AU2014273490B2 - Methods for engineering T cells for immunotherapy by using RNA-guided Cas nuclease system - Google Patents

Info

Publication number

AU2014273490B2

AU2014273490B2 AU2014273490A AU2014273490A AU2014273490B2 AU 2014273490 B2 AU2014273490 B2 AU 2014273490B2 AU 2014273490 A AU2014273490 A AU 2014273490A AU 2014273490 A AU2014273490 A AU 2014273490A AU 2014273490 B2 AU2014273490 B2 AU 2014273490B2

Authority

AU

Australia

Prior art keywords

cells

cell

rna

cas9

gene

Prior art date

2013-05-29

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 223
• 238000000034 method Methods 0.000 title claims abstract description 118
• 238000009169 immunotherapy Methods 0.000 title claims abstract description 33
• 101710163270 Nuclease Proteins 0.000 title description 24
• 210000004027 cell Anatomy 0.000 claims abstract description 239
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 149
• 108091033409 CRISPR Proteins 0.000 claims abstract description 130
• 108010042407 Endonucleases Proteins 0.000 claims abstract description 86
• 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 75
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
• 201000011510 cancer Diseases 0.000 claims abstract description 16
• 150000007523 nucleic acids Chemical class 0.000 claims description 82
• 108091008874 T cell receptors Proteins 0.000 claims description 80
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 79
• 102100031780 Endonuclease Human genes 0.000 claims description 66
• 108020005004 Guide RNA Proteins 0.000 claims description 54
• 108020004414 DNA Proteins 0.000 claims description 49
• 239000013598 vector Substances 0.000 claims description 47
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 43
• 102000039446 nucleic acids Human genes 0.000 claims description 41
• 108020004707 nucleic acids Proteins 0.000 claims description 41
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 39
• 238000011282 treatment Methods 0.000 claims description 39
• 229920001184 polypeptide Polymers 0.000 claims description 31
• -1 pVEC Proteins 0.000 claims description 25
• 108020004999 messenger RNA Proteins 0.000 claims description 23
• 230000014509 gene expression Effects 0.000 claims description 22
• 108010065524 CD52 Antigen Proteins 0.000 claims description 20
• 239000003018 immunosuppressive agent Substances 0.000 claims description 20
• 238000004520 electroporation Methods 0.000 claims description 19
• 229940125721 immunosuppressive agent Drugs 0.000 claims description 18
• 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims description 15
• 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims description 15
• 230000004913 activation Effects 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 230000035772 mutation Effects 0.000 claims description 15
• 102000003676 Glucocorticoid Receptors Human genes 0.000 claims description 14
• 108090000079 Glucocorticoid Receptors Proteins 0.000 claims description 14
• 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 14
• 241000193996 Streptococcus pyogenes Species 0.000 claims description 13
• 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
• 239000013612 plasmid Substances 0.000 claims description 13
• 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 10
• 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 10
• 208000015181 infectious disease Diseases 0.000 claims description 10
• 208000023275 Autoimmune disease Diseases 0.000 claims description 9
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 9
• 102000004190 Enzymes Human genes 0.000 claims description 9
• 108090000790 Enzymes Proteins 0.000 claims description 9
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 9
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 9
• 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims description 9
• 238000002744 homologous recombination Methods 0.000 claims description 9
• 230000006801 homologous recombination Effects 0.000 claims description 9
• 102100024263 CD160 antigen Human genes 0.000 claims description 8
• 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 8
• 101000761938 Homo sapiens CD160 antigen Proteins 0.000 claims description 8
• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 8
• 102000017578 LAG3 Human genes 0.000 claims description 8
• 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 claims description 8
• 238000000338 in vitro Methods 0.000 claims description 8
• 102000008203 CTLA-4 Antigen Human genes 0.000 claims description 7
• 229940045513 CTLA4 antagonist Drugs 0.000 claims description 7
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 6
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 6
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 6
• 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 claims description 6
• 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 6
• 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 claims description 6
• 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 claims description 6
• 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 claims description 5
• 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 claims description 5
• 101000824278 Homo sapiens Acyl-[acyl-carrier-protein] hydrolase Proteins 0.000 claims description 5
• 101000884270 Homo sapiens Natural killer cell receptor 2B4 Proteins 0.000 claims description 5
• 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 claims description 5
• 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 claims description 5
• 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 5
• 102100035268 T-cell surface protein tactile Human genes 0.000 claims description 5
• 238000013518 transcription Methods 0.000 claims description 5
• 230000035897 transcription Effects 0.000 claims description 5
• CDKIEBFIMCSCBB-UHFFFAOYSA-N 1-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-3-(1-methyl-2-phenylpyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one;hydrochloride Chemical compound Cl.C1C=2C=C(OC)C(OC)=CC=2CCN1C(=O)C=CC(C1=CC=CN=C1N1C)=C1C1=CC=CC=C1 CDKIEBFIMCSCBB-UHFFFAOYSA-N 0.000 claims description 4
• 102100022970 Basic leucine zipper transcriptional factor ATF-like Human genes 0.000 claims description 4
• 108090000397 Caspase 3 Proteins 0.000 claims description 4
• 102100026549 Caspase-10 Human genes 0.000 claims description 4
• 102100029855 Caspase-3 Human genes 0.000 claims description 4
• 102100038918 Caspase-6 Human genes 0.000 claims description 4
• 102100038902 Caspase-7 Human genes 0.000 claims description 4
• 102100026548 Caspase-8 Human genes 0.000 claims description 4
• 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 0.000 claims description 4
• 102100026693 FAS-associated death domain protein Human genes 0.000 claims description 4
• 102100040754 Guanylate cyclase soluble subunit alpha-1 Human genes 0.000 claims description 4
• 102100040735 Guanylate cyclase soluble subunit alpha-2 Human genes 0.000 claims description 4
• 102100040739 Guanylate cyclase soluble subunit beta-1 Human genes 0.000 claims description 4
• 102100028963 Guanylate cyclase soluble subunit beta-2 Human genes 0.000 claims description 4
• 102100035081 Homeobox protein TGIF1 Human genes 0.000 claims description 4
• 101000903742 Homo sapiens Basic leucine zipper transcriptional factor ATF-like Proteins 0.000 claims description 4
• 101000983518 Homo sapiens Caspase-10 Proteins 0.000 claims description 4
• 101000741087 Homo sapiens Caspase-6 Proteins 0.000 claims description 4
• 101000741014 Homo sapiens Caspase-7 Proteins 0.000 claims description 4
• 101000983528 Homo sapiens Caspase-8 Proteins 0.000 claims description 4
• 101000911074 Homo sapiens FAS-associated death domain protein Proteins 0.000 claims description 4
• 101001038755 Homo sapiens Guanylate cyclase soluble subunit alpha-1 Proteins 0.000 claims description 4
• 101001038749 Homo sapiens Guanylate cyclase soluble subunit alpha-2 Proteins 0.000 claims description 4
• 101001038731 Homo sapiens Guanylate cyclase soluble subunit beta-1 Proteins 0.000 claims description 4
• 101001059095 Homo sapiens Guanylate cyclase soluble subunit beta-2 Proteins 0.000 claims description 4
• 101000596925 Homo sapiens Homeobox protein TGIF1 Proteins 0.000 claims description 4
• 101001083151 Homo sapiens Interleukin-10 receptor subunit alpha Proteins 0.000 claims description 4
