CA3055200A1 - Compositions and methods for immunotherapy - Google Patents
Compositions and methods for immunotherapy Download PDFInfo
- Publication number
- CA3055200A1 CA3055200A1 CA3055200A CA3055200A CA3055200A1 CA 3055200 A1 CA3055200 A1 CA 3055200A1 CA 3055200 A CA3055200 A CA 3055200A CA 3055200 A CA3055200 A CA 3055200A CA 3055200 A1 CA3055200 A1 CA 3055200A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- car
- amino acid
- domain
- acid sequence
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 76
- 238000000034 method Methods 0.000 title claims abstract description 64
- 238000009169 immunotherapy Methods 0.000 title description 30
- 239000012636 effector Substances 0.000 claims abstract description 128
- 230000028993 immune response Effects 0.000 claims abstract description 18
- 230000001939 inductive effect Effects 0.000 claims abstract description 18
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 280
- 108090000623 proteins and genes Proteins 0.000 claims description 169
- 210000004027 cell Anatomy 0.000 claims description 139
- 102000004169 proteins and genes Human genes 0.000 claims description 139
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims description 137
- 239000000427 antigen Substances 0.000 claims description 101
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 100
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 98
- 108091007433 antigens Proteins 0.000 claims description 98
- 102000036639 antigens Human genes 0.000 claims description 98
- 101000908713 Homo sapiens Dihydrofolate reductase Proteins 0.000 claims description 87
- 206010028980 Neoplasm Diseases 0.000 claims description 81
- 239000003446 ligand Substances 0.000 claims description 81
- 230000027455 binding Effects 0.000 claims description 79
- 101150029707 ERBB2 gene Proteins 0.000 claims description 69
- 102000040430 polynucleotide Human genes 0.000 claims description 69
- 108091033319 polynucleotide Proteins 0.000 claims description 69
- 239000002157 polynucleotide Substances 0.000 claims description 69
- 150000001413 amino acids Chemical class 0.000 claims description 68
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 59
- 102100038078 CD276 antigen Human genes 0.000 claims description 57
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 55
- 108010002350 Interleukin-2 Proteins 0.000 claims description 49
- 102000000588 Interleukin-2 Human genes 0.000 claims description 49
- 230000008685 targeting Effects 0.000 claims description 49
- 230000011664 signaling Effects 0.000 claims description 48
- 239000012634 fragment Substances 0.000 claims description 46
- 230000014509 gene expression Effects 0.000 claims description 46
- 230000001105 regulatory effect Effects 0.000 claims description 44
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 43
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 43
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 40
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 40
- 102000004127 Cytokines Human genes 0.000 claims description 37
- 108090000695 Cytokines Proteins 0.000 claims description 37
- -1 IL10C Proteins 0.000 claims description 36
- 238000003776 cleavage reaction Methods 0.000 claims description 36
- 230000007017 scission Effects 0.000 claims description 36
- 230000006870 function Effects 0.000 claims description 35
- 210000002865 immune cell Anatomy 0.000 claims description 35
- 230000035772 mutation Effects 0.000 claims description 35
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 34
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 claims description 34
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 claims description 34
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 33
- 230000000368 destabilizing effect Effects 0.000 claims description 33
- 239000002955 immunomodulating agent Substances 0.000 claims description 33
- 239000013598 vector Substances 0.000 claims description 32
- 201000011510 cancer Diseases 0.000 claims description 29
- 102000005962 receptors Human genes 0.000 claims description 28
- 108020003175 receptors Proteins 0.000 claims description 28
- 230000004068 intracellular signaling Effects 0.000 claims description 26
- 102000015696 Interleukins Human genes 0.000 claims description 24
- 108010063738 Interleukins Proteins 0.000 claims description 24
- 102100027581 Forkhead box protein P3 Human genes 0.000 claims description 20
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 claims description 20
- 108090000566 Caspase-9 Proteins 0.000 claims description 16
- 102000004039 Caspase-9 Human genes 0.000 claims description 15
- 108091008874 T cell receptors Proteins 0.000 claims description 14
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 14
- 239000013603 viral vector Substances 0.000 claims description 14
- 108010076667 Caspases Proteins 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 13
- 102000011727 Caspases Human genes 0.000 claims description 12
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 12
- 108091027981 Response element Proteins 0.000 claims description 12
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 12
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 12
- 102220195383 rs1057517839 Human genes 0.000 claims description 12
- 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 claims description 11
- 229960000485 methotrexate Drugs 0.000 claims description 11
- 102200080790 rs1057520333 Human genes 0.000 claims description 11
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims description 10
- 102220467332 Protein BEX4_L94A_mutation Human genes 0.000 claims description 10
- 102220564041 Synphilin-1_K99R_mutation Human genes 0.000 claims description 10
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 10
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 10
- 102200067619 rs80357382 Human genes 0.000 claims description 10
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 claims description 10
- 108020004705 Codon Proteins 0.000 claims description 9
- 102220526135 Dihydrofolate reductase_N65F_mutation Human genes 0.000 claims description 9
- 102220526133 Dihydrofolate reductase_Q36K_mutation Human genes 0.000 claims description 9
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 9
- 102220283791 rs1555932650 Human genes 0.000 claims description 9
- 102200065445 rs193929333 Human genes 0.000 claims description 9
- 102220326936 rs45517095 Human genes 0.000 claims description 9
- 102220578645 Chorion-specific transcription factor GCMb_N65A_mutation Human genes 0.000 claims description 8
- 102220578647 Chorion-specific transcription factor GCMb_N65D_mutation Human genes 0.000 claims description 8
- 102220553748 Cyclic GMP-AMP synthase_K47R_mutation Human genes 0.000 claims description 8
- 102220517095 Jerky protein homolog-like_I72V_mutation Human genes 0.000 claims description 8
- 102220516830 Peroxisomal membrane protein PEX14_K56E_mutation Human genes 0.000 claims description 8
- 102220533819 Protein BEX2_K19E_mutation Human genes 0.000 claims description 8
- 102220419550 c.160G>A Human genes 0.000 claims description 8
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 8
- 108020004999 messenger RNA Proteins 0.000 claims description 8
- 102200081454 rs1048108 Human genes 0.000 claims description 8
- 102200147641 rs104894534 Human genes 0.000 claims description 8
- 102220289727 rs1253463092 Human genes 0.000 claims description 8
- 102200026990 rs137852764 Human genes 0.000 claims description 8
- 102220091389 rs145538358 Human genes 0.000 claims description 8
- 102220078654 rs147697562 Human genes 0.000 claims description 8
- 102220288810 rs1554539977 Human genes 0.000 claims description 8
- 102220150245 rs200516165 Human genes 0.000 claims description 8
- 102200065572 rs28364364 Human genes 0.000 claims description 8
- 102220005448 rs28928876 Human genes 0.000 claims description 8
- 102200082872 rs34866629 Human genes 0.000 claims description 8
- 102220021057 rs397508897 Human genes 0.000 claims description 8
- 102220225986 rs537881554 Human genes 0.000 claims description 8
- 102220057450 rs730881811 Human genes 0.000 claims description 8
- 102220159135 rs764865890 Human genes 0.000 claims description 8
- 102220022272 rs80357266 Human genes 0.000 claims description 8
- 102220087418 rs864622444 Human genes 0.000 claims description 8
- 102220119381 rs886042300 Human genes 0.000 claims description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 7
- 102220546996 Actin, gamma-enteric smooth muscle_I72K_mutation Human genes 0.000 claims description 7
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 7
- 102220491272 Peripheral myelin protein 22_L80P_mutation Human genes 0.000 claims description 7
- 102100022353 Ribosyldihydronicotinamide dehydrogenase [quinone] Human genes 0.000 claims description 7
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 claims description 7
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 7
- 102220257199 rs1553408408 Human genes 0.000 claims description 7
- 102200164348 rs41295282 Human genes 0.000 claims description 7
- 102220044643 rs587781450 Human genes 0.000 claims description 7
- 102200119608 rs62641235 Human genes 0.000 claims description 7
- 102220032039 rs67418243 Human genes 0.000 claims description 7
- 102220277052 rs757815307 Human genes 0.000 claims description 7
- 102220232854 rs766277488 Human genes 0.000 claims description 7
- 102220061202 rs786203440 Human genes 0.000 claims description 7
- 102220323326 rs796360127 Human genes 0.000 claims description 7
- 238000012546 transfer Methods 0.000 claims description 7
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 6
- 102100027207 CD27 antigen Human genes 0.000 claims description 6
- 108010012236 Chemokines Proteins 0.000 claims description 6
- 102000019034 Chemokines Human genes 0.000 claims description 6
- 108020004414 DNA Proteins 0.000 claims description 6
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 claims description 6
- 102220526130 Dihydrofolate reductase_N65S_mutation Human genes 0.000 claims description 6
- 102220526132 Dihydrofolate reductase_Q36S_mutation Human genes 0.000 claims description 6
- 241000588724 Escherichia coli Species 0.000 claims description 6
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 6
- 101001010591 Homo sapiens Interleukin-20 Proteins 0.000 claims description 6
