CA3007473A1 - Dual controls for therapeutic cell activation or elimination - Google Patents
Dual controls for therapeutic cell activation or elimination Download PDFInfo
- Publication number
- CA3007473A1 CA3007473A1 CA3007473A CA3007473A CA3007473A1 CA 3007473 A1 CA3007473 A1 CA 3007473A1 CA 3007473 A CA3007473 A CA 3007473A CA 3007473 A CA3007473 A CA 3007473A CA 3007473 A1 CA3007473 A1 CA 3007473A1
- Authority
- CA
- Canada
- Prior art keywords
- polypeptide
- cell
- ligand
- nucleic acid
- modified
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 30
- 230000008030 elimination Effects 0.000 title abstract description 12
- 238000003379 elimination reaction Methods 0.000 title abstract description 12
- 230000009977 dual effect Effects 0.000 title description 10
- 230000020411 cell activation Effects 0.000 title description 3
- 210000004027 cell Anatomy 0.000 claims abstract description 619
- 239000003446 ligand Substances 0.000 claims abstract description 295
- 238000000034 method Methods 0.000 claims abstract description 193
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 94
- 230000000694 effects Effects 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 108091008874 T cell receptors Proteins 0.000 claims abstract description 26
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims abstract description 26
- 201000010099 disease Diseases 0.000 claims abstract description 23
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 703
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 702
- 229920001184 polypeptide Polymers 0.000 claims description 701
- 150000007523 nucleic acids Chemical class 0.000 claims description 207
- 102000039446 nucleic acids Human genes 0.000 claims description 200
- 108020004707 nucleic acids Proteins 0.000 claims description 200
- 230000000861 pro-apoptotic effect Effects 0.000 claims description 185
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 claims description 138
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 claims description 137
- 229960002930 sirolimus Drugs 0.000 claims description 136
- 108090000566 Caspase-9 Proteins 0.000 claims description 123
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 122
- 102000004039 Caspase-9 Human genes 0.000 claims description 118
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 116
- 239000000427 antigen Substances 0.000 claims description 103
- 108091007433 antigens Proteins 0.000 claims description 103
- 102000036639 antigens Human genes 0.000 claims description 103
- 102000040430 polynucleotide Human genes 0.000 claims description 101
- 108091033319 polynucleotide Proteins 0.000 claims description 101
- 239000002157 polynucleotide Substances 0.000 claims description 101
- 108090000623 proteins and genes Proteins 0.000 claims description 101
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 claims description 99
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 claims description 99
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 91
- 101150013553 CD40 gene Proteins 0.000 claims description 79
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 79
- 230000027455 binding Effects 0.000 claims description 64
- GQLCLPLEEOUJQC-ZTQDTCGGSA-N [(1r)-3-(3,4-dimethoxyphenyl)-1-[3-[2-[2-[[2-[3-[(1r)-3-(3,4-dimethoxyphenyl)-1-[(2s)-1-[(2s)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidine-2-carbonyl]oxypropyl]phenoxy]acetyl]amino]ethylamino]-2-oxoethoxy]phenyl]propyl] (2s)-1-[(2s)-2-(3,4,5-trimethoxyph Chemical compound C([C@@H](OC(=O)[C@@H]1CCCCN1C(=O)[C@@H](CC)C=1C=C(OC)C(OC)=C(OC)C=1)C=1C=C(OCC(=O)NCCNC(=O)COC=2C=C(C=CC=2)[C@@H](CCC=2C=C(OC)C(OC)=CC=2)OC(=O)[C@H]2N(CCCC2)C(=O)[C@@H](CC)C=2C=C(OC)C(OC)=C(OC)C=2)C=CC=1)CC1=CC=C(OC)C(OC)=C1 GQLCLPLEEOUJQC-ZTQDTCGGSA-N 0.000 claims description 62
- 102000004169 proteins and genes Human genes 0.000 claims description 62
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 57
- 235000018102 proteins Nutrition 0.000 claims description 56
- 229950004008 rimiducid Drugs 0.000 claims description 56
- 102000011727 Caspases Human genes 0.000 claims description 51
- 108010076667 Caspases Proteins 0.000 claims description 51
- 230000001939 inductive effect Effects 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 44
- 230000014509 gene expression Effects 0.000 claims description 41
- 206010028980 Neoplasm Diseases 0.000 claims description 40
- 230000001086 cytosolic effect Effects 0.000 claims description 40
- 239000013598 vector Substances 0.000 claims description 35
- 235000001014 amino acid Nutrition 0.000 claims description 34
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 28
- 208000024908 graft versus host disease Diseases 0.000 claims description 28
- 238000006467 substitution reaction Methods 0.000 claims description 26
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 25
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 25
- -1 Muc16 Proteins 0.000 claims description 24
- 239000012634 fragment Substances 0.000 claims description 23
- 230000007812 deficiency Effects 0.000 claims description 21
- 102000002164 CARD domains Human genes 0.000 claims description 20
- 108050009503 CARD domains Proteins 0.000 claims description 20
- 241000700605 Viruses Species 0.000 claims description 20
- 210000004881 tumor cell Anatomy 0.000 claims description 17
- 230000000139 costimulatory effect Effects 0.000 claims description 16
- 238000013519 translation Methods 0.000 claims description 16
- 210000004369 blood Anatomy 0.000 claims description 14
- 239000008280 blood Substances 0.000 claims description 14
- 210000001185 bone marrow Anatomy 0.000 claims description 13
- 230000004936 stimulating effect Effects 0.000 claims description 13
- 230000006044 T cell activation Effects 0.000 claims description 12
- 210000000822 natural killer cell Anatomy 0.000 claims description 12
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 12
- 238000002659 cell therapy Methods 0.000 claims description 11
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 11
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims description 10
- 102100036735 Prostate stem cell antigen Human genes 0.000 claims description 10
- 125000000539 amino acid group Chemical group 0.000 claims description 10
- 230000001276 controlling effect Effects 0.000 claims description 10
- 230000001965 increasing effect Effects 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 claims description 10
- 102100038713 Death domain-containing protein CRADD Human genes 0.000 claims description 9
- 101000957914 Homo sapiens Death domain-containing protein CRADD Proteins 0.000 claims description 9
- 210000004700 fetal blood Anatomy 0.000 claims description 9
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 9
- 230000003463 hyperproliferative effect Effects 0.000 claims description 9
- 230000028993 immune response Effects 0.000 claims description 9
- 238000001727 in vivo Methods 0.000 claims description 9
- 238000001890 transfection Methods 0.000 claims description 9
- 241000699666 Mus <mouse, genus> Species 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 208000014951 hematologic disease Diseases 0.000 claims description 7
- 239000011886 peripheral blood Substances 0.000 claims description 7
- 210000005259 peripheral blood Anatomy 0.000 claims description 7
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 7
- 208000019838 Blood disease Diseases 0.000 claims description 6
- 206010053138 Congenital aplastic anaemia Diseases 0.000 claims description 6
- 230000000890 antigenic effect Effects 0.000 claims description 6
- 208000015322 bone marrow disease Diseases 0.000 claims description 6
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 6
- 208000002491 severe combined immunodeficiency Diseases 0.000 claims description 6
- 210000000130 stem cell Anatomy 0.000 claims description 6
- 230000004083 survival effect Effects 0.000 claims description 6
- 230000008685 targeting Effects 0.000 claims description 6
- 108090000397 Caspase 3 Proteins 0.000 claims description 5
- 108090000426 Caspase-1 Proteins 0.000 claims description 5
- 102100035904 Caspase-1 Human genes 0.000 claims description 5
- 108090000552 Caspase-2 Proteins 0.000 claims description 5
- 108090000538 Caspase-8 Proteins 0.000 claims description 5
- 208000032672 Histiocytosis haematophagic Diseases 0.000 claims description 5
- 208000030289 Lymphoproliferative disease Diseases 0.000 claims description 5
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 5
- 108010018550 caspase 13 Proteins 0.000 claims description 5
- 210000002540 macrophage Anatomy 0.000 claims description 5
- 210000004986 primary T-cell Anatomy 0.000 claims description 5
- 208000007056 sickle cell anemia Diseases 0.000 claims description 5
- 108090000425 Caspase 6 Proteins 0.000 claims description 4
- 108090000567 Caspase 7 Proteins 0.000 claims description 4
- 108090000572 Caspase-10 Proteins 0.000 claims description 4
- 108090000570 Caspase-12 Proteins 0.000 claims description 4
- 108090001132 Caspase-14 Proteins 0.000 claims description 4
- 101710090338 Caspase-4 Proteins 0.000 claims description 4
- 101710090333 Caspase-5 Proteins 0.000 claims description 4
- 101000933115 Mus musculus Caspase-4 Proteins 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 230000007423 decrease Effects 0.000 claims description 4
- 210000002950 fibroblast Anatomy 0.000 claims description 4
- 230000021633 leukocyte mediated immunity Effects 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 102100033051 40S ribosomal protein S19 Human genes 0.000 claims description 3
- 208000033932 Blackfan-Diamond anemia Diseases 0.000 claims description 3
- 201000007155 CD40 ligand deficiency Diseases 0.000 claims description 3
- 208000004918 Cartilage-hair hypoplasia Diseases 0.000 claims description 3
- 206010010356 Congenital anomaly Diseases 0.000 claims description 3
- 206010062759 Congenital dyskeratosis Diseases 0.000 claims description 3
- 208000025212 Constitutional neutropenia Diseases 0.000 claims description 3
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 claims description 3
- 201000004449 Diamond-Blackfan anemia Diseases 0.000 claims description 3
- 201000004939 Fanconi anemia Diseases 0.000 claims description 3
- 208000000259 GATA2 Deficiency Diseases 0.000 claims description 3
- 208000022140 GATA2 deficiency with susceptibility to MDS/AML Diseases 0.000 claims description 3
- 206010052210 Infantile genetic agranulocytosis Diseases 0.000 claims description 3
- 201000001779 Leukocyte adhesion deficiency Diseases 0.000 claims description 3
- 208000035809 Lymphohistiocytosis Diseases 0.000 claims description 3
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims description 3
- 208000025237 Polyendocrinopathy Diseases 0.000 claims description 3
- 201000004283 Shwachman-Diamond syndrome Diseases 0.000 claims description 3
- 208000010346 Sphingolipidoses Diseases 0.000 claims description 3
- 201000001307 Sphingolipidosis Diseases 0.000 claims description 3
- 208000016532 chronic granulomatous disease Diseases 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 230000007547 defect Effects 0.000 claims description 3
- 208000009356 dyskeratosis congenita Diseases 0.000 claims description 3
- 208000037902 enteropathy Diseases 0.000 claims description 3
- 208000034737 hemoglobinopathy Diseases 0.000 claims description 3
- 230000003258 hemophagocytic effect Effects 0.000 claims description 3
- 208000014165 immunodeficiency 21 Diseases 0.000 claims description 3
- 208000028774 intestinal disease Diseases 0.000 claims description 3
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 3
- 210000002997 osteoclast Anatomy 0.000 claims description 3
- 208000002865 osteopetrosis Diseases 0.000 claims description 3
- 208000028529 primary immunodeficiency disease Diseases 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 claims 96
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 claims 96
- 101100346932 Mus musculus Muc1 gene Proteins 0.000 claims 9
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims 8
- 108010058905 CD44v6 antigen Proteins 0.000 claims 8
- 101150029707 ERBB2 gene Proteins 0.000 claims 8
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims 8
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims 8
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims 8
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims 8
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims 8
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims 8
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 claims 8
- 102000003735 Mesothelin Human genes 0.000 claims 8
- 108090000015 Mesothelin Proteins 0.000 claims 8
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims 8
- 230000001580 bacterial effect Effects 0.000 claims 8
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims 8
- 230000003612 virological effect Effects 0.000 claims 8
- 102000009438 IgE Receptors Human genes 0.000 claims 7
- 108010073816 IgE Receptors Proteins 0.000 claims 7
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 claims 4
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 claims 4
- 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 claims 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 4
- 108060006580 PRAME Proteins 0.000 claims 4
- 102000036673 PRAME Human genes 0.000 claims 4
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 claims 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 4
- 208000033779 X-linked lymphoproliferative disease Diseases 0.000 claims 4
- 235000004279 alanine Nutrition 0.000 claims 4
- 239000004474 valine Substances 0.000 claims 4
- 102100034524 Apoptotic protease-activating factor 1 Human genes 0.000 claims 3
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 claims 3
- 102100026693 FAS-associated death domain protein Human genes 0.000 claims 3
- 101000924629 Homo sapiens Apoptotic protease-activating factor 1 Proteins 0.000 claims 3
- 101000911074 Homo sapiens FAS-associated death domain protein Proteins 0.000 claims 3
- 101001089266 Homo sapiens Receptor-interacting serine/threonine-protein kinase 3 Proteins 0.000 claims 3
- 102100033729 Receptor-interacting serine/threonine-protein kinase 3 Human genes 0.000 claims 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims 3
- 238000004520 electroporation Methods 0.000 claims 3
- 210000002443 helper t lymphocyte Anatomy 0.000 claims 3
- 210000005260 human cell Anatomy 0.000 claims 3
- 210000002510 keratinocyte Anatomy 0.000 claims 3
- 150000002632 lipids Chemical class 0.000 claims 3
- 230000000527 lymphocytic effect Effects 0.000 claims 3
- 239000002105 nanoparticle Substances 0.000 claims 3
- 210000000581 natural killer T-cell Anatomy 0.000 claims 3
- 239000002245 particle Substances 0.000 claims 3
- 229920000642 polymer Polymers 0.000 claims 3
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims 2
- VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 claims 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims 2
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 claims 2
- 208000002903 Thalassemia Diseases 0.000 claims 2
- 208000006110 Wiskott-Aldrich syndrome Diseases 0.000 claims 2
- 102000055574 bcl-2 Homologous Antagonist-Killer Human genes 0.000 claims 2
- 102000055102 bcl-2-Associated X Human genes 0.000 claims 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims 2
- 230000002503 metabolic effect Effects 0.000 claims 2
- RVNZEJNWTUDQSC-JOCHJYFZSA-N (2r)-n-(6-aminohexyl)-1-tridecanoylpyrrolidine-2-carboxamide Chemical compound CCCCCCCCCCCCC(=O)N1CCC[C@@H]1C(=O)NCCCCCCN RVNZEJNWTUDQSC-JOCHJYFZSA-N 0.000 claims 1
- 241000251468 Actinopterygii Species 0.000 claims 1
- 241000283690 Bos taurus Species 0.000 claims 1
- 241000283707 Capra Species 0.000 claims 1
- 241000700199 Cavia porcellus Species 0.000 claims 1
- 241000282693 Cercopithecidae Species 0.000 claims 1
- 241000699800 Cricetinae Species 0.000 claims 1
- 241000283073 Equus caballus Species 0.000 claims 1
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 1
- 241001494479 Pecora Species 0.000 claims 1
- 241000700159 Rattus Species 0.000 claims 1
- 241000282898 Sus scrofa Species 0.000 claims 1
- 230000007498 myristoylation Effects 0.000 claims 1
- 238000005516 engineering process Methods 0.000 abstract description 9
- 239000013612 plasmid Substances 0.000 description 65
- 230000006907 apoptotic process Effects 0.000 description 36
- 238000006471 dimerization reaction Methods 0.000 description 29
- 238000003556 assay Methods 0.000 description 25
- 230000004913 activation Effects 0.000 description 21
- 230000011664 signaling Effects 0.000 description 21
- 229940079593 drug Drugs 0.000 description 18
- 239000003814 drug Substances 0.000 description 18
- 239000013604 expression vector Substances 0.000 description 17
- 238000010361 transduction Methods 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 12
- 239000000411 inducer Substances 0.000 description 12
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 11
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 11
- 230000006870 function Effects 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 239000000833 heterodimer Substances 0.000 description 9
- 210000000952 spleen Anatomy 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 102000047934 Caspase-3/7 Human genes 0.000 description 8
- 108700037887 Caspase-3/7 Proteins 0.000 description 8
- 230000030833 cell death Effects 0.000 description 8
- 230000022534 cell killing Effects 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 230000001640 apoptogenic effect Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 6
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 6
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000005090 green fluorescent protein Substances 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 230000007115 recruitment Effects 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 238000005415 bioluminescence Methods 0.000 description 5
- 230000029918 bioluminescence Effects 0.000 description 5
- 206010052015 cytokine release syndrome Diseases 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000006882 induction of apoptosis Effects 0.000 description 5
- 230000004073 interleukin-2 production Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000002773 nucleotide Substances 0.000 description 5
- 125000003729 nucleotide group Chemical group 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 230000000735 allogeneic effect Effects 0.000 description 4
- 210000000601 blood cell Anatomy 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000005734 heterodimerization reaction Methods 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 108020001756 ligand binding domains Proteins 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 238000001000 micrograph Methods 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 230000001177 retroviral effect Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 210000002536 stromal cell Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000009258 tissue cross reactivity Effects 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 108700028369 Alleles Proteins 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000006384 oligomerization reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 102000021350 Caspase recruitment domains Human genes 0.000 description 2
- 108091011189 Caspase recruitment domains Proteins 0.000 description 2
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000000311 Cytosine Deaminase Human genes 0.000 description 2
- 108010080611 Cytosine Deaminase Proteins 0.000 description 2
- 208000008334 Dermatofibrosarcoma Diseases 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 208000004987 Macrophage activation syndrome Diseases 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 206010045170 Tumour lysis syndrome Diseases 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 230000005775 apoptotic pathway Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000000710 homodimer Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000004324 lymphatic system Anatomy 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 239000002062 molecular scaffold Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000002894 multi-fate stem cell Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 102000034285 signal transducing proteins Human genes 0.000 description 2
- 108091006024 signal transducing proteins Proteins 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 208000010380 tumor lysis syndrome Diseases 0.000 description 2
- 210000003954 umbilical cord Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- BCHIXGBGRHLSBE-UHFFFAOYSA-N (4-methyl-2-oxochromen-7-yl) dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C=CC2=C1OC(=O)C=C2C BCHIXGBGRHLSBE-UHFFFAOYSA-N 0.000 description 1
- 102100022464 5'-nucleotidase Human genes 0.000 description 1
- 208000037540 Alveolar soft tissue sarcoma Diseases 0.000 description 1
- 102000000412 Annexin Human genes 0.000 description 1
- 108050008874 Annexin Proteins 0.000 description 1
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 1
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 1
- 108010089941 Apoptosomes Proteins 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102000004046 Caspase-2 Human genes 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 206010008583 Chloroma Diseases 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 206010057070 Dermatofibrosarcoma protuberans Diseases 0.000 description 1
- 102100037241 Endoglin Human genes 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102100027286 Fanconi anemia group C protein Human genes 0.000 description 1
- 102000010579 Fas-Associated Death Domain Protein Human genes 0.000 description 1
- 108010077716 Fas-Associated Death Domain Protein Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 1
- 108010075704 HLA-A Antigens Proteins 0.000 description 1
- 208000006050 Hemangiopericytoma Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 1
- 101000983523 Homo sapiens Caspase-9 Proteins 0.000 description 1
- 101000881679 Homo sapiens Endoglin Proteins 0.000 description 1
- 101100446641 Homo sapiens FKBP1A gene Proteins 0.000 description 1
- 101000914680 Homo sapiens Fanconi anemia group C protein Proteins 0.000 description 1
- 101000914053 Homo sapiens Peptidyl-prolyl cis-trans isomerase FKBP2 Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 240000001812 Hyssopus officinalis Species 0.000 description 1
- 235000010650 Hyssopus officinalis Nutrition 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004551 Interleukin-10 Receptors Human genes 0.000 description 1
- 108010017550 Interleukin-10 Receptors Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 238000010824 Kaplan-Meier survival analysis Methods 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 102000008072 Lymphokines Human genes 0.000 description 1
- 108010074338 Lymphokines Proteins 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 101000914065 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) FK506-binding protein 2 Proteins 0.000 description 1
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 1
- 102100026408 Peptidyl-prolyl cis-trans isomerase FKBP2 Human genes 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010037868 Rash maculo-papular Diseases 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010061228 Sialomucins Proteins 0.000 description 1
- 102000012010 Sialomucins Human genes 0.000 description 1
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical class C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 206010043395 Thalassaemia sickle cell Diseases 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 208000008524 alveolar soft part sarcoma Diseases 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 230000005735 apoptotic response Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002449 bone cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 102000054766 genetic haplotypes Human genes 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 208000017750 granulocytic sarcoma Diseases 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 102000055209 human FKBP1A Human genes 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 239000002596 immunotoxin Substances 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 208000012965 maculopapular rash Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000005987 myeloid sarcoma Diseases 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 208000029974 neurofibrosarcoma Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 229940023146 nucleic acid vaccine Drugs 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000025915 regulation of apoptotic process Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 102200015453 rs121912293 Human genes 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6472—Cysteine endopeptidases (3.4.22)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- 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
-
- 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
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/32—T-cell receptors [TCR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4203—Receptors for growth factors
- A61K40/4205—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/421—Immunoglobulin superfamily
- A61K40/4211—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4214—Receptors for cytokines
- A61K40/4217—Receptors for interleukins [IL]
-
- 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
- A61K40/4267—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K40/427—PRAME
-
- 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
- A61K40/4274—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; Prostatic acid phosphatase [PAP]; Prostate-specific G-protein-coupled receptor [PSGR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4705—Regulators; Modulating activity stimulating, promoting or activating activity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/90—Isomerases (5.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y207/00—Transferases transferring phosphorus-containing groups (2.7)
- C12Y207/11—Protein-serine/threonine kinases (2.7.11)
- C12Y207/11001—Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/22—Cysteine endopeptidases (3.4.22)
- C12Y304/22062—Caspase-9 (3.4.22.62)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y502/00—Cis-trans-isomerases (5.2)
- C12Y502/01—Cis-trans-Isomerases (5.2.1)
- C12Y502/01008—Peptidylprolyl isomerase (5.2.1.8), i.e. cyclophilin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal 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
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- 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
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/23—On/off switch
-
- 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
- A61K2239/54—Pancreas
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Mycology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Transplantation (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562267277P | 2015-12-14 | 2015-12-14 | |
| US62/267,277 | 2015-12-14 | ||
| PCT/US2016/066371 WO2017106185A2 (en) | 2015-12-14 | 2016-12-13 | Dual controls for therapeutic cell activation or elimination |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3007473A1 true CA3007473A1 (en) | 2017-06-22 |
Family
ID=57799788
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3007473A Pending CA3007473A1 (en) | 2015-12-14 | 2016-12-13 | Dual controls for therapeutic cell activation or elimination |
Country Status (9)
| Country | Link |
|---|---|
| US (3) | US20170166877A1 (enExample) |
| EP (1) | EP3390434A2 (enExample) |
| JP (4) | JP2019506143A (enExample) |
| KR (1) | KR20180087423A (enExample) |
| CN (2) | CN117402829A (enExample) |
| AU (1) | AU2016370470B2 (enExample) |
| CA (1) | CA3007473A1 (enExample) |
| SG (1) | SG11201804694SA (enExample) |
| WO (1) | WO2017106185A2 (enExample) |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9745548B2 (en) | 2012-03-15 | 2017-08-29 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| US9950282B2 (en) | 2012-03-15 | 2018-04-24 | Flodesign Sonics, Inc. | Electronic configuration and control for acoustic standing wave generation |
| US10322949B2 (en) | 2012-03-15 | 2019-06-18 | Flodesign Sonics, Inc. | Transducer and reflector configurations for an acoustophoretic device |
| US9752113B2 (en) | 2012-03-15 | 2017-09-05 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| US10689609B2 (en) | 2012-03-15 | 2020-06-23 | Flodesign Sonics, Inc. | Acoustic bioreactor processes |
| US10967298B2 (en) | 2012-03-15 | 2021-04-06 | Flodesign Sonics, Inc. | Driver and control for variable impedence load |
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| US9458450B2 (en) | 2012-03-15 | 2016-10-04 | Flodesign Sonics, Inc. | Acoustophoretic separation technology using multi-dimensional standing waves |
| US10737953B2 (en) | 2012-04-20 | 2020-08-11 | Flodesign Sonics, Inc. | Acoustophoretic method for use in bioreactors |
| WO2014100615A1 (en) | 2012-12-20 | 2014-06-26 | Purdue Research Foundation | Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics |
| US9745569B2 (en) | 2013-09-13 | 2017-08-29 | Flodesign Sonics, Inc. | System for generating high concentration factors for low cell density suspensions |
| US9725710B2 (en) | 2014-01-08 | 2017-08-08 | Flodesign Sonics, Inc. | Acoustophoresis device with dual acoustophoretic chamber |
| US9744483B2 (en) | 2014-07-02 | 2017-08-29 | Flodesign Sonics, Inc. | Large scale acoustic separation device |
| CA2959168A1 (en) | 2014-09-02 | 2016-03-10 | Bellicum Pharmaceuticals, Inc. | Costimulation of chimeric antigen receptors by myd88 and cd40 polypeptides |
| AU2016230828B2 (en) * | 2015-03-10 | 2020-10-22 | ACADEMISCH ZIEKENHUIS LEIDEN (h.o.d.n. LUMC) | T-cell receptors directed against the preferentially expressed antigen of melanoma and uses thereof |
| US11021699B2 (en) | 2015-04-29 | 2021-06-01 | FioDesign Sonics, Inc. | Separation using angled acoustic waves |
| US11377651B2 (en) | 2016-10-19 | 2022-07-05 | Flodesign Sonics, Inc. | Cell therapy processes utilizing acoustophoresis |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
| US11474085B2 (en) | 2015-07-28 | 2022-10-18 | Flodesign Sonics, Inc. | Expanded bed affinity selection |
| US11459540B2 (en) | 2015-07-28 | 2022-10-04 | Flodesign Sonics, Inc. | Expanded bed affinity selection |
| CA3008641A1 (en) | 2015-12-16 | 2017-06-22 | Gritstone Oncology, Inc. | Neoantigen identification, manufacture, and use |
| US11325948B2 (en) | 2016-03-19 | 2022-05-10 | Exuma Biotech Corp. | Methods and compositions for genetically modifying lymphocytes to express polypeptides comprising the intracellular domain of MPL |
| US11111505B2 (en) | 2016-03-19 | 2021-09-07 | Exuma Biotech, Corp. | Methods and compositions for transducing lymphocytes and regulating the activity thereof |
| US12144850B2 (en) | 2016-04-08 | 2024-11-19 | Purdue Research Foundation | Methods and compositions for car T cell therapy |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| US11085035B2 (en) | 2016-05-03 | 2021-08-10 | Flodesign Sonics, Inc. | Therapeutic cell washing, concentration, and separation utilizing acoustophoresis |
| JP2020513248A (ja) | 2016-10-19 | 2020-05-14 | フロデザイン ソニックス, インク.Flodesign Sonics, Inc. | 音響による親和性細胞抽出 |
| JP7206214B2 (ja) | 2016-12-13 | 2023-01-17 | シアトル チルドレンズ ホスピタル (ディービーエイ シアトル チルドレンズ リサーチ インスティテュート) | インビトロ及びインビボで操作された細胞において発現された化学誘導シグナル伝達複合体の外因性薬物活性化の方法 |
| CA3051481A1 (en) | 2017-02-07 | 2018-08-16 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Phospholipid ether (ple) car t cell tumor targeting (ctct) agents |
| ES3010559T3 (en) | 2017-02-28 | 2025-04-03 | Endocyte Inc | Compositions and methods for car t cell therapy |
| US20210147507A1 (en) | 2017-05-09 | 2021-05-20 | Bellicum Pharmaceuticals, Inc. | Methods to augment or alter signal transduction |
| EP3664830A4 (en) | 2017-08-07 | 2020-07-01 | The Regents of the University of California | RISK-FREE CELL THERAPEUTIC GENERATION PLATFORM |
| CN111479921B (zh) * | 2017-09-18 | 2024-08-02 | 埃克苏马生物技术公司 | 用于以基因方式修饰且扩增淋巴细胞以及调节其活性的方法及组合物 |
| WO2019075112A1 (en) | 2017-10-10 | 2019-04-18 | Gritstone Oncology, Inc. | IDENTIFICATION OF NEO-ANTIGENS USING HOT POINTS |
| EP3714275A4 (en) | 2017-11-22 | 2021-10-27 | Gritstone bio, Inc. | REDUCTION OF JUNCTION EPITOPIC PRESENTATION FOR NEOANTIGENS |
| CA3084190A1 (en) | 2017-12-08 | 2019-06-13 | Bellicum Pharmaceuticals, Inc. | Methods for enhancing and maintaining car-t cell efficacy |
| US10785574B2 (en) | 2017-12-14 | 2020-09-22 | Flodesign Sonics, Inc. | Acoustic transducer driver and controller |
| EP3728189A1 (en) | 2017-12-20 | 2020-10-28 | Bellicum Pharmaceuticals, Inc. | Multimeric piperidine derivatives |
| ES3037765T3 (en) | 2017-12-22 | 2025-10-07 | Fate Therapeutics Inc | Enhanced immune effector cells and use thereof |
| JP7549303B2 (ja) | 2018-01-22 | 2024-09-11 | エンドサイト・インコーポレイテッド | Car t細胞の使用方法 |
| CN111936518A (zh) | 2018-02-06 | 2020-11-13 | 西雅图儿童医院(Dba西雅图儿童研究所) | 对fl-ple标记的肿瘤表现出最佳的t细胞功能的荧光素特异性car |
| CN112105382A (zh) | 2018-02-23 | 2020-12-18 | 恩多塞特公司 | 用于car t细胞疗法的顺序方法 |
| WO2019168984A1 (en) | 2018-02-27 | 2019-09-06 | Gritstone Oncology, Inc. | Neoantigen identification with pan-allele models |
| CA3093020A1 (en) | 2018-03-29 | 2019-10-03 | Fate Therapeutics, Inc. | Engineered immune effector cells and use thereof |
| CA3091490A1 (en) * | 2018-04-27 | 2019-10-31 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Rapamycin resistant cells |
| US12448426B2 (en) | 2018-05-17 | 2025-10-21 | St. Jude Children's Research Hospital, Inc. | Chimeric antigen receptors with MYD88 and CD40 costimulatory domains |
| EP3734700B1 (en) | 2018-07-26 | 2025-06-04 | LG Energy Solution, Ltd. | Separator and electrochemical device comprising same |
| WO2020117526A1 (en) | 2018-12-02 | 2020-06-11 | Fate Therapeutics, Inc. | IMMUNOTHERAPIES USING ENHANCED iPSC DERIVED EFFECTOR CELLS |
| AU2019397048A1 (en) * | 2018-12-13 | 2021-06-24 | Bellicum Pharmaceuticals, Inc. | PSCA CAR-T cells |
| WO2020163408A2 (en) * | 2019-02-04 | 2020-08-13 | Oisin Biotechnologies, Inc. | Fusogenic lipid nanoparticles for the target cell-specific production of rapamycin inducible therapeutic proteins |
| US20220204575A1 (en) * | 2019-04-23 | 2022-06-30 | The Regents Of The University Of California | Modulating survival of therapeutic cells and methods, cells and nucleic acids related thereto |
| CN110079504A (zh) * | 2019-05-06 | 2019-08-02 | 山东大学第二医院 | 一种含有不稳定结构域的car-t细胞及其制备方法和调节car-t细胞功能方法 |
| US20220273717A1 (en) * | 2019-08-12 | 2022-09-01 | Bellicum Pharmaceuticals, Inc. | Improved formulations for immune cells |
| CN110592014A (zh) * | 2019-08-14 | 2019-12-20 | 广东美赛尔细胞生物科技有限公司 | 一种在nk细胞治疗中免辐照体外体内持续去除饲养细胞的方法 |
| CN112430578A (zh) * | 2019-08-26 | 2021-03-02 | 深圳宾德生物技术有限公司 | 携带安全开关并靶向Her2的嵌合抗原受体T细胞及其制备方法和应用 |
| AU2020340424A1 (en) * | 2019-08-30 | 2022-03-31 | Shattuck Labs, Inc. | Chimeric proteins in autoimmunity |
| WO2021155369A1 (en) * | 2020-01-31 | 2021-08-05 | The Board Of Trustees Of The Leland Stanford Junior University | Systems and methods to identify genetic silencers and applications thereof |
| WO2021231806A1 (en) * | 2020-05-13 | 2021-11-18 | Rapa Therapeutics, Llc | Antigen presenting t cells, sensitized, manufactured t cells and methods of treatment using the same |
| WO2021257574A1 (en) * | 2020-06-15 | 2021-12-23 | Kiromic Biopharma Inc. | Tri-switch technology for multi-dimensional control of cell therapy |
| AU2021292695A1 (en) | 2020-06-19 | 2023-02-02 | Fate Therapeutics, Inc. | Combining iPSC-derived effector cell types for immunotherapy use |
| CN112575035B (zh) * | 2020-12-09 | 2022-11-29 | 贵州医科大学 | 一种诱导细胞凋亡的载体系统 |
| CN119256075A (zh) | 2022-04-08 | 2025-01-03 | 菲特治疗公司 | 具有实体瘤靶向骨架的细胞及其用途 |
| US20250222029A1 (en) | 2022-04-08 | 2025-07-10 | Fate Therapeutics, Inc. | Chimeric antigen receptor for tumor targeting |
| IL317038A (en) * | 2022-05-16 | 2025-01-01 | Childrens Medical Ct Corp | Compositions and methods for treating a cardiac disease |
| EP4634216A1 (en) | 2022-12-16 | 2025-10-22 | Repertoire Immune Medicines, Inc. | T cell receptors binding hpv-16 epitopes |
| WO2025054345A1 (en) * | 2023-09-05 | 2025-03-13 | Remedium Bio, Inc. | Genetic elements for adjustment of expression |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6187757B1 (en) * | 1995-06-07 | 2001-02-13 | Ariad Pharmaceuticals, Inc. | Regulation of biological events using novel compounds |
| EP1045915A2 (en) * | 1998-01-15 | 2000-10-25 | Ariad Gene Therapeutics, Inc. | Regulation of biological events using multimeric chimeric proteins |
| WO2014151960A2 (en) * | 2013-03-14 | 2014-09-25 | Bellicum Pharmaceuticals, Inc. | Methods for controlling t cell proliferation |
| EP3569253A1 (en) * | 2013-06-05 | 2019-11-20 | Bellicum Pharmaceuticals, Inc. | Methods for inducing partial apoptosis using caspase polypeptides |
| US10196444B2 (en) * | 2013-07-29 | 2019-02-05 | Bluebird Bio, Inc. | Multipartite signaling proteins and uses thereof |
| CA2937750A1 (en) * | 2014-02-14 | 2015-08-20 | Bellicum Pharmaceuticals, Inc. | Methods for activating t cells using an inducible chimeric polypeptide |
| GB201503133D0 (en) * | 2015-02-24 | 2015-04-08 | Ucl Business Plc And Syncona Partners Llp | Chimeric protein |
-
2016
- 2016-12-13 CA CA3007473A patent/CA3007473A1/en active Pending
- 2016-12-13 CN CN202310839876.4A patent/CN117402829A/zh active Pending
- 2016-12-13 KR KR1020187020145A patent/KR20180087423A/ko not_active Ceased
- 2016-12-13 AU AU2016370470A patent/AU2016370470B2/en not_active Ceased
- 2016-12-13 CN CN201680081930.1A patent/CN108779163A/zh active Pending
- 2016-12-13 JP JP2018530845A patent/JP2019506143A/ja not_active Withdrawn
- 2016-12-13 WO PCT/US2016/066371 patent/WO2017106185A2/en not_active Ceased
- 2016-12-13 SG SG11201804694SA patent/SG11201804694SA/en unknown
- 2016-12-13 US US15/377,776 patent/US20170166877A1/en not_active Abandoned
- 2016-12-13 EP EP16826509.8A patent/EP3390434A2/en active Pending
-
2021
- 2021-03-31 US US17/219,116 patent/US20230065562A1/en not_active Abandoned
- 2021-12-10 JP JP2021200645A patent/JP2022031906A/ja not_active Withdrawn
-
2023
- 2023-09-21 US US18/471,761 patent/US20240368574A1/en active Pending
-
2024
- 2024-06-28 JP JP2024105063A patent/JP2024120106A/ja active Pending
- 2024-06-28 JP JP2024105062A patent/JP2024120105A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2019506143A (ja) | 2019-03-07 |
| US20170166877A1 (en) | 2017-06-15 |
| AU2016370470A8 (en) | 2018-12-13 |
| CN117402829A (zh) | 2024-01-16 |
| JP2024120105A (ja) | 2024-09-03 |
| US20230065562A1 (en) | 2023-03-02 |
| JP2024120106A (ja) | 2024-09-03 |
| JP2022031906A (ja) | 2022-02-22 |
| EP3390434A2 (en) | 2018-10-24 |
| WO2017106185A8 (en) | 2018-06-21 |
| KR20180087423A (ko) | 2018-08-01 |
| AU2016370470B2 (en) | 2022-05-12 |
| WO2017106185A3 (en) | 2017-07-27 |
| SG11201804694SA (en) | 2018-07-30 |
| US20240368574A1 (en) | 2024-11-07 |
| WO2017106185A2 (en) | 2017-06-22 |
| CN108779163A (zh) | 2018-11-09 |
| AU2016370470A1 (en) | 2018-06-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240368574A1 (en) | Dual controls for therapeutic cell activation or elimination | |
| US20220125837A1 (en) | Methods for controlled elimination of therapeutic cells | |
| EP3234145B1 (en) | Methods for controlled activation or elimination of therapeutic cells | |
| US11839647B2 (en) | Methods for inducing partial apoptosis using caspase polypeptides | |
| EP2967081B1 (en) | Modified caspase polypeptides and uses thereof | |
| HK1245827A1 (en) | Methods for controlled activation or elimination of therapeutic cells | |
| US20150328292A1 (en) | Caspase polypeptides having modified activity and uses thereof | |
| HK40022584A (en) | Methods for controlled activation or elimination of therapeutic cells | |
| HK1223647B (en) | Methods for inducing partial apoptosis using caspase polypeptides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20211206 |
|
| EEER | Examination request |
Effective date: 20211206 |
|
| EEER | Examination request |
Effective date: 20211206 |
|
| EEER | Examination request |
Effective date: 20211206 |
|
| EEER | Examination request |
Effective date: 20211206 |
|
| EEER | Examination request |
Effective date: 20211206 |
|
| EEER | Examination request |
Effective date: 20211206 |