• 101001003149 Homo sapiens Interleukin-10 receptor subunit beta Proteins 0.000 claims description 4
• 101000599048 Homo sapiens Interleukin-6 receptor subunit alpha Proteins 0.000 claims description 4
• 101000599056 Homo sapiens Interleukin-6 receptor subunit beta Proteins 0.000 claims description 4
• 101001091194 Homo sapiens Peptidyl-prolyl cis-trans isomerase G Proteins 0.000 claims description 4
• 101000692259 Homo sapiens Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 Proteins 0.000 claims description 4
• 101001068027 Homo sapiens Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Proteins 0.000 claims description 4
• 101001068019 Homo sapiens Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform Proteins 0.000 claims description 4
• 101000863883 Homo sapiens Sialic acid-binding Ig-like lectin 9 Proteins 0.000 claims description 4
• 101000688930 Homo sapiens Signaling threshold-regulating transmembrane adapter 1 Proteins 0.000 claims description 4
• 101000688996 Homo sapiens Ski-like protein Proteins 0.000 claims description 4
• 101000740162 Homo sapiens Sodium- and chloride-dependent transporter XTRP3 Proteins 0.000 claims description 4
• 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 claims description 4
• 101001135589 Homo sapiens Tyrosine-protein phosphatase non-receptor type 22 Proteins 0.000 claims description 4
• 101000617285 Homo sapiens Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 claims description 4
• 102100030236 Interleukin-10 receptor subunit alpha Human genes 0.000 claims description 4
• 102100020788 Interleukin-10 receptor subunit beta Human genes 0.000 claims description 4
• 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 claims description 4
• 102100037795 Interleukin-6 receptor subunit beta Human genes 0.000 claims description 4
• 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 claims description 4
• 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 claims description 4
• 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 claims description 4
• 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 claims description 4
• 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 claims description 4
• 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 claims description 4
• 102100024894 PR domain zinc finger protein 1 Human genes 0.000 claims description 4
• 102100026066 Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 Human genes 0.000 claims description 4
• 108010009975 Positive Regulatory Domain I-Binding Factor 1 Proteins 0.000 claims description 4
• 102100034464 Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform Human genes 0.000 claims description 4
• 102100034470 Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform Human genes 0.000 claims description 4
• 102100024453 Signaling threshold-regulating transmembrane adapter 1 Human genes 0.000 claims description 4
• 102100029969 Ski oncogene Human genes 0.000 claims description 4
• 102100024451 Ski-like protein Human genes 0.000 claims description 4
• 101000987219 Sus scrofa Pregnancy-associated glycoprotein 1 Proteins 0.000 claims description 4
• 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 4
• 108091007178 TNFRSF10A Proteins 0.000 claims description 4
• 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 claims description 4
• 102100031167 Tyrosine-protein kinase CSK Human genes 0.000 claims description 4
• 102100033138 Tyrosine-protein phosphatase non-receptor type 22 Human genes 0.000 claims description 4
• 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 claims description 4
• 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 claims description 4
• 101000964894 Bos taurus 14-3-3 protein zeta/delta Proteins 0.000 claims description 3
• 101000809594 Escherichia coli (strain K12) Shikimate kinase 1 Proteins 0.000 claims description 3
• 102100028008 Heme oxygenase 2 Human genes 0.000 claims description 3
• 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 claims description 3
• 101001079615 Homo sapiens Heme oxygenase 2 Proteins 0.000 claims description 3
• 101000863882 Homo sapiens Sialic acid-binding Ig-like lectin 7 Proteins 0.000 claims description 3
• 101000863692 Homo sapiens Ski oncogene Proteins 0.000 claims description 3
• 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 claims description 3
• 101000922131 Homo sapiens Tyrosine-protein kinase CSK Proteins 0.000 claims description 3
• 101000926525 Homo sapiens eIF-2-alpha kinase GCN2 Proteins 0.000 claims description 3
• 102100029946 Sialic acid-binding Ig-like lectin 7 Human genes 0.000 claims description 3
• 102100029965 Sialic acid-binding Ig-like lectin 9 Human genes 0.000 claims description 3
• 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 claims description 3
• 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 claims description 3
• 102100034175 eIF-2-alpha kinase GCN2 Human genes 0.000 claims description 3
• 210000002443 helper t lymphocyte Anatomy 0.000 claims description 3
• 108010078791 Carrier Proteins Proteins 0.000 claims description 2
• 102100027581 Forkhead box protein P3 Human genes 0.000 claims description 2
• 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 2
• 230000001687 destabilization Effects 0.000 claims description 2
• 230000002757 inflammatory effect Effects 0.000 claims description 2
• 108010043655 penetratin Proteins 0.000 claims description 2
• MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical group C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 claims description 2
• 230000000149 penetrating effect Effects 0.000 claims description 2
• 108010011110 polyarginine Proteins 0.000 claims description 2
• 210000004896 polypeptide structure Anatomy 0.000 claims description 2
• 210000003289 regulatory T cell Anatomy 0.000 claims description 2
• 108010062760 transportan Proteins 0.000 claims description 2
• PBKWZFANFUTEPS-CWUSWOHSSA-N transportan Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(N)=O)[C@@H](C)CC)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CC=C(O)C=C1 PBKWZFANFUTEPS-CWUSWOHSSA-N 0.000 claims description 2
• 108020005345 3' Untranslated Regions Proteins 0.000 claims 1
• 108020003589 5' Untranslated Regions Proteins 0.000 claims 1
• 101710085003 Alpha-tubulin N-acetyltransferase Proteins 0.000 claims 1
• 101710085461 Alpha-tubulin N-acetyltransferase 1 Proteins 0.000 claims 1
• 102100024217 CAMPATH-1 antigen Human genes 0.000 claims 1
• 108091029865 Exogenous DNA Proteins 0.000 claims 1
• 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 claims 1
• 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 claims 1
• 101710175714 Tyrosine aminotransferase Proteins 0.000 claims 1
• 230000008488 polyadenylation Effects 0.000 claims 1
• 102000004533 Endonucleases Human genes 0.000 abstract description 20
• 208000036142 Viral infection Diseases 0.000 abstract description 10
• 230000009385 viral infection Effects 0.000 abstract description 9
• 230000003211 malignant effect Effects 0.000 abstract description 4
• 230000005965 immune activity Effects 0.000 abstract description 2
• 238000010354 CRISPR gene editing Methods 0.000 abstract 1
• 102000004169 proteins and genes Human genes 0.000 description 57
• 235000018102 proteins Nutrition 0.000 description 50
• 229920002477 rna polymer Polymers 0.000 description 50
• 102000053602 DNA Human genes 0.000 description 45
• 108091028043 Nucleic acid sequence Proteins 0.000 description 43
• 239000000427 antigen Substances 0.000 description 40
• 108091007433 antigens Proteins 0.000 description 40
• 102000036639 antigens Human genes 0.000 description 40
• 235000021251 pulses Nutrition 0.000 description 36
• 230000027455 binding Effects 0.000 description 30
• 235000001014 amino acid Nutrition 0.000 description 28
• 241000700605 Viruses Species 0.000 description 27
• 206010059866 Drug resistance Diseases 0.000 description 26
• 230000000670 limiting effect Effects 0.000 description 25
• 230000011664 signaling Effects 0.000 description 25
• 229940024606 amino acid Drugs 0.000 description 24
• 150000001413 amino acids Chemical class 0.000 description 23
• 230000000295 complement effect Effects 0.000 description 23
• 238000003776 cleavage reaction Methods 0.000 description 22
• 230000007017 scission Effects 0.000 description 22
• 125000003729 nucleotide group Chemical group 0.000 description 20
• 239000003446 ligand Substances 0.000 description 19
