivation Effects 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 239000003112 inhibitor Substances 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
• 238000005304 joining Methods 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 208000037819 metastatic cancer Diseases 0.000 description 2
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 2
• 230000003472 neutralizing effect Effects 0.000 description 2
• 230000009871 nonspecific binding Effects 0.000 description 2
• 229960004110 olsalazine Drugs 0.000 description 2
• QQBDLJCYGRGAKP-FOCLMDBBSA-N olsalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=C(C(O)=CC=2)C(O)=O)=C1 QQBDLJCYGRGAKP-FOCLMDBBSA-N 0.000 description 2
• 210000002741 palatine tonsil Anatomy 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• 230000000704 physical effect Effects 0.000 description 2
• 230000001737 promoting effect Effects 0.000 description 2
• 210000003289 regulatory T cell Anatomy 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 238000001542 size-exclusion chromatography Methods 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 206010041823 squamous cell carcinoma Diseases 0.000 description 2
• 238000012409 standard PCR amplification Methods 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
• 210000001541 thymus gland Anatomy 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 238000012448 transchromosomic mouse model Methods 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 230000002100 tumorsuppressive effect Effects 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
• AGGWFDNPHKLBBV-YUMQZZPRSA-N (2s)-2-[[(2s)-2-amino-3-methylbutanoyl]amino]-5-(carbamoylamino)pentanoic acid Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=O AGGWFDNPHKLBBV-YUMQZZPRSA-N 0.000 description 1
• VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
• 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 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
• WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
• WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.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=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 241000235389 Absidia Species 0.000 description 1
• 241000224422 Acanthamoeba Species 0.000 description 1
• 206010000830 Acute leukaemia Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 206010001382 Adrenal suppression Diseases 0.000 description 1
• AAQGRPOPTAUUBM-ZLUOBGJFSA-N Ala-Ala-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O AAQGRPOPTAUUBM-ZLUOBGJFSA-N 0.000 description 1
• ZIBWKCRKNFYTPT-ZKWXMUAHSA-N Ala-Asn-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O ZIBWKCRKNFYTPT-ZKWXMUAHSA-N 0.000 description 1
• LIWMQSWFLXEGMA-WDSKDSINSA-N Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)N LIWMQSWFLXEGMA-WDSKDSINSA-N 0.000 description 1
• 102100021266 Alpha-(1,6)-fucosyltransferase Human genes 0.000 description 1
• 241000224489 Amoeba Species 0.000 description 1
• 241000228212 Aspergillus Species 0.000 description 1
• 241001225321 Aspergillus fumigatus Species 0.000 description 1
• 241000228245 Aspergillus niger Species 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 229930192334 Auxin Natural products 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 241000223836 Babesia Species 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 241000193738 Bacillus anthracis Species 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 108700031361 Brachyury Proteins 0.000 description 1
• 241000219198 Brassica Species 0.000 description 1
• 235000011331 Brassica Nutrition 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 101150075764 CD4 gene Proteins 0.000 description 1
• 101150013553 CD40 gene Proteins 0.000 description 1
• 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000222120 Candida <Saccharomycetales> Species 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 241000606161 Chlamydia Species 0.000 description 1
• 206010008631 Cholera Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 241000223782 Ciliophora Species 0.000 description 1
• 241000223203 Coccidioides Species 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• 241000709687 Coxsackievirus Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 241000938605 Crocodylia Species 0.000 description 1
• 239000004971 Cross linker Substances 0.000 description 1
• 201000007336 Cryptococcosis Diseases 0.000 description 1
• 241000221204 Cryptococcus neoformans Species 0.000 description 1
• 241000223935 Cryptosporidium Species 0.000 description 1
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
• 102000003849 Cytochrome P450 Human genes 0.000 description 1
• 101710112752 Cytotoxin Proteins 0.000 description 1
• 101150074155 DHFR gene Proteins 0.000 description 1
• 239000012625 DNA intercalator Substances 0.000 description 1
• 239000012626 DNA minor groove binder Substances 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• 241000725619 Dengue virus Species 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical group SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• 101100012887 Drosophila melanogaster btl gene Proteins 0.000 description 1
• 101100012878 Drosophila melanogaster htl gene Proteins 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 241001466953 Echovirus Species 0.000 description 1
• 206010014612 Encephalitis viral Diseases 0.000 description 1
• 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 241000709661 Enterovirus Species 0.000 description 1
• 241000991587 Enterovirus C Species 0.000 description 1
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 201000001342 Fallopian tube cancer Diseases 0.000 description 1
• 208000013452 Fallopian tube neoplasm Diseases 0.000 description 1
• 108010008177 Fd immunoglobulins Proteins 0.000 description 1
• 241000710831 Flavivirus Species 0.000 description 1
• 102000006471 Fucosyltransferases Human genes 0.000 description 1
