AU2020383021A1 - Renal cell carcinoma (RCC) therapy using genetically engineered T cells targeting CD70 - Google Patents
Renal cell carcinoma (RCC) therapy using genetically engineered T cells targeting CD70 Download PDFInfo
- Publication number
- AU2020383021A1 AU2020383021A1 AU2020383021A AU2020383021A AU2020383021A1 AU 2020383021 A1 AU2020383021 A1 AU 2020383021A1 AU 2020383021 A AU2020383021 A AU 2020383021A AU 2020383021 A AU2020383021 A AU 2020383021A AU 2020383021 A1 AU2020383021 A1 AU 2020383021A1
- Authority
- AU
- Australia
- Prior art keywords
- cells
- car
- dose
- ctx130
- human patient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 304
- 208000006265 Renal cell carcinoma Diseases 0.000 title claims abstract description 127
- 102100025221 CD70 antigen Human genes 0.000 title claims abstract 6
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 title claims abstract 6
- 238000002560 therapeutic procedure Methods 0.000 title claims description 29
- 230000008685 targeting Effects 0.000 title description 26
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 314
- 238000011282 treatment Methods 0.000 claims abstract description 127
- 238000000034 method Methods 0.000 claims abstract description 118
- 210000004027 cell Anatomy 0.000 claims description 436
- 206010028980 Neoplasm Diseases 0.000 claims description 113
- 238000001802 infusion Methods 0.000 claims description 109
- 206010052015 cytokine release syndrome Diseases 0.000 claims description 103
- 108090000623 proteins and genes Proteins 0.000 claims description 101
- 108020005004 Guide RNA Proteins 0.000 claims description 92
- 108091033409 CRISPR Proteins 0.000 claims description 61
- 230000004044 response Effects 0.000 claims description 61
- 102100029452 T cell receptor alpha chain constant Human genes 0.000 claims description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 57
- 201000010099 disease Diseases 0.000 claims description 54
- 230000007135 neurotoxicity Effects 0.000 claims description 42
- 125000006850 spacer group Chemical group 0.000 claims description 42
- 231100000228 neurotoxicity Toxicity 0.000 claims description 41
- 231100000371 dose-limiting toxicity Toxicity 0.000 claims description 40
- 239000002773 nucleotide Substances 0.000 claims description 40
- 230000000694 effects Effects 0.000 claims description 38
- 125000003729 nucleotide group Chemical group 0.000 claims description 38
- 230000001988 toxicity Effects 0.000 claims description 38
- 231100000419 toxicity Toxicity 0.000 claims description 38
- 206010044221 Toxic encephalopathy Diseases 0.000 claims description 36
- 201000011510 cancer Diseases 0.000 claims description 34
- 208000015181 infectious disease Diseases 0.000 claims description 33
- 206010029350 Neurotoxicity Diseases 0.000 claims description 29
- 238000010362 genome editing Methods 0.000 claims description 29
- 101150088890 CD70 gene Proteins 0.000 claims description 26
- 230000001154 acute effect Effects 0.000 claims description 25
- 206010045170 Tumour lysis syndrome Diseases 0.000 claims description 24
- 208000010380 tumor lysis syndrome Diseases 0.000 claims description 24
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 19
- 230000001394 metastastic effect Effects 0.000 claims description 18
- 238000011161 development Methods 0.000 claims description 17
- 230000018109 developmental process Effects 0.000 claims description 17
- 238000012217 deletion Methods 0.000 claims description 16
- 230000037430 deletion Effects 0.000 claims description 16
- 210000000056 organ Anatomy 0.000 claims description 16
- 208000001953 Hypotension Diseases 0.000 claims description 15
- 230000036543 hypotension Effects 0.000 claims description 15
- 230000011664 signaling Effects 0.000 claims description 15
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 14
- 239000012642 immune effector Substances 0.000 claims description 14
- 229940121354 immunomodulator Drugs 0.000 claims description 14
- 230000007059 acute toxicity Effects 0.000 claims description 13
- 231100000403 acute toxicity Toxicity 0.000 claims description 13
- 229960000390 fludarabine Drugs 0.000 claims description 13
- 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 claims description 13
- 210000003169 central nervous system Anatomy 0.000 claims description 12
- 230000036961 partial effect Effects 0.000 claims description 12
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 11
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 11
- 229960004397 cyclophosphamide Drugs 0.000 claims description 11
- 230000036210 malignancy Effects 0.000 claims description 11