- 102100033461 Interleukin-17A Human genes 0.000 claims description 6
- 102100030692 Interleukin-20 Human genes 0.000 claims description 6
- 108091007973 Interleukin-36 Proteins 0.000 claims description 6
- 108010021466 Mutant Proteins Proteins 0.000 claims description 6
- 102000008300 Mutant Proteins Human genes 0.000 claims description 6
- 101150098694 PDE5A gene Proteins 0.000 claims description 6
- 108010016731 PPAR gamma Proteins 0.000 claims description 6
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 6
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 6
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 claims description 6
- 102200090745 rs137852499 Human genes 0.000 claims description 6
- 102220164875 rs199968672 Human genes 0.000 claims description 6
- 102200027869 rs62517167 Human genes 0.000 claims description 6
- 102220082831 rs780379280 Human genes 0.000 claims description 6
- 102220227609 rs913563840 Human genes 0.000 claims description 6
- 102220279469 rs992385562 Human genes 0.000 claims description 6
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 6
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 claims description 6
- 101710185679 CD276 antigen Proteins 0.000 claims description 5
- 101150013553 CD40 gene Proteins 0.000 claims description 5
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 claims description 5
- 108090000144 Human Proteins Proteins 0.000 claims description 5
- 102000003839 Human Proteins Human genes 0.000 claims description 5
- 108010050904 Interferons Proteins 0.000 claims description 5
- 102000014150 Interferons Human genes 0.000 claims description 5
- 108090000176 Interleukin-13 Proteins 0.000 claims description 5
- 102000003816 Interleukin-13 Human genes 0.000 claims description 5
- 102100036680 Interleukin-25 Human genes 0.000 claims description 5
- 102100036678 Interleukin-27 subunit alpha Human genes 0.000 claims description 5
- 102100033502 Interleukin-37 Human genes 0.000 claims description 5
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 claims description 5
- 102000000536 PPAR gamma Human genes 0.000 claims description 5
- 102220640878 Pregnancy-specific beta-1-glycoprotein 3_L23S_mutation Human genes 0.000 claims description 5
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 5
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 5
- 230000005975 antitumor immune response Effects 0.000 claims description 5
- 102220398030 c.50T>A Human genes 0.000 claims description 5
- 238000001514 detection method Methods 0.000 claims description 5
- 230000001177 retroviral effect Effects 0.000 claims description 5
- 102220286181 rs730881811 Human genes 0.000 claims description 5
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 4
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 4
- 101000998146 Homo sapiens Interleukin-17A Proteins 0.000 claims description 4
- 101001040964 Homo sapiens Interleukin-36 receptor antagonist protein Proteins 0.000 claims description 4
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 claims description 4
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 claims description 4
- 102100021150 Interleukin-36 receptor antagonist protein Human genes 0.000 claims description 4
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 claims description 4
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 claims description 4
- 239000003862 glucocorticoid Substances 0.000 claims description 4
- 239000003102 growth factor Substances 0.000 claims description 4
- 210000002443 helper t lymphocyte Anatomy 0.000 claims description 4
- 102220280971 rs1253463092 Human genes 0.000 claims description 4
- 101001059929 Caenorhabditis elegans Forkhead box protein O Proteins 0.000 claims description 3
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 claims description 3
- 102000053602 DNA Human genes 0.000 claims description 3
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 claims description 3
- 101100286700 Homo sapiens IL1F10 gene Proteins 0.000 claims description 3
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 claims description 3
- 101000998178 Homo sapiens Interleukin-17C Proteins 0.000 claims description 3
- 101000998151 Homo sapiens Interleukin-17F Proteins 0.000 claims description 3
- 101000960946 Homo sapiens Interleukin-19 Proteins 0.000 claims description 3
- 101001010626 Homo sapiens Interleukin-22 Proteins 0.000 claims description 3
- 101000852980 Homo sapiens Interleukin-23 subunit alpha Proteins 0.000 claims description 3
- 101000853009 Homo sapiens Interleukin-24 Proteins 0.000 claims description 3
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 claims description 3
- 101000998139 Homo sapiens Interleukin-32 Proteins 0.000 claims description 3
- 101000998132 Homo sapiens Interleukin-34 Proteins 0.000 claims description 3
- 101000998122 Homo sapiens Interleukin-37 Proteins 0.000 claims description 3
- 102000026633 IL6 Human genes 0.000 claims description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 3
- 102100020990 Interferon lambda-1 Human genes 0.000 claims description 3
- 102100026015 Interleukin-1 family member 10 Human genes 0.000 claims description 3
- 101800003050 Interleukin-16 Proteins 0.000 claims description 3
- 102000049772 Interleukin-16 Human genes 0.000 claims description 3
- 102100033105 Interleukin-17C Human genes 0.000 claims description 3
- 102100033454 Interleukin-17F Human genes 0.000 claims description 3
- 102000003810 Interleukin-18 Human genes 0.000 claims description 3
- 108090000171 Interleukin-18 Proteins 0.000 claims description 3
- 102100039879 Interleukin-19 Human genes 0.000 claims description 3
- 102100030703 Interleukin-22 Human genes 0.000 claims description 3
- 108010065637 Interleukin-23 Proteins 0.000 claims description 3
- 102000013264 Interleukin-23 Human genes 0.000 claims description 3
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 claims description 3
- 102100036671 Interleukin-24 Human genes 0.000 claims description 3
- 102100036679 Interleukin-26 Human genes 0.000 claims description 3
- 108010066979 Interleukin-27 Proteins 0.000 claims description 3
- 102100033501 Interleukin-32 Human genes 0.000 claims description 3
- 102100033499 Interleukin-34 Human genes 0.000 claims description 3
- 108090001005 Interleukin-6 Proteins 0.000 claims description 3
- 102100021592 Interleukin-7 Human genes 0.000 claims description 3
- 108010002586 Interleukin-7 Proteins 0.000 claims description 3
- 102000017578 LAG3 Human genes 0.000 claims description 3
- 108010079855 Peptide Aptamers Proteins 0.000 claims description 3
- 108020001096 dihydrofolate reductase Proteins 0.000 claims description 3
- 229940079322 interferon Drugs 0.000 claims description 3
- 210000003071 memory t lymphocyte Anatomy 0.000 claims description 3
- 102200013899 rs10258719 Human genes 0.000 claims description 3
- 102220242566 rs754509338 Human genes 0.000 claims description 3
- 239000013607 AAV vector Substances 0.000 claims description 2
- 108010040471 CC Chemokines Proteins 0.000 claims description 2
- 102000001902 CC Chemokines Human genes 0.000 claims description 2
- 108050006947 CXC Chemokine Proteins 0.000 claims description 2
- 102000019388 CXC chemokine Human genes 0.000 claims description 2
- 101100232738 Gallus gallus IFNL3 gene Proteins 0.000 claims description 2
- 101000998181 Homo sapiens Interleukin-17B Proteins 0.000 claims description 2
- 101000852998 Homo sapiens Interleukin-27 subunit alpha Proteins 0.000 claims description 2
- 101001043821 Homo sapiens Interleukin-31 Proteins 0.000 claims description 2
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 2
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 claims description 2
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 claims description 2
- 108050003558 Interleukin-17 Proteins 0.000 claims description 2
- 102100033101 Interleukin-17B Human genes 0.000 claims description 2
- 102100030704 Interleukin-21 Human genes 0.000 claims description 2
- 102100021596 Interleukin-31 Human genes 0.000 claims description 2
- 108010067003 Interleukin-33 Proteins 0.000 claims description 2
- 102000017761 Interleukin-33 Human genes 0.000 claims description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 2
- 230000000735 allogeneic effect Effects 0.000 claims description 2
- 210000004443 dendritic cell Anatomy 0.000 claims description 2
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 2
- 108010074108 interleukin-21 Proteins 0.000 claims description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 claims description 2
- 210000000581 natural killer T-cell Anatomy 0.000 claims description 2
- 230000000174 oncolytic effect Effects 0.000 claims description 2
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 2
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 5
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims 5
- 102100024746 Dihydrofolate reductase Human genes 0.000 claims 2
- 102220511074 Hydroxycarboxylic acid receptor 3_E31D_mutation Human genes 0.000 claims 2
- 102220525890 NADH-ubiquinone oxidoreductase chain 4L_I61T_mutation Human genes 0.000 claims 2
- 108010017405 NRH - quinone oxidoreductase2 Proteins 0.000 claims 2
- 102220502001 U3 small nucleolar RNA-interacting protein 2_C7R_mutation Human genes 0.000 claims 2
- 102220349478 c.40T>A Human genes 0.000 claims 2
- 102200068689 rs281865205 Human genes 0.000 claims 2
- 102200068687 rs281865206 Human genes 0.000 claims 2
- 102200068694 rs281865207 Human genes 0.000 claims 2
- 102200094314 rs74315399 Human genes 0.000 claims 2
- 102220083619 rs863224719 Human genes 0.000 claims 2
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims 1
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 claims 1
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 claims 1
- 102000003814 Interleukin-10 Human genes 0.000 claims 1
- 108090000174 Interleukin-10 Proteins 0.000 claims 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims 1
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims 1
- 239000013612 plasmid Substances 0.000 claims 1
- 102220044621 rs587781437 Human genes 0.000 claims 1
- 238000002619 cancer immunotherapy Methods 0.000 abstract description 9
- 230000001093 anti-cancer Effects 0.000 abstract description 6
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 133
