ES2907819T3 - Receptor novedoso de linfocitos T - Google Patents
Receptor novedoso de linfocitos TInfo
- Publication number
- ES2907819T3 ES2907819T3 ES18795783T ES18795783T ES2907819T3 ES 2907819 T3 ES2907819 T3 ES 2907819T3 ES 18795783 T ES18795783 T ES 18795783T ES 18795783 T ES18795783 T ES 18795783T ES 2907819 T3 ES2907819 T3 ES 2907819T3
- Authority
- ES
- Spain
- Prior art keywords
- tcr
- seq
- cells
- cell
- clone
- 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.)
- Active
Links
- 108091008874 T cell receptors Proteins 0.000 title claims abstract description 149
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 title claims abstract description 139
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 114
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims abstract description 17
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 10
- 210000004027 cell Anatomy 0.000 claims description 191
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 95
- 201000011510 cancer Diseases 0.000 claims description 82
- 239000003446 ligand Substances 0.000 claims description 55
- 201000001441 melanoma Diseases 0.000 claims description 32
- 239000013598 vector Substances 0.000 claims description 17
- 230000009258 tissue cross reactivity Effects 0.000 claims description 10
- 230000003834 intracellular effect Effects 0.000 claims description 7
- 210000003734 kidney Anatomy 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 5
- 210000000481 breast Anatomy 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 210000002865 immune cell Anatomy 0.000 claims description 4
- 210000004877 mucosa Anatomy 0.000 claims description 4
- 210000003679 cervix uteri Anatomy 0.000 claims description 3
- 108020003175 receptors Proteins 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 2
- 210000001728 clone cell Anatomy 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 3
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 description 29
- 108091033409 CRISPR Proteins 0.000 description 27
- 230000014509 gene expression Effects 0.000 description 26
- 238000003556 assay Methods 0.000 description 24
- 230000004913 activation Effects 0.000 description 23
- 238000001994 activation Methods 0.000 description 23
- 238000010186 staining Methods 0.000 description 18
- 238000010354 CRISPR gene editing Methods 0.000 description 15
- DDBCPKAHJKOGKK-UHFFFAOYSA-N N(2)-acetyl-6-formylpterin Chemical compound O=CC1=CN=C2NC(NC(=O)C)=NC(=O)C2=N1 DDBCPKAHJKOGKK-UHFFFAOYSA-N 0.000 description 15
- 108020005004 Guide RNA Proteins 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 12
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 10
- 102220471943 Interferon-induced helicase C domain-containing protein 1_K43A_mutation Human genes 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 238000010361 transduction Methods 0.000 description 9
- 230000026683 transduction Effects 0.000 description 9
- 108700012920 TNF Proteins 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 230000002018 overexpression Effects 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 7
- 229910052804 chromium Inorganic materials 0.000 description 7
- 239000011651 chromium Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 6
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 6
- 230000005859 cell recognition Effects 0.000 description 6
- 230000009089 cytolysis Effects 0.000 description 6
- 238000002784 cytotoxicity assay Methods 0.000 description 6
- 231100000263 cytotoxicity test Toxicity 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 238000012163 sequencing technique Methods 0.000 description 6
- LXKLTDXEFFOBPT-CEKOQDAHSA-N 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil Chemical compound CC(=O)\C=N\C1=C(NC[C@H](O)[C@H](O)[C@H](O)CO)NC(=O)NC1=O LXKLTDXEFFOBPT-CEKOQDAHSA-N 0.000 description 5
- 241000713666 Lentivirus Species 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 210000002307 prostate Anatomy 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 101000708766 Homo sapiens Structural maintenance of chromosomes protein 3 Proteins 0.000 description 4
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 4
- 102100032723 Structural maintenance of chromosomes protein 3 Human genes 0.000 description 4