• 239000002773 nucleotide Substances 0.000 description 19
• 230000008685 targeting Effects 0.000 description 19
• 230000000694 effects Effects 0.000 description 18
• 230000001506 immunosuppresive effect Effects 0.000 description 18
• 108020001756 ligand binding domains Proteins 0.000 description 18
• 230000000735 allogeneic effect Effects 0.000 description 17
• 230000006870 function Effects 0.000 description 15
• 230000003612 virological effect Effects 0.000 description 15
• 102000013135 CD52 Antigen Human genes 0.000 description 14
• 239000003795 chemical substances by application Substances 0.000 description 14
• 230000002779 inactivation Effects 0.000 description 14
• 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 13
• 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 13
• 239000011324 bead Substances 0.000 description 13
• 230000000415 inactivating effect Effects 0.000 description 13
• 102000040430 polynucleotide Human genes 0.000 description 13
• 108091033319 polynucleotide Proteins 0.000 description 13
• 239000002157 polynucleotide Substances 0.000 description 13
• 102000005962 receptors Human genes 0.000 description 13
• 108020003175 receptors Proteins 0.000 description 13
• 241000282414 Homo sapiens Species 0.000 description 12
• 208000024908 graft versus host disease Diseases 0.000 description 12
• 210000002865 immune cell Anatomy 0.000 description 12
• 102000004631 Calcineurin Human genes 0.000 description 11
• 108010042955 Calcineurin Proteins 0.000 description 11
• 108091028113 Trans-activating crRNA Proteins 0.000 description 11
• 238000012546 transfer Methods 0.000 description 11
• 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 10
• 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 10
• 208000009329 Graft vs Host Disease Diseases 0.000 description 10
• 230000003197 catalytic effect Effects 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 108700018351 Major Histocompatibility Complex Proteins 0.000 description 9
• 108010022394 Threonine synthase Proteins 0.000 description 9
• 238000002512 chemotherapy Methods 0.000 description 9
• 102000004419 dihydrofolate reductase Human genes 0.000 description 9
• 238000012545 processing Methods 0.000 description 9
• 230000035755 proliferation Effects 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 238000006467 substitution reaction Methods 0.000 description 9
• 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 9
• 102000000588 Interleukin-2 Human genes 0.000 description 8
• 108010002350 Interleukin-2 Proteins 0.000 description 8
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 8
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 8
• 238000012217 deletion Methods 0.000 description 8
• 230000037430 deletion Effects 0.000 description 8
• 239000012634 fragment Substances 0.000 description 8
• 230000004927 fusion Effects 0.000 description 8
• 238000012239 gene modification Methods 0.000 description 8
• 238000010362 genome editing Methods 0.000 description 8
• 238000001727 in vivo Methods 0.000 description 8
• 239000003112 inhibitor Substances 0.000 description 8
• 230000036210 malignancy Effects 0.000 description 8
• 229960000485 methotrexate Drugs 0.000 description 8
• 239000000203 mixture Substances 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 210000000130 stem cell Anatomy 0.000 description 8
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 238000002560 therapeutic procedure Methods 0.000 description 8
• 238000001890 transfection Methods 0.000 description 8
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 7
• 108010036949 Cyclosporine Proteins 0.000 description 7
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 7
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 238000000684 flow cytometry Methods 0.000 description 7
• 230000005017 genetic modification Effects 0.000 description 7
• 235000013617 genetically modified food Nutrition 0.000 description 7
• 230000006780 non-homologous end joining Effects 0.000 description 7
• 239000002245 particle Substances 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 230000002463 transducing effect Effects 0.000 description 7
• 238000010361 transduction Methods 0.000 description 7
• 101001076642 Homo sapiens Inosine-5'-monophosphate dehydrogenase 2 Proteins 0.000 description 6
• 206010025323 Lymphomas Diseases 0.000 description 6
• 230000001086 cytosolic effect Effects 0.000 description 6
• 238000005516 engineering process Methods 0.000 description 6
• 239000000833 heterodimer Substances 0.000 description 6
• 238000003780 insertion Methods 0.000 description 6
• 230000037431 insertion Effects 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 230000001177 retroviral effect Effects 0.000 description 6
• 125000006850 spacer group Chemical group 0.000 description 6
• 230000026683 transduction Effects 0.000 description 6
• 239000013603 viral vector Substances 0.000 description 6
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
• 229930105110 Cyclosporin A Natural products 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 5
• 108090000695 Cytokines Proteins 0.000 description 5
• 102100025891 Inosine-5'-monophosphate dehydrogenase 2 Human genes 0.000 description 5
• 102100034343 Integrase Human genes 0.000 description 5
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 5
• 230000006044 T cell activation Effects 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 210000004369 blood Anatomy 0.000 description 5
• 239000008280 blood Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 210000000805 cytoplasm Anatomy 0.000 description 5
• 231100000433 cytotoxic Toxicity 0.000 description 5
• 230000001472 cytotoxic effect Effects 0.000 description 5
• 238000002716 delivery method Methods 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 239000012636 effector Substances 0.000 description 5
• 230000002616 endonucleolytic effect Effects 0.000 description 5
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 5
• 230000028993 immune response Effects 0.000 description 5
• 230000001939 inductive effect Effects 0.000 description 5
• 210000004698 lymphocyte Anatomy 0.000 description 5
• 239000011159 matrix material Substances 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 230000010076 replication Effects 0.000 description 5
• 150000003384 small molecules Chemical class 0.000 description 5
• 235000000346 sugar Nutrition 0.000 description 5
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 5
• 102000006306 Antigen Receptors Human genes 0.000 description 4
• 108010083359 Antigen Receptors Proteins 0.000 description 4
• 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 4
• 241000725303 Human immunodeficiency virus Species 0.000 description 4
• 108010061833 Integrases Proteins 0.000 description 4
• 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 4
• 241000699666 Mus <mouse, genus> Species 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• 206010039491 Sarcoma Diseases 0.000 description 4
• 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 4
• 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 210000003719 b-lymphocyte Anatomy 0.000 description 4
• 230000001580 bacterial effect Effects 0.000 description 4
• 210000001185 bone marrow Anatomy 0.000 description 4
• 238000004113 cell culture Methods 0.000 description 4
• 230000010261 cell growth Effects 0.000 description 4
• 210000000170 cell membrane Anatomy 0.000 description 4
• 239000012829 chemotherapy agent Substances 0.000 description 4
• 210000000349 chromosome Anatomy 0.000 description 4
• 229960001265 ciclosporin Drugs 0.000 description 4
• 238000005520 cutting process Methods 0.000 description 4
• 229930182912 cyclosporin Natural products 0.000 description 4
• 241001493065 dsRNA viruses Species 0.000 description 4
• 239000004052 folic acid antagonist Substances 0.000 description 4
• 230000030279 gene silencing Effects 0.000 description 4
• 230000036737 immune function Effects 0.000 description 4
• 238000011065 in-situ storage Methods 0.000 description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 208000032839 leukemia Diseases 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 230000004048 modification Effects 0.000 description 4
• 238000012986 modification Methods 0.000 description 4
• 238000004806 packaging method and process Methods 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