- 235000018102 proteins Nutrition 0.000 description 118
- 230000003834 intracellular effect Effects 0.000 description 106
- 235000001014 amino acid Nutrition 0.000 description 70
- 229940024606 amino acid Drugs 0.000 description 69
- 102000004196 processed proteins & peptides Human genes 0.000 description 60
- 229920001184 polypeptide Polymers 0.000 description 38
- 230000000694 effects Effects 0.000 description 29
- 239000002773 nucleotide Substances 0.000 description 29
- 125000003729 nucleotide group Chemical group 0.000 description 29
- 102000004419 dihydrofolate reductase Human genes 0.000 description 27
- 108010022394 Threonine synthase Proteins 0.000 description 26
- 150000007523 nucleic acids Chemical class 0.000 description 25
- 102000039446 nucleic acids Human genes 0.000 description 24
- 108020004707 nucleic acids Proteins 0.000 description 24
- 230000004913 activation Effects 0.000 description 22
- 150000003384 small molecules Chemical class 0.000 description 21
- 229960002087 pertuzumab Drugs 0.000 description 20
- 230000004044 response Effects 0.000 description 20
- 230000004048 modification Effects 0.000 description 18
- 210000001519 tissue Anatomy 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 238000012986 modification Methods 0.000 description 17
- 102200015453 rs121912293 Human genes 0.000 description 17
- 230000000139 costimulatory effect Effects 0.000 description 16
- 210000004881 tumor cell Anatomy 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 238000006471 dimerization reaction Methods 0.000 description 15
- 230000004936 stimulating effect Effects 0.000 description 15
- 108010080611 Cytosine Deaminase Proteins 0.000 description 14
- 102000000311 Cytosine Deaminase Human genes 0.000 description 14
- 108060003951 Immunoglobulin Proteins 0.000 description 14
- 102000035195 Peptidases Human genes 0.000 description 14
- 108091005804 Peptidases Proteins 0.000 description 14
- 102000037865 fusion proteins Human genes 0.000 description 14
- 108020001507 fusion proteins Proteins 0.000 description 14
- 102000018358 immunoglobulin Human genes 0.000 description 14
- 230000000670 limiting effect Effects 0.000 description 14
- 108700011259 MicroRNAs Proteins 0.000 description 13
- 150000002270 gangliosides Chemical class 0.000 description 13
- 239000002679 microRNA Substances 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 230000001988 toxicity Effects 0.000 description 13
- 231100000419 toxicity Toxicity 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 12
- 239000002777 nucleoside Substances 0.000 description 12
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 11
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 11
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 11
- 230000033228 biological regulation Effects 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 11
- 238000006731 degradation reaction Methods 0.000 description 11
- 230000004927 fusion Effects 0.000 description 11
- 235000019833 protease Nutrition 0.000 description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 9
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 9
- 102220355759 c.313A>G Human genes 0.000 description 9
- 210000000170 cell membrane Anatomy 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- 239000012642 immune effector Substances 0.000 description 9
- 230000005847 immunogenicity Effects 0.000 description 9
- 229940121354 immunomodulator Drugs 0.000 description 9
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 8
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 8
- 230000001086 cytosolic effect Effects 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 229940088598 enzyme Drugs 0.000 description 8
- 210000000822 natural killer cell Anatomy 0.000 description 8
- 210000003289 regulatory T cell Anatomy 0.000 description 8
- 101001070329 Geobacillus stearothermophilus 50S ribosomal protein L18 Proteins 0.000 description 7
- 102100040247 Tumor necrosis factor Human genes 0.000 description 7
- 125000000539 amino acid group Chemical group 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- OZRNSSUDZOLUSN-LBPRGKRZSA-N dihydrofolic acid Chemical compound N=1C=2C(=O)NC(N)=NC=2NCC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OZRNSSUDZOLUSN-LBPRGKRZSA-N 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 150000003833 nucleoside derivatives Chemical class 0.000 description 7
- 230000000149 penetrating effect Effects 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 125000006850 spacer group Chemical group 0.000 description 7
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 6
- 208000009329 Graft vs Host Disease Diseases 0.000 description 6
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 6
- 102220498732 Interleukin-6 receptor subunit alpha_T57A_mutation Human genes 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 230000009977 dual effect Effects 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 208000024908 graft versus host disease Diseases 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 210000004379 membrane Anatomy 0.000 description 6
- 125000003835 nucleoside group Chemical group 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 102220131582 rs753924720 Human genes 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- 229960001082 trimethoprim Drugs 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- 102100024633 Carbonic anhydrase 2 Human genes 0.000 description 5
- 101710167917 Carbonic anhydrase 2 Proteins 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 5
- 101000633786 Homo sapiens SLAM family member 6 Proteins 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 108700020796 Oncogene Proteins 0.000 description 5
- 101710131813 Ribosyldihydronicotinamide dehydrogenase [quinone] Proteins 0.000 description 5
- 102100029197 SLAM family member 6 Human genes 0.000 description 5
- 102100029215 Signaling lymphocytic activation molecule Human genes 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 230000010261 cell growth Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 235000019152 folic acid Nutrition 0.000 description 5
- 229940022353 herceptin Drugs 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 102220010999 rs104894360 Human genes 0.000 description 5
- JLIDBLDQVAYHNE-YKALOCIXSA-N (+)-Abscisic acid Chemical compound OC(=O)/C=C(/C)\C=C\[C@@]1(O)C(C)=CC(=O)CC1(C)C JLIDBLDQVAYHNE-YKALOCIXSA-N 0.000 description 4
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 4
- 102000006306 Antigen Receptors Human genes 0.000 description 4
- 108010083359 Antigen Receptors Proteins 0.000 description 4
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 4
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 4
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 4
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 4
- 102100035233 Furin Human genes 0.000 description 4
- 108090001126 Furin Proteins 0.000 description 4
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 4
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 4
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 4
- 102000004310 Ion Channels Human genes 0.000 description 4
- 108090000862 Ion Channels Proteins 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- 241001648840 Thosea asigna virus Species 0.000 description 4
- 108010065323 Tumor Necrosis Factor Ligand Superfamily Member 13 Proteins 0.000 description 4
- NMFHJNAPXOMSRX-PUPDPRJKSA-N [(1r)-3-(3,4-dimethoxyphenyl)-1-[3-(2-morpholin-4-ylethoxy)phenyl]propyl] (2s)-1-[(2s)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carboxylate Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCCN2CCOCC2)C=CC=1)CC1=CC=C(OC)C(OC)=C1 NMFHJNAPXOMSRX-PUPDPRJKSA-N 0.000 description 4
- 230000001851 biosynthetic effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 238000007385 chemical modification Methods 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 102000003675 cytokine receptors Human genes 0.000 description 4
- 108010057085 cytokine receptors Proteins 0.000 description 4
- 206010052015 cytokine release syndrome Diseases 0.000 description 4
- 230000001687 destabilization Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 4
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000002688 persistence Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 4
- 108020001580 protein domains Proteins 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 238000011105 stabilization Methods 0.000 description 4
- 230000000087 stabilizing effect Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 238000002604 ultrasonography Methods 0.000 description 4
- 108010030526 1-aminocyclopropanecarboxylate synthase Proteins 0.000 description 3
- 108020003589 5' Untranslated Regions Proteins 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 102220602660 Argininosuccinate synthase_V69A_mutation Human genes 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
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 102100029855 Caspase-3 Human genes 0.000 description 3
- 101150090033 DRB2 gene Proteins 0.000 description 3
- 102100039694 Death-associated protein 1 Human genes 0.000 description 3
- 241000214054 Equine rhinitis A virus Species 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 3
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 3
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 3
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 description 3
- 102100032818 Integrin alpha-4 Human genes 0.000 description 3
- 102100032816 Integrin alpha-6 Human genes 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 102000004856 Lectins Human genes 0.000 description 3
- 108090001090 Lectins Proteins 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
- 101100117568 Oryza sativa subsp. japonica DRB5 gene Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 3
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 3
- 102100029198 SLAM family member 7 Human genes 0.000 description 3
- 229940124639 Selective inhibitor Drugs 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 230000006044 T cell activation Effects 0.000 description 3
- 102000006601 Thymidine Kinase Human genes 0.000 description 3
- 108020004440 Thymidine kinase Proteins 0.000 description 3
- 102220535821 Transcription factor JunD_E31D_mutation Human genes 0.000 description 3
- 206010045170 Tumour lysis syndrome Diseases 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- GQLCLPLEEOUJQC-ZTQDTCGGSA-N [(1r)-3-(3,4-dimethoxyphenyl)-1-[3-[2-[2-[[2-[3-[(1r)-3-(3,4-dimethoxyphenyl)-1-[(2s)-1-[(2s)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetyl]amino]ethylamino]-2-oxoethoxy]phenyl]propyl] (2s)-1-[(2s)-2-(3,4,5-trimethoxyph Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCC(=O)NCCNC(=O)COC=2C=C(C=CC=2)[C@@H](CCC=2C=C(OC)C(OC)=CC=2)OC(=O)[C@H]2N(CCCC2)C(=O)[C@@H](CC)C=2C=C(OC)C(OC)=C(OC)C=2)C=CC=1)CC1=CC=C(OC)C(OC)=C1 GQLCLPLEEOUJQC-ZTQDTCGGSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940014144 folate Drugs 0.000 description 3
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 3
- 239000011724 folic acid Substances 0.000 description 3
- 150000002224 folic acids Chemical class 0.000 description 3
- 229960002963 ganciclovir Drugs 0.000 description 3
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000010189 intracellular transport Effects 0.000 description 3
- 239000002523 lectin Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 102200053439 rs72466487 Human genes 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 229960000575 trastuzumab Drugs 0.000 description 3
- 208000010380 tumor lysis syndrome Diseases 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 239000004474 valine Substances 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
- LSHVYAFMTMFKBA-TZIWHRDSSA-N (-)-epicatechin-3-O-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-TZIWHRDSSA-N 0.000 description 2
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- 108020005345 3' Untranslated Regions Proteins 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 108010032595 Antibody Binding Sites Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 2
- 101710201279 Biotin carboxyl carrier protein Proteins 0.000 description 2
- 102100024263 CD160 antigen Human genes 0.000 description 2
- 102100038077 CD226 antigen Human genes 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 108090000567 Caspase 7 Proteins 0.000 description 2
- 102000021350 Caspase recruitment domains Human genes 0.000 description 2
- 108091011189 Caspase recruitment domains Proteins 0.000 description 2
- 102100035904 Caspase-1 Human genes 0.000 description 2
- 108090000426 Caspase-1 Proteins 0.000 description 2
- 102100038902 Caspase-7 Human genes 0.000 description 2
- 108090000538 Caspase-8 Proteins 0.000 description 2
- 102100026548 Caspase-8 Human genes 0.000 description 2
- 102100039061 Cytokine receptor common subunit beta Human genes 0.000 description 2
- LSHVYAFMTMFKBA-UHFFFAOYSA-N ECG Natural products C=1C=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010067770 Endopeptidase K Proteins 0.000 description 2
- 108010013369 Enteropeptidase Proteins 0.000 description 2
- 102100029727 Enteropeptidase Human genes 0.000 description 2
- 108010074860 Factor Xa Proteins 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000001398 Granzyme Human genes 0.000 description 2
- 108060005986 Granzyme Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 101710154606 Hemagglutinin Proteins 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 208000032672 Histiocytosis haematophagic Diseases 0.000 description 2
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 2
- 101000884298 Homo sapiens CD226 antigen Proteins 0.000 description 2
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101100396740 Homo sapiens IL37 gene Proteins 0.000 description 2
- 101001078158 Homo sapiens Integrin alpha-1 Proteins 0.000 description 2
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 2
- 101001046687 Homo sapiens Integrin alpha-E Proteins 0.000 description 2
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 2
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101000998124 Homo sapiens Interleukin-36 gamma Proteins 0.000 description 2
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 2
- 101000971538 Homo sapiens Killer cell lectin-like receptor subfamily F member 1 Proteins 0.000 description 2
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 2
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 2
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 101000633778 Homo sapiens SLAM family member 5 Proteins 0.000 description 2
- 101000633782 Homo sapiens SLAM family member 8 Proteins 0.000 description 2
- 101000633780 Homo sapiens Signaling lymphocytic activation molecule Proteins 0.000 description 2
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 2
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 2
- 101000648507 Homo sapiens Tumor necrosis factor receptor superfamily member 14 Proteins 0.000 description 2
- 102100025323 Integrin alpha-1 Human genes 0.000 description 2
- 102100022341 Integrin alpha-E Human genes 0.000 description 2
- 102100025304 Integrin beta-1 Human genes 0.000 description 2
- 102100025390 Integrin beta-2 Human genes 0.000 description 2
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 102220470904 Interferon-induced protein with tetratricopeptide repeats 5_K48E_mutation Human genes 0.000 description 2
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 2
- 102100020881 Interleukin-1 alpha Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108090000172 Interleukin-15 Proteins 0.000 description 2
- 102000003812 Interleukin-15 Human genes 0.000 description 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 2
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 2
- 102100033503 Interleukin-36 gamma Human genes 0.000 description 2
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 102100021458 Killer cell lectin-like receptor subfamily F member 1 Human genes 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-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
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 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
- 208000004987 Macrophage activation syndrome Diseases 0.000 description 2
- 101710125418 Major capsid protein Proteins 0.000 description 2
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102100029083 Minor histocompatibility antigen H13 Human genes 0.000 description 2
- 101100181099 Mus musculus Klra1 gene Proteins 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 108091008877 NK cell receptors Proteins 0.000 description 2
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 description 2
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 description 2
- 208000009869 Neu-Laxova syndrome Diseases 0.000 description 2
- 102000048238 Neuregulin-1 Human genes 0.000 description 2
- 108090000556 Neuregulin-1 Proteins 0.000 description 2
- 108010066154 Nuclear Export Signals Proteins 0.000 description 2
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 2
- 102100023421 Nuclear receptor ROR-gamma Human genes 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 108010076039 Polyproteins Proteins 0.000 description 2
- 241001672814 Porcine teschovirus 1 Species 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 101710176177 Protein A56 Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 102000014128 RANK Ligand Human genes 0.000 description 2
- 108010025832 RANK Ligand Proteins 0.000 description 2
- 108091008773 RAR-related orphan receptors γ Proteins 0.000 description 2
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 2
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 102220509344 Retinoic acid early transcript 1E_R12H_mutation Human genes 0.000 description 2
- 102100029216 SLAM family member 5 Human genes 0.000 description 2
- 102100029214 SLAM family member 8 Human genes 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 102100027744 Semaphorin-4D Human genes 0.000 description 2
- 108010029180 Sialic Acid Binding Ig-like Lectin 3 Proteins 0.000 description 2
- 102220471540 Single-stranded DNA cytosine deaminase_Y31H_mutation Human genes 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 2
- 108700012920 TNF Proteins 0.000 description 2
- 108090001109 Thermolysin Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 102000050862 Transmembrane Activator and CAML Interactor Human genes 0.000 description 2
- 102000005937 Tropomyosin Human genes 0.000 description 2
- 108010030743 Tropomyosin Proteins 0.000 description 2
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 2
- 101710178302 Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000011467 adoptive cell therapy Methods 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000003432 anti-folate effect Effects 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 229940127074 antifolate Drugs 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000001574 biopsy Methods 0.000 description 2
- 229940022399 cancer vaccine Drugs 0.000 description 2
- 238000009566 cancer vaccine Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000030570 cellular localization Effects 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 108090001092 clostripain Proteins 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- FCRACOPGPMPSHN-UHFFFAOYSA-N desoxyabscisic acid Natural products OC(=O)C=C(C)C=CC1C(C)=CC(=O)CC1(C)C FCRACOPGPMPSHN-UHFFFAOYSA-N 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 2
- 229960004413 flucytosine Drugs 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 239000004052 folic acid antagonist Substances 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 239000000185 hemagglutinin Substances 0.000 description 2
- 238000005734 heterodimerization reaction Methods 0.000 description 2
- 230000006058 immune tolerance Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000001024 immunotherapeutic effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000000506 liquid--solid chromatography Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000031852 maintenance of location in cell Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 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
- 235000008729 phenylalanine Nutrition 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical group [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000008298 phosphoramidates Chemical class 0.000 description 2
- 238000000053 physical method Methods 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 230000001884 polyglutamylation Effects 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 230000009145 protein modification Effects 0.000 description 2