- 238000002619 cancer immunotherapy Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 238000009169 immunotherapy Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000004005 microsphere Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 210000004882 non-tumor cell Anatomy 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- POVNCJSPYFCWJR-USZUGGBUSA-N (4s)-4-[[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-5-[(2s)-2-[[2-[(2s)-2-[[(2s)-1-[[(2s,3r)-1-[[(1s)-1-carboxy-2-methylpropyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1- Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O)C1=CC=C(O)C=C1 POVNCJSPYFCWJR-USZUGGBUSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 238000010356 CRISPR-Cas9 genome editing Methods 0.000 description 3
- 101100125371 Caenorhabditis elegans cil-1 gene Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 3
- 101150082764 MR1 gene Proteins 0.000 description 3
- 241000187480 Mycobacterium smegmatis Species 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 102100021043 Regulatory factor X-associated protein Human genes 0.000 description 3
- 108700019146 Transgenes Proteins 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000000422 nocturnal effect Effects 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 206010005949 Bone cancer Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- VYZAMTAEIAYCRO-BJUDXGSMSA-N Chromium-51 Chemical compound [51Cr] VYZAMTAEIAYCRO-BJUDXGSMSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 101000705592 Cucumis melo Phytoene synthase, chloroplastic Proteins 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- 101001075466 Homo sapiens Regulatory factor X-associated protein Proteins 0.000 description 2
- 101000645329 Homo sapiens T cell receptor alpha joining 31 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 2
- 108700011259 MicroRNAs Proteins 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 108010047620 Phytohemagglutinins Proteins 0.000 description 2
- 102000013968 STAT6 Transcription Factor Human genes 0.000 description 2
- 108010011005 STAT6 Transcription Factor Proteins 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- 102100026276 T cell receptor alpha joining 31 Human genes 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 229940127174 UCHT1 Drugs 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 101150063416 add gene Proteins 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 230000005880 cancer cell killing Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 208000030381 cutaneous melanoma Diseases 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 208000021039 metastatic melanoma Diseases 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000001885 phytohemagglutinin Effects 0.000 description 2
- 239000003909 protein kinase inhibitor Substances 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 235000019192 riboflavin Nutrition 0.000 description 2
- 239000002151 riboflavin Substances 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 201000003708 skin melanoma Diseases 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 238000010200 validation analysis Methods 0.000 description 2
- CRCPLBFLOSEABN-BEVDRBHNSA-N (2r)-n-[(2s)-1-[[(2s)-1-amino-1-oxopropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n'-hydroxy-2-(2-methylpropyl)butanediamide Chemical compound C1=CC=CC2=CC(C[C@H](NC(=O)[C@@H](CC(=O)NO)CC(C)C)C(=O)N[C@@H](C)C(N)=O)=CC=C21 CRCPLBFLOSEABN-BEVDRBHNSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 102000008102 Ankyrins Human genes 0.000 description 1
- 108010049777 Ankyrins Proteins 0.000 description 1
- 101100124527 Bos taurus MR1 gene Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 238000010453 CRISPR/Cas method Methods 0.000 description 1
- 101100156338 Caenorhabditis elegans vit-4 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 102100021044 DNA-binding protein RFXANK Human genes 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 101001075464 Homo sapiens DNA-binding protein RFXANK Proteins 0.000 description 1
- 101000756759 Homo sapiens MHC class II regulatory factor RFX1 Proteins 0.000 description 1
- 101000772138 Homo sapiens T cell receptor alpha variable 1-2 Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- -1 Miltenyi Biotec) Proteins 0.000 description 1
- 101100194606 Mus musculus Rfxank gene Proteins 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102000005945 Regulatory Factor X1 Human genes 0.000 description 1
- 108010030933 Regulatory Factor X1 Proteins 0.000 description 1
- 101710189356 Regulatory factor X-associated protein Proteins 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 229940126530 T cell activator Drugs 0.000 description 1
- 230000037453 T cell priming Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102100029308 T cell receptor alpha variable 1-2 Human genes 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000011467 adoptive cell therapy Methods 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 210000000215 ciliated epithelial cell Anatomy 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000011181 container closure integrity test Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 238000007857 nested PCR Methods 0.000 description 1
- 238000007481 next generation sequencing Methods 0.000 description 1
- 230000005257 nucleotidylation Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003287 riboflavins Chemical class 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- PXLIDIMHPNPGMH-UHFFFAOYSA-N sodium chromate Chemical compound [Na+].[Na+].[O-][Cr]([O-])(=O)=O PXLIDIMHPNPGMH-UHFFFAOYSA-N 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 238000003239 susceptibility assay Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000012418 validation experiment Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/32—T-cell receptors [TCR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- 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
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- 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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Hematology (AREA)
- Developmental Biology & Embryology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1717578.7A GB201717578D0 (en) | 2017-10-26 | 2017-10-26 | Novel T-cell receptor |
| GBGB1806155.6A GB201806155D0 (en) | 2017-10-26 | 2018-04-16 | Novel t-cell receptor |
| PCT/GB2018/053045 WO2019081902A1 (en) | 2017-10-26 | 2018-10-22 | NEW LYMPHOCYTE RECEPTOR T |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2907819T3 true ES2907819T3 (es) | 2022-04-26 |
Family
ID=60580240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18795783T Active ES2907819T3 (es) | 2017-10-26 | 2018-10-22 | Receptor novedoso de linfocitos T |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US11725039B2 (enExample) |
| EP (2) | EP4039700A1 (enExample) |
| JP (1) | JP7289311B2 (enExample) |
| KR (1) | KR20200078497A (enExample) |
| CN (1) | CN111278855B (enExample) |
| AU (2) | AU2018356944A1 (enExample) |
| BR (1) | BR112020007880A2 (enExample) |
| CA (1) | CA3077635A1 (enExample) |
| DK (1) | DK3700925T3 (enExample) |
| EA (1) | EA202091015A1 (enExample) |
| ES (1) | ES2907819T3 (enExample) |
| GB (2) | GB201717578D0 (enExample) |
| IL (1) | IL274025A (enExample) |
| MX (1) | MX2020004334A (enExample) |
| PL (1) | PL3700925T3 (enExample) |
| SG (1) | SG11202002537WA (enExample) |
| WO (1) | WO2019081902A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201717578D0 (en) * | 2017-10-26 | 2017-12-13 | Univ College Cardiff Consultants Ltd | Novel T-cell receptor |
| JP2023510806A (ja) * | 2020-01-09 | 2023-03-15 | ビオミュネクス・ファーマシューティカルズ | Ｍａｉｔ及び腫瘍細胞の両方に結合する多重特異性抗体 |
| JP7680769B2 (ja) * | 2020-01-16 | 2025-05-21 | ウニヴェルズィテート バーゼル | 免疫調節用のｍｒ１リガンド及び医薬組成物 |
| KR20210153539A (ko) * | 2020-06-10 | 2021-12-17 | 주식회사 유틸렉스 | Mr1에 결합하는 t-세포 수용체 및 이의 용도 |
| KR20230096110A (ko) * | 2020-11-04 | 2023-06-29 | 페이트 세러퓨틱스, 인코포레이티드 | 고형 종양을 표적화하는 멀티플렉스화된 조작 iPSC 및 면역 효과기 세포 |
| WO2022118043A1 (en) | 2020-12-03 | 2022-06-09 | Enara Bio Limited | Novel protein-ligand complex |
| WO2022248881A1 (en) | 2021-05-28 | 2022-12-01 | Enara Bio Limited | Novel protein-ligand complex |
| AU2022310862A1 (en) | 2021-07-14 | 2024-02-01 | Regeneron Pharmaceuticals, Inc. | Engineered t cell receptors fused to binding domains from antibodies |
| WO2023002204A1 (en) | 2021-07-21 | 2023-01-26 | Enara Bio Limited | T-cell receptor |
| WO2023106894A1 (ko) * | 2021-12-10 | 2023-06-15 | 주식회사 유틸렉스 | Mr1 제한적 panck t 세포 및 이의 제조방법 |
| EP4472742A1 (en) | 2022-02-03 | 2024-12-11 | University College Cardiff Consultants Limited | Novel t-cell receptor |
| AU2023248532A1 (en) | 2022-04-08 | 2024-11-21 | Regeneron Pharmaceuticals, Inc. | Multipartite receptor and signaling complexes |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI636065B (zh) * | 2013-08-05 | 2018-09-21 | 伊瑪提克斯生物科技有限公司 | 新穎肽類，細胞及其用於治療多種腫瘤的用途，其製造方法及包含其等之醫藥組成物 |
| CN106103711A (zh) * | 2013-11-21 | 2016-11-09 | 组库创世纪株式会社 | T细胞受体和b细胞受体库分析系统及其在治疗和诊断中的应用 |
| JP7233103B2 (ja) * | 2017-03-07 | 2023-03-06 | ウニヴェルズィテート バーゼル | 癌免疫療法用ｍｒ１制限ｔ細胞受容体 |
| GB201717578D0 (en) * | 2017-10-26 | 2017-12-13 | Univ College Cardiff Consultants Ltd | Novel T-cell receptor |
-
2017
- 2017-10-26 GB GBGB1717578.7A patent/GB201717578D0/en not_active Ceased
-
2018
- 2018-04-16 GB GBGB1806155.6A patent/GB201806155D0/en not_active Ceased
- 2018-10-22 EA EA202091015A patent/EA202091015A1/ru unknown
- 2018-10-22 PL PL18795783T patent/PL3700925T3/pl unknown
- 2018-10-22 ES ES18795783T patent/ES2907819T3/es active Active
- 2018-10-22 CN CN201880069546.9A patent/CN111278855B/zh not_active Expired - Fee Related
- 2018-10-22 EP EP21214567.6A patent/EP4039700A1/en not_active Withdrawn
- 2018-10-22 KR KR1020207011102A patent/KR20200078497A/ko not_active Ceased
- 2018-10-22 SG SG11202002537WA patent/SG11202002537WA/en unknown
- 2018-10-22 AU AU2018356944A patent/AU2018356944A1/en not_active Abandoned
- 2018-10-22 MX MX2020004334A patent/MX2020004334A/es unknown
- 2018-10-22 EP EP18795783.2A patent/EP3700925B8/en active Active
- 2018-10-22 JP JP2020543406A patent/JP7289311B2/ja active Active
- 2018-10-22 CA CA3077635A patent/CA3077635A1/en active Pending
- 2018-10-22 BR BR112020007880-8A patent/BR112020007880A2/pt unknown
- 2018-10-22 WO PCT/GB2018/053045 patent/WO2019081902A1/en not_active Ceased
- 2018-10-22 DK DK18795783.2T patent/DK3700925T3/da active
-
2020
- 2020-04-19 IL IL274025A patent/IL274025A/en unknown
- 2020-04-24 US US16/858,082 patent/US11725039B2/en active Active
-
2021
- 2021-01-20 US US17/153,329 patent/US11078252B2/en active Active
-
2024
- 2024-04-26 AU AU2024202735A patent/AU2024202735A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2024202735A1 (en) | 2024-05-30 |
| GB201806155D0 (en) | 2018-05-30 |
| SG11202002537WA (en) | 2020-05-28 |
| PL3700925T3 (pl) | 2022-05-02 |
| US20200369742A1 (en) | 2020-11-26 |
| JP2021500406A (ja) | 2021-01-07 |
| CA3077635A1 (en) | 2019-05-02 |
| EP3700925A1 (en) | 2020-09-02 |
| EP3700925B8 (en) | 2022-02-16 |
| AU2018356944A1 (en) | 2020-04-16 |
| US11725039B2 (en) | 2023-08-15 |
| US20210147506A1 (en) | 2021-05-20 |
| BR112020007880A2 (pt) | 2020-10-27 |
| JP7289311B2 (ja) | 2023-06-09 |
| EP4039700A1 (en) | 2022-08-10 |
| CN111278855A (zh) | 2020-06-12 |
| DK3700925T3 (en) | 2022-04-04 |
| CN111278855B (zh) | 2024-04-02 |
| EA202091015A1 (ru) | 2020-07-17 |
| IL274025A (en) | 2020-06-30 |
| KR20200078497A (ko) | 2020-07-01 |
| GB201717578D0 (en) | 2017-12-13 |
| WO2019081902A1 (en) | 2019-05-02 |
| EP3700925B1 (en) | 2021-12-29 |
| MX2020004334A (es) | 2020-08-03 |
| US11078252B2 (en) | 2021-08-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2907819T3 (es) | Receptor novedoso de linfocitos T | |
| Klebanoff et al. | T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome | |
| AU2021202223B2 (en) | Methods of isolating T cells having antigenic specificity for a cancer-specific mutation | |
| ES3027565T3 (en) | Tcr and peptides | |
| ES2875959T3 (es) | Composiciones y métodos para reprogramación de receptores de linfocitos T mediante el uso de proteínas de fusión | |
| EP3200818B1 (en) | Methods of isolating t cell receptors having antigenic specificity for a cancer-specific mutation | |
| CN116731156A (zh) | 用于癌症免疫治疗的转染t细胞和t细胞受体 | |
| CN115073583A (zh) | 识别hla-cw8限制性突变kras的t细胞受体 | |
| JP2016512435A (ja) | 腫瘍抗原を直接認識するために組換えｔ細胞レセプターを使用するための組成物及び方法 | |
| US20210214686A1 (en) | Production and selection of tumor uber reactive immune cells (turics) | |
| CN113195527A (zh) | Tcr和肽 | |
| MD3430037T2 (ro) | Celule T transfectate și receptori de celule T pentru utilizare în imunoterapie împotriva cancerelor | |
| Chervin et al. | Design of T-cell receptor libraries with diverse binding properties to examine adoptive T-cell responses | |
| CN111372944A (zh) | 新型γδT细胞受体和其配体 | |
| US12479903B2 (en) | CD5 specific T cell receptor cell or gene therapy | |
| HK40034405B (en) | Novel t-cell receptor | |
| HK40034405A (en) | Novel t-cell receptor | |
| EA045252B1 (ru) | Новый т-клеточный рецептор | |
| RU2777284C2 (ru) | Сконструированные клетки - естественные киллеры и их применение | |
| Rosenberger | Comparing the therapeutic potential of T cell receptors from tumors and healthy donors for adoptive T cell therapy in cancer | |
| Wheeler | Identifying a novel γδ T-cell stress ligand: Potential for cancer immunotherapy | |
| BR122024024508A2 (pt) | Construto reconhecedor de antígeno, ácido nucleico, vetor, célula hospedeira, composição farmacêutica e método de fabricação de uma linhagem celular que expressa um construto reconhecedor de antígeno aat específico |