• 239000010452 phosphate Substances 0.000 description 4
• 235000021317 phosphate Nutrition 0.000 description 4
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 4
• 230000008439 repair process Effects 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 229960002930 sirolimus Drugs 0.000 description 4
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 4
• 239000000243 solution Substances 0.000 description 4
• 241000894007 species Species 0.000 description 4
• 230000001131 transforming effect Effects 0.000 description 4
• 241000701161 unidentified adenovirus Species 0.000 description 4
• 241001430294 unidentified retrovirus Species 0.000 description 4
• 101150013553 CD40 gene Proteins 0.000 description 3
• 102000001301 EGF receptor Human genes 0.000 description 3
• 108060006698 EGF receptor Proteins 0.000 description 3
• 108060002716 Exonuclease Proteins 0.000 description 3
• 108010087819 Fc receptors Proteins 0.000 description 3
• 102000009109 Fc receptors Human genes 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 101150046249 Havcr2 gene Proteins 0.000 description 3
• 101000836954 Homo sapiens Sialic acid-binding Ig-like lectin 10 Proteins 0.000 description 3
• 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 3
• 108091092195 Intron Proteins 0.000 description 3
• 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 description 3
• 102100025825 Methylated-DNA-protein-cysteine methyltransferase Human genes 0.000 description 3
• 108060004795 Methyltransferase Proteins 0.000 description 3
• KRWMERLEINMZFT-UHFFFAOYSA-N O6-benzylguanine Chemical compound C=12NC=NC2=NC(N)=NC=1OCC1=CC=CC=C1 KRWMERLEINMZFT-UHFFFAOYSA-N 0.000 description 3
• 102100027164 Sialic acid-binding Ig-like lectin 10 Human genes 0.000 description 3
• 241000700584 Simplexvirus Species 0.000 description 3
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 3
• 102000040945 Transcription factor Human genes 0.000 description 3
• 108091023040 Transcription factor Proteins 0.000 description 3
• 108700019146 Transgenes Proteins 0.000 description 3
• 102000008579 Transposases Human genes 0.000 description 3
• 108010020764 Transposases Proteins 0.000 description 3
• 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 3
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 3
• 239000012190 activator Substances 0.000 description 3
• 108010026331 alpha-Fetoproteins Proteins 0.000 description 3
• 102000013529 alpha-Fetoproteins Human genes 0.000 description 3
• 230000000259 anti-tumor effect Effects 0.000 description 3
• 210000000612 antigen-presenting cell Anatomy 0.000 description 3
• 239000002246 antineoplastic agent Substances 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 210000004899 c-terminal region Anatomy 0.000 description 3
• 101150038500 cas9 gene Proteins 0.000 description 3
• 125000002091 cationic group Chemical group 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 230000002759 chromosomal effect Effects 0.000 description 3
• 230000000139 costimulatory effect Effects 0.000 description 3
• 230000005684 electric field Effects 0.000 description 3
• 102000013165 exonuclease Human genes 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 230000001965 increasing effect Effects 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 230000010354 integration Effects 0.000 description 3
• 239000003550 marker Substances 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 201000001441 melanoma Diseases 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 108040008770 methylated-DNA-[protein]-cysteine S-methyltransferase activity proteins Proteins 0.000 description 3
• 201000006417 multiple sclerosis Diseases 0.000 description 3
• 230000002035 prolonged effect Effects 0.000 description 3
• 238000001959 radiotherapy Methods 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 210000002966 serum Anatomy 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 229960004964 temozolomide Drugs 0.000 description 3
• 231100000331 toxic Toxicity 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000002103 transcriptional effect Effects 0.000 description 3
• 230000009261 transgenic effect Effects 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• 230000003827 upregulation Effects 0.000 description 3
• 230000035899 viability Effects 0.000 description 3
• MXBUWHDMZGKTHK-INIZCTEOSA-N (2s)-2-[[4-[[(2-amino-4-oxo-1h-quinazolin-6-yl)amino]methyl]benzoyl]amino]pentanedioic acid Chemical compound C=1C=C2NC(N)=NC(=O)C2=CC=1NCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MXBUWHDMZGKTHK-INIZCTEOSA-N 0.000 description 2
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
• 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 2
• 108010013043 Acetylesterase Proteins 0.000 description 2
• 108700028369 Alleles Proteins 0.000 description 2
• 241000710929 Alphavirus Species 0.000 description 2
• 108010031480 Artificial Receptors Proteins 0.000 description 2
• 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 2
• 102100038080 B-cell receptor CD22 Human genes 0.000 description 2
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
• 102100038078 CD276 antigen Human genes 0.000 description 2
• 102100035793 CD83 antigen Human genes 0.000 description 2
• 108091079001 CRISPR RNA Proteins 0.000 description 2
• 238000010446 CRISPR interference Methods 0.000 description 2
• 238000010453 CRISPR/Cas method Methods 0.000 description 2
• 229940122739 Calcineurin inhibitor Drugs 0.000 description 2
• 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 description 2
• 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
• 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 229940123169 Caspase inhibitor Drugs 0.000 description 2
• 101150043916 Cd52 gene Proteins 0.000 description 2
• 241000711573 Coronaviridae Species 0.000 description 2
• 102100026280 Cryptochrome-2 Human genes 0.000 description 2
• 101710119767 Cryptochrome-2 Proteins 0.000 description 2
• 102000001493 Cyclophilins Human genes 0.000 description 2
• 108010068682 Cyclophilins Proteins 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• 241000701022 Cytomegalovirus Species 0.000 description 2
• 230000006820 DNA synthesis Effects 0.000 description 2
• 241000450599 DNA viruses Species 0.000 description 2
• 101710088194 Dehydrogenase Proteins 0.000 description 2
• 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
• 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
• 241000702421 Dependoparvovirus Species 0.000 description 2
• 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 2
• 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 2
• 108700024394 Exon Proteins 0.000 description 2
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
• 241000710831 Flavivirus Species 0.000 description 2
• 208000000666 Fowlpox Diseases 0.000 description 2
• 102100039554 Galectin-8 Human genes 0.000 description 2
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
• 241000941423 Grom virus Species 0.000 description 2
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
• 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 2
• 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 2
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
• 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 2
• 101000608769 Homo sapiens Galectin-8 Proteins 0.000 description 2
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
• 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 2
• 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 2
• 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 2
• 101000835093 Homo sapiens Transferrin receptor protein 1 Proteins 0.000 description 2
• 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 2
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
• 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 2
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
• 108060003951 Immunoglobulin Proteins 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 2
• 102100034872 Kallikrein-4 Human genes 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 241000713666 Lentivirus Species 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 102000003960 Ligases Human genes 0.000 description 2
• 108090000364 Ligases Proteins 0.000 description 2
• 108060001084 Luciferase Proteins 0.000 description 2
• 239000005089 Luciferase Substances 0.000 description 2