- 230000007026 protein scission Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 108010054624 red fluorescent protein Proteins 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229950004008 rimiducid Drugs 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 102200038856 rs150565592 Human genes 0.000 description 2
- 102220050130 rs187015338 Human genes 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000005460 tetrahydrofolate Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 102000035160 transmembrane proteins Human genes 0.000 description 2
- 108091005703 transmembrane proteins Proteins 0.000 description 2
- 102000027257 transmembrane receptors Human genes 0.000 description 2
- 108091008578 transmembrane receptors Proteins 0.000 description 2
- 230000034512 ubiquitination Effects 0.000 description 2
- 238000010798 ubiquitination Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 1
- JARGNLJYKBUKSJ-KGZKBUQUSA-N (2r)-2-amino-5-[[(2r)-1-(carboxymethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydrobromide Chemical compound Br.OC(=O)[C@H](N)CCC(=O)N[C@H](CO)C(=O)NCC(O)=O JARGNLJYKBUKSJ-KGZKBUQUSA-N 0.000 description 1
- FFILOTSTFMXQJC-QCFYAKGBSA-N (2r,4r,5s,6s)-2-[3-[(2s,3s,4r,6s)-6-[(2s,3r,4r,5s,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2r,3s,4r,5r,6r)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(e)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hy Chemical compound O[C@@H]1[C@@H](O)[C@H](OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 FFILOTSTFMXQJC-QCFYAKGBSA-N 0.000 description 1
- KJBJPJYEPGYTJX-ZBRNBAAYSA-N (2s)-2-aminobutanedioic acid;(2s)-pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1.OC(=O)[C@@H](N)CC(O)=O KJBJPJYEPGYTJX-ZBRNBAAYSA-N 0.000 description 1
- WQAVPPWWLLVGFK-FRDWYVIJSA-N (2s)-3-(4-methoxyphenyl)-n-[(2s)-1-[(2s)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]-2-[[(2s)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)[C@@]1(C)OC1)NC(=O)[C@H](C)NC(=O)CN1CCOCC1 WQAVPPWWLLVGFK-FRDWYVIJSA-N 0.000 description 1
- 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 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- 108010052418 (N-(2-((4-((2-((4-(9-acridinylamino)phenyl)amino)-2-oxoethyl)amino)-4-oxobutyl)amino)-1-(1H-imidazol-4-ylmethyl)-1-oxoethyl)-6-(((-2-aminoethyl)amino)methyl)-2-pyridinecarboxamidato) iron(1+) Proteins 0.000 description 1
- DQACSDIFXYEAFK-CMDGGOBGSA-N (e)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(2-methoxypyrimidin-5-yl)-1h-phthalazin-2-yl]prop-2-en-1-one Chemical compound C1=NC(OC)=NC=C1C1C2=CC=CC=C2C=NN1C(=O)\C=C\C1=CC(CC=2C(=NC(N)=NC=2)N)=CC(OC)=C1OC DQACSDIFXYEAFK-CMDGGOBGSA-N 0.000 description 1
- YTQNXENPQFRJGI-BQYQJAHWSA-N (e)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-(2-morpholin-4-ylpyrimidin-5-yl)-1h-phthalazin-2-yl]prop-2-en-1-one Chemical compound C=1C(\C=C\C(=O)N2C(C3=CC=CC=C3C=N2)C=2C=NC(=NC=2)N2CCOCC2)=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N YTQNXENPQFRJGI-BQYQJAHWSA-N 0.000 description 1
- MMLDINXSLFMQNR-MDZDMXLPSA-N (e)-3-[5-[(2,4-diaminopyrimidin-5-yl)methyl]-2,3-dimethoxyphenyl]-1-[1-[2-(dimethylamino)pyrimidin-5-yl]-1h-phthalazin-2-yl]prop-2-en-1-one Chemical compound C=1C(\C=C\C(=O)N2C(C3=CC=CC=C3C=N2)C=2C=NC(=NC=2)N(C)C)=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N MMLDINXSLFMQNR-MDZDMXLPSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- NYQPLPNEESYGNO-IBGZPJMESA-N 2-[[(4s)-4-carboxy-4-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]butyl]carbamoyl]benzoic acid Chemical compound C([C@H](NC(=O)C1=CC=C(C=C1)NCC1=NC2=C(N)N=C(N=C2N=C1)N)C(O)=O)CCNC(=O)C1=CC=CC=C1C(O)=O NYQPLPNEESYGNO-IBGZPJMESA-N 0.000 description 1
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 101710113902 26S proteasome non-ATPase regulatory subunit 10 Proteins 0.000 description 1
- 102100036734 26S proteasome non-ATPase regulatory subunit 10 Human genes 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CUVGUPIVTLGRGI-UHFFFAOYSA-N 4-(3-phosphonopropyl)piperazine-2-carboxylic acid Chemical compound OC(=O)C1CN(CCCP(O)(O)=O)CCN1 CUVGUPIVTLGRGI-UHFFFAOYSA-N 0.000 description 1
- LKDMKWNDBAVNQZ-UHFFFAOYSA-N 4-[[1-[[1-[2-[[1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NC(C)C(=O)NC(C)C(=O)N1CCCC1C(=O)NC(C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- HWJPWWYTGBZDEG-UHFFFAOYSA-N 5-[(2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC(C3CC3)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N HWJPWWYTGBZDEG-UHFFFAOYSA-N 0.000 description 1
- VJXSSYDSOJBUAV-UHFFFAOYSA-N 6-(2,5-dimethoxy-benzyl)-5-methyl-pyrido[2,3-d]pyrimidine-2,4-diamine Chemical compound COC1=CC=C(OC)C(CC=2C(=C3C(N)=NC(N)=NC3=NC=2)C)=C1 VJXSSYDSOJBUAV-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 241000590020 Achromobacter Species 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 101000760456 Anguilla japonica Bilirubin-inducible fluorescent protein UnaG Proteins 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 241000219194 Arabidopsis Species 0.000 description 1
- 101100340331 Arabidopsis thaliana IDM1 gene Proteins 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 108091005502 Aspartic proteases Proteins 0.000 description 1
- 102000035101 Aspartic proteases Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- BXTVQNYQYUTQAZ-UHFFFAOYSA-N BNPS-skatole Chemical compound N=1C2=CC=CC=C2C(C)(Br)C=1SC1=CC=CC=C1[N+]([O-])=O BXTVQNYQYUTQAZ-UHFFFAOYSA-N 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 108010056102 CD100 antigen Proteins 0.000 description 1
- 108010017009 CD11b Antigen Proteins 0.000 description 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 102100036008 CD48 antigen Human genes 0.000 description 1
- 108010062802 CD66 antigens Proteins 0.000 description 1
- 102100025221 CD70 antigen Human genes 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 102100027217 CD82 antigen Human genes 0.000 description 1
- 101710139831 CD82 antigen Proteins 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 101000611262 Caenorhabditis elegans Probable protein phosphatase 2C T23F11.1 Proteins 0.000 description 1
- 101000708016 Caenorhabditis elegans Sentrin-specific protease Proteins 0.000 description 1
- 108090000236 Calpain-1 Proteins 0.000 description 1
- 102000003895 Calpain-1 Human genes 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 101710202144 Capsid polyprotein Proteins 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 101710082751 Carboxypeptidase S1 homolog A Proteins 0.000 description 1
- 108010080937 Carboxypeptidases A Proteins 0.000 description 1
- 102000000496 Carboxypeptidases A Human genes 0.000 description 1
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 102100026549 Caspase-10 Human genes 0.000 description 1
- 108090000572 Caspase-10 Proteins 0.000 description 1
- 102100032616 Caspase-2 Human genes 0.000 description 1
- 108090000552 Caspase-2 Proteins 0.000 description 1
- 102100025597 Caspase-4 Human genes 0.000 description 1
- 101710090338 Caspase-4 Proteins 0.000 description 1
- 102100038916 Caspase-5 Human genes 0.000 description 1
- 101710090333 Caspase-5 Proteins 0.000 description 1
- 108010059081 Cathepsin A Proteins 0.000 description 1
- 102000005572 Cathepsin A Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000267 Cathepsin C Proteins 0.000 description 1
- 102000003902 Cathepsin C Human genes 0.000 description 1
- 108090000617 Cathepsin G Proteins 0.000 description 1
- 102000004173 Cathepsin G Human genes 0.000 description 1
- 108090000619 Cathepsin H Proteins 0.000 description 1
- 102000004175 Cathepsin H Human genes 0.000 description 1
- 108090000625 Cathepsin K Proteins 0.000 description 1
- 102000004171 Cathepsin K Human genes 0.000 description 1
- 108090000624 Cathepsin L Proteins 0.000 description 1
- 102000004172 Cathepsin L Human genes 0.000 description 1
- 102100026540 Cathepsin L2 Human genes 0.000 description 1
- 108090000613 Cathepsin S Proteins 0.000 description 1
- 102100035654 Cathepsin S Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 101710171638 Chanoclavine-I dehydrogenase easD Proteins 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 102100024539 Chymase Human genes 0.000 description 1
- 108090000227 Chymases Proteins 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 101710094648 Coat protein Proteins 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 241000186031 Corynebacteriaceae Species 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102100027419 Cytochrome P450 4B1 Human genes 0.000 description 1
- 102100026234 Cytokine receptor common subunit gamma Human genes 0.000 description 1
- 206010050685 Cytokine storm Diseases 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 102000036292 Death effector domains Human genes 0.000 description 1
- 108091010866 Death effector domains Proteins 0.000 description 1
- URRAHSMDPCMOTH-LNLFQRSKSA-N Denagliptin Chemical compound C=1C=C(F)C=CC=1C([C@H](N)C(=O)N1[C@@H](C[C@H](F)C1)C#N)C1=CC=C(F)C=C1 URRAHSMDPCMOTH-LNLFQRSKSA-N 0.000 description 1
- 101000617550 Dictyostelium discoideum Presenilin-A Proteins 0.000 description 1
- 102000004860 Dipeptidases Human genes 0.000 description 1
- 108090001081 Dipeptidases Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 102000005593 Endopeptidases Human genes 0.000 description 1
- 108010059378 Endopeptidases Proteins 0.000 description 1
- 101100316904 Enterobacteria phage P4 Epsilon gene Proteins 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 108010019957 Escherichia coli periplasmic proteinase Proteins 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 229940102550 Estrogen receptor antagonist Drugs 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 101150064015 FAS gene Proteins 0.000 description 1
- 102100026693 FAS-associated death domain protein Human genes 0.000 description 1
- XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 1
- 102000002090 Fibronectin type III Human genes 0.000 description 1
- 108050009401 Fibronectin type III Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 229930191978 Gibberellin Natural products 0.000 description 1
- KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
- 108010051815 Glutamyl endopeptidase Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
- 108010004901 Haloalkane dehalogenase Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100038006 High affinity immunoglobulin epsilon receptor subunit alpha Human genes 0.000 description 1
- 108050001540 High affinity immunoglobulin epsilon receptor subunit beta Proteins 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 1
- 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 1
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000983577 Homo sapiens Cathepsin L2 Proteins 0.000 description 1
- 101001055227 Homo sapiens Cytokine receptor common subunit gamma Proteins 0.000 description 1
- 101000886250 Homo sapiens Death-associated protein 1 Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101000911074 Homo sapiens FAS-associated death domain protein Proteins 0.000 description 1
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 101001035237 Homo sapiens Integrin alpha-D Proteins 0.000 description 1
- 101001046683 Homo sapiens Integrin alpha-L Proteins 0.000 description 1
- 101001046668 Homo sapiens Integrin alpha-X Proteins 0.000 description 1
- 101001015037 Homo sapiens Integrin beta-7 Proteins 0.000 description 1
- 101001002469 Homo sapiens Interferon lambda-2 Proteins 0.000 description 1
- 101001002634 Homo sapiens Interleukin-1 alpha Proteins 0.000 description 1
- 101001076422 Homo sapiens Interleukin-1 receptor type 2 Proteins 0.000 description 1
- 101001003142 Homo sapiens Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 1
- 101001003135 Homo sapiens Interleukin-13 receptor subunit alpha-1 Proteins 0.000 description 1
- 101001003132 Homo sapiens Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 1
- 101001019598 Homo sapiens Interleukin-17 receptor A Proteins 0.000 description 1
- 101000998137 Homo sapiens Interleukin-33 Proteins 0.000 description 1
- 101001033312 Homo sapiens Interleukin-4 receptor subunit alpha Proteins 0.000 description 1
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 description 1
- 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 description 1
- 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 description 1
- 101001027081 Homo sapiens Killer cell immunoglobulin-like receptor 2DL1 Proteins 0.000 description 1
- 101000945335 Homo sapiens Killer cell immunoglobulin-like receptor 2DL5B Proteins 0.000 description 1
- 101000945343 Homo sapiens Killer cell immunoglobulin-like receptor 2DS3 Proteins 0.000 description 1
- 101000945342 Homo sapiens Killer cell immunoglobulin-like receptor 2DS4 Proteins 0.000 description 1
- 101000945346 Homo sapiens Killer cell immunoglobulin-like receptor 2DS5 Proteins 0.000 description 1
- 101000945490 Homo sapiens Killer cell immunoglobulin-like receptor 3DL2 Proteins 0.000 description 1
- 101000945493 Homo sapiens Killer cell immunoglobulin-like receptor 3DL3 Proteins 0.000 description 1
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 1
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 1
- 101001047640 Homo sapiens Linker for activation of T-cells family member 1 Proteins 0.000 description 1
- 101001090688 Homo sapiens Lymphocyte cytosolic protein 2 Proteins 0.000 description 1
- 101000589305 Homo sapiens Natural cytotoxicity triggering receptor 2 Proteins 0.000 description 1
- 101000873418 Homo sapiens P-selectin glycoprotein ligand 1 Proteins 0.000 description 1
- 101000702132 Homo sapiens Protein spinster homolog 1 Proteins 0.000 description 1
- 101000633792 Homo sapiens SLAM family member 9 Proteins 0.000 description 1
- 101000990915 Homo sapiens Stromelysin-1 Proteins 0.000 description 1
- 101000980827 Homo sapiens T-cell surface glycoprotein CD1a Proteins 0.000 description 1
- 101000716149 Homo sapiens T-cell surface glycoprotein CD1b Proteins 0.000 description 1
- 101000716124 Homo sapiens T-cell surface glycoprotein CD1c Proteins 0.000 description 1
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 1
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 101000679857 Homo sapiens Tumor necrosis factor receptor superfamily member 3 Proteins 0.000 description 1
- 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 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 1
- 108010049171 IPSI-001 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100039904 Integrin alpha-D Human genes 0.000 description 1
- 102100022339 Integrin alpha-L Human genes 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- 108010041100 Integrin alpha6 Proteins 0.000 description 1
- 108010030465 Integrin alpha6beta1 Proteins 0.000 description 1
- 102100033016 Integrin beta-7 Human genes 0.000 description 1
- 102100020989 Interferon lambda-2 Human genes 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102100026017 Interleukin-1 receptor type 2 Human genes 0.000 description 1
- 102000003815 Interleukin-11 Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 1
- 102100020791 Interleukin-13 receptor subunit alpha-1 Human genes 0.000 description 1
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 1
- 102100035018 Interleukin-17 receptor A Human genes 0.000 description 1
- 108010082786 Interleukin-1alpha Proteins 0.000 description 1
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 1
- 102100033500 Interleukin-33 Human genes 0.000 description 1
- 102100039078 Interleukin-4 receptor subunit alpha Human genes 0.000 description 1
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 1
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
- 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 description 1
- 102100037363 Killer cell immunoglobulin-like receptor 2DL1 Human genes 0.000 description 1
- 102100033628 Killer cell immunoglobulin-like receptor 2DL5B Human genes 0.000 description 1
- 102100033625 Killer cell immunoglobulin-like receptor 2DS3 Human genes 0.000 description 1
- 102100033624 Killer cell immunoglobulin-like receptor 2DS4 Human genes 0.000 description 1
- 102100033626 Killer cell immunoglobulin-like receptor 2DS5 Human genes 0.000 description 1
- 102100034840 Killer cell immunoglobulin-like receptor 3DL2 Human genes 0.000 description 1
- 102100034834 Killer cell immunoglobulin-like receptor 3DL3 Human genes 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 102100033467 L-selectin Human genes 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 108700042652 LMP-2 Proteins 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 101000688229 Leishmania chagasi Protein phosphatase 2C Proteins 0.000 description 1
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 1
- 102100024032 Linker for activation of T-cells family member 1 Human genes 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 101710195102 Lymphocyte cytosolic protein 2 Proteins 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 102100039373 Membrane cofactor protein Human genes 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091093082 MiR-146 Proteins 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000998127 Mus musculus Interleukin-36 alpha Proteins 0.000 description 1
- 101100181101 Mus musculus Klra3 gene Proteins 0.000 description 1
- 101100236305 Mus musculus Ly9 gene Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 108010001657 NK Cell Lectin-Like Receptor Subfamily K Proteins 0.000 description 1
- 102000000812 NK Cell Lectin-Like Receptor Subfamily K Human genes 0.000 description 1
- 102000027581 NK cell receptors Human genes 0.000 description 1
- 108010004217 Natural Cytotoxicity Triggering Receptor 1 Proteins 0.000 description 1
- 108010004222 Natural Cytotoxicity Triggering Receptor 3 Proteins 0.000 description 1
- 102100032870 Natural cytotoxicity triggering receptor 1 Human genes 0.000 description 1
- 102100032851 Natural cytotoxicity triggering receptor 2 Human genes 0.000 description 1
- 102100032852 Natural cytotoxicity triggering receptor 3 Human genes 0.000 description 1
- 101710141230 Natural killer cell receptor 2B4 Proteins 0.000 description 1
- 102100021462 Natural killer cells antigen CD94 Human genes 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 101000687784 Nora virus RNA-directed RNA polymerase Proteins 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 101710141454 Nucleoprotein Proteins 0.000 description 1
- 241001195348 Nusa Species 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102100021079 Ornithine decarboxylase Human genes 0.000 description 1
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 description 1
- 101150023417 PPARG gene Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 241000233870 Pneumocystis Species 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710083689 Probable capsid protein Proteins 0.000 description 1
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 102000056251 Prolyl Oligopeptidases Human genes 0.000 description 1
- 108700015930 Prolyl Oligopeptidases Proteins 0.000 description 1
- 102100023832 Prolyl endopeptidase FAP Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100039808 Receptor-type tyrosine-protein phosphatase eta Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108010084054 SBI-087 Proteins 0.000 description 1
- 102100029196 SLAM family member 9 Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 108010029157 Sialic Acid Binding Ig-like Lectin 2 Proteins 0.000 description 1
- 102000001555 Sialic Acid Binding Ig-like Lectin 3 Human genes 0.000 description 1
- 108010047827 Sialic Acid Binding Immunoglobulin-like Lectins Proteins 0.000 description 1
- 102000007073 Sialic Acid Binding Immunoglobulin-like Lectins Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 102100023119 Sperm-egg fusion protein Juno Human genes 0.000 description 1
- 101710093389 Sperm-egg fusion protein Juno Proteins 0.000 description 1
- 102220622777 Sphingomyelin phosphodiesterase_N88G_mutation Human genes 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 102100024219 T-cell surface glycoprotein CD1a Human genes 0.000 description 1
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 1
- 108010076818 TEV protease Proteins 0.000 description 1
- 108700042805 TRU-015 Proteins 0.000 description 1
- 241000249107 Teschovirus A Species 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102220572243 Toll-interacting protein_N29S_mutation Human genes 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 102100023118 Transcription factor JunD Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- 241000223104 Trypanosoma Species 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 1
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
- 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 description 1
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 1
- 108010068081 UK 101 Proteins 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102220635500 Vacuolar protein sorting-associated protein 33A_I35L_mutation Human genes 0.000 description 1
- 241000002219 Vanilla distortion mosaic virus Species 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 101001038499 Yarrowia lipolytica (strain CLIB 122 / E 150) Lysine acetyltransferase Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 239000000061 acid fraction Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 108090000350 actinidain Proteins 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 230000009831 antigen interaction Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- UKGGPJNBONZZCM-UHFFFAOYSA-N aspartyl-proline Chemical group OC(=O)CC(N)C(=O)N1CCCC1C(O)=O UKGGPJNBONZZCM-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-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
- 239000000090 biomarker Substances 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 102220348979 c.262A>G Human genes 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 108010054847 carboxypeptidase P Proteins 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000000205 computational method Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 108091008034 costimulatory receptors Proteins 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-XVFCMESISA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-XVFCMESISA-N 0.000 description 1
- 108010018719 cytochrome P-450 CYP4B1 Proteins 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229950010300 denagliptin Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- LDBTVAXGKYIFHO-UHFFFAOYSA-N diaveridine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=CN=C(N)N=C1N LDBTVAXGKYIFHO-UHFFFAOYSA-N 0.000 description 1
- 229950000246 diaveridine Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- NYDXNILOWQXUOF-UHFFFAOYSA-L disodium;2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)NC(CCC([O-])=O)C([O-])=O)C=C1 NYDXNILOWQXUOF-UHFFFAOYSA-L 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 102000018823 fas Receptor Human genes 0.000 description 1
- 108010052621 fas Receptor Proteins 0.000 description 1
- 231100001264 fatal toxicity Toxicity 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 1
- 108010044804 gamma-glutamyl-seryl-glycine Proteins 0.000 description 1
- 229920000370 gamma-poly(glutamate) polymer Polymers 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- IXORZMNAPKEEDV-UHFFFAOYSA-N gibberellic acid GA3 Natural products OC(=O)C1C2(C3)CC(=C)C3(O)CCC2C2(C=CC3O)C1C3(C)C(=O)O2 IXORZMNAPKEEDV-UHFFFAOYSA-N 0.000 description 1
- 239000003448 gibberellin Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 229960001925 iclaprim Drugs 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000005746 immune checkpoint blockade Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 108010093036 interleukin receptors Proteins 0.000 description 1
- 102000002467 interleukin receptors Human genes 0.000 description 1
- 108010052754 interleukin-14 receptor Proteins 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 108091007420 miR‐142 Proteins 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000000897 modulatory effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 108091005763 multidomain proteins Proteins 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 238000007481 next generation sequencing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000003071 parasitic effect Effects 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
- 230000037361 pathway Effects 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- 229960003349 pemetrexed disodium Drugs 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
- 229960004448 pentamidine Drugs 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 230000003094 perturbing effect Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- IFZDCYWLUQXIAN-UHFFFAOYSA-N phosphoric acid;7h-purin-6-amine;pyridine-3-carboxamide Chemical compound OP(O)(O)=O.NC(=O)C1=CC=CN=C1.NC1=NC=NC2=C1NC=N2 IFZDCYWLUQXIAN-UHFFFAOYSA-N 0.000 description 1
- 150000008299 phosphorodiamidates Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229950001030 piritrexim Drugs 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 108010087782 poly(glycyl-alanyl) Proteins 0.000 description 1
- 229920000232 polyglycine polymer Polymers 0.000 description 1
- 230000027317 positive regulation of immune response Effects 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 229960000214 pralatrexate Drugs 0.000 description 1
- OGSBUKJUDHAQEA-WMCAAGNKSA-N pralatrexate Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CC(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OGSBUKJUDHAQEA-WMCAAGNKSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 229960005385 proguanil Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 238000002818 protein evolution Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 150000003195 pteridines Chemical class 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 150000008518 pyridopyrimidines Chemical class 0.000 description 1
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 1
- 229960000611 pyrimethamine Drugs 0.000 description 1
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical group NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000029610 recognition of host Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008726 retinoic acid receptors α Proteins 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 102200037023 rs387907270 Human genes 0.000 description 1
- 102220118255 rs886041732 Human genes 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 108010033693 saxagliptin Proteins 0.000 description 1
- 229960004937 saxagliptin Drugs 0.000 description 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- JRPHGDYSKGJTKZ-UHFFFAOYSA-N selenophosphoric acid Chemical class OP(O)([SeH])=O JRPHGDYSKGJTKZ-UHFFFAOYSA-N 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 108010031009 signal peptide peptidase Proteins 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical class 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
- 229960002930 sirolimus Drugs 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- HKSZLNNOFSGOKW-HMWZOHBLSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@@H]1C[C@H](NC)[C@H](OC)[C@@]4(C)O1 HKSZLNNOFSGOKW-HMWZOHBLSA-N 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BRBKOPJOKNSWSG-UHFFFAOYSA-N sulfaguanidine Chemical compound NC(=N)NS(=O)(=O)C1=CC=C(N)C=C1 BRBKOPJOKNSWSG-UHFFFAOYSA-N 0.000 description 1
- 229960004257 sulfaguanidine Drugs 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229950000453 talotrexin Drugs 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
- 229940124598 therapeutic candidate Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 125000002264 triphosphate group Chemical group [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 230000002476 tumorcidal 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
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 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 1
- 229960002381 vardenafil Drugs 0.000 description 1
- 108700001624 vesicular stomatitis virus G Proteins 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/31—Chimeric antigen receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4203—Receptors for growth factors
- A61K40/4205—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/421—Immunoglobulin superfamily
- A61K40/4211—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4214—Receptors for cytokines
- A61K40/4215—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4244—Enzymes
- A61K40/4252—Phosphatases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4256—Tumor associated carbohydrates
- A61K40/4258—Gangliosides, e.g. GM2, GD2 or GD3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/55—IL-2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0012—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7)
- C12N9/0026—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on CH-NH groups of donors (1.5)
- C12N9/0028—Oxidoreductases (1.) acting on nitrogen containing compounds as donors (1.4, 1.5, 1.6, 1.7) acting on CH-NH groups of donors (1.5) with NAD or NADP as acceptor (1.5.1)
- C12N9/003—Dihydrofolate reductase [DHFR] (1.5.1.3)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0055—Oxidoreductases (1.) acting on diphenols and related substances as donors (1.10)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/485—Exopeptidases (3.4.11-3.4.19)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6472—Cysteine endopeptidases (3.4.22)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/88—Lyases (4.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/90—Isomerases (5.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y105/00—Oxidoreductases acting on the CH-NH group of donors (1.5)
- C12Y105/01—Oxidoreductases acting on the CH-NH group of donors (1.5) with NAD+ or NADP+ as acceptor (1.5.1)
- C12Y105/01003—Dihydrofolate reductase (1.5.1.3)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/04—Phosphoric diester hydrolases (3.1.4)
- C12Y301/04053—3',5'-Cyclic-AMP phosphodiesterase (3.1.4.53)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/14—Dipeptidyl-peptidases and tripeptidyl-peptidases (3.4.14)
- C12Y304/14005—Dipeptidyl-peptidase IV (3.4.14.5)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y402/00—Carbon-oxygen lyases (4.2)
- C12Y402/01—Hydro-lyases (4.2.1)
- C12Y402/01001—Carbonate dehydratase (4.2.1.1), i.e. carbonic anhydrase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y502/00—Cis-trans-isomerases (5.2)
- C12Y502/01—Cis-trans-Isomerases (5.2.1)
- C12Y502/01008—Peptidylprolyl isomerase (5.2.1.8), i.e. cyclophilin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55522—Cytokines; Lymphokines; Interferons
- A61K2039/55527—Interleukins
- A61K2039/55533—IL-2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/82—Colon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/27—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by targeting or presenting multiple antigens
- A61K2239/29—Multispecific CARs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16211—Lymphocryptovirus, e.g. human herpesvirus 4, Epstein-Barr Virus
- C12N2710/16234—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Cell Biology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762466601P | 2017-03-03 | 2017-03-03 | |
| US62/466,601 | 2017-03-03 | ||
| US201762484063P | 2017-04-11 | 2017-04-11 | |
| US62/484,063 | 2017-04-11 | ||
| US201762542402P | 2017-08-08 | 2017-08-08 | |
| US62/542,402 | 2017-08-08 | ||
| PCT/US2018/020704 WO2018160993A1 (en) | 2017-03-03 | 2018-03-02 | Compositions and methods for immunotherapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3055200A1 true CA3055200A1 (en) | 2018-09-07 |
Family
ID=63370245
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3055200A Pending CA3055200A1 (en) | 2017-03-03 | 2018-03-02 | Compositions and methods for immunotherapy |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3589373A4 (enExample) |
| JP (3) | JP7660343B2 (enExample) |
| CN (1) | CN110913954A (enExample) |
| AU (1) | AU2018226857B2 (enExample) |
| CA (1) | CA3055200A1 (enExample) |
| WO (1) | WO2018160993A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112912400A (zh) * | 2018-10-19 | 2021-06-04 | 明尼苏达大学董事会 | Nk接合子分子及其使用方法 |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| CA2935960C (en) | 2014-01-08 | 2023-01-10 | Bart Lipkens | Acoustophoresis device with dual acoustophoretic chamber |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| SG10202111394XA (en) | 2017-04-13 | 2021-12-30 | Senti Biosciences Inc | Combinatorial cancer immunotherapy |
| MA49403A (fr) | 2017-06-12 | 2021-03-24 | Obsidian Therapeutics Inc | Compositions de pde5 et méthodes d'immunothérapie |
| WO2018237323A1 (en) * | 2017-06-23 | 2018-12-27 | The Board Of Trustees Of The Leland Stanford Junior University | Pde5a destabilizing domains |
| KR20220066413A (ko) | 2017-12-14 | 2022-05-24 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| JP7520818B2 (ja) * | 2018-09-13 | 2024-07-23 | ンカルタ・インコーポレイテッド | 腫瘍を治療するためのナチュラルキラー細胞組成物および免疫療法の方法 |
| WO2020069005A1 (en) * | 2018-09-28 | 2020-04-02 | Harrow Health, Inc. | Pharmaceutical compositions for prevention or treatment of cytokine release syndrome |
| US11419898B2 (en) | 2018-10-17 | 2022-08-23 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| AU2019359890B2 (en) | 2018-10-17 | 2024-10-24 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| EP3893901A4 (en) * | 2018-12-11 | 2023-01-04 | The Regents of the University of California | COMPOSITIONS AND METHODS FOR IMMUNOTHERAPIES |
| CN109735558B (zh) * | 2018-12-12 | 2022-04-15 | 中南大学 | 一种重组car19-il24基因、慢病毒载体、car19-il24-t细胞及应用 |
| EP3927728A2 (en) | 2019-02-21 | 2021-12-29 | Xencor, Inc. | Untargeted and targeted il-10 fc-fusion proteins |
| EP3773918A4 (en) | 2019-03-05 | 2022-01-05 | Nkarta, Inc. | ANTI-CD19 CHEMERIC ANTIGEN RECEPTORS AND THEIR USE IN IMMUNOTHERAPY |
| KR20210149251A (ko) * | 2019-03-08 | 2021-12-08 | 옵시디안 테라퓨틱스, 인크. | 조율가능한 조절을 위한 인간 탄산 무수화효소 2 조성물 및 방법 |
| CA3132817A1 (en) | 2019-03-08 | 2020-09-17 | Obsidian Therapeutics, Inc. | Cd40l compositions and methods for tunable regulation |
| JP2022526671A (ja) * | 2019-04-11 | 2022-05-25 | エンクリアー セラピーズ, インク. | 脳脊髄液の改善の方法ならびにそのためのデバイスおよびシステム |
| US20220378824A1 (en) * | 2019-04-30 | 2022-12-01 | Myeloid Therapeutics, Inc. | Engineered chimeric fusion protein compositions and methods of use thereof |
| EP3983538A1 (en) * | 2019-06-12 | 2022-04-20 | Obsidian Therapeutics, Inc. | Ca2 compositions and methods for tunable regulation |
| EP3987028A4 (en) * | 2019-06-21 | 2023-07-19 | Kernal Biologics, Inc. | MODIFIED ONCOSELECTIVE PROTEIN EXPRESSION |
| US20230092895A1 (en) | 2019-08-30 | 2023-03-23 | Obsidian Therapeutics, Inc. | Tandem cd19 car-based compositions and methods for immunotherapy |
| WO2021050789A1 (en) | 2019-09-10 | 2021-03-18 | Obsidian Therapeutics, Inc. | Ca2-il15 fusion proteins for tunable regulation |
| CN114599676A (zh) * | 2019-10-24 | 2022-06-07 | 诺华康制药股份公司 | 新型抗-Nogo-A抗体 |
| WO2021202581A1 (en) * | 2020-03-30 | 2021-10-07 | WUGEN, Inc. | Engineered immune cells for adoptive cell therapy |
| PE20221759A1 (es) * | 2020-03-31 | 2022-11-11 | Hanmi Pharm Ind Co Ltd | Nuevos analogos de il-2 inmunoestimuladores |
| US20230287081A1 (en) * | 2020-04-16 | 2023-09-14 | Nantong Yichen Biopharma. Co. Ltd. | PD-1 mutant polypeptide and preparation and application thereof |
| WO2022060806A1 (en) * | 2020-09-16 | 2022-03-24 | Obsidian Therapeutics, Inc. | Compositions and methods for expression of anti-bcma chimeric antigen receptors with small molecule-regulated il15 in t cells |
| WO2022072558A1 (en) | 2020-09-29 | 2022-04-07 | Enclear Therapies, Inc. | Subarachnoid fluid management method and system |
| US12012441B2 (en) | 2020-10-26 | 2024-06-18 | Neptune Biosciences Llc | Engineered human IL-21 cytokines and methods for using the same |
| CN112225807B (zh) * | 2020-10-30 | 2021-09-07 | 上海洛启生物医药技术有限公司 | 抗il5纳米抗体及其应用 |
| CN117642173A (zh) * | 2020-12-07 | 2024-03-01 | 华东理工大学 | 用于诱导对基因递送靶媒剂的免疫耐受性的方法和试剂盒 |
| AU2021401934A1 (en) * | 2020-12-14 | 2023-06-22 | Allogene Therapeutics, Inc. | Methods and reagents for characterizing car t cells for therapies |
| CN114685683B (zh) * | 2020-12-31 | 2025-07-08 | 博生吉医药科技(苏州)有限公司 | 靶向gd2的car-t细胞及其制备和应用 |
| CN112795543B (zh) * | 2021-02-04 | 2022-09-27 | 华中农业大学 | 杂交瘤细胞株及其分泌的抗草鱼IL-15Rα单克隆抗体和应用 |
| CN116406426A (zh) * | 2021-04-29 | 2023-07-07 | 苏州沙砾生物科技有限公司 | 一种修饰的肿瘤浸润淋巴细胞及其用途 |
| IL310386A (en) * | 2021-07-28 | 2024-03-01 | Prescient Therapeutics Ltd | Universal receptor immune cell therapy |
| CN116082515A (zh) * | 2021-11-08 | 2023-05-09 | 浙江海隆生物科技有限公司 | 一种在大肠杆菌中可溶性表达的口蹄疫病毒衣壳融合蛋白及其制备方法 |
| CN114317385B (zh) * | 2021-11-11 | 2024-02-13 | 元本(珠海横琴)生物科技有限公司 | 一种促进her2亲和体蛋白分泌表达的发酵培养基及发酵工艺 |
| EP4620978A1 (en) * | 2022-11-04 | 2025-09-24 | T-Maximum Pharmaceutical (Suzhou) Co., Ltd. | Universal car-t cell targeting b7h3, and preparation method therefor and use thereof |
| CN115558641B (zh) * | 2022-11-14 | 2023-05-12 | 四川新生命干细胞科技股份有限公司 | 高纯度效应免疫细胞群及其培养方法、试剂组合物和应用 |
| CN115645515A (zh) * | 2022-12-28 | 2023-01-31 | 北京圣美细胞生命科学工程研究院有限公司 | 肿瘤治疗组合物及应用、药物组合物和细胞生长抑制方法 |
| CN120712345A (zh) * | 2022-12-30 | 2025-09-26 | 上药生物治疗(香港)有限公司 | 表达趋化因子受体的细胞及其用途 |
| US20250032612A1 (en) * | 2023-03-10 | 2025-01-30 | The Regents Of The University Of Colorado, A Body Corporate | Anti-cd276 and anti-cd99 logic gated chimeric antigen receptors for the treatment of cancer |
| KR20250164239A (ko) | 2023-03-15 | 2025-11-24 | 교토후고리츠다이가쿠호진 | 펩티드 발현 구축물 및 그의 용도 |
| WO2025160432A1 (en) * | 2024-01-26 | 2025-07-31 | Poseida Therapeutics, Inc. | Methods and compositions for enhancing in vivo persistence and potency of cell therapy |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7198917B2 (en) * | 1997-11-21 | 2007-04-03 | Genentech, Inc. | Compounds, compositions and methods for the treatment of diseases characterized by A-33 related antigens |
| CN101355928B (zh) * | 2005-04-26 | 2013-05-22 | 卫材R&D管理株式会社 | 用于癌症免疫疗法的组合物和方法 |
| CA2638865A1 (en) * | 2006-02-13 | 2007-10-18 | Genentech, Inc. | Methods and compositions for targeting relt |
| US8173792B2 (en) * | 2007-02-09 | 2012-05-08 | The Board Of Trustees Of The Leland Stanford Junior University | Method for regulating protein function in cells using synthetic small molecules |
| US8530636B2 (en) * | 2008-05-07 | 2013-09-10 | The Board Of Trustees Of The Leland Stanford Junior University | Method for regulating protein function in cells in vivo using synthetic small molecules |
| WO2011146568A1 (en) * | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
| MX370348B (es) * | 2013-07-19 | 2019-12-10 | Vib Vzw | Miembros de la familia il-1 modificados dirigidos. |
| WO2017180587A2 (en) * | 2016-04-11 | 2017-10-19 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
-
2018
- 2018-03-02 JP JP2019568591A patent/JP7660343B2/ja active Active
- 2018-03-02 AU AU2018226857A patent/AU2018226857B2/en active Active
- 2018-03-02 EP EP18761512.5A patent/EP3589373A4/en active Pending
- 2018-03-02 CA CA3055200A patent/CA3055200A1/en active Pending
- 2018-03-02 WO PCT/US2018/020704 patent/WO2018160993A1/en not_active Ceased
- 2018-03-02 CN CN201880029032.0A patent/CN110913954A/zh active Pending
-
2021
- 2021-03-02 JP JP2021032321A patent/JP2021088598A/ja active Pending
-
2024
- 2024-10-17 JP JP2024182138A patent/JP2025013868A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112912400A (zh) * | 2018-10-19 | 2021-06-04 | 明尼苏达大学董事会 | Nk接合子分子及其使用方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2021088598A (ja) | 2021-06-10 |
| WO2018160993A1 (en) | 2018-09-07 |
| JP2020511528A (ja) | 2020-04-16 |
| AU2018226857A1 (en) | 2019-09-19 |
| JP2025013868A (ja) | 2025-01-28 |
| EP3589373A4 (en) | 2020-12-23 |
| AU2018226857B2 (en) | 2025-01-02 |
| CN110913954A (zh) | 2020-03-24 |
| JP7660343B2 (ja) | 2025-04-11 |
| EP3589373A1 (en) | 2020-01-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7660343B2 (ja) | 免疫療法のための組成物及び方法 | |
| US12104178B2 (en) | DHFR tunable protein regulation | |
| CN110831961B (zh) | 用于免疫疗法的cd19组合物和方法 | |
| JP7620560B2 (ja) | 調整可能な制御のためのヒトカルボニックアンヒドラーゼ2組成物及び方法 | |
| EP3806888B1 (en) | Pde5 derived regulatory constructs and methods of use in immunotherapy | |
| WO2018161026A1 (en) | Il15 compositions and methods for immunotherapy | |
| BR112019018288A2 (pt) | Métodos e composições para transduzir e expandir linfócitos e regular a atividade dos mesmos | |
| CN111107866A (zh) | 用于免疫疗法的pde5组合物和方法 | |
| WO2018161038A1 (en) | Il12 compositions and methods for immunotherapy | |
| US20230092895A1 (en) | Tandem cd19 car-based compositions and methods for immunotherapy | |
| CN114450308A (zh) | 用于调节性调控的ca2组合物和方法 | |
| JP2025185029A (ja) | 免疫療法のためのcd19組成物及び方法 | |
| HK40026640A (en) | Compositions and methods for immunotherapy | |
| US20220348937A1 (en) | Compositions and methods for dhfr tunable protein regulation | |
| HK40023885B (zh) | 用於免疫疗法的cd19组合物和方法 | |
| HK40023885A (en) | Cd19 compositions and methods for immunotherapy | |
| HK40029493A (en) | Pde5 compositions and methods for immunotherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220308 |
|
| EEER | Examination request |
Effective date: 20220308 |
|
| EEER | Examination request |
Effective date: 20220308 |
|
| EEER | Examination request |
Effective date: 20220308 |
|
| EEER | Examination request |
Effective date: 20220308 |
|
| EEER | Examination request |
Effective date: 20220308 |