• 101150074355 GS gene Proteins 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 229930182566 Gentamicin Natural products 0.000 description 1
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
• 241000224466 Giardia Species 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma 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
• 239000004471 Glycine Substances 0.000 description 1
• 102000051366 Glycosyltransferases Human genes 0.000 description 1
• 108700023372 Glycosyltransferases Proteins 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
• 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
• 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
• 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
• 241000228402 Histoplasma Species 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000819490 Homo sapiens Alpha-(1,6)-fucosyltransferase Proteins 0.000 description 1
• 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
• 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
• 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
• 101000958041 Homo sapiens Musculin Proteins 0.000 description 1
• 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
• 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
• 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
• 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
• 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
• 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 241000701460 JC polyomavirus Species 0.000 description 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 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
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-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
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
• 102400000401 Latency-associated peptide Human genes 0.000 description 1
• 241000589248 Legionella Species 0.000 description 1
• 208000007764 Legionnaires' Disease Diseases 0.000 description 1
• 241000222722 Leishmania <genus> Species 0.000 description 1
• 241000222727 Leishmania donovani Species 0.000 description 1
• 241000209499 Lemna Species 0.000 description 1
• 206010024238 Leptospirosis Diseases 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 208000016604 Lyme disease Diseases 0.000 description 1
• 206010052178 Lymphocytic lymphoma Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• NVGBPTNZLWRQSY-UWVGGRQHSA-N Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN NVGBPTNZLWRQSY-UWVGGRQHSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 241000712079 Measles morbillivirus Species 0.000 description 1
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
• 241000235395 Mucor Species 0.000 description 1
• 241000711386 Mumps virus Species 0.000 description 1
• 101000924587 Mus musculus Adenomatous polyposis coli protein Proteins 0.000 description 1
• 101000859077 Mus musculus Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
• 241000186359 Mycobacterium Species 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
• OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
• MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
• 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
• 241001045988 Neogene Species 0.000 description 1
• 241000421135 Nezula grisea Species 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
• 206010061336 Pelvic neoplasm 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
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 201000005746 Pituitary adenoma Diseases 0.000 description 1
• 206010061538 Pituitary tumour benign Diseases 0.000 description 1
• 206010035148 Plague Diseases 0.000 description 1
• 241000223810 Plasmodium vivax Species 0.000 description 1
• 241000288935 Platyrrhini Species 0.000 description 1
• 241000233872 Pneumocystis carinii Species 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 241001505332 Polyomavirus sp. Species 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 108091000054 Prion Proteins 0.000 description 1
• 102000029797 Prion Human genes 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 229940079156 Proteasome inhibitor Drugs 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 241000192142 Proteobacteria Species 0.000 description 1
• 241000125945 Protoparvovirus Species 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
• 238000011530 RNeasy Mini Kit Methods 0.000 description 1
• 241000711798 Rabies lyssavirus Species 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 241000725643 Respiratory syncytial virus Species 0.000 description 1
• 241000235527 Rhizopus Species 0.000 description 1
• 241000606701 Rickettsia Species 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 241000702670 Rotavirus Species 0.000 description 1
• 241000710799 Rubella virus Species 0.000 description 1
• 241000607142 Salmonella Species 0.000 description 1
• 238000012300 Sequence Analysis Methods 0.000 description 1
• 241000607720 Serratia Species 0.000 description 1
• 201000004283 Shwachman-Diamond syndrome Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 241000217849 Sporomusa sphaeroides Species 0.000 description 1
• 241000191940 Staphylococcus Species 0.000 description 1
• 241000191967 Staphylococcus aureus Species 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 241000194017 Streptococcus Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 230000024932 T cell mediated immunity Effects 0.000 description 1
• 208000000389 T-cell leukemia Diseases 0.000 description 1
• 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
• 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 1
• 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 1
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
• 108010017842 Telomerase Proteins 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• 206010043376 Tetanus Diseases 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 101710183280 Topoisomerase Proteins 0.000 description 1
• 241000223996 Toxoplasma Species 0.000 description 1
• 241000223105 Trypanosoma brucei Species 0.000 description 1
• 241000223109 Trypanosoma cruzi Species 0.000 description 1
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
• 206010046392 Ureteric cancer Diseases 0.000 description 1
• 206010046431 Urethral cancer Diseases 0.000 description 1
• 206010046458 Urethral neoplasms Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 241000700618 Vaccinia virus Species 0.000 description 1
• QRZVUAAKNRHEOP-GUBZILKMSA-N Val-Ala-Val Chemical compound [H]N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O QRZVUAAKNRHEOP-GUBZILKMSA-N 0.000 description 1
• AEMPCGRFEZTWIF-IHRRRGAJSA-N Val-Leu-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O AEMPCGRFEZTWIF-IHRRRGAJSA-N 0.000 description 1
• JKHXYJKMNSSFFL-IUCAKERBSA-N Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@H](C(O)=O)CCCCN JKHXYJKMNSSFFL-IUCAKERBSA-N 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 238000012452 Xenomouse strains Methods 0.000 description 1
• 241000607479 Yersinia pestis Species 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000001919 adrenal effect Effects 0.000 description 1
• 201000005188 adrenal gland cancer Diseases 0.000 description 1
• 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229960000548 alemtuzumab Drugs 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
• 229960003556 aminophylline Drugs 0.000 description 1
• LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
• 229960003022 amoxicillin Drugs 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 238000012197 amplification kit Methods 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940124650 anti-cancer therapies Drugs 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 238000009175 antibody therapy Methods 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 230000009831 antigen interaction Effects 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 230000005975 antitumor immune response Effects 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 238000000149 argon plasma sintering Methods 0.000 description 1
• 239000010425 asbestos Substances 0.000 description 1
• 210000001815 ascending colon Anatomy 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 229940091771 aspergillus fumigatus Drugs 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• 239000002363 auxin Substances 0.000 description 1
• 210000003050 axon Anatomy 0.000 description 1
• 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 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
• 201000008680 babesiosis Diseases 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 244000052616 bacterial pathogen Species 0.000 description 1
• 229960004168 balsalazide Drugs 0.000 description 1
• IPOKCKJONYRRHP-FMQUCBEESA-N balsalazide Chemical compound C1=CC(C(=O)NCCC(=O)O)=CC=C1\N=N\C1=CC=C(O)C(C(O)=O)=C1 IPOKCKJONYRRHP-FMQUCBEESA-N 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 235000013405 beer Nutrition 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 229920000249 biocompatible polymer Polymers 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 229960004395 bleomycin sulfate Drugs 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000008499 blood brain barrier function Effects 0.000 description 1
• 210000001218 blood-brain barrier Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 229940089093 botox Drugs 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 238000009395 breeding Methods 0.000 description 1
• 230000001488 breeding effect Effects 0.000 description 1
• 230000003139 buffering effect Effects 0.000 description 1
• DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 230000004611 cancer cell death Effects 0.000 description 1
• 229960005243 carmustine Drugs 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000007910 cell fusion Effects 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 229940030156 cell vaccine Drugs 0.000 description 1
• 230000010001 cellular homeostasis Effects 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 238000002983 circular dichroism Methods 0.000 description 1
• 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 210000004071 colonic pouch Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000004154 complement system Effects 0.000 description 1
• 239000000356 contaminant Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229940028617 conventional vaccine Drugs 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
• 239000002254 cytotoxic agent Substances 0.000 description 1
• 239000002619 cytotoxin Substances 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 206010013023 diphtheria Diseases 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000002222 downregulating effect Effects 0.000 description 1
• 208000001848 dysentery Diseases 0.000 description 1
• 230000005014 ectopic expression Effects 0.000 description 1
• 239000012893 effector ligand Substances 0.000 description 1
• 235000013601 eggs Nutrition 0.000 description 1
• 230000005684 electric field Effects 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 238000012407 engineering method Methods 0.000 description 1
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 239000005038 ethylene vinyl acetate Substances 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000010195 expression analysis Methods 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 238000010579 first pass effect Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 244000053095 fungal pathogen Species 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 230000004545 gene duplication Effects 0.000 description 1
• 238000012637 gene transfection Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 238000010362 genome editing Methods 0.000 description 1
• 229960002518 gentamicin Drugs 0.000 description 1
• 210000004907 gland Anatomy 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 210000002503 granulosa cell Anatomy 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000002443 helper t lymphocyte Anatomy 0.000 description 1
• 230000010224 hepatic metabolism Effects 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
• 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
• 208000018821 hormone-resistant prostate carcinoma Diseases 0.000 description 1
• 230000028996 humoral immune response Effects 0.000 description 1
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• DFIWPZCPDJDKLF-UHFFFAOYSA-N hydroxyurea;1h-indole Chemical compound NC(=O)NO.C1=CC=C2NC=CC2=C1 DFIWPZCPDJDKLF-UHFFFAOYSA-N 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000008004 immune attack Effects 0.000 description 1
• 239000003022 immunostimulating agent Substances 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 230000000415 inactivating effect Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000007689 inspection Methods 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 230000004073 interleukin-2 production Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000004347 intestinal mucosa Anatomy 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 230000021633 leukocyte mediated immunity Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 108010054155 lysyllysine Proteins 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 201000004792 malaria Diseases 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 208000029559 malignant endocrine neoplasm Diseases 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 238000013507 mapping Methods 0.000 description 1
• 238000001906 matrix-assisted laser desorption--ionisation mass spectrometry Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 210000002752 melanocyte Anatomy 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 208000021039 metastatic melanoma Diseases 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000009149 molecular binding Effects 0.000 description 1
• 238000000329 molecular dynamics simulation Methods 0.000 description 1
• 230000004001 molecular interaction Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 229950006780 n-acetylglucosamine Drugs 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 101150091879 neo gene Proteins 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 230000030147 nuclear export Effects 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 230000006548 oncogenic transformation Effects 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 201000003913 parathyroid carcinoma Diseases 0.000 description 1
• 208000017954 parathyroid gland carcinoma Diseases 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 229940023041 peptide vaccine Drugs 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
• 210000001539 phagocyte Anatomy 0.000 description 1
• 210000004214 philadelphia chromosome Anatomy 0.000 description 1
• 208000021310 pituitary gland adenoma Diseases 0.000 description 1
• 231100000572 poisoning Toxicity 0.000 description 1
• 230000000607 poisoning effect Effects 0.000 description 1
• 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 239000004633 polyglycolic acid Substances 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention 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
• 210000001236 prokaryotic cell Anatomy 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
• 239000003207 proteasome inhibitor Substances 0.000 description 1
• 229940121649 protein inhibitor Drugs 0.000 description 1
• 239000012268 protein inhibitor Substances 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 231100000336 radiotoxic Toxicity 0.000 description 1
• 230000001690 radiotoxic effect Effects 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000010188 recombinant method Methods 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000001718 repressive effect Effects 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 230000000284 resting effect Effects 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229910052895 riebeckite Inorganic materials 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• 239000006152 selective media Substances 0.000 description 1
• 238000012163 sequencing technique Methods 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 230000036332 sexual response Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 201000002314 small intestine cancer Diseases 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 210000004989 spleen cell Anatomy 0.000 description 1
• 210000004988 splenocyte Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 238000012289 standard assay Methods 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• 229910021653 sulphate ion Inorganic materials 0.000 description 1
• 230000008093 supporting effect Effects 0.000 description 1
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• 102000055501 telomere Human genes 0.000 description 1
• 108091035539 telomere Proteins 0.000 description 1
• 210000003411 telomere Anatomy 0.000 description 1
• ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 230000036962 time dependent Effects 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000759 toxicological effect Toxicity 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000014723 transformation of host cell by virus Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 241001430294 unidentified retrovirus Species 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 239000012646 vaccine adjuvant Substances 0.000 description 1
• 229940124931 vaccine adjuvant Drugs 0.000 description 1
• 206010046885 vaginal cancer Diseases 0.000 description 1
• 208000013139 vaginal neoplasm Diseases 0.000 description 1
• 229940005605 valeric acid Drugs 0.000 description 1
• 108010073969 valyllysine Proteins 0.000 description 1
• 201000002498 viral encephalitis Diseases 0.000 description 1
• 208000013013 vulvar carcinoma Diseases 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1