• 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 2
• 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 2
• 201000005505 Measles Diseases 0.000 description 2
• 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
• 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
• 102000018697 Membrane Proteins Human genes 0.000 description 2
• 108010052285 Membrane Proteins Proteins 0.000 description 2
• 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 2
• 102000011279 Multidrug resistance protein 1 Human genes 0.000 description 2
• 101100298534 Mus musculus Prnp gene Proteins 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• 241000714209 Norwalk virus Species 0.000 description 2
• 241000702244 Orthoreovirus Species 0.000 description 2
• 108091093037 Peptide nucleic acid Proteins 0.000 description 2
• 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 2
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 2
• 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 2
• 241000709664 Picornaviridae Species 0.000 description 2
• 108010076039 Polyproteins Proteins 0.000 description 2
• 108010029485 Protein Isoforms Proteins 0.000 description 2
• 102000001708 Protein Isoforms Human genes 0.000 description 2
• 102000001253 Protein Kinase Human genes 0.000 description 2
• 102000055027 Protein Methyltransferases Human genes 0.000 description 2
• 108700040121 Protein Methyltransferases Proteins 0.000 description 2
• 108010076504 Protein Sorting Signals Proteins 0.000 description 2
• 241000125945 Protoparvovirus Species 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 206010037742 Rabies Diseases 0.000 description 2
• 241000711798 Rabies lyssavirus Species 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 102000018120 Recombinases Human genes 0.000 description 2
• 108010091086 Recombinases Proteins 0.000 description 2
• 241000712907 Retroviridae Species 0.000 description 2
• 102000003661 Ribonuclease III Human genes 0.000 description 2
• 108010057163 Ribonuclease III Proteins 0.000 description 2
• 241000713675 Spumavirus Species 0.000 description 2
• 241000194020 Streptococcus thermophilus Species 0.000 description 2
• 108091027544 Subgenomic mRNA Proteins 0.000 description 2
• 102100035721 Syndecan-1 Human genes 0.000 description 2
• 230000006052 T cell proliferation Effects 0.000 description 2
• 108700042076 T-Cell Receptor alpha Genes Proteins 0.000 description 2
• 108700042077 T-Cell Receptor beta Genes Proteins 0.000 description 2
• 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 2
• 101710183280 Topoisomerase Proteins 0.000 description 2
• 102000004357 Transferases Human genes 0.000 description 2
• 108090000992 Transferases Proteins 0.000 description 2
• 102100026144 Transferrin receptor protein 1 Human genes 0.000 description 2
• 206010052779 Transplant rejections Diseases 0.000 description 2
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
• 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 2
• 206010046865 Vaccinia virus infection Diseases 0.000 description 2
• 241000711975 Vesicular stomatitis virus Species 0.000 description 2
• 238000010317 ablation therapy Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 2
• 229960000548 alemtuzumab Drugs 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
• 230000003432 anti-folate effect Effects 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 230000006023 anti-tumor response Effects 0.000 description 2
• 229940127074 antifolate Drugs 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 239000003972 antineoplastic antibiotic Substances 0.000 description 2
• 235000009697 arginine Nutrition 0.000 description 2
• 230000003190 augmentative effect Effects 0.000 description 2
• 208000004668 avian leukosis Diseases 0.000 description 2
• 101150038738 ble gene Proteins 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 229940112129 campath Drugs 0.000 description 2
• 238000002659 cell therapy Methods 0.000 description 2
• 230000033077 cellular process Effects 0.000 description 2
• 229940044683 chemotherapy drug Drugs 0.000 description 2
• 230000003750 conditioning effect Effects 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 238000012937 correction Methods 0.000 description 2
• 239000003246 corticosteroid Substances 0.000 description 2
• 210000005220 cytoplasmic tail Anatomy 0.000 description 2
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
• 229940127089 cytotoxic agent Drugs 0.000 description 2
• 230000003013 cytotoxicity Effects 0.000 description 2
• 231100000135 cytotoxicity Toxicity 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 239000000412 dendrimer Substances 0.000 description 2
• 229920000736 dendritic polymer Polymers 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 238000006471 dimerization reaction Methods 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 210000004700 fetal blood Anatomy 0.000 description 2
• 229940126864 fibroblast growth factor Drugs 0.000 description 2
• 108091006047 fluorescent proteins Proteins 0.000 description 2
• 102000034287 fluorescent proteins Human genes 0.000 description 2
• 229940014144 folate Drugs 0.000 description 2
• OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical class 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 2
• 235000019152 folic acid Nutrition 0.000 description 2
• 239000011724 folic acid Substances 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 108700004026 gag Genes Proteins 0.000 description 2
• 238000001476 gene delivery Methods 0.000 description 2
• 238000003209 gene knockout Methods 0.000 description 2
• 238000001415 gene therapy Methods 0.000 description 2
• 238000010353 genetic engineering Methods 0.000 description 2
• 230000030414 genetic transfer Effects 0.000 description 2
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
• 208000006454 hepatitis Diseases 0.000 description 2
• 231100000283 hepatitis Toxicity 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 230000005931 immune cell recruitment Effects 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 102000018358 immunoglobulin Human genes 0.000 description 2
• 238000002650 immunosuppressive therapy Methods 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• 230000017730 intein-mediated protein splicing Effects 0.000 description 2
• 230000004068 intracellular signaling Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
• 229960000310 isoleucine Drugs 0.000 description 2
• 238000005304 joining Methods 0.000 description 2
• 108010024383 kallikrein 4 Proteins 0.000 description 2
• 101150066555 lacZ gene Proteins 0.000 description 2
• 108010025001 leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 2
• 235000018977 lysine Nutrition 0.000 description 2
• 101150023497 mcrA gene Proteins 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 210000003470 mitochondria Anatomy 0.000 description 2
• 238000010369 molecular cloning Methods 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 238000002703 mutagenesis Methods 0.000 description 2
• 231100000350 mutagenesis Toxicity 0.000 description 2
• 229960004866 mycophenolate mofetil Drugs 0.000 description 2
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 2
• HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 2
• 239000002105 nanoparticle Substances 0.000 description 2
• 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 2
• 210000004940 nucleus Anatomy 0.000 description 2
• 230000009437 off-target effect Effects 0.000 description 2
• 210000003463 organelle Anatomy 0.000 description 2
• 230000005298 paramagnetic effect Effects 0.000 description 2
• 108700004029 pol Genes Proteins 0.000 description 2
• 238000003752 polymerase chain reaction Methods 0.000 description 2
• 231100000683 possible toxicity Toxicity 0.000 description 2
• 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 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 108020001580 protein domains Proteins 0.000 description 2
• 108060006633 protein kinase Proteins 0.000 description 2
• 150000003212 purines Chemical class 0.000 description 2
• 150000003230 pyrimidines Chemical class 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 230000006798 recombination Effects 0.000 description 2
• 238000005215 recombination Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 108091008146 restriction endonucleases Proteins 0.000 description 2
• 238000010839 reverse transcription Methods 0.000 description 2
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 229960001967 tacrolimus Drugs 0.000 description 2
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
• 229960003087 tioguanine Drugs 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 108091006106 transcriptional activators Proteins 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 241001529453 unidentified herpesvirus Species 0.000 description 2
• 241000712461 unidentified influenza virus Species 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 208000007089 vaccinia Diseases 0.000 description 2
• 230000010464 virion assembly Effects 0.000 description 2
• 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
• 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 1
• 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 description 1
• 102000002627 4-1BB Ligand Human genes 0.000 description 1
• 108010082808 4-1BB Ligand Proteins 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
• ZUQBAQVRAURMCL-SWLSCSKDSA-N 5,10-dideazatetrahydrofolic acid Chemical compound C([C@H]1CC=2C(=O)N=C(NC=2NC1)N)CC1=CC=C(C(=O)N[C@H](CCC(O)=O)C(O)=O)C=C1 ZUQBAQVRAURMCL-SWLSCSKDSA-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
• 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
• 208000026872 Addison Disease Diseases 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
• 101800002011 Amphipathic peptide Proteins 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 108700031308 Antennapedia Homeodomain Proteins 0.000 description 1
• 108700042778 Antimicrobial Peptides Proteins 0.000 description 1
• 102000044503 Antimicrobial Peptides Human genes 0.000 description 1
• 101100279855 Arabidopsis thaliana EPFL5 gene Proteins 0.000 description 1
• 101100484243 Arabidopsis thaliana UVR8 gene Proteins 0.000 description 1
• 241000203069 Archaea Species 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003445 Ascites Diseases 0.000 description 1
• 101001093708 Autographa californica nuclear polyhedrosis virus Per os infectivity factor 6 Proteins 0.000 description 1
• 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 102100026094 C-type lectin domain family 12 member A Human genes 0.000 description 1
• 102100027207 CD27 antigen Human genes 0.000 description 1
• 102100025221 CD70 antigen Human genes 0.000 description 1
• 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
• 101150031358 COLEC10 gene Proteins 0.000 description 1
• 108060001826 COP1 Proteins 0.000 description 1
• 102100032216 Calcium and integrin-binding protein 1 Human genes 0.000 description 1
• 102000000584 Calmodulin Human genes 0.000 description 1
• 108010041952 Calmodulin Proteins 0.000 description 1
• 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
• 108010051152 Carboxylesterase Proteins 0.000 description 1
• 102000013392 Carboxylesterase Human genes 0.000 description 1
• 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 1
• 102100025634 Caspase recruitment domain-containing protein 16 Human genes 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
• 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
• VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 description 1
• 108020004638 Circular DNA Proteins 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 108010073254 Colicins Proteins 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 101710095468 Cyclase Proteins 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 241001044073 Cypa Species 0.000 description 1
• 102000013816 Cytotoxic T-lymphocyte antigen 4 Human genes 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 230000033616 DNA repair Effects 0.000 description 1
• 230000007018 DNA scission Effects 0.000 description 1
• 102000052510 DNA-Binding Proteins Human genes 0.000 description 1
• 108700020911 DNA-Binding Proteins Proteins 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 101150029707 ERBB2 gene Proteins 0.000 description 1
• 102100037241 Endoglin Human genes 0.000 description 1
• 108010036395 Endoglin Proteins 0.000 description 1
• 102100023721 Ephrin-B2 Human genes 0.000 description 1
• 108010044090 Ephrin-B2 Proteins 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 102100031507 Fc receptor-like protein 5 Human genes 0.000 description 1
• 101150032879 Fcrl5 gene Proteins 0.000 description 1
• 208000001640 Fibromyalgia Diseases 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 102000016359 Fibronectins Human genes 0.000 description 1
• YPINZEGNLULHHT-UHFFFAOYSA-N Fujimycin Natural products COC1CC(CCC1O)C=C(/C)C2OC(=O)C3CCCCCN3C(=O)C(=O)C4(O)OC(C(CC4C)OC)C(OC)C(C)CC(=CC(CC=C)C(=O)CC(O)C2C)C YPINZEGNLULHHT-UHFFFAOYSA-N 0.000 description 1
• 102100021197 G-protein coupled receptor family C group 5 member D Human genes 0.000 description 1
• 101150106478 GPS1 gene Proteins 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100028113 Granulocyte-macrophage colony-stimulating factor receptor subunit alpha Human genes 0.000 description 1
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
• HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical group 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 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 1
• 108010024164 HLA-G Antigens Proteins 0.000 description 1
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
• 108091027305 Heteroduplex Proteins 0.000 description 1
• 102100022132 High affinity immunoglobulin epsilon receptor subunit gamma Human genes 0.000 description 1
• 108091010847 High affinity immunoglobulin epsilon receptor subunit gamma 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
• 241000282412 Homo Species 0.000 description 1
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 1
• 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
• 101100496086 Homo sapiens CLEC12A gene Proteins 0.000 description 1
• 101000741445 Homo sapiens Calcitonin Proteins 0.000 description 1
• 101000943475 Homo sapiens Calcium and integrin-binding protein 1 Proteins 0.000 description 1
• 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
• 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 1
• 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 1
• 101000744174 Homo sapiens DNA-3-methyladenine glycosylase Proteins 0.000 description 1
• 101001040713 Homo sapiens G-protein coupled receptor family C group 5 member D Proteins 0.000 description 1
• 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 1
• 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
• 101000916625 Homo sapiens Granulocyte-macrophage colony-stimulating factor receptor subunit alpha Proteins 0.000 description 1
• 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
• 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
• 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 description 1
• 101000994322 Homo sapiens Integrin alpha-8 Proteins 0.000 description 1
• 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
• 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
• 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 1
• 101000984189 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 2 Proteins 0.000 description 1
• 101000984186 Homo sapiens Leukocyte immunoglobulin-like receptor subfamily B member 4 Proteins 0.000 description 1
• 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
• 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
• 101001014223 Homo sapiens MAPK/MAK/MRK overlapping kinase Proteins 0.000 description 1
• 101001008874 Homo sapiens Mast/stem cell growth factor receptor Kit Proteins 0.000 description 1
• 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
• 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 1
• 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 description 1
• 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 description 1
• 101000891028 Homo sapiens Peptidyl-prolyl cis-trans isomerase FKBP11 Proteins 0.000 description 1
• 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 1
• 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 1
• 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
• 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 1
• 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
• 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
• 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 1
• 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 1
• 101100207070 Homo sapiens TNFSF8 gene Proteins 0.000 description 1
• 101000655352 Homo sapiens Telomerase reverse transcriptase Proteins 0.000 description 1
• 101000711846 Homo sapiens Transcription factor SOX-9 Proteins 0.000 description 1
• 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 description 1
• 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
• 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
• 101710203526 Integrase Proteins 0.000 description 1
• 102000012330 Integrases Human genes 0.000 description 1
• 102100032825 Integrin alpha-8 Human genes 0.000 description 1
• 102000008607 Integrin beta3 Human genes 0.000 description 1
• 108010020950 Integrin beta3 Proteins 0.000 description 1
• 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
• 102000003814 Interleukin-10 Human genes 0.000 description 1
• 108090000174 Interleukin-10 Proteins 0.000 description 1
• 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 108020003285 Isocitrate lyase Proteins 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• STECJAGHUSJQJN-USLFZFAMSA-N LSM-4015 Chemical compound C1([C@@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-USLFZFAMSA-N 0.000 description 1
• 101710128836 Large T antigen Proteins 0.000 description 1
• 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
• 108010028275 Leukocyte Elastase Proteins 0.000 description 1
• 102100025583 Leukocyte immunoglobulin-like receptor subfamily B member 2 Human genes 0.000 description 1
• 102100025578 Leukocyte immunoglobulin-like receptor subfamily B member 4 Human genes 0.000 description 1
• 241000186805 Listeria innocua Species 0.000 description 1
• 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
• 102000018170 Lymphotoxin beta Receptor Human genes 0.000 description 1
• 108010091221 Lymphotoxin beta Receptor Proteins 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 102100031520 MAPK/MAK/MRK overlapping kinase Human genes 0.000 description 1
• 102100030301 MHC class I polypeptide-related sequence A Human genes 0.000 description 1
• 239000007993 MOPS buffer Substances 0.000 description 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
• 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
• 108090000015 Mesothelin Proteins 0.000 description 1
• 102000003735 Mesothelin Human genes 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 102000016397 Methyltransferase Human genes 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101000687343 Mus musculus PR domain zinc finger protein 1 Proteins 0.000 description 1
• 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 1
• 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
• 101100368144 Mus musculus Synb gene Proteins 0.000 description 1
• 101100207071 Mus musculus Tnfsf8 gene Proteins 0.000 description 1
• 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 1
• 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 description 1
• 102100033174 Neutrophil elastase Human genes 0.000 description 1
• 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
• 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
• 101800001014 Non-structural protein 5A Proteins 0.000 description 1
• 101710153660 Nuclear receptor corepressor 2 Proteins 0.000 description 1
• 102000002488 Nucleoplasmin Human genes 0.000 description 1
• 102000004473 OX40 Ligand Human genes 0.000 description 1
• 108010042215 OX40 Ligand Proteins 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 208000030852 Parasitic disease Diseases 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 108010088535 Pep-1 peptide Proteins 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 108010033276 Peptide Fragments Proteins 0.000 description 1
• 102000007079 Peptide Fragments Human genes 0.000 description 1
• 102100040348 Peptidyl-prolyl cis-trans isomerase FKBP11 Human genes 0.000 description 1
• 108010067965 Phytochrome B Proteins 0.000 description 1
• 102000052376 Piwi domains Human genes 0.000 description 1
• 108700038049 Piwi domains Proteins 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 208000002151 Pleural effusion Diseases 0.000 description 1
• 206010036030 Polyarthritis Diseases 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
• 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 102100040120 Prominin-1 Human genes 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102000003923 Protein Kinase C Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
• 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
• 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
• 108010083644 Ribonucleases Proteins 0.000 description 1
• 102000006382 Ribonucleases Human genes 0.000 description 1
• 102100029198 SLAM family member 7 Human genes 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 238000012300 Sequence Analysis Methods 0.000 description 1
• 101710189648 Serine/threonine-protein phosphatase Proteins 0.000 description 1
• 102100038081 Signal transducer CD24 Human genes 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 102100037253 Solute carrier family 45 member 3 Human genes 0.000 description 1
• 230000005867 T cell response Effects 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
• 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
• 101710192266 Tegument protein VP22 Proteins 0.000 description 1
• 108010017842 Telomerase Proteins 0.000 description 1
• 102000007000 Tenascin Human genes 0.000 description 1
• 108010008125 Tenascin Proteins 0.000 description 1
• 108091036066 Three prime untranslated region Proteins 0.000 description 1
• 108010034949 Thyroglobulin Proteins 0.000 description 1
• 102000009843 Thyroglobulin Human genes 0.000 description 1
• 102100034204 Transcription factor SOX-9 Human genes 0.000 description 1
• 101710195626 Transcriptional activator protein Proteins 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• 101800000385 Transmembrane protein Proteins 0.000 description 1
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
• 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 1
• 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
• 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 108020005202 Viral DNA Proteins 0.000 description 1
• 108020000999 Viral RNA Proteins 0.000 description 1
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 210000005006 adaptive immune system Anatomy 0.000 description 1
• 230000002730 additional effect Effects 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 210000004504 adult stem cell Anatomy 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000011543 agarose gel Substances 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 230000000961 alloantigen Effects 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 229960003896 aminopterin Drugs 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000845 anti-microbial effect Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 238000009175 antibody therapy Methods 0.000 description 1
• 229940034982 antineoplastic agent Drugs 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 238000003491 array Methods 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 239000002551 biofuel Substances 0.000 description 1
• 230000008436 biogenesis Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 201000000053 blastoma Diseases 0.000 description 1
• OYVAGSVQBOHSSS-WXFSZRTFSA-O bleomycin Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](OC1C(C(O)C(O)C(CO)O1)OC1C(C(OC(N)=O)C(O)C(CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-WXFSZRTFSA-O 0.000 description 1
• 239000010836 blood and blood product Substances 0.000 description 1
• 229940125691 blood product Drugs 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 238000010504 bond cleavage reaction Methods 0.000 description 1
• 238000010322 bone marrow transplantation Methods 0.000 description 1
• 229960005520 bryostatin Drugs 0.000 description 1
• MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
• MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
• 108010040767 buforin I Proteins 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 239000003710 calcium ionophore Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 108020001778 catalytic domains Proteins 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 230000005859 cell recognition Effects 0.000 description 1
• 239000002458 cell surface marker Substances 0.000 description 1
• 230000004637 cellular stress Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000010382 chemical cross-linking Methods 0.000 description 1
• 230000007073 chemical hydrolysis Effects 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
• 208000012191 childhood neoplasm Diseases 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• 229960000724 cidofovir Drugs 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 230000004186 co-expression Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 150000001875 compounds Chemical class 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 102000003675 cytokine receptors Human genes 0.000 description 1
• 108010057085 cytokine receptors Proteins 0.000 description 1
• 230000001461 cytolytic effect Effects 0.000 description 1
• 229940104302 cytosine Drugs 0.000 description 1
• 210000000172 cytosol Anatomy 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 230000001085 cytostatic effect Effects 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 230000030609 dephosphorylation Effects 0.000 description 1
• 238000006209 dephosphorylation reaction Methods 0.000 description 1
• 230000000779 depleting effect Effects 0.000 description 1
• 230000000368 destabilizing effect Effects 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 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 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 125000002228 disulfide group Chemical group 0.000 description 1
• 230000005782 double-strand break Effects 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 239000002961 echo contrast media Substances 0.000 description 1
• 230000005014 ectopic expression Effects 0.000 description 1
• FSIRXIHZBIXHKT-MHTVFEQDSA-N edatrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CC(CC)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FSIRXIHZBIXHKT-MHTVFEQDSA-N 0.000 description 1
• 229950006700 edatrexate Drugs 0.000 description 1
• 201000008184 embryoma Diseases 0.000 description 1
• 210000001671 embryonic stem cell Anatomy 0.000 description 1
• 230000012202 endocytosis Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000007071 enzymatic hydrolysis Effects 0.000 description 1
• 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
• 210000000267 erythroid cell Anatomy 0.000 description 1
• 230000000925 erythroid effect Effects 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 238000002710 external beam radiation therapy Methods 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 229960000390 fludarabine Drugs 0.000 description 1
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
• 150000002224 folic acids Chemical class 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 238000010230 functional analysis Methods 0.000 description 1
• 238000010363 gene targeting Methods 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 150000002339 glycosphingolipids Chemical class 0.000 description 1
• 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000009931 harmful effect Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 238000001794 hormone therapy Methods 0.000 description 1
• 102000056799 human IMPDH2 Human genes 0.000 description 1
• 229940045644 human calcitonin Drugs 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 210000001822 immobilized cell Anatomy 0.000 description 1
• 230000006450 immune cell response Effects 0.000 description 1
• 229940126546 immune checkpoint molecule Drugs 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 230000037189 immune system physiology Effects 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 229940124589 immunosuppressive drug Drugs 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
• 210000002602 induced regulatory T cell Anatomy 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 235000013902 inosinic acid Nutrition 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
• PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 239000003287 lymphocyte surface marker Substances 0.000 description 1
• 208000003747 lymphoid leukemia Diseases 0.000 description 1
• 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 230000005291 magnetic effect Effects 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000037353 metabolic pathway Effects 0.000 description 1
• 239000010445 mica Substances 0.000 description 1
• 229910052618 mica group Inorganic materials 0.000 description 1
• HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
• 238000012737 microarray-based gene expression Methods 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 238000012243 multiplex automated genomic engineering Methods 0.000 description 1
• 229940014456 mycophenolate Drugs 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
• 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 1
• 231100000804 nongenotoxic Toxicity 0.000 description 1
• 210000004492 nuclear pore Anatomy 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• 230000001293 nucleolytic effect Effects 0.000 description 1
• 108060005597 nucleoplasmin Proteins 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 238000002515 oligonucleotide synthesis Methods 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 230000008823 permeabilization Effects 0.000 description 1
• 108091008695 photoreceptors Proteins 0.000 description 1
• 238000001126 phototherapy Methods 0.000 description 1
• 238000000053 physical method Methods 0.000 description 1
• 229950001030 piritrexim Drugs 0.000 description 1
• 108010058237 plasma protein fraction Proteins 0.000 description 1
• 229940002993 plasmanate Drugs 0.000 description 1
• 239000013600 plasmid vector Substances 0.000 description 1
• 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 1
• 208000030428 polyarticular arthritis Diseases 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 108010079891 prostein Proteins 0.000 description 1
• 239000002213 purine nucleotide Substances 0.000 description 1
• 239000002719 pyrimidine nucleotide Substances 0.000 description 1
• 238000002708 random mutagenesis Methods 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 230000029610 recognition of host Effects 0.000 description 1
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
• 230000003252 repetitive effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 210000003660 reticulum Anatomy 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• 229960003452 romidepsin Drugs 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000001235 sensitizing effect Effects 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 230000009131 signaling function Effects 0.000 description 1
• 229940054269 sodium pyruvate Drugs 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 230000010473 stable expression Effects 0.000 description 1
• 238000011272 standard treatment Methods 0.000 description 1
• 238000011476 stem cell transplantation Methods 0.000 description 1
• 239000003270 steroid hormone Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 108010066762 sweet arrow peptide Proteins 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 101150047061 tag-72 gene Proteins 0.000 description 1
• 229950010127 teplizumab Drugs 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 239000005460 tetrahydrofolate Substances 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
• 150000003573 thiols Chemical class 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229940113082 thymine Drugs 0.000 description 1
• 210000001541 thymus gland Anatomy 0.000 description 1
• 229960002175 thyroglobulin Drugs 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 230000019432 tissue death Effects 0.000 description 1
• 210000003014 totipotent stem cell Anatomy 0.000 description 1
• 230000005029 transcription elongation Effects 0.000 description 1
• 238000003151 transfection method Methods 0.000 description 1
• 238000003146 transient transfection Methods 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 238000011277 treatment modality Methods 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
• 229960001099 trimetrexate Drugs 0.000 description 1
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
• 231100000588 tumorigenic Toxicity 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 108020005087 unfolded proteins Proteins 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 210000000605 viral structure Anatomy 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1