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 10
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 10
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 10
- 238000011319 anticancer therapy Methods 0.000 claims description 10
- 206010003119 arrhythmia Diseases 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 230000003092 anti-cytokine Effects 0.000 claims description 9
- 210000001185 bone marrow Anatomy 0.000 claims description 9
- 230000024245 cell differentiation Effects 0.000 claims description 9
- 230000006052 T cell proliferation Effects 0.000 claims description 8
- 238000012544 monitoring process Methods 0.000 claims description 8
- 210000000963 osteoblast Anatomy 0.000 claims description 8
- 238000002054 transplantation Methods 0.000 claims description 8
- 229940124572 antihypotensive agent Drugs 0.000 claims description 7
- 210000004185 liver Anatomy 0.000 claims description 7
- 230000000153 supplemental effect Effects 0.000 claims description 7
- 239000005526 vasoconstrictor agent Substances 0.000 claims description 7
- 238000002659 cell therapy Methods 0.000 claims description 6
- 210000000981 epithelium Anatomy 0.000 claims description 6
- 206010003445 Ascites Diseases 0.000 claims description 5
- 230000001086 cytosolic effect Effects 0.000 claims description 5
- 210000000822 natural killer cell Anatomy 0.000 claims description 5
- 230000004768 organ dysfunction Effects 0.000 claims description 5
- 206010002388 Angina unstable Diseases 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 4
- 208000002151 Pleural effusion Diseases 0.000 claims description 4
- 208000007814 Unstable Angina Diseases 0.000 claims description 4
- 230000006793 arrhythmia Effects 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 238000002650 immunosuppressive therapy Methods 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- 108700026220 vif Genes Proteins 0.000 claims description 4
- 241000411851 herbal medicine Species 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 3
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 3
- 229960005486 vaccine Drugs 0.000 claims description 3
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 239000003102 growth factor Substances 0.000 claims description 2
- 101710153660 Nuclear receptor corepressor 2 Proteins 0.000 claims 4
- 238000010354 CRISPR gene editing Methods 0.000 claims 3
- 230000006444 vascular growth Effects 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 5
- 208000015347 renal cell adenocarcinoma Diseases 0.000 abstract 2
- 101000634853 Homo sapiens T cell receptor alpha chain constant Proteins 0.000 description 88
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 84
- 230000003902 lesion Effects 0.000 description 70
- 208000024891 symptom Diseases 0.000 description 58
- 238000002512 chemotherapy Methods 0.000 description 57
- 208000009329 Graft vs Host Disease Diseases 0.000 description 47
- 208000024908 graft versus host disease Diseases 0.000 description 47
- 238000004458 analytical method Methods 0.000 description 39
- 238000012216 screening Methods 0.000 description 39
- 210000004369 blood Anatomy 0.000 description 33
- 239000008280 blood Substances 0.000 description 33
- 239000000427 antigen Substances 0.000 description 32
- 108091007433 antigens Proteins 0.000 description 32
- 102000036639 antigens Human genes 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 32
- 108091027544 Subgenomic mRNA Proteins 0.000 description 31
- 108091008874 T cell receptors Proteins 0.000 description 31
- 235000018102 proteins Nutrition 0.000 description 31
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 30
- 150000007523 nucleic acids Chemical class 0.000 description 30
- 238000002591 computed tomography Methods 0.000 description 27
- 230000014509 gene expression Effects 0.000 description 27
- 241000699670 Mus sp. Species 0.000 description 26
- 108020004707 nucleic acids Proteins 0.000 description 26
- 102000039446 nucleic acids Human genes 0.000 description 26
- 238000007920 subcutaneous administration Methods 0.000 description 25
- 108020004414 DNA Proteins 0.000 description 24
- 238000007726 management method Methods 0.000 description 24
- 238000001574 biopsy Methods 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 23
- 230000034994 death Effects 0.000 description 23
- 231100000517 death Toxicity 0.000 description 23
- 238000002595 magnetic resonance imaging Methods 0.000 description 23
- 102000004127 Cytokines Human genes 0.000 description 22
- 108090000695 Cytokines Proteins 0.000 description 22
- 230000000735 allogeneic effect Effects 0.000 description 22
- 239000003814 drug Substances 0.000 description 22
- 238000011156 evaluation Methods 0.000 description 22
- 239000012634 fragment Substances 0.000 description 22
- 238000011357 CAR T-cell therapy Methods 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- 239000008194 pharmaceutical composition Substances 0.000 description 19
- 229940079593 drug Drugs 0.000 description 18
- 208000036066 Hemophagocytic Lymphohistiocytosis Diseases 0.000 description 17
- 208000032672 Histiocytosis haematophagic Diseases 0.000 description 17
- 208000014752 hemophagocytic syndrome Diseases 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- 208000030808 Clear cell renal carcinoma Diseases 0.000 description 15
- 206010061818 Disease progression Diseases 0.000 description 15
- 206010037660 Pyrexia Diseases 0.000 description 15
- 230000002411 adverse Effects 0.000 description 15
- 230000005750 disease progression Effects 0.000 description 15
- 230000002496 gastric effect Effects 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 230000022534 cell killing Effects 0.000 description 13
- 230000009850 completed effect Effects 0.000 description 13
- 239000000306 component Substances 0.000 description 13
- 238000002483 medication Methods 0.000 description 13
- 230000002688 persistence Effects 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 102100020870 La-related protein 6 Human genes 0.000 description 12
- 108050008265 La-related protein 6 Proteins 0.000 description 12
- 102000018697 Membrane Proteins Human genes 0.000 description 12
- 108010052285 Membrane Proteins Proteins 0.000 description 12
- 101710163270 Nuclease Proteins 0.000 description 12
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 12
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 12
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 12
- 108010002350 Interleukin-2 Proteins 0.000 description 11
- 102000000588 Interleukin-2 Human genes 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 11
- -1 coatings Substances 0.000 description 11
- 230000005782 double-strand break Effects 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 11
- 230000028327 secretion Effects 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 230000000747 cardiac effect Effects 0.000 description 10
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 10
- 230000007774 longterm Effects 0.000 description 10
- 208000037821 progressive disease Diseases 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 230000004614 tumor growth Effects 0.000 description 10
- 238000010453 CRISPR/Cas method Methods 0.000 description 9
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 9
- KYIKRXIYLAGAKQ-UHFFFAOYSA-N abcn Chemical compound C1CCCCC1(C#N)N=NC1(C#N)CCCCC1 KYIKRXIYLAGAKQ-UHFFFAOYSA-N 0.000 description 9
- 239000000090 biomarker Substances 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000009593 lumbar puncture Methods 0.000 description 9
- 210000004698 lymphocyte Anatomy 0.000 description 9
- 238000011160 research Methods 0.000 description 9
- 210000002966 serum Anatomy 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
- 108010074051 C-Reactive Protein Proteins 0.000 description 8
- 102100032752 C-reactive protein Human genes 0.000 description 8
- 108091079001 CRISPR RNA Proteins 0.000 description 8
- 241000702421 Dependoparvovirus Species 0.000 description 8
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 8
- 230000000295 complement effect Effects 0.000 description 8
- 230000003750 conditioning effect Effects 0.000 description 8
- 238000009169 immunotherapy Methods 0.000 description 8
- 238000003780 insertion Methods 0.000 description 8
- 230000037431 insertion Effects 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 150000003431 steroids Chemical class 0.000 description 8
- 230000003612 virological effect Effects 0.000 description 8
- 206010021143 Hypoxia Diseases 0.000 description 7
- 208000007125 Neurotoxicity Syndromes Diseases 0.000 description 7
- 206010038389 Renal cancer Diseases 0.000 description 7
- 230000002159 abnormal effect Effects 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 230000010261 cell growth Effects 0.000 description 7
- 238000013461 design Methods 0.000 description 7
- 239000012636 effector Substances 0.000 description 7
- 238000000684 flow cytometry Methods 0.000 description 7
- 230000007954 hypoxia Effects 0.000 description 7
- 238000009533 lab test Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 238000011321 prophylaxis Methods 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 238000013414 tumor xenograft model Methods 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- 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 6
- 108010082126 Alanine transaminase Proteins 0.000 description 6
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 6
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 208000008839 Kidney Neoplasms Diseases 0.000 description 6
- 206010033661 Pancytopenia Diseases 0.000 description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 6
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 6
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 230000001364 causal effect Effects 0.000 description 6
- 210000000349 chromosome Anatomy 0.000 description 6
- 238000005138 cryopreservation Methods 0.000 description 6
- 208000024389 cytopenia Diseases 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 201000010982 kidney cancer Diseases 0.000 description 6
- 210000001165 lymph node Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000006780 non-homologous end joining Effects 0.000 description 6
- 229960005489 paracetamol Drugs 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000008439 repair process Effects 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 238000011269 treatment regimen Methods 0.000 description 6
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 5
- 101150076800 B2M gene Proteins 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 206010053567 Coagulopathies Diseases 0.000 description 5
- 206010028813 Nausea Diseases 0.000 description 5
- 208000001647 Renal Insufficiency Diseases 0.000 description 5
- 238000012054 celltiter-glo Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229940109239 creatinine Drugs 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 201000006370 kidney failure Diseases 0.000 description 5
- 230000003211 malignant effect Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 230000008693 nausea Effects 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000002106 pulse oximetry Methods 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 238000009121 systemic therapy Methods 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 4
- 208000014644 Brain disease Diseases 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 208000032274 Encephalopathy Diseases 0.000 description 4
- 206010017533 Fungal infection Diseases 0.000 description 4
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 4
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 4
- 206010019233 Headaches Diseases 0.000 description 4
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- 241000700721 Hepatitis B virus Species 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 208000031888 Mycoses Diseases 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 238000010459 TALEN Methods 0.000 description 4
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 4
- 208000036142 Viral infection Diseases 0.000 description 4
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000010836 blood and blood product Substances 0.000 description 4
- 208000015294 blood coagulation disease Diseases 0.000 description 4
- 229940125691 blood product Drugs 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 230000001747 exhibiting effect Effects 0.000 description 4
- 231100000869 headache Toxicity 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 238000011835 investigation Methods 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 238000003752 polymerase chain reaction Methods 0.000 description 4
- 238000009597 pregnancy test Methods 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 206010048962 Brain oedema Diseases 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 102100031780 Endonuclease Human genes 0.000 description 3
- 108010042407 Endonucleases Proteins 0.000 description 3
- 208000010201 Exanthema Diseases 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
- 102000008946 Fibrinogen Human genes 0.000 description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 241000711549 Hepacivirus C Species 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010061598 Immunodeficiency Diseases 0.000 description 3
- 206010051792 Infusion related reaction Diseases 0.000 description 3
- 102000003812 Interleukin-15 Human genes 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 108010002586 Interleukin-7 Proteins 0.000 description 3
- 102000000704 Interleukin-7 Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000193996 Streptococcus pyogenes Species 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000001754 anti-pyretic effect Effects 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 229940121375 antifungal agent Drugs 0.000 description 3
- 239000002221 antipyretic Substances 0.000 description 3
- 229940125716 antipyretic agent Drugs 0.000 description 3
- 201000007201 aphasia Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
- 238000004820 blood count Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 208000006752 brain edema Diseases 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 229940000406 drug candidate Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 201000005884 exanthem Diseases 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- 229940012952 fibrinogen Drugs 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 229940100994 interleukin-7 Drugs 0.000 description 3
- 230000004068 intracellular signaling Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 208000004235 neutropenia Diseases 0.000 description 3
- 230000002853 ongoing effect Effects 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 206010037844 rash Diseases 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 231100000279 safety data Toxicity 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 230000003319 supportive effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229960003989 tocilizumab Drugs 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 2
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 2
- AOYNUTHNTBLRMT-SLPGGIOYSA-N 2-deoxy-2-fluoro-aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](F)C=O AOYNUTHNTBLRMT-SLPGGIOYSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 102100027207 CD27 antigen Human genes 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 2
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 208000022540 Consciousness disease Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010072268 Drug-induced liver injury Diseases 0.000 description 2
- 108050000784 Ferritin Proteins 0.000 description 2
- 102000008857 Ferritin Human genes 0.000 description 2
- 238000008416 Ferritin Methods 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 206010059282 Metastases to central nervous system Diseases 0.000 description 2
- 206010027457 Metastases to liver Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 108091092724 Noncoding DNA Proteins 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 208000009989 Posterior Leukoencephalopathy Syndrome Diseases 0.000 description 2
- 206010071066 Posterior reversible encephalopathy syndrome Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
- 108010000499 Thromboplastin Proteins 0.000 description 2
- 102000002262 Thromboplastin Human genes 0.000 description 2
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 208000027119 bilirubin metabolic disease Diseases 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000008416 bone turnover Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 201000010240 chromophobe renal cell carcinoma Diseases 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 208000035850 clinical syndrome Diseases 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 230000000139 costimulatory effect Effects 0.000 description 2
- 229940108608 cyclophosphamide 500 mg Drugs 0.000 description 2
- 238000002784 cytotoxicity assay Methods 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 208000010710 hepatitis C virus infection Diseases 0.000 description 2
- 208000036796 hyperbilirubinemia Diseases 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 238000007449 liver function test Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000013059 nephrectomy Methods 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 201000010279 papillary renal cell carcinoma Diseases 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
- 231100000683 possible toxicity Toxicity 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 229960000424 rasburicase Drugs 0.000 description 2
- 108010084837 rasburicase Proteins 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000036387 respiratory rate Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000009120 supportive therapy Methods 0.000 description 2
- 238000002626 targeted therapy Methods 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 239000000439 tumor marker Substances 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- 230000002861 ventricular Effects 0.000 description 2
- 230000036642 wellbeing Effects 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- ALNDFFUAQIVVPG-NGJCXOISSA-N (2r,3r,4r)-3,4,5-trihydroxy-2-methoxypentanal Chemical compound CO[C@@H](C=O)[C@H](O)[C@H](O)CO ALNDFFUAQIVVPG-NGJCXOISSA-N 0.000 description 1
- BRCNMMGLEUILLG-NTSWFWBYSA-N (4s,5r)-4,5,6-trihydroxyhexan-2-one Chemical group CC(=O)C[C@H](O)[C@H](O)CO BRCNMMGLEUILLG-NTSWFWBYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- 239000013607 AAV vector Substances 0.000 description 1
- 206010000077 Abdominal mass Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000212384 Bifora Species 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 238000003734 CellTiter-Glo Luminescent Cell Viability Assay Methods 0.000 description 1
- 208000015879 Cerebellar disease Diseases 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 102100036213 Collagen alpha-2(I) chain Human genes 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 206010012373 Depressed level of consciousness Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010012741 Diarrhoea haemorrhagic Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 206010014612 Encephalitis viral Diseases 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000287227 Fringillidae Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000009139 Gilbert Disease Diseases 0.000 description 1
- 208000022412 Gilbert syndrome Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102100028967 HLA class I histocompatibility antigen, alpha chain G Human genes 0.000 description 1
- 101710197836 HLA class I histocompatibility antigen, alpha chain G Proteins 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000875067 Homo sapiens Collagen alpha-2(I) chain Proteins 0.000 description 1
- 101001014223 Homo sapiens MAPK/MAK/MRK overlapping kinase Proteins 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000701027 Human herpesvirus 6 Species 0.000 description 1
- 208000002682 Hyperkalemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 201000001431 Hyperuricemia Diseases 0.000 description 1
- 208000013038 Hypocalcemia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 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
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010048294 Mental status changes Diseases 0.000 description 1
- 206010051696 Metastases to meninges Diseases 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 208000008457 Neurologic Manifestations Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 206010068786 Overlap syndrome Diseases 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 241000873939 Parechovirus A Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 208000005228 Pericardial Effusion Diseases 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010050808 Procollagen Proteins 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 206010037868 Rash maculo-papular Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 108091028113 Trans-activating crRNA Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 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
- 208000002579 Wernicke Aphasia Diseases 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
- 238000002679 ablation Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 235000015107 ale Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000573 anti-seizure effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 229950009579 axicabtagene ciloleucel Drugs 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000007698 birth defect Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 238000009640 blood culture Methods 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 238000007470 bone biopsy Methods 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 101150058049 car gene Proteins 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 230000007681 cardiovascular toxicity Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 238000011976 chest X-ray Methods 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000011970 concomitant therapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002338 cryopreservative effect Effects 0.000 description 1
- 230000001955 cumulated effect Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- OWZREIFADZCYQD-NSHGMRRFSA-N deltamethrin Chemical compound CC1(C)[C@@H](C=C(Br)Br)[C@H]1C(=O)O[C@H](C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 OWZREIFADZCYQD-NSHGMRRFSA-N 0.000 description 1
- 108010017271 denileukin diftitox Proteins 0.000 description 1
- 229960002923 denileukin diftitox Drugs 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229940119744 dextran 40 Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000000104 diagnostic biomarker Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 238000003748 differential diagnosis Methods 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003386 epithelial cell of thymus gland Anatomy 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001036 exonucleolytic effect Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- BQSJTQLCZDPROO-UHFFFAOYSA-N febuxostat Chemical compound C1=C(C#N)C(OCC(C)C)=CC=C1C1=NC(C)=C(C(O)=O)S1 BQSJTQLCZDPROO-UHFFFAOYSA-N 0.000 description 1
- 229960005101 febuxostat Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000009459 flexible packaging Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 230000008571 general function Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 231100001156 grade 3 toxicity Toxicity 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 description 1
- 208000027700 hepatic dysfunction Diseases 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000049409 human MOK Human genes 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000037417 hyperactivation Effects 0.000 description 1
- 201000005991 hyperphosphatemia Diseases 0.000 description 1
- 230000000705 hypocalcaemia Effects 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration 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
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229940045426 kymriah Drugs 0.000 description 1
- 238000011545 laboratory measurement Methods 0.000 description 1
- 239000006101 laboratory sample Substances 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960004002 levetiracetam Drugs 0.000 description 1
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 238000011469 lymphodepleting chemotherapy Methods 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000012965 maculopapular rash Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 208000018731 motor weakness Diseases 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 210000004882 non-tumor cell Anatomy 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 230000030648 nucleus localization Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000011375 palliative radiation therapy Methods 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical class [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000306 qrs interval Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 208000026759 receptive aphasia Diseases 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 230000008263 repair mechanism Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 238000009094 second-line therapy Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 108010078373 tisagenlecleucel Proteins 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 208000030218 transient fever Diseases 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 230000024883 vasodilation Effects 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
- 201000002498 viral encephalitis Diseases 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000007419 viral reactivation Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229940045208 yescarta Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001136—Cytokines
- A61K39/001138—Tumor necrosis factors [TNF] or CD70
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/31—Chimeric antigen receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4231—Cytokines
- A61K40/4232—Tumor necrosis factors [TNF] or CD70
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/868—Vaccine for a specifically defined cancer kidney
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
- A61K2239/56—Kidney
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/50—Cellular immunotherapy characterised by the use of allogeneic cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hematology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962934961P | 2019-11-13 | 2019-11-13 | |
| US62/934,961 | 2019-11-13 | ||
| US202063034552P | 2020-06-04 | 2020-06-04 | |
| US63/034,552 | 2020-06-04 | ||
| PCT/IB2020/060719 WO2021095010A1 (en) | 2019-11-13 | 2020-11-13 | Renal cell carcinoma (rcc) therapy using genetically engineered t cells targeting cd70 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2020383021A1 true AU2020383021A1 (en) | 2022-05-19 |
Family
ID=73695085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2020383021A Abandoned AU2020383021A1 (en) | 2019-11-13 | 2020-11-13 | Renal cell carcinoma (RCC) therapy using genetically engineered T cells targeting CD70 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20220387572A1 (enExample) |
| EP (1) | EP4058053A1 (enExample) |
| JP (1) | JP2023501602A (enExample) |
| KR (1) | KR20220100913A (enExample) |
| CN (1) | CN114929267A (enExample) |
| AU (1) | AU2020383021A1 (enExample) |
| BR (1) | BR112022009204A2 (enExample) |
| CA (1) | CA3158110A1 (enExample) |
| IL (1) | IL292468A (enExample) |
| MX (1) | MX2022005821A (enExample) |
| WO (1) | WO2021095010A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210137085A (ko) | 2019-03-05 | 2021-11-17 | 엔카르타, 인크. | Cd19 유도된 키메라 항원 수용체 및 면역 요법에서 이의 용도 |
| KR20220101128A (ko) * | 2019-11-13 | 2022-07-19 | 크리스퍼 테라퓨틱스 아게 | Cd70을 표적화하는 유전자 조작된 t 세포를 사용하는 cd70+ 고형 종양 치료법 |
| MX2022015586A (es) | 2020-06-12 | 2023-03-15 | Nkarta Inc | Linfocitos citolíticos naturales modificados genéticamente para inmunoterapia de cáncer dirigida a cd70. |
| EP4305153A1 (en) * | 2021-03-09 | 2024-01-17 | CRISPR Therapeutics AG | Genetically engineered t cells with ptpn2 knockout have improved functionality and anti-tumor activity |
| US20220378829A1 (en) * | 2021-05-12 | 2022-12-01 | Crispr Therapeutics Ag | Genetically engineered immune cells targeting cd70 for use in treating solid tumors |
| WO2023072307A1 (zh) * | 2021-10-25 | 2023-05-04 | 重庆精准生物技术有限公司 | 一种靶向cd70的抗原结合片段、单链抗体和嵌合抗原受体及其应用 |
| EP4482872A4 (en) * | 2022-03-07 | 2026-03-18 | Nkarta Inc | Multiplex gene-edited cells for CD70-led cancer immunotherapy |
| KR20250109947A (ko) | 2024-01-11 | 2025-07-18 | 재단법인 아산사회복지재단 | 흉선 세포 또는 흉선 상피세포를 유효성분으로 포함하는 암 예방용 약학적 조성물 |
| CN117844811A (zh) * | 2024-03-08 | 2024-04-09 | 上海恒润达生生物科技股份有限公司 | 靶向敲除CD70基因的sgRNA组合物及其应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11352631B2 (en) * | 2015-12-18 | 2022-06-07 | Sangamo Therapeutics, Inc. | Targeted disruption of the T cell receptor |
| US11466291B2 (en) * | 2016-07-06 | 2022-10-11 | Cellectis | Sequential gene editing in primary immune cells |
| BR112019023608A2 (pt) * | 2017-05-12 | 2020-05-26 | Crispr Therapeutics Ag | Materiais e métodos para células manipuladas e seus usos em imuno-oncologia |
| MX2020008184A (es) * | 2018-02-01 | 2020-09-22 | Pfizer | Receptores de antigeno quimericos dirigidos a cd70. |
| US20200063100A1 (en) | 2018-05-11 | 2020-02-27 | Crispr Therapeutics Ag | Methods and compositions for treating cancer |
| KR20220101128A (ko) * | 2019-11-13 | 2022-07-19 | 크리스퍼 테라퓨틱스 아게 | Cd70을 표적화하는 유전자 조작된 t 세포를 사용하는 cd70+ 고형 종양 치료법 |
-
2020
- 2020-11-13 KR KR1020227019520A patent/KR20220100913A/ko not_active Withdrawn
- 2020-11-13 AU AU2020383021A patent/AU2020383021A1/en not_active Abandoned
- 2020-11-13 CA CA3158110A patent/CA3158110A1/en active Pending
- 2020-11-13 BR BR112022009204A patent/BR112022009204A2/pt not_active Application Discontinuation
- 2020-11-13 IL IL292468A patent/IL292468A/en unknown
- 2020-11-13 MX MX2022005821A patent/MX2022005821A/es unknown
- 2020-11-13 CN CN202080090978.5A patent/CN114929267A/zh active Pending
- 2020-11-13 EP EP20817494.6A patent/EP4058053A1/en not_active Withdrawn
- 2020-11-13 JP JP2022527773A patent/JP2023501602A/ja active Pending
- 2020-11-13 WO PCT/IB2020/060719 patent/WO2021095010A1/en not_active Ceased
- 2020-11-13 US US17/776,860 patent/US20220387572A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA3158110A1 (en) | 2021-05-20 |
| US20220387572A1 (en) | 2022-12-08 |
| CN114929267A (zh) | 2022-08-19 |
| JP2023501602A (ja) | 2023-01-18 |
| IL292468A (en) | 2022-06-01 |
| WO2021095010A1 (en) | 2021-05-20 |
| MX2022005821A (es) | 2022-08-16 |
| EP4058053A1 (en) | 2022-09-21 |
| BR112022009204A2 (pt) | 2022-07-26 |
| KR20220100913A (ko) | 2022-07-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20220387572A1 (en) | Renal cell carcinoma (rcc) therapy using genetically engineered t cells targeting cd70 | |
| EP4058054A1 (en) | Cd70+ solid tumor therapy using genetically engineered t cells targeting cd70 | |
| US11389481B2 (en) | Allogeneic cell therapy of B cell malignancies using genetically engineered T cells targeting CD19 | |
| WO2021095009A1 (en) | Therapy for hematopoietic cell malignancies using genetically engineered t cells targeting cd70 | |
| AU2021366431A1 (en) | Allogeneic cell therapy of b cell malignancies using genetically engineered t cells targeting cd19 | |
| US20220378829A1 (en) | Genetically engineered immune cells targeting cd70 for use in treating solid tumors | |
| US20230220059A1 (en) | Genetically engineered t cells expressing bcma-specific chimeric antigen receptors and uses thereof in cancer therapy | |
| WO2024079592A1 (en) | Genetically engineered anti-cd19 car-t cells for use in treating b-cell malignancies | |
| CN116685337A (zh) | 使用靶向cd19的基因工程化t细胞的b细胞恶性肿瘤的同种异体细胞疗法 | |
| HK40068210A (en) | Allogeneic cell therapy of b cell malignancies using genetically engineered t cells targeting cd19 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |