JP2015535689A - 免疫療法のための組成物および方法 - Google Patents
免疫療法のための組成物および方法 Download PDFInfo
- Publication number
- JP2015535689A JP2015535689A JP2015534828A JP2015534828A JP2015535689A JP 2015535689 A JP2015535689 A JP 2015535689A JP 2015534828 A JP2015534828 A JP 2015534828A JP 2015534828 A JP2015534828 A JP 2015534828A JP 2015535689 A JP2015535689 A JP 2015535689A
- Authority
- JP
- Japan
- Prior art keywords
- cells
- antigen
- cell
- receptor
- immune response
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 100
- 239000000203 mixture Substances 0.000 title description 33
- 238000009169 immunotherapy Methods 0.000 title description 3
- 210000004027 cell Anatomy 0.000 claims abstract description 327
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 284
- 239000000427 antigen Substances 0.000 claims abstract description 271
- 102000036639 antigens Human genes 0.000 claims abstract description 271
- 108091007433 antigens Proteins 0.000 claims abstract description 271
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 185
- 108091008034 costimulatory receptors Proteins 0.000 claims abstract description 115
- 230000028993 immune response Effects 0.000 claims abstract description 99
- 108020003175 receptors Proteins 0.000 claims abstract description 70
- 230000009826 neoplastic cell growth Effects 0.000 claims abstract description 46
- 238000011282 treatment Methods 0.000 claims abstract description 42
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims abstract description 30
- 210000003289 regulatory T cell Anatomy 0.000 claims abstract description 5
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 119
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 88
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 88
- 102000005962 receptors Human genes 0.000 claims description 67
- 102100036735 Prostate stem cell antigen Human genes 0.000 claims description 66
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 53
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 53
- 230000014509 gene expression Effects 0.000 claims description 40
- 150000007523 nucleic acids Chemical group 0.000 claims description 36
- 239000003446 ligand Substances 0.000 claims description 35
- 239000013598 vector Substances 0.000 claims description 35
- 241000701022 Cytomegalovirus Species 0.000 claims description 33
- 210000004881 tumor cell Anatomy 0.000 claims description 33
- 108091008874 T cell receptors Proteins 0.000 claims description 26
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 25
- -1 EGP-40 Proteins 0.000 claims description 24
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 23
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 23
- 208000015181 infectious disease Diseases 0.000 claims description 21
- 206010060862 Prostate cancer Diseases 0.000 claims description 20
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 20
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 19
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 19
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 claims description 17
- 102000003735 Mesothelin Human genes 0.000 claims description 17
- 108090000015 Mesothelin Proteins 0.000 claims description 17
- 230000001717 pathogenic effect Effects 0.000 claims description 17
- 230000011664 signaling Effects 0.000 claims description 17
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 claims description 16
- 102100040120 Prominin-1 Human genes 0.000 claims description 16
- 244000052769 pathogen Species 0.000 claims description 16
- 102100032912 CD44 antigen Human genes 0.000 claims description 14
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 claims description 14
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims description 14
- 230000004068 intracellular signaling Effects 0.000 claims description 13
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 claims description 12
- 230000003612 virological effect Effects 0.000 claims description 12
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 11
- 206010006187 Breast cancer Diseases 0.000 claims description 10
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims description 10
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims description 10
- 230000001605 fetal effect Effects 0.000 claims description 10
- 210000004698 lymphocyte Anatomy 0.000 claims description 10
- 230000004936 stimulating effect Effects 0.000 claims description 10
- 101000920667 Homo sapiens Epithelial cell adhesion molecule Proteins 0.000 claims description 9
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 claims description 9
- 102100032816 Integrin alpha-6 Human genes 0.000 claims description 9
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 9
- 229940014144 folate Drugs 0.000 claims description 9
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 9
- 235000019152 folic acid Nutrition 0.000 claims description 9
- 239000011724 folic acid Substances 0.000 claims description 9
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims description 8
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 claims description 8
- 102000003729 Neprilysin Human genes 0.000 claims description 8
- 108090000028 Neprilysin Proteins 0.000 claims description 8
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims description 8
- 102100035721 Syndecan-1 Human genes 0.000 claims description 8
- 230000001939 inductive effect Effects 0.000 claims description 8
- 102000006306 Antigen Receptors Human genes 0.000 claims description 7
- 108010083359 Antigen Receptors Proteins 0.000 claims description 7
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 7
- 206010033128 Ovarian cancer Diseases 0.000 claims description 7
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 7
- 230000003213 activating effect Effects 0.000 claims description 7
- 102100032937 CD40 ligand Human genes 0.000 claims description 6
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 claims description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 6
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 claims description 6
- 230000030833 cell death Effects 0.000 claims description 6
- 108700012439 CA9 Proteins 0.000 claims description 5
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 claims description 5
- 108010009685 Cholinergic Receptors Proteins 0.000 claims description 5
- 208000034578 Multiple myelomas Diseases 0.000 claims description 5
- 102000034337 acetylcholine receptors Human genes 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 4
- 208000004736 B-Cell Leukemia Diseases 0.000 claims description 4
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 4
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 4
- 102000016289 Cell Adhesion Molecules Human genes 0.000 claims description 4
- 108010067225 Cell Adhesion Molecules Proteins 0.000 claims description 4
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 claims description 4
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims description 4
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 4
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 4
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 4
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 claims description 4
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 claims description 4
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims description 4
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 claims description 4
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 4
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 claims description 4
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 4
- 102100025306 Integrin alpha-IIb Human genes 0.000 claims description 4
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 4
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 4
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 4
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 4
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 4
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 4
- 102100026423 Adhesion G protein-coupled receptor E5 Human genes 0.000 claims description 3
- 102100027207 CD27 antigen Human genes 0.000 claims description 3
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 claims description 3
- 101000718243 Homo sapiens Adhesion G protein-coupled receptor E5 Proteins 0.000 claims description 3
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 3
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 claims description 3
- 101001103039 Homo sapiens Inactive tyrosine-protein kinase transmembrane receptor ROR1 Proteins 0.000 claims description 3
- 101001103036 Homo sapiens Nuclear receptor ROR-alpha Proteins 0.000 claims description 3
- 102100039615 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Human genes 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 claims 7
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 claims 6
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 claims 4
- 102100034256 Mucin-1 Human genes 0.000 claims 4
- 102100022019 Pregnancy-specific beta-1-glycoprotein 2 Human genes 0.000 claims 4
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 claims 3
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 claims 3
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 claims 3
- 101150047061 tag-72 gene Proteins 0.000 claims 2
- 230000001965 increasing effect Effects 0.000 abstract description 12
- 230000003902 lesion Effects 0.000 abstract description 3
- 101710120463 Prostate stem cell antigen Proteins 0.000 description 59
- 241000699670 Mus sp. Species 0.000 description 46
- 108090000765 processed proteins & peptides Proteins 0.000 description 44
- 102000004196 processed proteins & peptides Human genes 0.000 description 40
- 229920001184 polypeptide Polymers 0.000 description 39
- 108090000623 proteins and genes Proteins 0.000 description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
- 102000039446 nucleic acids Human genes 0.000 description 28
- 108020004707 nucleic acids Proteins 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 25
- 230000004913 activation Effects 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 235000018102 proteins Nutrition 0.000 description 24
- 241000700605 Viruses Species 0.000 description 21
- 230000008029 eradication Effects 0.000 description 21
- 102000004127 Cytokines Human genes 0.000 description 20
- 108090000695 Cytokines Proteins 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 19
- 238000010361 transduction Methods 0.000 description 18
- 230000026683 transduction Effects 0.000 description 18
- 201000010099 disease Diseases 0.000 description 17
- 239000012634 fragment Substances 0.000 description 17
- 230000009089 cytolysis Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 230000006044 T cell activation Effects 0.000 description 14
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 14
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 14
- 150000001413 amino acids Chemical group 0.000 description 14
- 238000013459 approach Methods 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 14
- 230000000139 costimulatory effect Effects 0.000 description 14
- 230000035755 proliferation Effects 0.000 description 14
- 230000001177 retroviral effect Effects 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 12
- 230000008685 targeting Effects 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 230000007774 longterm Effects 0.000 description 11
- 238000004020 luminiscence type Methods 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 102000040430 polynucleotide Human genes 0.000 description 11
- 108091033319 polynucleotide Proteins 0.000 description 11
- 239000002157 polynucleotide Substances 0.000 description 11
- 208000023958 prostate neoplasm Diseases 0.000 description 11
- 230000001225 therapeutic effect Effects 0.000 description 11
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 10
- 108700010039 chimeric receptor Proteins 0.000 description 10
- 239000001509 sodium citrate Substances 0.000 description 10
- 230000009885 systemic effect Effects 0.000 description 10
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 10
- 229940038773 trisodium citrate Drugs 0.000 description 10
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000001086 cytosolic effect Effects 0.000 description 9
- 210000000822 natural killer cell Anatomy 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 230000002265 prevention Effects 0.000 description 9
- 230000000638 stimulation Effects 0.000 description 9
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 8
- 239000005090 green fluorescent protein Substances 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 206010061598 Immunodeficiency Diseases 0.000 description 7
- 108060003951 Immunoglobulin Proteins 0.000 description 7
- 206010039491 Sarcoma Diseases 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 102000018358 immunoglobulin Human genes 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 210000005259 peripheral blood Anatomy 0.000 description 7
- 239000011886 peripheral blood Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 230000028327 secretion Effects 0.000 description 7
- 210000000130 stem cell Anatomy 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 description 6
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 6
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 6
- 108010008707 Mucin-1 Proteins 0.000 description 6
- 102000007298 Mucin-1 Human genes 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000006052 T cell proliferation Effects 0.000 description 6
- 102100022748 Wilms tumor protein Human genes 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 208000009956 adenocarcinoma Diseases 0.000 description 6
- 230000004940 costimulation Effects 0.000 description 6
- 230000009977 dual effect Effects 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 230000009257 reactivity Effects 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 5
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 5
- 201000009030 Carcinoma Diseases 0.000 description 5
- 208000035473 Communicable disease Diseases 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 101001039269 Rattus norvegicus Glycine N-methyltransferase Proteins 0.000 description 5
- 230000000890 antigenic effect Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000006037 cell lysis Effects 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 201000001441 melanoma Diseases 0.000 description 5
- 230000009401 metastasis Effects 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 230000009385 viral infection Effects 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- 241000194017 Streptococcus Species 0.000 description 4
- 238000000692 Student's t-test Methods 0.000 description 4
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 4
- 230000000735 allogeneic effect Effects 0.000 description 4
- 238000011316 allogeneic transplantation Methods 0.000 description 4
- 230000006023 anti-tumor response Effects 0.000 description 4
- 210000003719 b-lymphocyte Anatomy 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229910052804 chromium Inorganic materials 0.000 description 4
- 239000011651 chromium Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000010494 dissociation reaction Methods 0.000 description 4
- 230000005593 dissociations Effects 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 208000026278 immune system disease Diseases 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 201000010198 papillary carcinoma Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012353 t test Methods 0.000 description 4
- 210000001541 thymus gland Anatomy 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- RJBDSRWGVYNDHL-XNJNKMBASA-N (2S,4R,5S,6S)-2-[(2S,3R,4R,5S,6R)-5-[(2S,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(E,2R,3S)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-5-amino-6-[(1S,2R)-2-[(2S,4R,5S,6S)-5-amino-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-1,3-dihydroxypropyl]-4-hydroxyoxane-2-carboxylic acid Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@H](CO[C@@H]1O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O[C@@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3NC(C)=O)[C@H](O[C@@]3(C[C@@H](O)[C@H](N)[C@H](O3)[C@H](O)[C@@H](CO)O[C@@]3(C[C@@H](O)[C@H](N)[C@H](O3)[C@H](O)[C@H](O)CO)C(O)=O)C(O)=O)[C@H]2O)[C@H](O)[C@H]1O)[C@@H](O)\C=C\CCCCCCCCCCCCC RJBDSRWGVYNDHL-XNJNKMBASA-N 0.000 description 3
- 108010082808 4-1BB Ligand Proteins 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 3
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 206010014967 Ependymoma Diseases 0.000 description 3
- 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 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 3
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 3
- 101000655352 Homo sapiens Telomerase reverse transcriptase Proteins 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 208000000172 Medulloblastoma Diseases 0.000 description 3
- 206010029260 Neuroblastoma Diseases 0.000 description 3
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 3
- 101000588258 Taenia solium Paramyosin Proteins 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 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 3
- 230000033228 biological regulation Effects 0.000 description 3
- 238000002659 cell therapy Methods 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 230000001613 neoplastic effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 108010054624 red fluorescent protein Proteins 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 201000005112 urinary bladder cancer Diseases 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 description 2
- 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
- 206010004593 Bile duct cancer Diseases 0.000 description 2
- 108010029697 CD40 Ligand Proteins 0.000 description 2
- 102100025221 CD70 antigen Human genes 0.000 description 2
- 208000005243 Chondrosarcoma Diseases 0.000 description 2
- 201000009047 Chordoma Diseases 0.000 description 2
- 208000006332 Choriocarcinoma Diseases 0.000 description 2
- 208000009798 Craniopharyngioma Diseases 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- 108090000176 Interleukin-13 Proteins 0.000 description 2
- 102000003816 Interleukin-13 Human genes 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- 206010027406 Mesothelioma Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 201000010133 Oligodendroglioma Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 208000007452 Plasmacytoma Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- 230000024932 T cell mediated immunity Effects 0.000 description 2
- 102000046283 TNF-Related Apoptosis-Inducing Ligand Human genes 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 101710097160 Tumor necrosis factor ligand superfamily member 10 Proteins 0.000 description 2
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 208000014070 Vestibular schwannoma Diseases 0.000 description 2
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 208000004064 acoustic neuroma Diseases 0.000 description 2
- 230000002424 anti-apoptotic effect Effects 0.000 description 2
- 230000000118 anti-neoplastic effect Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 230000007503 antigenic stimulation Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 208000024207 chronic leukemia Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 208000002445 cystadenocarcinoma Diseases 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 208000010932 epithelial neoplasm Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 230000005714 functional activity Effects 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 208000025750 heavy chain disease Diseases 0.000 description 2
- 201000002222 hemangioblastoma Diseases 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 230000021633 leukocyte mediated immunity Effects 0.000 description 2
- 206010024627 liposarcoma Diseases 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 208000012804 lymphangiosarcoma Diseases 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 208000001611 myxosarcoma Diseases 0.000 description 2
- 201000008026 nephroblastoma Diseases 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 230000020978 protein processing Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 210000003708 urethra Anatomy 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 1
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
- 206010048998 Acute phase reaction Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 241000701242 Adenoviridae Species 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000701386 African swine fever virus Species 0.000 description 1
- 241000004176 Alphacoronavirus Species 0.000 description 1
- 241000712892 Arenaviridae Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 208000005440 Basal Cell Neoplasms Diseases 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 108010046080 CD27 Ligand Proteins 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 241000422252 Cales Species 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000193449 Clostridium tetani Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000186227 Corynebacterium diphtheriae Species 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 241000252233 Cyprinus carpio Species 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 241001466953 Echovirus Species 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000000832 Equine Encephalomyelitis Diseases 0.000 description 1
- 241000186810 Erysipelothrix rhusiopathiae Species 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 102000015212 Fas Ligand Protein Human genes 0.000 description 1
- 108010039471 Fas Ligand Protein Proteins 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000605986 Fusobacterium nucleatum Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 206010061192 Haemorrhagic fever Diseases 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 208000037262 Hepatitis delta Diseases 0.000 description 1
- 206010019786 Hepatitis non-A non-B Diseases 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 1
- 101000904196 Homo sapiens Pancreatic secretory granule membrane major glycoprotein GP2 Proteins 0.000 description 1
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102100020793 Interleukin-13 receptor subunit alpha-2 Human genes 0.000 description 1
- 101710112634 Interleukin-13 receptor subunit alpha-2 Proteins 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102100030704 Interleukin-21 Human genes 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 241000701377 Iridoviridae Species 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 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
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000589902 Leptospira Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 102000003959 Lymphotoxin-beta Human genes 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 208000030070 Malignant epithelial tumor of ovary Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 241000187484 Mycobacterium gordonae Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 241000588650 Neisseria meningitidis Species 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 241000714209 Norwalk virus Species 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 102000004473 OX40 Ligand Human genes 0.000 description 1
- 108010042215 OX40 Ligand Proteins 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 241000702259 Orbivirus Species 0.000 description 1
- 241000713112 Orthobunyavirus Species 0.000 description 1
- 241000150452 Orthohantavirus Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
- 102100024019 Pancreatic secretory granule membrane major glycoprotein GP2 Human genes 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241000606860 Pasteurella Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 108010047620 Phytohemagglutinins Proteins 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241001505332 Polyomavirus sp. Species 0.000 description 1
- 241000700625 Poxviridae Species 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000702247 Reoviridae Species 0.000 description 1
- 241000702263 Reovirus sp. Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 241000711931 Rhabdoviridae Species 0.000 description 1
- 241000606701 Rickettsia Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000702670 Rotavirus Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241001478880 Streptobacillus moniliformis Species 0.000 description 1
- 241000194049 Streptococcus equinus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 206010043515 Throat cancer Diseases 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 101800000385 Transmembrane protein Proteins 0.000 description 1
- 102000008579 Transposases Human genes 0.000 description 1
- 108010020764 Transposases Proteins 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 241000589904 Treponema pallidum subsp. pertenue Species 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 102000012883 Tumor Necrosis Factor Ligand Superfamily Member 14 Human genes 0.000 description 1
- 108010065158 Tumor Necrosis Factor Ligand Superfamily Member 14 Proteins 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 description 1
- 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 1
- 108091005956 Type II transmembrane proteins Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 0.000 description 1
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
- 101710127857 Wilms tumor protein Proteins 0.000 description 1
- 241000710772 Yellow fever virus Species 0.000 description 1
- 108010017070 Zinc Finger Nucleases Proteins 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
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
- 230000004658 acute-phase response Effects 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 244000309743 astrovirus Species 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 201000007180 bile duct carcinoma Diseases 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000003714 breast lobular carcinoma Diseases 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000008614 cellular interaction Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000009614 chemical analysis method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000012707 chemical precursor Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000003145 cytotoxic factor Substances 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000005860 defense response to virus Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 239000012645 endogenous antigen Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- JKLNYGDWYRKFKR-UHFFFAOYSA-N ethyl methyl sulfate Chemical compound CCOS(=O)(=O)OC JKLNYGDWYRKFKR-UHFFFAOYSA-N 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000029570 hepatitis D virus infection Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008004 immune attack Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000004073 interleukin-2 production Effects 0.000 description 1
- 108010074108 interleukin-21 Proteins 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 208000037829 lymphangioendotheliosarcoma Diseases 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000004882 non-tumor cell Anatomy 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009589 pathological growth Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001885 phytohemagglutinin Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 210000004560 pineal gland Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 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 compound [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
- 230000003449 preventive effect Effects 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940021993 prophylactic vaccine Drugs 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 208000028172 protozoa infectious disease Diseases 0.000 description 1
- 210000000512 proximal kidney tubule Anatomy 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 201000007321 sebaceous carcinoma Diseases 0.000 description 1
- 208000018964 sebaceous gland cancer Diseases 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 201000008759 sweat gland cancer Diseases 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 201000008753 synovium neoplasm Diseases 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000009258 tissue cross reactivity Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000005102 tumor initiating cell Anatomy 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 241000724775 unclassified viruses Species 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Images
Classifications
-
- 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
- C07K16/2803—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 immunoglobulin superfamily
- C07K16/2809—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 immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- 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
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- 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
- A61K39/0011—Cancer antigens
-
- 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
- A61K39/001102—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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001106—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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001109—Vascular endothelial growth factor receptors [VEGFR]
-
- 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
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001111—Immunoglobulin superfamily
- A61K39/001113—CD22, BL-CAM, siglec-2 or sialic acid- binding Ig-related lectin 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001111—Immunoglobulin superfamily
- A61K39/001114—CD74, Ii, MHC class II invariant chain or MHC class II gamma chain
-
- 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
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001116—Receptors for cytokines
- A61K39/001117—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR] or CD30
-
- 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
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001116—Receptors for cytokines
- A61K39/001119—Receptors for interleukins [IL]
-
- 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
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001124—CD20
-
- 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
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001128—CD44 not IgG
-
- 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
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001129—Molecules with a "CD" designation not provided for elsewhere
-
- 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
- A61K39/001152—Transcription factors, e.g. SOX or c-MYC
- A61K39/001153—Wilms tumor 1 [WT1]
-
- 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
- A61K39/001154—Enzymes
- A61K39/001157—Telomerase or TERT [telomerase reverse transcriptase]
-
- 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
- A61K39/001166—Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
-
- 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
- A61K39/001166—Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
- A61K39/001168—Mesothelin [MSLN]
-
- 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
- A61K39/001169—Tumor associated carbohydrates
- A61K39/00117—Mucins, e.g. MUC-1
-
- 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
- A61K39/001169—Tumor associated carbohydrates
- A61K39/001171—Gangliosides, e.g. GM2, GD2 or GD3
-
- 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
- A61K39/00118—Cancer antigens from embryonic or fetal origin
-
- 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
- A61K39/00118—Cancer antigens from embryonic or fetal origin
- A61K39/001182—Carcinoembryonic antigen [CEA]
-
- 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
- A61K39/001184—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K39/001186—MAGE
-
- 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
- A61K39/001184—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K39/001188—NY-ESO
-
- 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
- A61K39/001193—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
-
- 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
- A61K39/001193—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
- A61K39/001195—Prostate specific membrane antigen [PSMA]
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/44—Antibodies bound to carriers
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- 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
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464493—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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464493—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]
- A61K39/464495—Prostate specific membrane antigen [PSMA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- 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
-
- 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
- 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
- C07K14/70517—CD8
-
- 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
- C07K14/70521—CD28, CD152
-
- 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
- C07K16/2803—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 immunoglobulin superfamily
-
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
-
- 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)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/74—Inducing cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
-
- 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
-
- 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
- C12N2999/00—Further aspects of viruses or vectors not covered by groups C12N2710/00 - C12N2796/00 or C12N2800/00
- C12N2999/002—Adverse teaching
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Developmental Biology & Embryology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Vascular Medicine (AREA)
- Virology (AREA)
Abstract
Description
本願は、2012年10月2日に出願された米国仮出願第61/709,072号に対する優先権を主張する通常出願である。米国仮出願第61/709,072号の内容は、ここで参照により本願に援用される。
本願は、配列表(2013年9月30日作製)を含み、そのファイル(ASCIIフォーマット)は、3314040AWO_Sequence Listing_ST25.txtと称され、サイズは27.5キロバイトである。上記配列表ファイルは、その全体において本願に参考として援用される。
前立腺がんは、米国の男性で最も頻度の高いがんであり、これが原因でほぼ31,000名が毎年死亡する。初期に診断されると、がんは、手術もしくは放射線療法によって効率的に処置され得る。術後の残存疾病は、放射線療法および/もしくはホルモン療法を要し、これらの療法は、腫瘍進行および転移を予防し得る。現時点で、ホルモン不応性の転移性前立腺がんの治癒措置はない。免疫療法は、このようながんの処置を原則として提供する標的療法である。
本発明は、一般に、免疫細胞活性化活性を有する抗原結合レセプター(例えば、CARもしくはTCR)およびキメラ共刺激レセプター(CCR)を発現する免疫応答細胞(T細胞およびナチュラルキラー(NK)細胞が挙げられる)、ならびに新形成、感染性疾患、および他の病変の処置のためのその使用法を提供する。
本明細書中で言及される全ての特許、公開特許出願、および他の参考文献は、本開示へと本明細書で参考として援用される。
哺乳動物の造血(血液)細胞は、多様な範囲の生理学的活性を提供する。造血細胞は、リンパ系統、骨髄系統および赤血球系統に分けられる。リンパ系統(B細胞、T細胞およびナチュラルキラー(NK)細胞を含む)は、抗体の生成、細胞免疫系の調節、血液中の外来因子の検出、宿主に対して外来の細胞の検出などを提供する。用語「T細胞」とは、本明細書で使用される場合、胸腺中で成熟し、細胞媒介性免疫を主に担うリンパ球をいう。T細胞は、獲得免疫系に関与する。用語「ナチュラルキラー(NK)細胞」とは、本明細書で使用される場合、細胞媒介性免疫の一部であり、先天性免疫応答の間に作用するリンパ球をいう。それらは、標的細胞に対してそれらの細胞傷害性効果を発揮するための、事前の活性化を必要としない。細胞傷害性T細胞(CTLもしくはキラーT細胞)は、感染した体細胞もしくは腫瘍細胞の死滅を誘導し得るTリンパ球のサブセットである。
本発明は、免疫応答細胞を活性化する抗原認識レセプター(例えば、TCR、CAR)およびキメラ共刺激レセプター(CCR)の組み合わせを発現する細胞、ならびに増強された免疫応答を必要とする疾患の処置のためにこのような細胞を使用する方法を提供する。1つのアプローチにおいて、腫瘍抗原特異的T細胞、NK細胞、CTL細胞もしくは他の免疫応答細胞は、新形成の処置もしくは予防のための1以上の共刺激リガンドを選択的富化するためのシャトル(shuttles)として使用される。例えば、CD19を認識するキメラ抗原レセプター19z1を発現するT細胞は、前立腺特異的膜抗原(PSMA)を認識しかつ結合するキメラ共刺激レセプターP28BBを発現するT細胞において共発現される。このような細胞は、前立腺がんの処置もしくは予防のために、その必要性のあるヒト被験体に投与される。別のアプローチにおいて、ウイルス抗原特異的T細胞、NK細胞、CTL細胞は、ウイルス疾患の処置のために使用され得る。例えば、第1のCMV抗原を認識するキメラ共刺激抗原レセプターおよび第2のCMV抗原を認識しかつ結合するキメラ抗原レセプターは、CMVの処置のために細胞傷害性T細胞で共発現される。
本発明の方法において使用され得る腫瘍抗原特異的ヒトリンパ球のタイプとしては、キメラ抗原レセプター(CAR)を発現するように遺伝子改変された末梢血ドナーリンパ球(Sadelain, M., et al. 2003 Nat Rev Cancer 3:35−45)、aおよびpヘテロダイマーを含む全長腫瘍抗原認識T細胞レセプター複合体を発現するように遺伝子改変された末梢血ドナーリンパ球(Morgan, R.A., et al. 2006 Science 314:126−129)、腫瘍生検における腫瘍浸潤リンパ球(TIL)に由来するリンパ球培養物(Panelli, M.C., et al. 2000 J Immunol 164:495−504; Panelli, M.C., et al. 2000 J Immunol 164:4382−4392)、および人工抗原提示細胞(AAPC)もしくはパルス樹状細胞を使用する選択的にインビトロで増大した抗原特異的末梢血白血球(Dupont, J., et al. 2005 Cancer Res 65:5417−5427; Papanicolaou, G.A., et al. 2003 Blood 102:2498−2505)が挙げられるが、これらに限定されない。上記T細胞は、自己由来であっても、同種異系であっても、操作された前駆細胞もしくは幹細胞からのインビトロ由来であってもよい。
病原体感染もしくは他の感染性疾患の処置において(例えば、免疫無防備状態の被験体において)使用するために適した抗原としては、サイトメガロウイルス(CMV)、エプスタイン・バーウイルス(EBV)、ヒト免疫不全ウイルス(HIV)、およびインフルエンザウイルスに存在するウイルス抗原が挙げられるが、これらに限定されない。
免疫応答細胞(例えば、T細胞、CTL細胞、NK細胞)の遺伝子改変は、実質的に均一な細胞組成物を組換えDNA構築物で形質導入することによって達成され得る。好ましくは、レトロウイルスベクター(γ−レトロウイルスベクターもしくはレンチウイルスベクターのいずれかの)は、上記DNA構築物を上記細胞へと導入するために使用される。例えば、抗原(例えば、腫瘍抗原、またはそのバリアントもしくはフラグメント)を結合するレセプターをコードするポリヌクレオチドは、レトロウイルスベクターにクローニングされ得、その内因性プロモーターから、レトロウイルスの長い末端反復配列から、もしくは目的の標的細胞型に特異的なプロモーターから、発現が駆動され得る。非ウイルスベクターも同様に使用され得る。
少なくとも1種の共刺激リガンドとの相互作用は、免疫細胞(例えば、T細胞)の完全な活性化のために重要な非抗原特異的シグナルを提供する。共刺激リガンドとしては、腫瘍壊死因子(TNF)リガンド、サイトカイン(例えば、IL−2、IL−12、IL−15もしくはIL21)、および免疫グロブリン(lg)スーパーファミリーリガンドが挙げられるが、これらに限定されない。
遺伝子改変された免疫応答細胞を含む本発明の組成物は、都合の良いことには、選択されたpHへと緩衝化され得る滅菌液体調製物(例えば、等張性水性溶液、懸濁物、エマルジョン、分散物、もしくは粘性組成物)として提供され得る。液体調製物は、通常は、ゲル、他の粘性組成物、および固体組成物より調製しやすい。さらに、液体組成物は、投与するのに(特に、注射によって)、いくらかはさらに都合が良い。粘性組成物は、他方で、特定の組織とのより長い接触期間を提供するために、適切な粘性範囲内で製剤化され得る。液体もしくは粘性組成物は、溶媒もしくは分散媒(例えば、水、食塩水、リン酸緩衝化食塩水、ポリオール(例えば、グリセロール、プロピレングリコール、液体ポリエチレングリコールなど)およびこれらの適切な混合物を含む)であり得るキャリアを含み得る。
被験体において新形成を処置するための方法が、本明細書で提供される。被験体(例えば、免疫無防備状態のヒト被験体)において病原体感染もしくは他の感染性疾患を処置するための方法もまた、本明細書で企図される。上記方法は、本発明のT細胞、NK細胞、もしくはCTL細胞を、所望の効果(それは、既存の状態の一時的緩和もしくは再発の防止である)を達成するために有効な量で投与する工程を包含する。処置に関しては、投与される量は、所望の効果を生じることにおいて有効な量である。有効な量は、1回もしくは一連の投与で提供され得る。有効な量は、ボーラスでもしくは連続灌流によって提供され得る。
本発明は、新形成、病原体感染、免疫障害もしくは同種異系移植の処置もしくは予防のためのキットを提供する。一実施形態において、上記キットは、単位投与形態において、活性化抗原レセプターおよび共刺激抗原レセプターを含む免疫応答細胞の有効量を含む治療用組成物もしくは予防用組成物を含む。特定の実施形態において、上記細胞は、共刺激リガンドをさらに含む。いくつかの実施形態において、上記キットは、治療ワクチンもしくは予防ワクチンを含む滅菌容器を含む;このような容器は、箱、アンプル、ボトル、バイアル、チューブ、バッグ、パウチ、ブリスターパック、もしくは当該分野で公知の他の適した容器形態であり得る。このような容器は、プラスチック、ガラス、ラミネート加工紙、金属ホイル、もしくは医薬を保持するために適した他の材料から作製され得る。
本発明は、腫瘍細胞によって共発現される2つの抗原を同時に結合する「腫瘍感知T細胞」を提供する。重要なことには、いずれかの抗原のみを発現する組織に対する反応性は、無視できる程度であり、両方の抗原の存在下でのみT細胞活性化を解放するが、いずれか一方のみでは解放しないということを見出した。本発明は、一部は、選択的T細胞免疫反応性を提供することと合わせて、このアプローチを臨床的に関連させるという発見に少なくとも基づく。第1は、T細胞活性化を1つの抗原(例えば、CD19もしくは前立腺幹細胞抗原、PSCA)に割り当てることであり、これは、T細胞レセプター(TCR)もしくはキメラ抗原レセプター(CAR)によって媒介され得る。共刺激は、独立して、「キメラ共刺激レセプター」(CCR)によって媒介され12,13、これは、第2の抗原(例えば、前立腺特異的膜抗原、PSMA)に標的化される。このアプローチは、二重抗原陽性(DP)腫瘍に対して増大した免疫反応性を生じたが、単一抗原陽性(SP)腫瘍に対する増強された免疫反応性は避けられなかった。腫瘍感知T細胞がDP腫瘍をSP腫瘍から区別するために重要な第2の原理は、T細胞活性化を、それだけでは有効でないが、独立した、共発現される抗原によって結合されるCCRによって腫瘍部位で機能的にレスキューされるレベルへと減少させることである。CARおよびCCRは、HLA−ペプチド複合体ではなく細胞表面抗原を認識するので、この様式で操作されたT細胞は、腫瘍に直接標的化され、標的とした抗原を交差提示する(cross−presenting)細胞との相互作用によって共刺激されない。本明細書で示されるように、このアプローチは、複数の腫瘍を有するマウスにおいて選択的腫瘍根絶を生じた。
γレトロウイルスベクターSFG−19z1は、広く記載されてきた14。この骨格構築物を、scFvを交換して、scFvの5’側に位置するNcoI部位およびscFvの3’側に位置するNod部位を利用する定方向クローニングによってSFG−Hzl、SFG−Mzl、およびSFG−Lzlを生成するために使用した。SFG-P28BBを生成するために、融合したCD28およびCD137ドメインを、SFG-P28BBz1からPCR増幅し、5’ NcoI部位および3’ BamHI部位を使用してPSMA scFvの3’側にライゲーションして、BBドメインの3’側の終止コドンを含めた一方で、CD3ドメインを除去した21。dsREDと共発現されるCARおよびhrGFPと共発現されるCCRのためのバイシストロン遺伝子発現を、以前に記載されるように、内部リボソーム導入部位を使用することによって達成した。ベクターを使用して、細胞株を一過性にトランスフェクトして、以前に記載されるとおりの安定なウイルス生成株を生成した。
3つの新規なPSCA特異的scFv(Hzl、Mzl、およびLzlといわれる)を、以前に記載されるように36ハイブリドーマから縮重プライマーを使用して、非重複エピトープのPSCA抗原特異性を付与する重鎖可変(VH)ドメインおよび軽鎖可変(VL)ドメインを増幅することによって生成した。これらのVHドメインおよびVLドメインを、リンカーを使用して一緒に融合し、5’ SphI部位から3’ NotI部位を使用してSFG−19z1骨格中のCD19 scFvを置き換えるために使用した。
末梢血白血球を、Ficoll勾配を使用して単離し、以前に記載されるように形質導入した。簡潔には、2 &g/mL フィトヘマグルチニンでの48時間の活性化後、細胞を、次の48時間にわたってレトロネチン被覆プレート上で1時間の遠心接種(spinoculation)を介して2回形質導入し、20 U/mLのIL−2を添加した。ベクター発現のために3日間静置した後、フローサイトメトリーによって形質導入効率を決定し、バルクのソートされていない細胞を、種々のアッセイもしくは養子移入のために使用した。
PC3ヒト前立腺腫瘍株を、ATCCから得、PC3−GFP/Lucを生成するためにレトロウイルスで16形質導入し、その後、これを使用して、10 PC3−CD19、PC3−PSMA、PC3−CD19−PSMA、PC3−PSCA、およびPC3−PSCA−PSMAをレトロウイルス形質導入によって生み出した。
所望の抗原を発現する標的細胞を51Crで標識し、エフェクター:標的比を減少させてT細胞と共培養した。4時間培養した後、上清を取り出し、クロムから放出された放射能を測定するために使用した。特異的溶解を、T細胞と培養しなかった標的細胞のバックグラウンド放射能を差し引いて、0.2% Triton X−100を使用することによって完全に溶解した標的細胞から測定した放射能で除算することによって決定した。
所望の抗原を発現する腫瘍細胞を、1.0×106 T細胞と5:1 エフェクター:標的比で共培養する前に、30Gyで照射した。T細胞を、Invitrogen Countess細胞カウンターを使用して毎週計数し、その後、照射した腫瘍細胞で再刺激した。これらの共培養物に外因性サイトカインは添加しなかった。
PC3腫瘍細胞を、Jackson Laboratories、もしくはMSKCC Institutional Animal Care and Use Committeeによって承認されたプロトコル04−10−024の下での施設内交配のいずれかから得たNOD/SCID−IL2Ryマウスへと注入した。全身腫瘍実験のために、2.0×106 腫瘍をマウスに注入し、14日後に、1.0×106 キメラレセプター陽性T細胞を注入した。皮下腫瘍実験のために、1腫瘍部位あたり1.0×106 腫瘍細胞を注射し、7日間にわたて確立した。その際に、1.0×106 キメラ陽性T細胞をIV注入した。
全身腫瘍実験に関して、生体発光画像化(BLI)を使用して、以前に記載されるようにIVIS 100システム(Caliper Life Sciences)を使用して、腫瘍負荷量の量を発光に相関させることによって、腫瘍負荷量を定量的に測定した。皮下腫瘍に関しては、カリパスを使用して、腫瘍サイズを測定した。各腫瘍の長さ、幅および高さを乗算することによって、腫瘍容積を計算した。
CD3特異的scFvに融合したPSCA特異的scFvを含む二重特異的抗体を、標準的な4時間のクロム放出アッセイにおいて、それぞれ、PSCA+ PC3と20:1比で共培養した形質導入していないT細胞に種々の量、添加した。
細胞を、LSRll フローサイトメーターを使用して分析するか、または以前に記載されるように16FACSAriaセルソーター(BO Biosciences)を使用してソートした。細胞表面でのキメラレセプターの検出を、AF647結合体化ヤギ抗マウス抗体(Invitrogen)を使用することによって直接達成し得る。CD4−PE−Cy7、CD8−Pacific Blue、およびCD19−APCに対する抗体を、Invitrogenから得た一方で、PSCA抗体を、ハイブリドーマ上清から精製し、PSMA抗体をMBL Interantionalから得た。
長期間のT細胞増殖実験からの第2の腫瘍刺激の48時間後に上清を採取し、カスタムマルチプレックスシステムHCYTMAG−60K(Millipore)を使用することによってサイトカイン分析のために使用し、以前に記載されるように21Luminex 100機器(Luminex)を使用して分析した。
長期間のT細胞増殖実験の最初の腫瘍刺激の24時間後に細胞を採取して、BclxL発現のウェスタンブロット分析のために使用した。ウェスタンブロットを、BclxLおよびAkt一次抗体(Cell Signaling Technology)を使用して以前に記載されるように21行った。
Claims (53)
- 免疫応答細胞であって、
a.低親和性で第1の抗原を結合する抗原認識レセプターであって、ここで該第1の抗原への該レセプターの結合は、該免疫応答細胞を活性化させる、抗原認識レセプター;および
b.第2の抗原を結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)、
を含む、免疫応答細胞。 - 前記細胞は、T細胞、ナチュラルキラー(NK)細胞、細胞傷害性Tリンパ球(CTL)、制御性T細胞、ヒト胚性幹細胞、およびリンパ系細胞に分化し得る多能性幹細胞からなる群より選択される、請求項1のいずれか1項に記載の免疫応答細胞。
- 前記抗原は、腫瘍抗原もしくは病原体抗原である、請求項1または2に記載の免疫応答細胞。
- 前記抗原認識レセプターは、T細胞レセプター(TCR)もしくはキメラ抗原レセプター(CAR)である、請求項1〜3のいずれかに記載の免疫応答細胞。
- 前記抗原認識レセプターは、外因性もしくは内因性である、請求項1〜4のいずれか1項に記載の免疫応答細胞。
- 前記抗原認識レセプターは、組換え発現される、請求項1〜5のいずれか1項に記載の免疫応答細胞。
- 前記抗原認識レセプターは、ベクターから発現される、請求項1〜6のいずれか1項に記載の免疫応答細胞。
- 前記キメラ共刺激レセプター(CCR)は、ベクターから発現される、請求項1〜7のいずれか1項に記載の免疫応答細胞。
- 前記免疫応答細胞は、自己由来である、請求項1〜8のいずれか1項に記載の免疫応答細胞。
- 前記第1のおよび第2の抗原は、CAIX、CEA、CDS、CD7、CD10、CD19、CD20、CD22、CD30、CD33、CD34、CD38、CD41、CD44、CD49f、CD56、CD74、CD133、CD138、サイトメガロウイルス(CMV)感染細胞抗原、EGP−2、EGP−40、EpCAM、erb−B2,3,4、FBP、胎児型アセチルコリンレセプター、葉酸レセプター−a、GD2、GD3、HER−2、hTERT、IL−13R−a2、x−軽鎖、KDR、LeY、LI細胞接着分子、MAGE−Al、MUC1、メソテリン、NKG2Dリガンド、NY−ESO−1、腫瘍胎児性抗原(h5T4)、PSCA、PSMA、ROR1、TAG−72、VEGF−R2、もしくはWT−1からなる群より選択される、請求項1〜9のいずれか1項に記載の免疫応答細胞。
- 前記第1のおよび第2の抗原は、CD133、サイトメガロウイルス(CMV)感染細胞抗原、erb−B2、KDRメソテリン、NKG2Dリガンド、NY−ES0−1、腫瘍胎児性抗原(h5T4)、PSCA、PSMA、CD19、VEGF−R2、およびWT−1からなる群より選択される別個の抗原である、請求項1〜9のいずれか1項に記載の免疫応答細胞。
- 前記第1のおよび第2の抗原は、HER2、MUC1、CD44、CD49f、EpCAM、CEA、CD133、サイトメガロウイルス(CMV)感染細胞抗原、EGP−2、EGP−40、EpCAM、erb−B2,3,4、FBP、KDR、メソテリン、NKG2Dリガンド、NY−ES0−1、腫瘍胎児性抗原(h5T4)、PSCA、PSMA、VEGF−R2、もしくはWT−1からなる群より選択される、請求項1〜9のいずれか1項に記載の免疫応答細胞。
- 前記第1のおよび第2の抗原は、CD10およびCD19である、請求項1〜11のいずれか1項に記載の免疫応答細胞。
- 前記第1のおよび第2の抗原は、CD56およびCD138である、請求項1〜11のいずれか1項に記載の免疫応答細胞。
- 前記第1のおよび第2の抗原は、メソテリン、葉酸レセプター−a、CD44、およびCD133からなる群より選択される別個の抗原である、請求項1〜11のいずれか1項に記載の免疫応答細胞。
- 前記抗原認識レセプターの細胞内シグナル伝達ドメインは、CD3鎖シグナル伝達ドメインである、請求項1〜15のいずれか1項に記載の免疫応答細胞。
- 前記キメラ共刺激レセプター(CCR)の細胞内シグナル伝達ドメインは、CD97、CD1 la−CD18、CD2、ICOS、CD27、CD154、CD5、OX40、4−1BBもしくはCD28シグナル伝達ドメインである、請求項1〜16のいずれか1項に記載の免疫応答細胞。
- 前記細胞は、19z1もしくはPz1である抗原レセプターを発現する、請求項1〜17のいずれか1項に記載の免疫応答細胞。
- 腫瘍において腫瘍細胞死を誘導するための方法であって、該方法は、該腫瘍細胞と、免疫応答細胞であって、第1の腫瘍抗原を低親和性で結合し、ここで該結合は該免疫応答細胞を活性化する抗原認識レセプター、および第2の腫瘍抗原を結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)を含む免疫応答細胞とを接触させ、それによって、該腫瘍において腫瘍細胞死を誘導する工程を包含する、方法。
- 前記方法は、腫瘍細胞数を減少させる、請求項19に記載の方法。
- 前記方法は、腫瘍サイズを縮小させる、請求項19に記載の方法。
- 前記方法は、前記腫瘍を根絶する、請求項19に記載の方法。
- 被験体において新形成を処置もしくは予防するための方法であって、該方法は、免疫応答細胞であって、第1の抗原を低親和性で結合し、ここで該結合は、該免疫応答細胞を活性化する抗原認識レセプター、および第2の抗原を結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)を含む、免疫応答細胞の有効量を投与し、それによって、該被験体において新形成を処置もしくは予防する工程、を包含する、方法。
- 前記新形成は、前立腺がん、乳がん、B細胞白血病、多発性骨髄腫、および卵巣がんからなる群より選択される、請求項23に記載の方法。
- 前記新形成は、乳がんであり、前記第1のおよび第2の腫瘍抗原は、HER2、MUC1、CD44、CD49f、EpCAM、CEA、CD133、サイトメガロウイルス(CMV)感染細胞抗原、EGP−2、EGP−40、EpCAM、erb−B2,3,4、FBP、KDR、メソテリン、NKG2Dリガンド、NY−ESO−1、腫瘍胎児性抗原(h5T4)、PSCA、PSMA、VEGF−R2、もしくはWT−1からなる群より選択される別個の抗原である、請求項23に記載の方法。
- 前記新形成は、B細胞白血病であり、前記第1のおよび第2の腫瘍抗原は、CD10およびCD19である、請求項23に記載の方法。
- 前記新形成は、多発性骨髄腫であり、前記第1のおよび第2の腫瘍抗原は、CD56およびCD138である、請求項24に記載の方法。
- 前記新形成は、卵巣がんであり、前記第1のおよび第2の腫瘍抗原は、メソテリン、葉酸レセプター−a、CD44、およびCD133からなる群より選択される別個の抗原である、請求項24に記載の方法。
- 前記免疫応答細胞は、低親和性を有する抗原認識レセプターを有するとして選択される、請求項23〜28のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、低親和性を有するとして前記細胞での発現に関して選択される、請求項23〜28のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、T細胞レセプター(TCR)もしくはキメラ抗原レセプター(CAR)である、請求項23〜28のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、外因性もしくは内因性である、請求項23〜28のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、ベクターから発現される、請求項23〜32のいずれか1項に記載の方法。
- 前記キメラ共刺激レセプター(CCR)は、ベクターから発現される、請求項23〜32のいずれか1項に記載の方法。
- 前記細胞は、T細胞、ナチュラルキラー(NK)細胞、細胞傷害性Tリンパ球(CTL)、制御性T細胞、ヒト胚性幹細胞、およびリンパ系細胞に分化し得る多能性幹細胞からなる群より選択される、請求項23〜34のいずれか1項に記載の方法。
- 前記方法は、前記被験体において腫瘍負荷量を減少させるかもしくは根絶する、請求項23〜35のいずれか1項に記載の方法。
- 腫瘍細胞死を誘導するための方法であって、該方法は、免疫応答細胞であって、低親和性で第1の抗原を結合し、ここで該結合は、該免疫応答細胞を活性化する抗原認識レセプター、および第2の抗原を結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)を含む免疫応答細胞の有効量を投与し、それによって、被験体において腫瘍細胞死を誘導する工程、を包含する、方法。
- 抗原特異的免疫応答細胞を生成するための方法であって、該方法は、該免疫応答細胞に、キメラ共刺激レセプター(CCR)をコードする核酸配列を導入する工程であって、ここで該キメラ共刺激レセプターは、免疫応答細胞を刺激する細胞内シグナル伝達ドメインに連結した抗原結合ドメインを含み、ここで該免疫応答細胞は、第1の抗原を低親和性で結合する抗原認識レセプターを含み、ここで該結合は、該免疫応答細胞を活性化する、工程を包含する、方法。
- 前記方法は、キメラ抗原レセプターをコードする第2の核酸配列を導入する工程をさらに包含し、ここで該キメラ抗原レセプターは、免疫応答細胞を活性化する第2の細胞内シグナル伝達ドメインに連結した第2の抗原結合ドメインを含む、請求項38に記載の方法。
- 前記腫瘍抗原は、CAIX、CEA、CD5、CD7、CD10、CD19、CD20、CD22、CD30、CD33、CD34、CD38、CD41、CD44、CD49f、CD56、CD74、CD133、CD138、サイトメガロウイルス(CMV)感染細胞抗原、EGP−2、EGP−40、EpCAM、erbB2,3,4、FBP、胎児型アセチルコリンレセプター、葉酸レセプター−a、GD2、GD3、HER−2,hTERT、IL−13R−a2、x−軽鎖、KDR、LeY、LI細胞接着分子、MAGE−Al、MUC1、メソテリン、NKG2Dリガンド、NY−ES0−1、腫瘍胎児性抗原(h5T4)、PSCA、PSMA、ROR1、TAG−72、VEGF−R2、もしくはWT−1からなる群より選択される別個の抗原である、請求項38〜39のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、T細胞レセプター(TCR)もしくはキメラ抗原レセプター(CAR)である、請求項38〜40のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、外因性もしくは内因性である、請求項38〜41のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、組換え発現される、請求項38〜42のいずれか1項に記載の方法。
- 前記抗原認識レセプターは、ベクターから発現される、請求項38〜43のいずれか1項に記載の方法。
- 前記キメラ共刺激レセプター(CCR)は、ベクターから発現される、請求項38〜44のいずれか1項に記載の方法。
- 前記細胞は、T細胞、ナチュラルキラー(NK)細胞、細胞傷害性Tリンパ球(CTL)、制御性T細胞、ヒト胚性幹細胞、およびリンパ系細胞に分化し得る多能性幹細胞からなる群より選択される、請求項38〜45のいずれか1項に記載の方法。
- 前記抗原認識レセプターの細胞内シグナル伝達ドメインは、CD3鎖シグナル伝達ドメインである、請求項38〜46のいずれか1項に記載の方法。
- 前記キメラ共刺激レセプター(CCR)の細胞内シグナル伝達ドメインは、CD97、CD11a−CD18、CD2、ICOS、CD27、CD154、CD5、OX40、4−1 BBもしくはCD28シグナル伝達ドメインである、請求項38〜47のいずれか1項に記載の方法。
- 前立腺がんの処置を必要とする被験体において前立腺がんを処置するための方法であって、該方法は、該被験体に、PSCAもしくはCD19を低親和性で結合し、ここで該結合は、免疫応答細胞を活性化する抗原認識レセプター、およびPSMAを結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)を含むT細胞の治療上有効な量を投与し、それによって、該被験体において前立腺がんを処置する工程、を包含する、方法。
- 請求項1〜18のいずれか1項に記載の免疫応答細胞および薬学的に受容可能な賦形剤を含む、薬学的組成物。
- 新形成もしくは腫瘍疾患の処置において使用するための、請求項1〜18のいずれかに記載の免疫応答細胞。
- 前立腺がんの処置において使用するための、PSCAもしくはCD19を低親和性で結合し、ここで該結合は、免疫応答細胞を活性化する抗原認識レセプター、およびPSMAを結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)を含む、T細胞。
- 免疫応答細胞であって、第1の抗原を結合し、該免疫応答細胞を活性化する抗原認識レセプター、および第2のウイルス抗原を結合し、該免疫応答細胞を刺激するキメラ共刺激レセプター(CCR)を含む免疫応答細胞を含む、キット。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261709072P | 2012-10-02 | 2012-10-02 | |
US61/709,072 | 2012-10-02 | ||
PCT/US2013/063097 WO2014055668A1 (en) | 2012-10-02 | 2013-10-02 | Compositions and methods for immunotherapy |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018047734A Division JP2018108111A (ja) | 2012-10-02 | 2018-03-15 | 免疫療法のための組成物および方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2015535689A true JP2015535689A (ja) | 2015-12-17 |
JP2015535689A5 JP2015535689A5 (ja) | 2016-12-01 |
JP6441802B2 JP6441802B2 (ja) | 2018-12-19 |
Family
ID=50435409
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015534828A Active JP6441802B2 (ja) | 2012-10-02 | 2013-10-02 | 免疫療法のための組成物および方法 |
JP2018047734A Withdrawn JP2018108111A (ja) | 2012-10-02 | 2018-03-15 | 免疫療法のための組成物および方法 |
JP2020024520A Active JP6963051B2 (ja) | 2012-10-02 | 2020-02-17 | 免疫療法のための組成物および方法 |
JP2020024521A Withdrawn JP2020096625A (ja) | 2012-10-02 | 2020-02-17 | 免疫療法のための組成物および方法 |
JP2021195401A Withdrawn JP2022024161A (ja) | 2012-10-02 | 2021-12-01 | 免疫療法のための組成物および方法 |
Family Applications After (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018047734A Withdrawn JP2018108111A (ja) | 2012-10-02 | 2018-03-15 | 免疫療法のための組成物および方法 |
JP2020024520A Active JP6963051B2 (ja) | 2012-10-02 | 2020-02-17 | 免疫療法のための組成物および方法 |
JP2020024521A Withdrawn JP2020096625A (ja) | 2012-10-02 | 2020-02-17 | 免疫療法のための組成物および方法 |
JP2021195401A Withdrawn JP2022024161A (ja) | 2012-10-02 | 2021-12-01 | 免疫療法のための組成物および方法 |
Country Status (17)
Country | Link |
---|---|
US (3) | US10654928B2 (ja) |
EP (2) | EP3597215A1 (ja) |
JP (5) | JP6441802B2 (ja) |
KR (1) | KR102198058B1 (ja) |
CN (3) | CN104853766A (ja) |
AU (3) | AU2013327136A1 (ja) |
CA (1) | CA2886859C (ja) |
ES (1) | ES2743738T3 (ja) |
HK (1) | HK1208631A1 (ja) |
IL (2) | IL238047B (ja) |
MX (1) | MX370148B (ja) |
NZ (2) | NZ746914A (ja) |
PH (2) | PH12015500747B1 (ja) |
RU (2) | RU2729401C2 (ja) |
SG (1) | SG11201502598SA (ja) |
WO (1) | WO2014055668A1 (ja) |
ZA (1) | ZA201502880B (ja) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018521663A (ja) * | 2015-07-31 | 2018-08-09 | キングス カレッジ ロンドンKings College London | 治療薬 |
JP2020517295A (ja) * | 2017-04-26 | 2020-06-18 | ユーリカ セラピューティックス, インコーポレイテッド | キメラ活性化受容体及びキメラ刺激受容体を発現する細胞並びにその使用 |
JP2021526844A (ja) * | 2018-06-18 | 2021-10-11 | ユーリカ セラピューティックス, インコーポレイテッド | 前立腺特異的膜抗原(psma)を標的とする構築物及びその使用 |
JP2021528995A (ja) * | 2018-03-30 | 2021-10-28 | エウレカ セラピューティクス インコーポレイテッド | Cd22を標的とする構築物及びその使用 |
Families Citing this family (300)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IN2014DN06522A (ja) * | 2012-02-22 | 2015-06-12 | Univ Pennsylvania | |
NZ746914A (en) | 2012-10-02 | 2020-03-27 | Memorial Sloan Kettering Cancer Center | Compositions and methods for immunotherapy |
US10117896B2 (en) | 2012-10-05 | 2018-11-06 | The Trustees Of The University Of Pennsylvania | Use of a trans-signaling approach in chimeric antigen receptors |
AU2013204922B2 (en) | 2012-12-20 | 2015-05-14 | Celgene Corporation | Chimeric antigen receptors |
SG11201505858VA (en) | 2013-01-28 | 2015-09-29 | St Jude Childrens Res Hospital | A chimeric receptor with nkg2d specificity for use in cell therapy against cancer and infectious disease |
WO2014124143A1 (en) * | 2013-02-06 | 2014-08-14 | Anthrogenesis Corporation | Modified t lymphocytes having improved specificity |
LT2961831T (lt) | 2013-02-26 | 2020-11-10 | Memorial Sloan Kettering Cancer Center | Kompozicijos ir būdai, skirti imunoterapijai |
EP2970372B1 (en) | 2013-03-15 | 2020-09-30 | Celgene Corporation | Modified t lymphocytes |
CA3185368A1 (en) * | 2013-04-03 | 2014-10-09 | Memorial Sloan-Kettering Cancer Center | Effective generation of tumor-targeted t cells derived from pluripotent stem cells |
ES2792849T3 (es) * | 2014-02-10 | 2020-11-12 | Univ Emory | Expresión de polipéptido químico con receptores de linfocitos variables en células inmunes y usos para tratar el cáncer |
DK3689899T3 (da) | 2014-04-25 | 2021-11-22 | 2Seventy Bio Inc | Kimære mnd-promotor-antigenreceptorer |
DK3143134T3 (da) | 2014-05-15 | 2021-01-04 | Nat Univ Singapore | Modificerede, naturlige dræberceller og anvendelser deraf |
EP3685842B1 (en) | 2014-06-06 | 2022-08-31 | Memorial Sloan-Kettering Cancer Center | Mesothelin-targeted chimeric antigen receptors and uses thereof |
WO2015188119A1 (en) * | 2014-06-06 | 2015-12-10 | Bluebird Bio, Inc. | Improved t cell compositions |
MA40253A (fr) | 2014-07-15 | 2017-05-24 | Juno Therapeutics Inc | Cellules modifiées pour thérapie cellulaire adoptive |
SG10201913765YA (en) | 2014-07-21 | 2020-03-30 | Novartis Ag | Treatment of cancer using a cd33 chimeric antigen receptor |
AU2015292590B2 (en) | 2014-07-24 | 2020-01-16 | 2Seventy Bio, Inc. | BCMA chimeric antigen receptors |
US10800830B2 (en) | 2014-08-08 | 2020-10-13 | The Board Of Trustees Of The Leland Stanford Junior University | High affinity PD-1 agents and methods of use |
TWI751102B (zh) | 2014-08-28 | 2022-01-01 | 美商奇諾治療有限公司 | 對cd19具專一性之抗體及嵌合抗原受體 |
EP2990416B1 (en) * | 2014-08-29 | 2018-06-20 | GEMoaB Monoclonals GmbH | Universal chimeric antigen receptor expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders |
KR20170068598A (ko) | 2014-10-20 | 2017-06-19 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 치료에서 복용을 위한 방법 및 조성물 |
WO2016070061A1 (en) * | 2014-10-31 | 2016-05-06 | The Trustees Of The University Of Pennsylvania | Methods and compositions for modified t cells |
RS60685B1 (sr) | 2014-11-05 | 2020-09-30 | Juno Therapeutics Inc | Postupci za transdukciju i obradu ćelija |
MX2017007138A (es) | 2014-12-03 | 2017-08-28 | Juno Therapeutics Inc | Metodos y composiciones para terapia celular adoptiva. |
NZ733025A (en) | 2014-12-12 | 2022-01-28 | 2Seventy Bio Inc | Bcma chimeric antigen receptors |
KR20200003939A (ko) | 2014-12-24 | 2020-01-10 | 유씨엘 비즈니스 리미티드 | 세포 |
MA41346A (fr) | 2015-01-12 | 2017-11-21 | Juno Therapeutics Inc | Eléments régulateurs post-transcriptionnels d'hépatite modifiée |
EP3245231B1 (en) | 2015-01-16 | 2020-08-12 | Juno Therapeutics, Inc. | Antibodies and chimeric antigen receptors specific for ror1 |
SG10202101358XA (en) | 2015-01-26 | 2021-03-30 | Fate Therapeutics Inc | Methods and compositions for inducing hematopoietic cell differentiation |
US20170151281A1 (en) | 2015-02-19 | 2017-06-01 | Batu Biologics, Inc. | Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer |
MX2017010721A (es) | 2015-02-24 | 2018-08-28 | Univ California | Interruptores transcripcionales activados mediante unión y métodos para su uso. |
CA2977106A1 (en) | 2015-02-27 | 2016-09-01 | Icell Gene Therapeutics Llc | Chimeric antigen receptors (cars) targeting hematologic malignancies, compositions and methods of use thereof |
WO2016161415A2 (en) * | 2015-04-02 | 2016-10-06 | Memorial Sloan Kettering Cancer Center | Tnfrsf14/ hvem proteins and methods of use thereof |
MX2017013247A (es) * | 2015-04-15 | 2018-08-15 | Prospect Chartercare Rwmc Llc D/B/A Roger Williams Medical Center | Infusion arterial hepatica de linfocitos t car. |
WO2016166568A1 (en) | 2015-04-16 | 2016-10-20 | Juno Therapeutics Gmbh | Methods, kits and apparatus for expanding a population of cells |
AU2016249005B2 (en) | 2015-04-17 | 2022-06-16 | Novartis Ag | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
WO2016172606A1 (en) * | 2015-04-23 | 2016-10-27 | Baylor College Of Medicine | Cd5 chimeric antigen receptor for adoptive t cell therapy |
US20180117155A1 (en) | 2015-04-25 | 2018-05-03 | The General Hospital Corporation | Anti-fugetactic agent and anti-cancer agent combination therapy and compositions for the treatment of cancer |
EP3466967A1 (en) | 2015-05-18 | 2019-04-10 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
JP6949728B2 (ja) | 2015-05-29 | 2021-10-13 | ジュノー セラピューティクス インコーポレイテッド | 遺伝子操作された細胞における阻害相互作用を調節するための組成物および方法 |
CN113502270B (zh) * | 2015-06-10 | 2024-06-18 | 南克维斯特公司 | 用于治疗癌症的修饰的nk-92细胞 |
US11173179B2 (en) | 2015-06-25 | 2021-11-16 | Icell Gene Therapeutics Llc | Chimeric antigen receptor (CAR) targeting multiple antigens, compositions and methods of use thereof |
JP6961497B2 (ja) | 2015-06-25 | 2021-11-05 | アイセル・ジーン・セラピューティクス・エルエルシー | キメラ抗体受容体(CARs)の構成およびその使用方法 |
MA42895A (fr) | 2015-07-15 | 2018-05-23 | Juno Therapeutics Inc | Cellules modifiées pour thérapie cellulaire adoptive |
EP3325504A1 (en) | 2015-07-21 | 2018-05-30 | Novartis AG | Methods for improving the efficacy and expansion of immune cells |
CA2994412A1 (en) | 2015-07-31 | 2017-02-09 | Memorial Sloan-Kettering Cancer Center | Antigen-binding proteins targeting cd56 and uses thereof |
CN108174604B (zh) | 2015-08-07 | 2023-06-23 | 西雅图儿童医院(Dba西雅图儿童研究所) | 用于实体瘤靶向的双特异性car t细胞 |
CN105087495B (zh) * | 2015-08-21 | 2016-04-27 | 深圳市茵冠生物科技有限公司 | 双嵌合抗原受体修饰的t淋巴细胞及其制备方法 |
CA2997551A1 (en) | 2015-09-04 | 2017-03-09 | Memorial Sloan Kettering Cancer Center | Immune cell compositions and methods of use |
WO2017049208A1 (en) | 2015-09-18 | 2017-03-23 | The General Hospital Corporation Dba Massachusetts General Hospital | Localized delivery of anti-fugetactic agent for treatment of cancer |
JP6955487B2 (ja) | 2015-09-24 | 2021-10-27 | アブビトロ, エルエルシー | Hiv抗体組成物および使用方法 |
CN105924529B (zh) * | 2015-10-13 | 2019-08-06 | 中国人民解放军总医院 | 嵌合抗原受体及其基因和重组表达载体、car138-nkt细胞及其制备方法和应用 |
MA45489A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés de culture de cellules, kits et appareil associés |
WO2017068419A2 (en) | 2015-10-22 | 2017-04-27 | Juno Therapeutics Gmbh | Methods, kits, agents and apparatuses for transduction |
MA45488A (fr) | 2015-10-22 | 2018-08-29 | Juno Therapeutics Gmbh | Procédés, kits et appareil de culture de cellules |
AU2016342041B2 (en) | 2015-10-23 | 2021-12-02 | Eureka Therapeutics, Inc. | Antibody/T-cell receptor chimeric constructs and uses thereof |
CN115927199A (zh) | 2015-11-04 | 2023-04-07 | 菲特治疗公司 | 用于诱导造血细胞分化的方法和组合物 |
CN108368520B (zh) | 2015-11-04 | 2023-01-17 | 菲特治疗公司 | 多能细胞的基因组工程改造 |
WO2017079703A1 (en) | 2015-11-05 | 2017-05-11 | Juno Therapeutics, Inc. | Vectors and genetically engineered immune cells expressing metabolic pathway modulators and uses in adoptive cell therapy |
MA44314A (fr) | 2015-11-05 | 2018-09-12 | Juno Therapeutics Inc | Récepteurs chimériques contenant des domaines induisant traf, et compositions et méthodes associées |
US20200297760A1 (en) | 2015-12-03 | 2020-09-24 | Juno Therapeutics, Inc. | Compositions and methods for reducing immune responses against chimeric antigen receptors |
CA3007262A1 (en) | 2015-12-03 | 2017-06-08 | Lucas James Thompson | Modified chimeric receptors and related compositions and methods |
ES2901795T3 (es) | 2015-12-04 | 2022-03-23 | Juno Therapeutics Inc | Métodos y composiciones relacionadas con la toxicidad asociada con la terapia celular |
CN108699557A (zh) | 2015-12-04 | 2018-10-23 | 诺华股份有限公司 | 用于免疫肿瘤学的组合物和方法 |
WO2017099712A1 (en) | 2015-12-07 | 2017-06-15 | Bluebird Bio, Inc. | Improved t cell compositions |
WO2017112877A1 (en) * | 2015-12-22 | 2017-06-29 | Icell Gene Therapeutics, Llc | Chimeric antigen receptors and enhancement of anti-tumor activity |
WO2017120501A1 (en) | 2016-01-07 | 2017-07-13 | Mayo Foundation For Medical Education And Research | Methods of treating cancer with interferon |
WO2017161208A1 (en) | 2016-03-16 | 2017-09-21 | Juno Therapeutics, Inc. | Methods for determining dosing of a therapeutic agent and related treatments |
MA43759A (fr) | 2016-03-16 | 2018-11-28 | Jason Connor | Procédés de conception adaptative d'un régime de traitement et traitements associés |
WO2017165571A1 (en) | 2016-03-22 | 2017-09-28 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Early intervention methods to prevent or ameliorate toxicity |
US11046782B2 (en) | 2016-03-30 | 2021-06-29 | Musc Foundation For Research Development | Methods for treatment and diagnosis of cancer by targeting glycoprotein A repetitions predominant (GARP) and for providing effective immunotherapy alone or in combination |
WO2017193059A1 (en) | 2016-05-06 | 2017-11-09 | The Regents Of The University Of California | Systems and methods for targeting cancer cells |
CN116850305A (zh) | 2016-05-06 | 2023-10-10 | 朱诺治疗学股份有限公司 | 基因工程化细胞及其制备方法 |
BR112018072305A2 (pt) * | 2016-05-25 | 2019-02-12 | The Council Of The Queensland Institute Of Medical Research | métodos de imunoterapia |
CN117431234A (zh) | 2016-05-27 | 2024-01-23 | 阿迪根有限公司 | 用于基因组编辑分子的细胞内递送的肽和纳米颗粒 |
JP2019517518A (ja) | 2016-06-03 | 2019-06-24 | メモリアル スローン ケタリング キャンサー センター | 早期治療選択肢としての養子細胞療法 |
MA45341A (fr) | 2016-06-06 | 2019-04-10 | Hutchinson Fred Cancer Res | Procédés de traitement de malignités de lymphocytes b au moyen d'une thérapie cellulaire adoptive |
JP7114490B2 (ja) | 2016-06-24 | 2022-08-08 | アイセル・ジーン・セラピューティクス・エルエルシー | キメラ抗体受容体(CARs)の構成およびその使用方法 |
EP3475446A1 (en) | 2016-06-27 | 2019-05-01 | Juno Therapeutics, Inc. | Method of identifying peptide epitopes, molecules that bind such epitopes and related uses |
MA45491A (fr) | 2016-06-27 | 2019-05-01 | Juno Therapeutics Inc | Épitopes à restriction cmh-e, molécules de liaison et procédés et utilisations associés |
JP7086928B2 (ja) * | 2016-07-25 | 2022-06-20 | ザ ユナイテッド ステイツ オブ アメリカ, アズ リプレゼンテッド バイ ザ セクレタリー, デパートメント オブ ヘルス アンド ヒューマン サービシーズ | 改変されたナチュラルキラー細胞を生成する方法および使用方法 |
ES2951552T3 (es) | 2016-07-29 | 2023-10-23 | Juno Therapeutics Inc | Polipéptidos inmunomoduladores y composiciones y métodos relacionados |
AU2017301887A1 (en) | 2016-07-29 | 2019-02-07 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies against anti-CD19 antibodies |
EP3491152B1 (en) | 2016-07-29 | 2022-06-29 | Juno Therapeutics, Inc. | Methods for assessing the presence or absence of replication competent virus |
WO2018026953A1 (en) | 2016-08-02 | 2018-02-08 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
EP3494132A4 (en) * | 2016-08-03 | 2020-03-18 | Washington University | GENITITATION OF CAR-T CELLS FOR TREATING T-CELL MALIGNOMAS WITH CHIMERIC ANTIGENT RECEPTORS |
CA3000514A1 (en) * | 2016-08-04 | 2018-02-08 | Memorial Sloan-Kettering Cancer Center | Cancer antigen targets and uses thereof |
SG11201901528RA (en) | 2016-08-23 | 2019-03-28 | Univ California | Proteolytically cleavable chimeric polypeptides and methods of use thereof |
CN109863242A (zh) | 2016-08-30 | 2019-06-07 | 纪念斯隆-凯特林癌症中心 | 用于治疗病毒感染和其它感染的免疫细胞组合物和使用方法 |
JP2019526269A (ja) | 2016-09-12 | 2019-09-19 | ジュノー セラピューティクス インコーポレイテッド | 灌流バイオリアクタバッグアセンブリ |
WO2018063985A1 (en) | 2016-09-28 | 2018-04-05 | Atossa Genetics Inc. | Methods of adoptive cell therapy |
CN110139873A (zh) | 2016-10-03 | 2019-08-16 | 朱诺治疗学股份有限公司 | Hpv特异性结合分子 |
IL292551B2 (en) | 2016-10-07 | 2023-10-01 | Tcr2 Therapeutics Inc | Preparations and methods for reprogramming T-cell receptors using fusion proteins |
EP4190335A1 (en) | 2016-10-13 | 2023-06-07 | Juno Therapeutics, Inc. | Immunotherapy methods and compositions involving tryptophan metabolic pathway modulators |
MA46783A (fr) | 2016-11-03 | 2019-09-11 | Juno Therapeutics Inc | Polythérapie de type thérapie cellulaire t et inhibiteur de btk |
CA3040914A1 (en) | 2016-11-03 | 2018-05-24 | Juno Therapeutics, Inc. | Combination therapy of a cell based therapy and a microglia inhibitor |
US11851491B2 (en) | 2016-11-22 | 2023-12-26 | TCR2 Therapeutics Inc. | Compositions and methods for TCR reprogramming using fusion proteins |
US11793833B2 (en) | 2016-12-02 | 2023-10-24 | Juno Therapeutics, Inc. | Engineered B cells and related compositions and methods |
BR112019011025A2 (pt) | 2016-12-03 | 2019-10-08 | Juno Therapeutics Inc | métodos para modulação de células t car |
MX2019006288A (es) | 2016-12-03 | 2020-10-01 | Juno Therapeutics Inc | Metodos y composiciones para el uso de celulas t terapeuticas en combinacion con inhibidores de quinasa. |
WO2018102787A1 (en) | 2016-12-03 | 2018-06-07 | Juno Therapeutics, Inc. | Methods for determining car-t cells dosing |
MA46998A (fr) | 2016-12-05 | 2019-10-09 | Juno Therapeutics Inc | Production de cellules modifiées pour une thérapie cellulaire adoptive |
CA3045665A1 (en) | 2016-12-12 | 2018-06-21 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Chimeric transcription factor variants with augmented sensitivity to drug ligand induction of transgene expression in mammalian cells |
EP3336107A1 (en) | 2016-12-15 | 2018-06-20 | Miltenyi Biotec GmbH | Immune cells expressing an antigen binding receptor and a chimeric costimulatory receptor |
CN106749677B (zh) * | 2017-01-04 | 2020-06-12 | 上海交通大学医学院附属瑞金医院 | 一种靶向mll白血病的双特异性嵌合抗原受体基因及其应用 |
WO2018132518A1 (en) | 2017-01-10 | 2018-07-19 | Juno Therapeutics, Inc. | Epigenetic analysis of cell therapy and related methods |
MA47325A (fr) | 2017-01-20 | 2019-11-27 | Juno Therapeutics Gmbh | Conjugués de surface cellulaire et compositions cellulaires et méthodes associées |
MX2019009552A (es) | 2017-02-17 | 2019-10-02 | Hutchinson Fred Cancer Res | Terapias de combinacion para el tratamiento de canceres relacionados con el antigeno de maduracion de celulas b (bcma) y trastornos autoinmunitarios. |
MX2019010171A (es) | 2017-02-27 | 2019-10-15 | Juno Therapeutics Inc | Composiciones, articulos de fabricacion y metodos relacionados con la dosificacion en la terapia celular. |
JP7178355B2 (ja) | 2017-02-28 | 2022-11-25 | エンドサイト・インコーポレイテッド | Car t細胞療法のための組成物および方法 |
AU2018231190B2 (en) | 2017-03-08 | 2023-05-25 | Memorial Sloan Kettering Cancer Center | Immune cell compositions and methods of use |
CN110913690A (zh) | 2017-03-14 | 2020-03-24 | 朱诺治疗学股份有限公司 | 用于低温储存的方法 |
JP7277388B2 (ja) | 2017-03-15 | 2023-05-18 | オックスフォード バイオメディカ(ユーケー)リミテッド | 方法 |
WO2018175636A2 (en) | 2017-03-22 | 2018-09-27 | Novartis Ag | Compositions and methods for immunooncology |
JP2020515542A (ja) | 2017-03-23 | 2020-05-28 | ザ ジェネラル ホスピタル コーポレイション | Cxcr4/cxcr7の遮断およびヒトパピローマウイルス関連疾患の治療 |
KR20240057444A (ko) | 2017-03-27 | 2024-05-02 | 내셔널 유니버시티 오브 싱가포르 | 절단된 nkg2d 키메라 수용체 및 자연 살해 세포 면역요법에서의 그의 용도 |
AU2018245749A1 (en) | 2017-03-27 | 2019-10-03 | National University Of Singapore | Stimulatory cell lines for ex vivo expansion and activation of natural killer cells |
IL269801B2 (en) | 2017-04-05 | 2024-02-01 | Korea Res Inst Bioscience & Biotechnology | A fusion protein that activates NK cells, an NK cell, and a pharmaceutical preparation that includes them |
CA3056261A1 (en) | 2017-04-07 | 2018-10-11 | Juno Therapeutics, Inc. | Engineered cells expressing prostate-specific membrane antigen (psma) or a modified form thereof and related methods |
JP7355650B2 (ja) | 2017-04-14 | 2023-10-03 | ジュノー セラピューティクス インコーポレイテッド | 細胞表面グリコシル化を評価するための方法 |
BR112019021745A2 (pt) | 2017-04-18 | 2020-05-05 | Fujifilm Cellular Dynamics Inc | células efetoras imunológicas antígeno-específicas |
CN111032850A (zh) | 2017-04-27 | 2020-04-17 | 朱诺治疗学有限公司 | 寡聚粒子试剂及其使用方法 |
PT3618842T (pt) | 2017-05-01 | 2024-01-12 | Juno Therapeutics Inc | Combinação de uma terapia celular e de um composto imunomodulador |
EP3631468A1 (en) | 2017-06-02 | 2020-04-08 | Juno Therapeutics, Inc. | Articles of manufacture and methods related to toxicity associated with cell therapy |
US11413310B2 (en) | 2017-06-02 | 2022-08-16 | Juno Therapeutics, Inc. | Articles of manufacture and methods for treatment using adoptive cell therapy |
PT3538645T (pt) | 2017-06-20 | 2021-04-15 | Inst Curie | Células imunológicas deficitárias em suv39h1 |
JP2020525010A (ja) | 2017-06-22 | 2020-08-27 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | 制御性免疫細胞を産生するための方法及びその使用 |
MX2019015155A (es) | 2017-06-29 | 2020-08-03 | Juno Therapeutics Inc | Modelo de raton para valorar toxicidades asociadas con inmunoterapias. |
CA3070573A1 (en) | 2017-07-29 | 2019-02-07 | Juno Therapeutics, Inc. | Reagents for expanding cells expressing recombinant receptors |
CN107326014B (zh) * | 2017-07-31 | 2019-09-24 | 时力生物科技(北京)有限公司 | 一种双特异性嵌合抗原受体修饰的t淋巴细胞及其制备方法和应用 |
EP3664835A1 (en) | 2017-08-09 | 2020-06-17 | Juno Therapeutics, Inc. | Methods and compositions for preparing genetically engineered cells |
BR112020001605A2 (pt) | 2017-08-09 | 2020-08-11 | Juno Therapeutics Inc | métodos para produzir composições de células geneticamente modificadas e composições relacionadas |
MA50057A (fr) | 2017-09-01 | 2020-07-08 | Juno Therapeutics Inc | Expression génique et évaluation d'un risque de développement d'une toxicité suite à une thérapie cellulaire |
EP3679370A1 (en) | 2017-09-07 | 2020-07-15 | Juno Therapeutics, Inc. | Methods of identifying cellular attributes related to outcomes associated with cell therapy |
CN109517820B (zh) | 2017-09-20 | 2021-09-24 | 北京宇繁生物科技有限公司 | 一种靶向HPK1的gRNA以及HPK1基因编辑方法 |
KR20200104284A (ko) | 2017-10-03 | 2020-09-03 | 주노 쎄러퓨티크스 인코퍼레이티드 | Hpv-특이적 결합 분자 |
MA49911A (fr) | 2017-11-01 | 2020-06-24 | Juno Therapeutics Inc | Anticorps et récepteurs antigéniques chimériques spécifiques de l'antigene de maturation des lymphocytes b |
US11564946B2 (en) | 2017-11-01 | 2023-01-31 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
MA50860A (fr) | 2017-11-01 | 2020-09-09 | Juno Therapeutics Inc | Récepterus chimériques d'antigène contre l'antigène de maturation des cellules b et polynucleotides codants |
WO2019089982A1 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Method of assessing activity of recombinant antigen receptors |
MA50855A (fr) | 2017-11-01 | 2020-09-09 | Juno Therapeutics Inc | Procédé de génération de compositions thérapeutiques de cellules modifiées |
CA3081456A1 (en) | 2017-11-01 | 2019-05-09 | Editas Medicine, Inc. | Methods, compositions and components for crispr-cas9 editing of tgfbr2 in t cells for immunotherapy |
WO2019089858A2 (en) | 2017-11-01 | 2019-05-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
MX2020004239A (es) | 2017-11-01 | 2020-09-09 | Juno Therapeutics Inc | Proceso para producir una composicion de celulas t. |
AU2018362014A1 (en) | 2017-11-03 | 2020-05-28 | Sorrento Therapeutics, Inc. | CD38-directed chimeric antigen receptor constructs |
JP2021502077A (ja) | 2017-11-06 | 2021-01-28 | エディタス・メディシン,インコーポレイテッド | 免疫療法のためのt細胞におけるcblbのcrispr−cas9編集のための方法、組成物および構成要素 |
MX2020004568A (es) | 2017-11-06 | 2020-10-05 | Juno Therapeutics Inc | Combinación de una terapia celular y un inhibidor de gamma secretasa. |
EP3706904A1 (en) | 2017-11-10 | 2020-09-16 | Juno Therapeutics, Inc. | Closed-system cryogenic vessels |
AU2018367452B2 (en) * | 2017-11-14 | 2024-06-13 | Memorial Sloan-Kettering Cancer Center | IL-36 secreting immunoresponsive cells and uses thereof |
MA51210A (fr) | 2017-12-01 | 2020-10-07 | Juno Therapeutics Inc | Procédés de dosage et de modulation de cellules génétiquement modifiées |
EP3720883B1 (en) | 2017-12-05 | 2023-04-19 | The Medical Research, Infrastructure, And Health Services Fund Of The Tel Aviv Medical Center | T-cells comprising anti-cd38 and anti-cd138 chimeric antigen receptors and uses thereof |
EP3720882A4 (en) * | 2017-12-05 | 2021-10-27 | The Medical Research, Infrastructure and Health Services Fund of the Tel Aviv Medical Center | T LYMPHOCYTES INCLUDING TWO DIFFERENT ANTIGENIC CHEMERICAL RECEPTORS AND THEIR USES |
EP3720949A1 (en) | 2017-12-08 | 2020-10-14 | Juno Therapeutics, Inc. | Serum-free media formulation for culturing cells and methods of use thereof |
AU2018379094A1 (en) | 2017-12-08 | 2020-06-25 | Juno Therapeutics, Inc. | Phenotypic markers for cell therapy and related methods |
US20200384025A1 (en) | 2017-12-08 | 2020-12-10 | Juno Therapeutics, Inc. | Process for producing a composition of engineered t cells |
US12006356B2 (en) | 2017-12-15 | 2024-06-11 | Juno Therapeutics, Inc. | Anti-CCT5 binding molecules and chimeric antigen receptors comprising the same |
CN109988242A (zh) * | 2018-01-02 | 2019-07-09 | 武汉波睿达生物科技有限公司 | 联合嵌合抗原受体、表达载体、慢病毒及t细胞 |
WO2019139972A1 (en) | 2018-01-09 | 2019-07-18 | Board Of Regents, The University Of Texas System | T cell receptors for immunotherapy |
WO2019141270A1 (zh) * | 2018-01-19 | 2019-07-25 | 科济生物医药(上海)有限公司 | SynNotch受体调控表达IL12 |
TW201940182A (zh) | 2018-01-22 | 2019-10-16 | 美商安德賽特公司 | Car t 細胞之使用方法 |
WO2019152747A1 (en) | 2018-01-31 | 2019-08-08 | Juno Therapeutics, Inc. | Methods and reagents for assessing the presence or absence of replication competent virus |
US20210069246A1 (en) | 2018-01-31 | 2021-03-11 | Celgene Corporation | Combination therapy using adoptive cell therapy and checkpoint inhibitor |
CN108314739B (zh) * | 2018-02-05 | 2020-07-14 | 深圳市默赛尔生物医学科技发展有限公司 | 多信号嵌合抗原受体及其表达基因、其修饰的nk细胞及应用 |
MX2020008390A (es) | 2018-02-11 | 2020-12-07 | Memorial Sloan Kettering Cancer Center | Receptores de linfocitos t no restringidos a antígenos leucocitarios humanos (hla) y usos de los mismos. |
SG11202007697VA (en) | 2018-02-15 | 2020-09-29 | Memorial Sloan Kettering Cancer Center | Foxp3 targeting agent compositions and methods of use for adoptive cell therapy |
US20210046159A1 (en) | 2018-03-09 | 2021-02-18 | Ospedale San Raffaele S.R.L. | Il-1 antagonist and toxicity induced by cell therapy |
EP3778649A4 (en) | 2018-03-09 | 2022-05-04 | CRAGE medical Co., Limited | METHOD AND COMPOSITION FOR TREATMENT OF TUMOR |
RU2020136054A (ru) | 2018-04-05 | 2022-05-06 | Джуно Терапьютикс, Инк. | Т-клетки, экспрессирующие рекомбинантный рецептор, соответствующие полинуклеотиды и способы |
CN112566698A (zh) | 2018-04-05 | 2021-03-26 | 朱诺治疗学股份有限公司 | T细胞受体和表达该t细胞受体的工程化细胞 |
BR112020020245A2 (pt) | 2018-04-05 | 2021-04-06 | Editas Medicine, Inc. | Métodos de produzir células expressando um receptor recombinante e composições relacionadas |
CN108864288A (zh) * | 2018-04-26 | 2018-11-23 | 上海怡豪生物科技有限公司 | 乳腺癌的双靶点car-t治疗载体及其构建方法和应用 |
CN112584902A (zh) | 2018-05-03 | 2021-03-30 | 朱诺治疗学股份有限公司 | 嵌合抗原受体(car)t细胞疗法和激酶抑制剂的组合疗法 |
SG11202011830SA (en) | 2018-06-13 | 2020-12-30 | Novartis Ag | Bcma chimeric antigen receptors and uses thereof |
CN110615843B (zh) * | 2018-06-20 | 2023-05-09 | 上海隆耀生物科技有限公司 | 一种包含第三信号受体的嵌合抗原受体及其应用 |
EP3834849A4 (en) | 2018-07-24 | 2022-08-03 | CRAGE medical Co., Limited | METHOD OF TREATMENT OF A TUMOR USING AN IMMUNE EFFECTOR CELL |
EP3833759A1 (en) | 2018-08-09 | 2021-06-16 | Juno Therapeutics, Inc. | Methods for assessing integrated nucleic acids |
US20210163893A1 (en) | 2018-08-09 | 2021-06-03 | Juno Therapeutics, Inc. | Processes for generating engineered cells and compositions thereof |
BR112021003631A2 (pt) * | 2018-09-05 | 2021-05-18 | Glaxosmithkline Intellectual Property Development Limited | modificação de célula t |
CN113167796A (zh) | 2018-09-11 | 2021-07-23 | 朱诺治疗学股份有限公司 | 对工程化细胞组合物进行质谱分析的方法 |
US20220031744A1 (en) | 2018-09-19 | 2022-02-03 | FUJIFILM Cellular Dynamics, Inc. | Protein l for activation and expansion of chimeric antigen receptor-modified immune cells |
US20220002669A1 (en) | 2018-10-31 | 2022-01-06 | Juno Therapeutics Gmbh | Methods for selection and stimulation of cells and apparatus for same |
MX2021005022A (es) | 2018-11-01 | 2021-09-08 | Juno Therapeutics Inc | Receptores de antigenos quimericos especificos para el miembro d del grupo 5 de la clase c del receptor acoplado a proteina g (gprc5d). |
KR20210113169A (ko) | 2018-11-01 | 2021-09-15 | 주노 쎄러퓨티크스 인코퍼레이티드 | Β세포 성숙 항원에 특이적인 키메라 항원 수용체를 이용한 치료 방법 |
ES2968737T3 (es) | 2018-11-06 | 2024-05-13 | Juno Therapeutics Inc | Proceso para producir células T manipuladas genéticamente |
CA3117978A1 (en) | 2018-11-08 | 2020-05-14 | Juno Therapeutics, Inc. | Methods and combinations for treatment and t cell modulation |
BR112021009420A2 (pt) | 2018-11-16 | 2021-11-23 | Juno Therapeutics Inc | Métodos de dosagem de células t manipuladas para o tratamento de malignidades de células b |
EP3883955A1 (en) | 2018-11-19 | 2021-09-29 | Board of Regents, The University of Texas System | A modular, polycistronic vector for car and tcr transduction |
US20220031749A1 (en) | 2018-11-28 | 2022-02-03 | Board Of Regents, The University Of Texas System | Multiplex genome editing of immune cells to enhance functionality and resistance to suppressive environment |
BR112021010248A2 (pt) | 2018-11-29 | 2021-08-17 | Board Of Regents, The University Of Texas System | métodos para expansão ex vivo de células naturais killer e uso dos mesmos |
US20220088070A1 (en) | 2018-11-30 | 2022-03-24 | Juno Therapeutics, Inc. | Methods for treatment using adoptive cell therapy |
EP3886894B1 (en) | 2018-11-30 | 2024-03-13 | Juno Therapeutics, Inc. | Methods for dosing and treatment of b cell malignancies in adoptive cell therapy |
EP3917570A1 (en) | 2019-01-29 | 2021-12-08 | Juno Therapeutics, Inc. | Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1) |
EP3920941A4 (en) * | 2019-02-08 | 2023-01-18 | Dna Twopointo Inc. | TRANSPOSON-BASED MODIFICATIONS OF IMMUNE CELLS |
GB201902277D0 (en) | 2019-02-19 | 2019-04-03 | King S College London | Therapeutic agents |
EP3773918A4 (en) | 2019-03-05 | 2022-01-05 | Nkarta, Inc. | CD19 DIRECTED CHIMERIC ANTIGEN RECEPTORS AND THEIR USES IN IMMUNOTHERAPY |
CA3134498A1 (en) * | 2019-03-22 | 2020-10-01 | The Regents Of The University Of California | Switchable chimeric antigen receptor-engineered human natural killer cells |
CN114007642A (zh) | 2019-04-30 | 2022-02-01 | 森迪生物科学公司 | 嵌合受体及其使用方法 |
MX2021013219A (es) | 2019-05-01 | 2022-02-17 | Juno Therapeutics Inc | Celulas que expresan un receptor recombinante de un locus de tgfbr2 modificado, polinucleotidos relacionados y metodos. |
CA3136742A1 (en) | 2019-05-01 | 2020-11-05 | Juno Therapeutics, Inc. | Cells expressing a chimeric receptor from a modified cd247 locus, related polynucleotides and methods |
JP2022535380A (ja) | 2019-06-07 | 2022-08-08 | ジュノー セラピューティクス インコーポレイテッド | 自動化t細胞培養 |
KR20220034782A (ko) | 2019-06-12 | 2022-03-18 | 주노 쎄러퓨티크스 인코퍼레이티드 | 세포 매개 세포 독성 요법 및 친생존 bcl2 패밀리 단백질 억제제의 병용 요법 |
CA3146895A1 (en) | 2019-07-23 | 2021-01-28 | Mnemo Therapeutics | Immune cells defective for suv39h1 |
US20220298222A1 (en) | 2019-08-22 | 2022-09-22 | Juno Therapeutics, Inc. | Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods |
JP2022547416A (ja) * | 2019-08-28 | 2022-11-14 | キングス・カレッジ・ロンドン | B細胞標的化並列CAR(pCAR)治療的薬剤 |
US20220392613A1 (en) | 2019-08-30 | 2022-12-08 | Juno Therapeutics, Inc. | Machine learning methods for classifying cells |
MX2022002578A (es) | 2019-09-02 | 2022-06-02 | Inst Curie | Inmunoterapia dirigida a peptidos neoantigenicos tumorales. |
EP4048304A1 (en) | 2019-10-22 | 2022-08-31 | Institut Curie | Immunotherapy targeting tumor neoantigenic peptides |
JP2023500318A (ja) | 2019-10-30 | 2023-01-05 | ジュノ セラピューティクス ゲーエムベーハー | 細胞選択および/または細胞刺激デバイスならびに使用方法 |
JP2022554348A (ja) | 2019-11-05 | 2022-12-28 | ジュノー セラピューティクス インコーポレイテッド | 治療用t細胞組成物の属性を決定する方法 |
CN114980918A (zh) | 2019-11-07 | 2022-08-30 | 朱诺治疗学股份有限公司 | T细胞疗法与(s)-3-[4-(4-吗啉-4-基甲基-苄氧基)-1-氧代-1,3-二氢-异吲哚-2-基]-哌啶-2,6-二酮的组合 |
CN114945382A (zh) | 2019-11-26 | 2022-08-26 | 诺华股份有限公司 | Cd19和cd22嵌合抗原受体及其用途 |
WO2021113776A1 (en) | 2019-12-06 | 2021-06-10 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to bcma-targeted binding domains and related compositions and methods |
MX2022006715A (es) | 2019-12-06 | 2022-09-23 | Juno Therapeutics Inc | Metodos relacionados con toxicidad y respuesta asociada con terapia celular para tratar neoplasias malignas de celulas b. |
KR20220122656A (ko) | 2019-12-06 | 2022-09-02 | 주노 쎄러퓨티크스 인코퍼레이티드 | Gprc5d-표적화 결합 도메인에 대한 항-이디오타입 항체 및 관련 조성물 및 방법 |
KR20220145341A (ko) | 2020-01-24 | 2022-10-28 | 주노 쎄러퓨티크스 인코퍼레이티드 | 입양 세포 요법에서 여포성 림프종 및 변연부 림프종의 투여 및 치료 방법 |
US20230090117A1 (en) | 2020-01-28 | 2023-03-23 | Juno Therapeutics, Inc. | Methods for t cell transduction |
EP4103203A1 (en) | 2020-02-12 | 2022-12-21 | Juno Therapeutics, Inc. | Bcma-directed chimeric antigen receptor t cell compositions and methods and uses thereof |
CA3169672A1 (en) | 2020-02-12 | 2021-08-19 | Juno Therapeutics, Inc. | Cd19-directed chimeric antigen receptor t cell compositions and methods and uses thereof |
EP4107173A1 (en) | 2020-02-17 | 2022-12-28 | Board of Regents, The University of Texas System | Methods for expansion of tumor infiltrating lymphocytes and use thereof |
US20230076164A1 (en) * | 2020-02-17 | 2023-03-09 | Miltenyi Biotec B.V. & Co. KG | Method for providing personalized cells with chimeric antigen receptors (CAR) against tumor microenvironment cells |
US20230149462A1 (en) | 2020-04-10 | 2023-05-18 | Juno Therapeutics, Inc. | Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen |
AU2021263765A1 (en) | 2020-04-28 | 2022-12-01 | Juno Therapeutics, Inc. | Combination of BCMA-directed T cell therapy and an immunomodulatory compound |
WO2021228999A1 (en) | 2020-05-12 | 2021-11-18 | Institut Curie | Neoantigenic epitopes associated with sf3b1 mutations |
JP2023528215A (ja) | 2020-05-13 | 2023-07-04 | ジュノー セラピューティクス インコーポレイテッド | 臨床応答に関連する特徴量の特定方法およびその使用 |
EP4150057A2 (en) | 2020-05-13 | 2023-03-22 | Juno Therapeutics, Inc. | Process for producing donor-batched cells expressing a recombinant receptor |
WO2021237068A2 (en) | 2020-05-21 | 2021-11-25 | Board Of Regents, The University Of Texas System | T cell receptors with vgll1 specificity and uses thereof |
US20240216508A1 (en) | 2020-06-26 | 2024-07-04 | Juno Therapeutics Gmbh | Engineered t cells conditionally expressing a recombinant receptor, related polynucleotides and methods |
CN116490518A (zh) | 2020-07-17 | 2023-07-25 | 西穆尔克斯股份有限公司 | 用于重定向免疫抑制信号传导的嵌合MyD88受体及相关组合物和方法 |
US20230303974A1 (en) | 2020-07-30 | 2023-09-28 | Institut Curie | Immune Cells Defective for SOCS1 |
WO2022029660A1 (en) | 2020-08-05 | 2022-02-10 | Juno Therapeutics, Inc. | Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods |
EP4232071A1 (en) | 2020-10-23 | 2023-08-30 | Asher Biotherapeutics, Inc. | Fusions with cd8 antigen binding molecules for modulating immune cell function |
US20230398148A1 (en) | 2020-11-04 | 2023-12-14 | Juno Therapeutics, Inc. | Cells expressing a chimeric receptor from a modified invariant cd3 immunoglobulin superfamily chain locus and related polynucleotides and methods |
WO2022098905A2 (en) | 2020-11-04 | 2022-05-12 | Myeloid Therapeutics, Inc. | Engineered chimeric fusion protein compositions and methods of use thereof |
WO2022104109A1 (en) | 2020-11-13 | 2022-05-19 | Catamaran Bio, Inc. | Genetically modified natural killer cells and methods of use thereof |
AU2021388155A1 (en) | 2020-11-25 | 2023-06-15 | Catamaran Bio, Inc. | Cellular therapeutics engineered with signal modulators and methods of use thereof |
US11661459B2 (en) | 2020-12-03 | 2023-05-30 | Century Therapeutics, Inc. | Artificial cell death polypeptide for chimeric antigen receptor and uses thereof |
WO2022133030A1 (en) | 2020-12-16 | 2022-06-23 | Juno Therapeutics, Inc. | Combination therapy of a cell therapy and a bcl2 inhibitor |
WO2022133169A1 (en) | 2020-12-18 | 2022-06-23 | Century Therapeutics, Inc. | Chimeric antigen receptor systems with adaptable receptor specificity |
AU2022206324A1 (en) | 2021-01-11 | 2023-07-20 | Sana Biotechnology, Inc. | Use of cd8-targeted viral vectors |
CN117693508A (zh) | 2021-03-03 | 2024-03-12 | 朱诺治疗学股份有限公司 | T细胞疗法和dgk抑制剂的组合 |
WO2022189626A2 (en) | 2021-03-11 | 2022-09-15 | Mnemo Therapeutics | Tumor neoantigenic peptides |
EP4304634A1 (en) | 2021-03-11 | 2024-01-17 | Institut Curie | Transmembrane neoantigenic peptides |
IL305809A (en) | 2021-03-11 | 2023-11-01 | Mnemo Therapeutics | Cancer neoantigenic peptides and their use |
CA3212398A1 (en) | 2021-03-17 | 2022-09-22 | Daniel Getts | Engineered chimeric fusion protein compositions and methods of use thereof |
CA3208944A1 (en) | 2021-03-22 | 2022-09-29 | Edith NALBANDIAN | Method to assess potency of viral vector particles |
CA3210581A1 (en) | 2021-03-22 | 2022-09-29 | Neil HAIG | Methods of determining potency of a therapeutic cell composition |
AU2022252220A1 (en) | 2021-03-29 | 2023-10-12 | Juno Therapeutics, Inc. | Combination of a car t cell therapy and an immunomodulatory compound for treatment of lymphoma |
BR112023019847A2 (pt) | 2021-03-29 | 2023-11-07 | Juno Therapeutics Inc | Métodos para dosagem e tratamento com uma combinação de uma terapia com inibidor de ponto de verificação e uma terapia com célula t car |
CA3214280A1 (en) | 2021-04-16 | 2022-10-20 | Julie Ann RYTLEWSKI | T cell therapy in patients who have had prior stem cell transplant |
IL307612A (en) | 2021-04-16 | 2023-12-01 | Celgene Corp | Combined therapies with BCMA-directed T-cell therapy |
CN117916256A (zh) | 2021-05-06 | 2024-04-19 | 朱诺治疗学有限公司 | 用于刺激和转导t细胞的方法 |
WO2022238386A1 (en) | 2021-05-10 | 2022-11-17 | Institut Curie | Methods for the treatment of cancer, inflammatory diseases and autoimmune diseases |
EP4346912A1 (en) | 2021-05-25 | 2024-04-10 | Institut Curie | Myeloid cells overexpressing bcl2 |
US11945876B2 (en) | 2021-06-16 | 2024-04-02 | Instil Bio (Uk) Limited | Receptors providing targeted costimulation for adoptive cell therapy |
WO2023288278A1 (en) | 2021-07-16 | 2023-01-19 | Instil Bio (Uk) Limited | Chimeric molecules providing targeted costimulation for adoptive cell therapy |
TW202321457A (zh) | 2021-08-04 | 2023-06-01 | 美商薩那生物科技公司 | 靶向cd4之病毒載體之用途 |
WO2023014922A1 (en) | 2021-08-04 | 2023-02-09 | The Regents Of The University Of Colorado, A Body Corporate | Lat activating chimeric antigen receptor t cells and methods of use thereof |
CN117836405A (zh) * | 2021-08-13 | 2024-04-05 | 先声创新公司 | 三维培养多能干细胞产生造血干细胞 |
WO2023081715A1 (en) | 2021-11-03 | 2023-05-11 | Viracta Therapeutics, Inc. | Combination of car t-cell therapy with btk inhibitors and methods of use thereof |
WO2023081735A1 (en) | 2021-11-03 | 2023-05-11 | Celgene Corporation | Chimeric antigen receptors specific for b-cell maturation antigen for use in treating myeloma |
WO2023081900A1 (en) | 2021-11-08 | 2023-05-11 | Juno Therapeutics, Inc. | Engineered t cells expressing a recombinant t cell receptor (tcr) and related systems and methods |
WO2023105000A1 (en) | 2021-12-09 | 2023-06-15 | Zygosity Limited | Vector |
TW202342498A (zh) | 2021-12-17 | 2023-11-01 | 美商薩那生物科技公司 | 經修飾副黏液病毒科融合醣蛋白 |
WO2023109900A1 (en) | 2021-12-17 | 2023-06-22 | Shanghai Henlius Biotech, Inc. | Anti-ox40 antibodies, multispecific antibodies and methods of use |
CA3240565A1 (en) | 2021-12-17 | 2023-06-22 | Wenfeng Xu | Anti-ox40 antibodies and methods of use |
WO2023115041A1 (en) | 2021-12-17 | 2023-06-22 | Sana Biotechnology, Inc. | Modified paramyxoviridae attachment glycoproteins |
WO2023126458A1 (en) | 2021-12-28 | 2023-07-06 | Mnemo Therapeutics | Immune cells with inactivated suv39h1 and modified tcr |
WO2023139269A1 (en) | 2022-01-21 | 2023-07-27 | Mnemo Therapeutics | Modulation of suv39h1 expression by rnas |
WO2023147515A1 (en) | 2022-01-28 | 2023-08-03 | Juno Therapeutics, Inc. | Methods of manufacturing cellular compositions |
WO2023150518A1 (en) | 2022-02-01 | 2023-08-10 | Sana Biotechnology, Inc. | Cd3-targeted lentiviral vectors and uses thereof |
WO2023164440A1 (en) | 2022-02-22 | 2023-08-31 | Juno Therapeutics, Inc. | Proteinase 3 (pr3) chimeric autoantibody receptor t cells and related methods and uses |
WO2023178348A1 (en) | 2022-03-18 | 2023-09-21 | The Regents Of The University Of Colorado, A Body Corporate | Genetically engineered t-cell co-receptors and methods of use thereof |
WO2023180552A1 (en) | 2022-03-24 | 2023-09-28 | Institut Curie | Immunotherapy targeting tumor transposable element derived neoantigenic peptides in glioblastoma |
WO2023187024A1 (en) | 2022-03-31 | 2023-10-05 | Institut Curie | Modified rela protein for inducing interferon expression and engineered immune cells with improved interferon expression |
WO2023193015A1 (en) | 2022-04-01 | 2023-10-05 | Sana Biotechnology, Inc. | Cytokine receptor agonist and viral vector combination therapies |
WO2023196933A1 (en) | 2022-04-06 | 2023-10-12 | The Regents Of The University Of Colorado, A Body Corporate | Chimeric antigen receptor t cells and methods of use thereof |
WO2023196921A1 (en) | 2022-04-06 | 2023-10-12 | The Regents Of The University Of Colorado, A Body Corporate | Granzyme expressing t cells and methods of use |
WO2023211972A1 (en) | 2022-04-28 | 2023-11-02 | Medical University Of South Carolina | Chimeric antigen receptor modified regulatory t cells for treating cancer |
WO2023213969A1 (en) | 2022-05-05 | 2023-11-09 | Juno Therapeutics Gmbh | Viral-binding protein and related reagents, articles, and methods of use |
WO2023220655A1 (en) | 2022-05-11 | 2023-11-16 | Celgene Corporation | Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy |
WO2023220641A2 (en) | 2022-05-11 | 2023-11-16 | Juno Therapeutics, Inc. | Methods and uses related to t cell therapy and production of same |
WO2023222617A1 (en) | 2022-05-16 | 2023-11-23 | Miltenyi Biotec B.V. & Co. KG | Endogenous signaling molecule activating chimeric antigen receptors and methods of generation thereof |
EP4279085A1 (en) | 2022-05-20 | 2023-11-22 | Mnemo Therapeutics | Compositions and methods for treating a refractory or relapsed cancer or a chronic infectious disease |
WO2023230548A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Method for predicting response to a t cell therapy |
WO2023230581A1 (en) | 2022-05-25 | 2023-11-30 | Celgene Corporation | Methods of manufacturing t cell therapies |
CN115058387B (zh) * | 2022-06-11 | 2023-12-01 | 重庆医科大学 | 一种人胚胎干细胞与前列腺癌细胞共培养制备抗前列腺癌药物的方法 |
WO2023250400A1 (en) | 2022-06-22 | 2023-12-28 | Juno Therapeutics, Inc. | Treatment methods for second line therapy of cd19-targeted car t cells |
WO2024006960A1 (en) | 2022-06-29 | 2024-01-04 | Juno Therapeutics, Inc. | Lipid nanoparticles for delivery of nucleic acids |
WO2024031091A2 (en) | 2022-08-05 | 2024-02-08 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for gprc5d and bcma |
WO2024044779A2 (en) | 2022-08-26 | 2024-02-29 | Juno Therapeutics, Inc. | Antibodies and chimeric antigen receptors specific for delta-like ligand 3 (dll3) |
WO2024054944A1 (en) | 2022-09-08 | 2024-03-14 | Juno Therapeutics, Inc. | Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing |
CN117736335A (zh) * | 2022-09-20 | 2024-03-22 | 深圳先进技术研究院 | 靶向间皮素和nkg2d配体的双靶向car-t细胞及其应用 |
WO2024062138A1 (en) | 2022-09-23 | 2024-03-28 | Mnemo Therapeutics | Immune cells comprising a modified suv39h1 gene |
WO2024081820A1 (en) | 2022-10-13 | 2024-04-18 | Sana Biotechnology, Inc. | Viral particles targeting hematopoietic stem cells |
WO2024097905A1 (en) | 2022-11-02 | 2024-05-10 | Celgene Corporation | Methods of treatment with t cell therapy and immunomodulatory agent maintenance therapy |
WO2024100604A1 (en) | 2022-11-09 | 2024-05-16 | Juno Therapeutics Gmbh | Methods for manufacturing engineered immune cells |
WO2024102948A1 (en) | 2022-11-11 | 2024-05-16 | Celgene Corporation | Fc receptor-homolog 5 (fcrh5) specific binding molecules and bispecific t-cell engaging antibodies including same and related methods |
WO2024124132A1 (en) | 2022-12-09 | 2024-06-13 | Juno Therapeutics, Inc. | Machine learning methods for predicting cell phenotype using holographic imaging |
WO2024129778A2 (en) | 2022-12-13 | 2024-06-20 | Juno Therapeutics, Inc. | Chimeric antigen receptors specific for baff-r and cd19 and methods and uses thereof |
WO2024129988A1 (en) | 2022-12-14 | 2024-06-20 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for delivery of therapeutic agents to bone |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010523083A (ja) * | 2007-03-30 | 2010-07-15 | メモリアル スローン−ケタリング キャンサー センター | 養子移入tリンパ球における副刺激リガンドの構成性発現 |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5399346A (en) | 1989-06-14 | 1995-03-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gene therapy |
US5712149A (en) | 1995-02-03 | 1998-01-27 | Cell Genesys, Inc. | Chimeric receptor molecules for delivery of co-stimulatory signals |
GB9605515D0 (en) | 1996-03-15 | 1996-05-15 | Medical Res Council | Improvements in or relating to cell stimulation |
US7446190B2 (en) * | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
US7629440B2 (en) * | 2002-08-20 | 2009-12-08 | Genitrix, Llc | Lectin compositions and methods for modulating an immune response to an antigen |
US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
US20050113564A1 (en) * | 2003-11-05 | 2005-05-26 | St. Jude Children's Research Hospital | Chimeric receptors with 4-1BB stimulatory signaling domain |
US8315214B2 (en) | 2007-05-18 | 2012-11-20 | Research In Motion Limited | Method and system for discontinuous reception de-synchronization detection |
US20140088019A1 (en) * | 2011-02-11 | 2014-03-27 | Zyngenia, Inc. | Monovalent and Multivalent Multispecific Complexes and Uses Thereof |
GB201108236D0 (en) * | 2011-05-17 | 2011-06-29 | Ucl Business Plc | Method |
CN107266584B (zh) * | 2011-07-29 | 2022-05-13 | 宾夕法尼亚大学董事会 | 转换共刺激受体 |
NZ746914A (en) * | 2012-10-02 | 2020-03-27 | Memorial Sloan Kettering Cancer Center | Compositions and methods for immunotherapy |
US10117896B2 (en) * | 2012-10-05 | 2018-11-06 | The Trustees Of The University Of Pennsylvania | Use of a trans-signaling approach in chimeric antigen receptors |
ES2745754T3 (es) | 2012-11-09 | 2020-03-03 | Dsm Ip Assets Bv | Procedimiento para la hidrólisis enzimática de material lignocelulósico mediante el uso de oxígeno |
WO2014124143A1 (en) | 2013-02-06 | 2014-08-14 | Anthrogenesis Corporation | Modified t lymphocytes having improved specificity |
ES2769574T3 (es) | 2013-03-15 | 2020-06-26 | Michael C Milone | Reconocimiento de células citotóxicas con receptores quiméricos para inmunoterapia adoptiva |
-
2013
- 2013-10-02 NZ NZ746914A patent/NZ746914A/en unknown
- 2013-10-02 WO PCT/US2013/063097 patent/WO2014055668A1/en active Application Filing
- 2013-10-02 KR KR1020157011160A patent/KR102198058B1/ko active IP Right Grant
- 2013-10-02 CN CN201380063036.8A patent/CN104853766A/zh active Pending
- 2013-10-02 CN CN202011103486.3A patent/CN112458057A/zh active Pending
- 2013-10-02 SG SG11201502598SA patent/SG11201502598SA/en unknown
- 2013-10-02 RU RU2015116901A patent/RU2729401C2/ru active
- 2013-10-02 ES ES13844468T patent/ES2743738T3/es active Active
- 2013-10-02 JP JP2015534828A patent/JP6441802B2/ja active Active
- 2013-10-02 EP EP19179456.9A patent/EP3597215A1/en active Pending
- 2013-10-02 RU RU2020124583A patent/RU2020124583A/ru unknown
- 2013-10-02 NZ NZ706541A patent/NZ706541A/en unknown
- 2013-10-02 CA CA2886859A patent/CA2886859C/en active Active
- 2013-10-02 AU AU2013327136A patent/AU2013327136A1/en not_active Abandoned
- 2013-10-02 EP EP13844468.2A patent/EP2903637B1/en active Active
- 2013-10-02 CN CN202011102703.7A patent/CN112430580A/zh active Pending
- 2013-10-02 MX MX2015004287A patent/MX370148B/es active IP Right Grant
-
2015
- 2015-03-30 IL IL238047A patent/IL238047B/en active IP Right Grant
- 2015-04-01 US US14/676,255 patent/US10654928B2/en active Active
- 2015-04-06 PH PH12015500747A patent/PH12015500747B1/en unknown
- 2015-04-28 ZA ZA201502880A patent/ZA201502880B/en unknown
- 2015-09-24 HK HK15109439.3A patent/HK1208631A1/xx unknown
-
2018
- 2018-03-15 JP JP2018047734A patent/JP2018108111A/ja not_active Withdrawn
- 2018-06-15 AU AU2018204297A patent/AU2018204297B2/en active Active
-
2019
- 2019-10-25 PH PH12019502424A patent/PH12019502424A1/en unknown
-
2020
- 2020-02-07 IL IL272539A patent/IL272539B/en active IP Right Grant
- 2020-02-17 JP JP2020024520A patent/JP6963051B2/ja active Active
- 2020-02-17 JP JP2020024521A patent/JP2020096625A/ja not_active Withdrawn
- 2020-04-13 US US16/847,059 patent/US11712469B2/en active Active
- 2020-12-24 AU AU2020294287A patent/AU2020294287B2/en active Active
-
2021
- 2021-12-01 JP JP2021195401A patent/JP2022024161A/ja not_active Withdrawn
-
2023
- 2023-06-13 US US18/333,753 patent/US20240091353A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010523083A (ja) * | 2007-03-30 | 2010-07-15 | メモリアル スローン−ケタリング キャンサー センター | 養子移入tリンパ球における副刺激リガンドの構成性発現 |
Non-Patent Citations (4)
Title |
---|
IMMUNOTHERAPY, vol. 3, no. 1, JPN6017037132, 2011, pages 33 - 48, ISSN: 0003838208 * |
INT. REV. IMMUNOL., vol. vol.30, no.5-6, JPN6017037131, 2011, pages 294 - 311, ISSN: 0003838207 * |
J. BIOMED. BIOTECHNOL., vol. ID.956304, JPN6018027036, 2010, pages 1 - 13, ISSN: 0003915671 * |
J. CLIN. IMMUNOL., vol. 32, no. 5, JPN6017037130, April 2012 (2012-04-01), pages 1059 - 1070, ISSN: 0003651138 * |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018521663A (ja) * | 2015-07-31 | 2018-08-09 | キングス カレッジ ロンドンKings College London | 治療薬 |
JP2021168675A (ja) * | 2015-07-31 | 2021-10-28 | キングス カレッジ ロンドンKings College London | 治療薬 |
JP7053037B2 (ja) | 2015-07-31 | 2022-04-12 | キングス カレッジ ロンドン | 治療薬 |
JP2020517295A (ja) * | 2017-04-26 | 2020-06-18 | ユーリカ セラピューティックス, インコーポレイテッド | キメラ活性化受容体及びキメラ刺激受容体を発現する細胞並びにその使用 |
US11613573B2 (en) | 2017-04-26 | 2023-03-28 | Eureka Therapeutics, Inc. | Chimeric antibody/T-cell receptor constructs and uses thereof |
US11965021B2 (en) | 2017-04-26 | 2024-04-23 | Eureka Therapeutics, Inc. | Cells expressing chimeric activating receptors and chimeric stimulating receptors and uses thereof |
JP2021528995A (ja) * | 2018-03-30 | 2021-10-28 | エウレカ セラピューティクス インコーポレイテッド | Cd22を標的とする構築物及びその使用 |
JP7414226B2 (ja) | 2018-03-30 | 2024-01-16 | エウレカ セラピューティクス インコーポレイテッド | Cd22を標的とする構築物及びその使用 |
JP2021526844A (ja) * | 2018-06-18 | 2021-10-11 | ユーリカ セラピューティックス, インコーポレイテッド | 前立腺特異的膜抗原(psma)を標的とする構築物及びその使用 |
US11993661B2 (en) | 2018-06-18 | 2024-05-28 | Eureka Therapeutics, Inc. | Constructs targeting prostate-specific membrane antigen (PSMA) and uses thereof |
JP7511308B2 (ja) | 2018-06-18 | 2024-07-05 | ユーリカ セラピューティックス, インコーポレイテッド | 前立腺特異的膜抗原(psma)を標的とする構築物及びその使用 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6963051B2 (ja) | 免疫療法のための組成物および方法 | |
JP7367104B2 (ja) | 免疫療法のための組成物および方法 | |
JP6857028B2 (ja) | 免疫治療のための組成物および方法 | |
JP6215265B2 (ja) | 養子移入tリンパ球における副刺激リガンドの構成性発現 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161003 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20161003 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20170831 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170929 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20171225 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180227 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180315 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180717 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181015 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20181107 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20181122 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6441802 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R157 | Certificate of patent or utility model (correction) |
Free format text: JAPANESE INTERMEDIATE CODE: R157 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |