JP7109789B2 - 融合タンパク質を使用したtcrの再プログラム化のための組成物及び方法 - Google Patents
融合タンパク質を使用したtcrの再プログラム化のための組成物及び方法 Download PDFInfo
- Publication number
- JP7109789B2 JP7109789B2 JP2019505451A JP2019505451A JP7109789B2 JP 7109789 B2 JP7109789 B2 JP 7109789B2 JP 2019505451 A JP2019505451 A JP 2019505451A JP 2019505451 A JP2019505451 A JP 2019505451A JP 7109789 B2 JP7109789 B2 JP 7109789B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- bcma
- tfp
- cell
- domain
- 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
- 238000000034 method Methods 0.000 title claims description 113
- 108020001507 fusion proteins Proteins 0.000 title claims description 28
- 102000037865 fusion proteins Human genes 0.000 title claims description 28
- 239000000203 mixture Substances 0.000 title description 37
- 230000008672 reprogramming Effects 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims description 460
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 315
- 108091008874 T cell receptors Proteins 0.000 claims description 269
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 267
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 174
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 174
- 230000027455 binding Effects 0.000 claims description 136
- 206010028980 Neoplasm Diseases 0.000 claims description 133
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 132
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 123
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 123
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 120
- 229920001184 polypeptide Polymers 0.000 claims description 114
- 150000007523 nucleic acids Chemical class 0.000 claims description 112
- 102000039446 nucleic acids Human genes 0.000 claims description 97
- 108020004707 nucleic acids Proteins 0.000 claims description 97
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 59
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 58
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 claims description 55
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 claims description 55
- 201000011510 cancer Diseases 0.000 claims description 54
- 230000004068 intracellular signaling Effects 0.000 claims description 54
- 230000011664 signaling Effects 0.000 claims description 49
- 239000003795 chemical substances by application Substances 0.000 claims description 42
- 230000002401 inhibitory effect Effects 0.000 claims description 42
- 230000003834 intracellular effect Effects 0.000 claims description 37
- 241000124008 Mammalia Species 0.000 claims description 25
- 230000004936 stimulating effect Effects 0.000 claims description 21
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 15
- 208000034578 Multiple myelomas Diseases 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 8
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 7
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 7
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 7
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 5
- 201000003444 follicular lymphoma Diseases 0.000 claims description 5
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 3
- 206010027406 Mesothelioma Diseases 0.000 claims description 3
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 3
- 230000003211 malignant effect Effects 0.000 claims description 3
- 208000007525 plasmablastic lymphoma Diseases 0.000 claims description 3
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 claims description 3
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 claims description 2
- 208000036764 Adenocarcinoma of the esophagus Diseases 0.000 claims description 2
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims description 2
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 claims description 2
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims description 2
- 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 claims description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 2
- 201000003791 MALT lymphoma Diseases 0.000 claims description 2
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 2
- 206010030137 Oesophageal adenocarcinoma Diseases 0.000 claims description 2
- 206010061328 Ovarian epithelial cancer Diseases 0.000 claims description 2
- 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 2
- 208000017414 Precursor T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 2
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 claims description 2
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 2
- 201000008274 breast adenocarcinoma Diseases 0.000 claims description 2
- 230000001413 cellular effect Effects 0.000 claims description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 2
- 230000002357 endometrial effect Effects 0.000 claims description 2
- 208000018463 endometrial serous adenocarcinoma Diseases 0.000 claims description 2
- 208000028653 esophageal adenocarcinoma Diseases 0.000 claims description 2
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims description 2
- 201000009277 hairy cell leukemia Diseases 0.000 claims description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 claims description 2
- 230000001589 lymphoproliferative effect Effects 0.000 claims description 2
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims description 2
- 208000021937 marginal zone lymphoma Diseases 0.000 claims description 2
- 208000030427 mucinous ovarian cancer Diseases 0.000 claims description 2
- 208000013371 ovarian adenocarcinoma Diseases 0.000 claims description 2
- 201000006588 ovary adenocarcinoma Diseases 0.000 claims description 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 claims description 2
- 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 claims 1
- 208000000649 small cell carcinoma Diseases 0.000 claims 1
- 239000013598 vector Substances 0.000 description 104
- 239000000427 antigen Substances 0.000 description 101
- 108091007433 antigens Proteins 0.000 description 101
- 102000036639 antigens Human genes 0.000 description 101
- 108090000623 proteins and genes Proteins 0.000 description 97
- 125000003275 alpha amino acid group Chemical group 0.000 description 80
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 70
- 230000014509 gene expression Effects 0.000 description 69
- 108020004414 DNA Proteins 0.000 description 60
- 102000053602 DNA Human genes 0.000 description 60
- 235000018102 proteins Nutrition 0.000 description 56
- 102000004169 proteins and genes Human genes 0.000 description 56
- 201000010099 disease Diseases 0.000 description 53
- 238000011282 treatment Methods 0.000 description 48
- 230000004048 modification Effects 0.000 description 47
- 238000012986 modification Methods 0.000 description 47
- 229920002477 rna polymer Polymers 0.000 description 41
- 238000000338 in vitro Methods 0.000 description 40
- 108020004999 messenger RNA Proteins 0.000 description 38
- 239000012634 fragment Substances 0.000 description 37
- 235000001014 amino acid Nutrition 0.000 description 36
- 108091028043 Nucleic acid sequence Proteins 0.000 description 34
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 33
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 33
- 125000003729 nucleotide group Chemical group 0.000 description 33
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 32
- 150000001413 amino acids Chemical class 0.000 description 32
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 30
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 30
- 239000002773 nucleotide Substances 0.000 description 30
- 238000003556 assay Methods 0.000 description 27
- 150000002632 lipids Chemical class 0.000 description 26
- 210000004881 tumor cell Anatomy 0.000 description 26
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 25
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 25
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 24
- 230000006870 function Effects 0.000 description 24
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 23
- 230000004913 activation Effects 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- 238000013518 transcription Methods 0.000 description 22
- 230000035897 transcription Effects 0.000 description 22
- 239000012636 effector Substances 0.000 description 20
- 210000003162 effector t lymphocyte Anatomy 0.000 description 20
- 238000003752 polymerase chain reaction Methods 0.000 description 20
- -1 CD86 Proteins 0.000 description 19
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 19
- 238000001727 in vivo Methods 0.000 description 19
- 239000013612 plasmid Substances 0.000 description 19
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 18
- 239000011324 bead Substances 0.000 description 18
- 102000040430 polynucleotide Human genes 0.000 description 18
- 108091033319 polynucleotide Proteins 0.000 description 18
- 239000002157 polynucleotide Substances 0.000 description 18
- 125000000539 amino acid group Chemical group 0.000 description 17
- 208000035475 disorder Diseases 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 238000006467 substitution reaction Methods 0.000 description 17
- 108060003951 Immunoglobulin Proteins 0.000 description 16
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 16
- 102000018358 immunoglobulin Human genes 0.000 description 16
- 230000002147 killing effect Effects 0.000 description 16
- 239000003446 ligand Substances 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 15
- 108090000695 Cytokines Proteins 0.000 description 15
- 210000003719 b-lymphocyte Anatomy 0.000 description 15
- 230000001461 cytolytic effect Effects 0.000 description 15
- 239000002502 liposome Substances 0.000 description 15
- 230000035755 proliferation Effects 0.000 description 15
- 238000002347 injection Methods 0.000 description 14
- 239000007924 injection Substances 0.000 description 14
- 239000013642 negative control Substances 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 108020005345 3' Untranslated Regions Proteins 0.000 description 13
- 108020003589 5' Untranslated Regions Proteins 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 239000013604 expression vector Substances 0.000 description 13
- 239000013641 positive control Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 238000012546 transfer Methods 0.000 description 13
- 101000801255 Homo sapiens Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 12
- 108010002350 Interleukin-2 Proteins 0.000 description 12
- 102000000588 Interleukin-2 Human genes 0.000 description 12
- 241000713666 Lentivirus Species 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 230000001086 cytosolic effect Effects 0.000 description 12
- 238000000684 flow cytometry Methods 0.000 description 12
- 230000001965 increasing effect Effects 0.000 description 12
- 108091026890 Coding region Proteins 0.000 description 11
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 11
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000002617 apheresis Methods 0.000 description 11
- 238000010361 transduction Methods 0.000 description 11
- 230000026683 transduction Effects 0.000 description 11
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 10
- 102100027207 CD27 antigen Human genes 0.000 description 10
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 10
- 108010074328 Interferon-gamma Proteins 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 239000000306 component Substances 0.000 description 10
- 102000046935 human TNFRSF17 Human genes 0.000 description 10
- 230000028993 immune response Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000006228 supernatant Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 238000013519 translation Methods 0.000 description 10
- 108010074708 B7-H1 Antigen Proteins 0.000 description 9
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 9
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 description 9
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 230000000875 corresponding effect Effects 0.000 description 9
- 230000000139 costimulatory effect Effects 0.000 description 9
- 230000003013 cytotoxicity Effects 0.000 description 9
- 231100000135 cytotoxicity Toxicity 0.000 description 9
- 230000000977 initiatory effect Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 238000001890 transfection Methods 0.000 description 9
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 8
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
- 108091036407 Polyadenylation Proteins 0.000 description 8
- 108700008625 Reporter Genes Proteins 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 238000004422 calculation algorithm Methods 0.000 description 8
- 238000010367 cloning Methods 0.000 description 8
- 230000000295 complement effect Effects 0.000 description 8
- 238000004520 electroporation Methods 0.000 description 8
- 239000005090 green fluorescent protein Substances 0.000 description 8
- 230000001976 improved effect Effects 0.000 description 8
- 230000036210 malignancy Effects 0.000 description 8
- 238000009126 molecular therapy Methods 0.000 description 8
- 230000002062 proliferating effect Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 230000001177 retroviral effect Effects 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 8
- 235000002374 tyrosine Nutrition 0.000 description 8
- 239000013603 viral vector Substances 0.000 description 8
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 7
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 7
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 7
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 7
- 108091023045 Untranslated Region Proteins 0.000 description 7
- 238000002659 cell therapy Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 6
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 6
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 6
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 6
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 6
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 6
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 6
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 6
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 6
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 6
- 108010073807 IgG Receptors Proteins 0.000 description 6
- 102000009490 IgG Receptors Human genes 0.000 description 6
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 6
- 108060001084 Luciferase Proteins 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 108091034057 RNA (poly(A)) Proteins 0.000 description 6
- 230000000735 allogeneic effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 238000002784 cytotoxicity assay Methods 0.000 description 6
- 231100000263 cytotoxicity test Toxicity 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 210000005259 peripheral blood Anatomy 0.000 description 6
- 239000011886 peripheral blood Substances 0.000 description 6
- 230000008488 polyadenylation Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- 102100024263 CD160 antigen Human genes 0.000 description 5
- 102100037904 CD9 antigen Human genes 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 239000004471 Glycine Substances 0.000 description 5
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 5
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 5
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 5
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 description 5
- 206010061598 Immunodeficiency Diseases 0.000 description 5
- 102100037850 Interferon gamma Human genes 0.000 description 5
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 5
- 206010025323 Lymphomas Diseases 0.000 description 5
- 208000006994 Precancerous Conditions Diseases 0.000 description 5
- 108020004511 Recombinant DNA Proteins 0.000 description 5
- 241000283984 Rodentia Species 0.000 description 5
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 5
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 description 5
- 101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 5
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 5
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 238000012258 culturing Methods 0.000 description 5
- 231100000050 cytotoxic potential Toxicity 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 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 5
- 239000003814 drug Substances 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 239000012642 immune effector Substances 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 238000002649 immunization Methods 0.000 description 5
- 229940121354 immunomodulator Drugs 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 208000026310 Breast neoplasm Diseases 0.000 description 4
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 4
- 206010008342 Cervix carcinoma Diseases 0.000 description 4
- 108091033380 Coding strand Proteins 0.000 description 4
- 108020004705 Codon Proteins 0.000 description 4
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 4
- 108010036949 Cyclosporine Proteins 0.000 description 4
- 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 4
- 102000001398 Granzyme Human genes 0.000 description 4
- 108060005986 Granzyme Proteins 0.000 description 4
- 208000032672 Histiocytosis haematophagic Diseases 0.000 description 4
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 description 4
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 4
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 description 4
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 4
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 4
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 4
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 4
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 4
- 241000725303 Human immunodeficiency virus Species 0.000 description 4
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 description 4
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 4
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 4
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 4
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 4
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 4
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
- 239000004473 Threonine Substances 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 4
- 102100033726 Tumor necrosis factor receptor superfamily member 17 Human genes 0.000 description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 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 4
- 239000000872 buffer Substances 0.000 description 4
- 208000029499 cancer-related condition Diseases 0.000 description 4
- 230000020411 cell activation Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 201000010881 cervical cancer Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960001265 ciclosporin Drugs 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 229930182912 cyclosporin Natural products 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000004927 fusion Effects 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000003463 hyperproliferative effect Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 239000000693 micelle Substances 0.000 description 4
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000002688 persistence Effects 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 235000004400 serine Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 4
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 4
- 235000008521 threonine Nutrition 0.000 description 4
- 230000005026 transcription initiation Effects 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 3
- 102000006306 Antigen Receptors Human genes 0.000 description 3
- 108010083359 Antigen Receptors Proteins 0.000 description 3
- 108010028006 B-Cell Activating Factor Proteins 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 241000282832 Camelidae Species 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical group ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 101100203200 Danio rerio shha gene Proteins 0.000 description 3
- 241000702421 Dependoparvovirus Species 0.000 description 3
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 3
- 108090000331 Firefly luciferases Proteins 0.000 description 3
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 3
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 3
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 3
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 3
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 description 3
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 102100025390 Integrin beta-2 Human genes 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 239000000232 Lipid Bilayer Substances 0.000 description 3
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 3
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 108010087408 alpha-beta T-Cell Antigen Receptors Proteins 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 229940112129 campath Drugs 0.000 description 3
- 238000002619 cancer immunotherapy Methods 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 206010052015 cytokine release syndrome Diseases 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010017758 gastric cancer Diseases 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000002489 hematologic effect Effects 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 229940125721 immunosuppressive agent Drugs 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 229960005386 ipilimumab Drugs 0.000 description 3
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- FVVLHONNBARESJ-NTOWJWGLSA-H magnesium;potassium;trisodium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;acetate;tetrachloride;nonahydrate Chemical compound O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Mg+2].[Cl-].[Cl-].[Cl-].[Cl-].[K+].CC([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O FVVLHONNBARESJ-NTOWJWGLSA-H 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 102000006240 membrane receptors Human genes 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 230000002463 transducing effect Effects 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 102000035160 transmembrane proteins Human genes 0.000 description 3
- 108091005703 transmembrane proteins Proteins 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 238000010200 validation analysis Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 108700012439 CA9 Proteins 0.000 description 2
- 102100038078 CD276 antigen Human genes 0.000 description 2
- 101710185679 CD276 antigen Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 102100035793 CD83 antigen Human genes 0.000 description 2
- 108091033409 CRISPR Proteins 0.000 description 2
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 2
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010008165 Etanercept Proteins 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 208000036066 Hemophagocytic Lymphohistiocytosis Diseases 0.000 description 2
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 2
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 2
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 2
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 2
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 description 2
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- 108010073816 IgE Receptors Proteins 0.000 description 2
- 102000009438 IgE Receptors Human genes 0.000 description 2
- 108010002386 Interleukin-3 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102100026964 M1-specific T cell receptor beta chain Human genes 0.000 description 2
- 208000004987 Macrophage activation syndrome Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 description 2
- 239000012570 Opti-MEM I medium Substances 0.000 description 2
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 101710124239 Poly(A) polymerase Proteins 0.000 description 2
- 102000015623 Polynucleotide Adenylyltransferase Human genes 0.000 description 2
- 108010024055 Polynucleotide adenylyltransferase Proteins 0.000 description 2
- 208000007541 Preleukemia Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 208000004346 Smoldering Multiple Myeloma Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 230000006052 T cell proliferation Effects 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 101710187885 Tumor necrosis factor receptor superfamily member 17 Proteins 0.000 description 2
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 230000005809 anti-tumor immunity Effects 0.000 description 2
- 238000009175 antibody therapy Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- 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 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000005138 cryopreservation Methods 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 229940119744 dextran 40 Drugs 0.000 description 2
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 229960000390 fludarabine Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000004554 glutamine Nutrition 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 238000003306 harvesting Methods 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 208000014752 hemophagocytic syndrome Diseases 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 238000001325 log-rank test Methods 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000001806 memory b lymphocyte Anatomy 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 229940014456 mycophenolate Drugs 0.000 description 2
- 229960000951 mycophenolic acid Drugs 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000002741 palatine tonsil Anatomy 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 210000003720 plasmablast Anatomy 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 229960003452 romidepsin Drugs 0.000 description 2
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000010187 selection method Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 208000010721 smoldering plasma cell myeloma Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000009258 tissue cross reactivity Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 230000010474 transient expression Effects 0.000 description 2
- 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 2
- 230000004614 tumor growth Effects 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 108010065816 zeta chain antigen T cell receptor Proteins 0.000 description 2
- DYWNLSQWJMTVGJ-UHFFFAOYSA-N (1-hydroxy-1-phenylpropan-2-yl)azanium;chloride Chemical compound Cl.CC(N)C(O)C1=CC=CC=C1 DYWNLSQWJMTVGJ-UHFFFAOYSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 1
- 108010082808 4-1BB Ligand Proteins 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- 108020005176 AU Rich Elements Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 241000588813 Alcaligenes faecalis Species 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 241000473391 Archosargus rhomboidalis Species 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000714230 Avian leukemia virus Species 0.000 description 1
- 108010046304 B-Cell Activation Factor Receptor Proteins 0.000 description 1
- 102000007536 B-Cell Activation Factor Receptor Human genes 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108091028732 Concatemer Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 1
- 206010058314 Dysplasia Diseases 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
- 108010037179 Endodeoxyribonucleases Proteins 0.000 description 1
- 102000011750 Endodeoxyribonucleases Human genes 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 241000701867 Enterobacteria phage T7 Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 1
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 1
- 102000006354 HLA-DR Antigens Human genes 0.000 description 1
- 108010058597 HLA-DR Antigens Proteins 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000878602 Homo sapiens Immunoglobulin alpha Fc receptor Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
- 101000971538 Homo sapiens Killer cell lectin-like receptor subfamily F member 1 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 description 1
- 101000634853 Homo sapiens T cell receptor alpha chain constant Proteins 0.000 description 1
- 101000851434 Homo sapiens Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 description 1
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 101150102264 IE gene Proteins 0.000 description 1
- 229940124790 IL-6 inhibitor Drugs 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102100038005 Immunoglobulin alpha Fc receptor Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 102000019145 JUN kinase activity proteins Human genes 0.000 description 1
- 102100021458 Killer cell lectin-like receptor subfamily F member 1 Human genes 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 208000022435 Light chain deposition disease Diseases 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 108090000015 Mesothelin Proteins 0.000 description 1
- 102000003735 Mesothelin Human genes 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108091008877 NK cell receptors Proteins 0.000 description 1
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 201000000023 Osteosclerosis Diseases 0.000 description 1
- 240000007019 Oxalis corniculata Species 0.000 description 1
- 206010053869 POEMS syndrome Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 1
- 102000002508 Peptide Elongation Factors Human genes 0.000 description 1
- 108010068204 Peptide Elongation Factors Proteins 0.000 description 1
- 102000004503 Perforin Human genes 0.000 description 1
- 108010056995 Perforin Proteins 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 208000021161 Plasma cell disease Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 102100037935 Polyubiquitin-C Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 108020005161 RNA Caps Proteins 0.000 description 1
- 108010065868 RNA polymerase SP6 Proteins 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 102100029198 SLAM family member 7 Human genes 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 description 1
- 102000008115 Signaling Lymphocytic Activation Molecule Family Member 1 Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 108010039445 Stem Cell Factor Proteins 0.000 description 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 102100029452 T cell receptor alpha chain constant Human genes 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 238000010459 TALEN Methods 0.000 description 1
- 101150090104 TNFRSF17 gene Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 102100037116 Transcription elongation factor 1 homolog Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 1
- 101710178300 Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
- 108010056354 Ubiquitin C Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940119059 actemra Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229940005347 alcaligenes faecalis Drugs 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 102000006707 alpha-beta T-Cell Antigen Receptors Human genes 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 210000000628 antibody-producing cell Anatomy 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 108010028263 bacteriophage T3 RNA polymerase Proteins 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000029918 bioluminescence Effects 0.000 description 1
- 238000005415 bioluminescence Methods 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229960005520 bryostatin Drugs 0.000 description 1
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 230000000981 bystander Effects 0.000 description 1
- 239000003710 calcium ionophore Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 229940030156 cell vaccine Drugs 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 239000013632 covalent dimer Substances 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940093541 dicetylphosphate Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 229960000284 efalizumab Drugs 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000010502 episomal replication Effects 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 230000001036 exonucleolytic effect Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012595 freezing medium Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 238000012215 gene cloning Methods 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 210000001102 germinal center b cell Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 108010033706 glycylserine Proteins 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 229940064366 hespan Drugs 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 102000055277 human IL2 Human genes 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000008004 immune attack Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000004073 interleukin-2 production Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012092 media component Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 108010069768 negative elongation factor Proteins 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000015270 non-secretory plasma cell myeloma Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940023041 peptide vaccine Drugs 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 208000031223 plasma cell leukemia Diseases 0.000 description 1
- 229940081858 plasmalyte a Drugs 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000010304 tumor cell viability Effects 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 238000013413 tumor xenograft mouse model Methods 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000011311 validation assay Methods 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229940055760 yervoy Drugs 0.000 description 1
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/10—Cellular immunotherapy characterised by the cell type used
- A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K40/31—Chimeric antigen receptors [CAR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
-
- 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
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—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
- C07K14/70521—CD28, CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
- A61K2035/124—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells the cells being hematopoietic, bone marrow derived or blood cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662370189P | 2016-08-02 | 2016-08-02 | |
| US62/370,189 | 2016-08-02 | ||
| PCT/US2017/045159 WO2018026953A1 (en) | 2016-08-02 | 2017-08-02 | Compositions and methods for tcr reprogramming using fusion proteins |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019531056A JP2019531056A (ja) | 2019-10-31 |
| JP2019531056A5 JP2019531056A5 (enExample) | 2020-09-10 |
| JP7109789B2 true JP7109789B2 (ja) | 2022-08-01 |
Family
ID=59650003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019505451A Active JP7109789B2 (ja) | 2016-08-02 | 2017-08-02 | 融合タンパク質を使用したtcrの再プログラム化のための組成物及び方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11242376B2 (enExample) |
| EP (1) | EP3494138A1 (enExample) |
| JP (1) | JP7109789B2 (enExample) |
| CN (1) | CN109715668A (enExample) |
| AU (1) | AU2017306432A1 (enExample) |
| CA (1) | CA3032498A1 (enExample) |
| WO (1) | WO2018026953A1 (enExample) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3298033T (pt) | 2015-05-18 | 2020-09-22 | Tcr2 Therapeutics Inc | Composições e utilizações médicas para reprogramação de tcr utilizando proteínas de fusão |
| CA2986575A1 (en) | 2015-05-21 | 2016-11-24 | Harpoon Therapeutics, Inc. | Trispecific binding proteins and methods of use |
| GB201604458D0 (en) | 2016-03-16 | 2016-04-27 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against cancers |
| SG11201810327XA (en) | 2016-05-20 | 2018-12-28 | Harpoon Therapeutics Inc | Single domain serum albumin binding protein |
| US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
| AU2017306432A1 (en) | 2016-08-02 | 2019-03-21 | TCR2 Therapeutics Inc. | Compositions and methods for TCR reprogramming using fusion proteins |
| US12350349B2 (en) | 2016-08-03 | 2025-07-08 | Washington University | Gene editing of CAR-T cells for the treatment of T cell malignancies with chimeric antigen receptors |
| CA3036745A1 (en) | 2016-10-07 | 2018-04-12 | TCR2 Therapeutics Inc. | Compositions and methods for t-cell receptors reprogramming using fusion proteins |
| CA3044593A1 (en) | 2016-11-22 | 2018-05-31 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
| JP2020513754A (ja) * | 2016-12-21 | 2020-05-21 | ティーシーアール2 セラピューティクス インク. | がん治療用に操作されたt細胞 |
| US11535668B2 (en) | 2017-02-28 | 2022-12-27 | Harpoon Therapeutics, Inc. | Inducible monovalent antigen binding protein |
| WO2018200583A1 (en) | 2017-04-26 | 2018-11-01 | Eureka Therapeutics, Inc. | Cells expressing chimeric activating receptors and chimeric stimulating receptors and uses thereof |
| SG10201913582XA (en) | 2017-04-26 | 2020-02-27 | Eureka Therapeutics Inc | Constructs specifically recognizing glypican 3 and uses thereof |
| EP3621994A4 (en) | 2017-05-12 | 2020-12-30 | Harpoon Therapeutics, Inc. | MESOTHELIN BINDING PROTEINS |
| CR20200013A (es) | 2017-07-14 | 2020-03-11 | Immatics Biotechnologies Gmbh | Molécula de polipéptido con especificidad dual mejorada |
| CN111630070B (zh) * | 2017-10-13 | 2024-07-30 | 哈普恩治疗公司 | 三特异性蛋白质及使用方法 |
| IL315737A (en) * | 2017-10-13 | 2024-11-01 | Harpoon Therapeutics Inc | B-cell maturation antigen-binding proteins |
| KR20200119840A (ko) * | 2018-02-09 | 2020-10-20 | 이매틱스 유에스 인코포레이티드 | T 세포의 제조 방법 |
| US20210137839A1 (en) | 2018-02-17 | 2021-05-13 | Flagship Pioneering Innovations V, Inc. | Compositions and methods for membrane protein delivery |
| CN119192397A (zh) | 2018-05-14 | 2024-12-27 | 哈普恩治疗公司 | 用于条件性激活免疫球蛋白分子的结合部分 |
| CN109134665B (zh) * | 2018-08-24 | 2021-06-11 | 上海先博生物科技有限公司 | 一种基于单域抗体的bcma嵌合抗原受体及应用 |
| WO2020061482A1 (en) | 2018-09-21 | 2020-03-26 | Harpoon Therapeutics, Inc. | Egfr binding proteins and methods of use |
| EP3856771A4 (en) | 2018-09-25 | 2022-06-29 | Harpoon Therapeutics, Inc. | Dll3 binding proteins and methods of use |
| CN112074279B (zh) * | 2019-01-16 | 2024-01-26 | 卡里布生物科学公司 | 人源化bcma抗体和bcma-car-t细胞 |
| EP3715368A1 (en) | 2019-03-28 | 2020-09-30 | Albert-Ludwigs-Universität Freiburg | Chimeric antigen receptors, vectors coding for such receptors and their use in the modification of t cells |
| US20220193137A1 (en) | 2019-04-04 | 2022-06-23 | Umc Utrecht Holding B.V. | Modified immune receptor constructs |
| EP3959307A4 (en) * | 2019-04-22 | 2023-08-23 | Nanjing Legend Biotech Co., Ltd. | Engineered cells and uses thereof |
| SG11202111943UA (en) | 2019-07-02 | 2021-11-29 | Hutchinson Fred Cancer Res | Recombinant ad35 vectors and related gene therapy improvements |
| DE102019121007A1 (de) | 2019-08-02 | 2021-02-04 | Immatics Biotechnologies Gmbh | Antigenbindende Proteine, die spezifisch an MAGE-A binden |
| WO2021035170A1 (en) * | 2019-08-21 | 2021-02-25 | Precision Biosciences, Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
| CN112500492B (zh) * | 2019-09-13 | 2023-08-04 | 中国科学院分子细胞科学卓越创新中心 | 一种嵌合抗原受体及其用途 |
| CN110964122B (zh) * | 2019-12-24 | 2022-04-15 | 南京北恒生物科技有限公司 | T细胞受体融合蛋白及其用途 |
| AU2021205501A1 (en) * | 2020-01-10 | 2022-08-18 | TCR2 Therapeutics Inc. | Compositions and methods for autoimmunity regulation |
| WO2022187591A1 (en) | 2021-03-05 | 2022-09-09 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
| IL308257A (en) | 2021-05-05 | 2024-01-01 | Immatics Biotechnologies Gmbh | Antigen binding proteins that uniquely bind PRAME |
| CA3225252A1 (en) * | 2021-07-14 | 2023-01-19 | Jordan JARJOUR | Engineered t cell receptors fused to binding domains from antibodies |
| WO2023081767A1 (en) | 2021-11-05 | 2023-05-11 | Precision Biosciences, Inc. | Methods for immunotherapy |
| US20250009800A1 (en) | 2021-11-16 | 2025-01-09 | Precision Biosciences, Inc. | Methods for cancer immunotherapy |
| WO2023108150A1 (en) | 2021-12-10 | 2023-06-15 | Precision Biosciences, Inc. | Methods for cancer immunotherapy |
| WO2024206329A1 (en) | 2023-03-27 | 2024-10-03 | Modernatx, Inc. | Nucleic acid molecules encoding bi-specific secreted engagers and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016014565A2 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
| JP2018515123A (ja) | 2015-05-18 | 2018-06-14 | ティーシーアール2 セラピューティクス インク. | 融合タンパク質を用いたtcrの再プログラミングのための組成物及び方法 |
Family Cites Families (217)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| US5858358A (en) | 1992-04-07 | 1999-01-12 | The United States Of America As Represented By The Secretary Of The Navy | Methods for selectively stimulating proliferation of T cells |
| US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| 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 |
| US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
| US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
| JP4124480B2 (ja) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | 免疫グロブリン変異体 |
| ES2136092T3 (es) | 1991-09-23 | 1999-11-16 | Medical Res Council | Procedimientos para la produccion de anticuerpos humanizados. |
| GB9125768D0 (en) | 1991-12-04 | 1992-02-05 | Hale Geoffrey | Therapeutic method |
| ATE249840T1 (de) | 1991-12-13 | 2003-10-15 | Xoma Corp | Verfahren und materialien zur herstellung von modifizierten variablen antikörperdomänen und ihre therapeutische verwendung |
| GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
| IL104570A0 (en) | 1992-03-18 | 1993-05-13 | Yeda Res & Dev | Chimeric genes and cells transformed therewith |
| US5350674A (en) | 1992-09-04 | 1994-09-27 | Becton, Dickinson And Company | Intrinsic factor - horse peroxidase conjugates and a method for increasing the stability thereof |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US6692964B1 (en) | 1995-05-04 | 2004-02-17 | The United States Of America As Represented By The Secretary Of The Navy | Methods for transfecting T cells |
| US7067318B2 (en) | 1995-06-07 | 2006-06-27 | The Regents Of The University Of Michigan | Methods for transfecting T cells |
| GB9809658D0 (en) | 1998-05-06 | 1998-07-01 | Celltech Therapeutics Ltd | Biological products |
| DK1180123T3 (da) | 1999-05-27 | 2008-10-13 | Us Gov Health & Human Serv | Immunkonjugater, der har höj bindingsaffinitet |
| AU1086501A (en) | 1999-10-15 | 2001-04-30 | Carnegie Institution Of Washington | Rna interference pathway genes as tools for targeted genetic interference |
| US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
| WO2001062895A2 (en) | 2000-02-24 | 2001-08-30 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
| US6797514B2 (en) | 2000-02-24 | 2004-09-28 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| AU2001275474A1 (en) | 2000-06-12 | 2001-12-24 | Akkadix Corporation | Materials and methods for the control of nematodes |
| US6822082B2 (en) | 2000-06-30 | 2004-11-23 | Zymogenetics, Inc. | Polynucleotides for mammalian secreted protein, Z1055G2P |
| CN1294148C (zh) | 2001-04-11 | 2007-01-10 | 中国科学院遗传与发育生物学研究所 | 环状单链三特异抗体 |
| EP1474451A2 (en) | 2002-02-13 | 2004-11-10 | Micromet AG | De-immunized (poly)peptide constructs |
| DE10244457A1 (de) | 2002-09-24 | 2004-04-01 | Johannes-Gutenberg-Universität Mainz | Verfahren zur rationalen Mutagenese von alpha/beta T-Zell Rezeptoren und entsprechend mutierte MDM2-Protein spezifische alpha/beta T-Zell Rezeptoren |
| CA2505325C (en) | 2002-11-08 | 2014-02-25 | Ablynx N.V. | Stabilized single domain antibodies |
| US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
| US7251470B2 (en) | 2003-06-25 | 2007-07-31 | Nokia Corporation | Emergency response system with personal emergency device |
| AU2004255216B2 (en) | 2003-07-01 | 2010-08-19 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
| US7902338B2 (en) | 2003-07-31 | 2011-03-08 | Immunomedics, Inc. | Anti-CD19 antibodies |
| US20050048617A1 (en) | 2003-08-18 | 2005-03-03 | Medimmune, Inc. | Humanization of antibodies |
| CA2537055A1 (en) | 2003-08-22 | 2005-04-21 | Medimmune, Inc. | Humanization of antibodies |
| DK1673398T3 (da) | 2003-10-16 | 2011-04-18 | Micromet Ag | Multispecifikke, deimmuniserede CD3-bindere |
| US20130266551A1 (en) | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
| JP2008512352A (ja) | 2004-07-17 | 2008-04-24 | イムクローン システムズ インコーポレイティド | 新規な四価の二重特異性抗体 |
| WO2006018833A2 (en) | 2004-08-16 | 2006-02-23 | Tadiran Spectralink Ltd. | A wearable device, system and method for measuring a pulse while a user is in motion |
| US9707302B2 (en) | 2013-07-23 | 2017-07-18 | Immunomedics, Inc. | Combining anti-HLA-DR or anti-Trop-2 antibodies with microtubule inhibitors, PARP inhibitors, bruton kinase inhibitors or phosphoinositide 3-kinase inhibitors significantly improves therapeutic outcome in cancer |
| EP2322560B1 (en) | 2005-03-10 | 2013-09-04 | Morphotek, Inc. | Anti-mesothelin antibodies |
| WO2006124641A2 (en) | 2005-05-12 | 2006-11-23 | The Government Of The United States, As Represented By The Secretary Of Health And Human Services, National Institutes Of Health | Anti-mesothelin antibodies useful for immunological assays |
| CA2618482C (en) | 2005-08-19 | 2014-10-07 | Abbott Laboratories | Dual variable domain immunoglobin and uses thereof |
| AT503861B1 (de) | 2006-07-05 | 2008-06-15 | F Star Biotech Forsch & Entw | Verfahren zur manipulation von t-zell-rezeptoren |
| SI2856876T1 (en) | 2007-03-30 | 2018-04-30 | Memorial Sloan-Kettering Cancer Center | Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes |
| SI2215121T1 (sl) | 2007-11-26 | 2016-06-30 | Bayer Intellectual Property Gmbh | Protitelesa anti-mezotelin in njihova uporaba |
| US9308257B2 (en) | 2007-11-28 | 2016-04-12 | Medimmune, Llc | Protein formulation |
| KR20090092900A (ko) | 2008-02-28 | 2009-09-02 | 신준호 | 어린이 및 노약자 안전보호시스템 |
| US20090322513A1 (en) | 2008-06-27 | 2009-12-31 | Franklin Dun-Jen Hwang | Medical emergency alert system and method |
| PL3006459T3 (pl) | 2008-08-26 | 2022-01-17 | City Of Hope | Sposób i kompozycje dla wzmocnionego działania efektorowego komórek t przeciw guzowi nowotworowemu |
| SG194399A1 (en) | 2008-10-01 | 2013-11-29 | Amgen Res Munich Gmbh | Cross-species-specific pscaxcd3, cd19xcd3, c-metxcd3, endosialinxcd3, epcamxcd3, igf-1rxcd3 or fapalpha xcd3 bispecific single chain antibody |
| WO2010052014A1 (en) | 2008-11-07 | 2010-05-14 | Micromet Ag | Treatment of acute lymphoblastic leukemia |
| MX2011009430A (es) | 2009-03-10 | 2011-11-18 | Biogen Idec Inc | Anticuerpos anti-bcma. |
| EP2421899B1 (en) | 2009-04-23 | 2016-06-08 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Anti-human ror1 antibodies |
| EP2258719A1 (en) | 2009-05-19 | 2010-12-08 | Max-Delbrück-Centrum für Molekulare Medizin (MDC) | Multiple target T cell receptor |
| EP3260092A1 (en) | 2009-10-23 | 2017-12-27 | Nexisvision, Inc. | Corneal denervation for treatment of ocular pain |
| WO2011059836A2 (en) | 2009-10-29 | 2011-05-19 | Trustees Of Dartmouth College | T cell receptor-deficient t cell compositions |
| EP2361936B1 (en) | 2010-02-25 | 2016-04-20 | Affimed GmbH | Antigen-binding molecule and uses thereof |
| CA3002192C (en) | 2010-03-26 | 2023-03-07 | Memorial Sloan-Kettering Cancer Center | Antibodies to muc16 and methods of use thereof |
| US10357577B2 (en) | 2010-07-16 | 2019-07-23 | Auckland Uniservices Limited | Bacterial nitroreductase enzymes and methods relating thereto |
| US9493740B2 (en) | 2010-09-08 | 2016-11-15 | Baylor College Of Medicine | Immunotherapy of cancer using genetically engineered GD2-specific T cells |
| AU2011322581B2 (en) | 2010-10-27 | 2015-04-23 | Amgen Research (Munich) Gmbh | Means and methods for treating DLBCL |
| CA2816379A1 (en) | 2010-10-27 | 2012-05-03 | Baylor College Of Medicine | Chimeric cd27 receptors for redirecting t cells to cd70-positive malignancies |
| AU2011336650B2 (en) | 2010-12-01 | 2016-12-08 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric rabbit/human ROR1 antibodies |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| GB201020995D0 (en) | 2010-12-10 | 2011-01-26 | Bioinvent Int Ab | Biological materials and uses thereof |
| US8911732B2 (en) | 2010-12-20 | 2014-12-16 | Genentech, Inc. | Anti-mesothelin antibodies and immunoconjugates |
| PT2663579T (pt) | 2011-01-14 | 2017-07-28 | Univ California | Terapêutica de anticorpos contra a proteína r0r-1 e métodos para sua utilização |
| CN103442768A (zh) | 2011-01-18 | 2013-12-11 | 宾夕法尼亚大学董事会 | 治疗癌的组合物和方法 |
| KR101551555B1 (ko) | 2011-03-17 | 2015-09-08 | 밀테니 비오텍 게앰베하 | Tcr 알파/베타가 고갈된 세포 제제 |
| ES2696000T3 (es) | 2011-04-08 | 2019-01-11 | Us Health | Receptores de antígenos quiméricos anti-variante III de receptor de factor de crecimiento epidérmico y uso de los mismos para el tratamiento de cáncer |
| CN103946952A (zh) | 2011-09-16 | 2014-07-23 | 宾夕法尼亚大学董事会 | 用于治疗癌症的rna改造的t细胞 |
| WO2013063419A2 (en) | 2011-10-28 | 2013-05-02 | The Trustees Of The University Of Pennsylvania | A fully human, anti-mesothelin specific chimeric immune receptor for redirected mesothelin-expressing cell targeting |
| WO2013067492A1 (en) | 2011-11-03 | 2013-05-10 | The Trustees Of The University Of Pennsylvania | Isolated b7-h4 specific compositions and methods of use thereof |
| WO2013070468A1 (en) | 2011-11-08 | 2013-05-16 | The Trustees Of The University Of Pennsylvania | Glypican-3-specific antibody and uses thereof |
| TWI679212B (zh) | 2011-11-15 | 2019-12-11 | 美商安進股份有限公司 | 針對bcma之e3以及cd3的結合分子 |
| US9447194B2 (en) | 2012-02-13 | 2016-09-20 | Seattle Children's Hospital | Bispecific chimeric antigen receptors and encoding polynucleotides thereof |
| KR20140127816A (ko) | 2012-02-22 | 2014-11-04 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 암의 치료에 유용한 t 세포의 지속성 집단을 생성시키기 위한 조성물 및 방법 |
| MX2014010185A (es) | 2012-02-22 | 2014-11-14 | Univ Pennsylvania | Uso de dominio de señalizacion cd2 en receptores de antigeno quimericos de segunda generacion. |
| AU2013235726B2 (en) | 2012-03-23 | 2017-04-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-mesothelin chimeric antigen receptors |
| RU2650805C2 (ru) | 2012-04-11 | 2018-04-17 | Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретари, Департмент Оф Хелс Энд Хьюман Сёрвисез | Химерные антигенные рецепторы, нацеленные на антиген созревания в-клеток |
| US20130280220A1 (en) | 2012-04-20 | 2013-10-24 | Nabil Ahmed | Chimeric antigen receptor for bispecific activation and targeting of t lymphocytes |
| WO2013176915A1 (en) | 2012-05-25 | 2013-11-28 | Roman Galetto | Methods for engineering allogeneic and immunosuppressive resistant t cell for immunotherapy |
| ES2786263T3 (es) | 2012-07-13 | 2020-10-09 | Univ Pennsylvania | Mejora de la actividad de los CAR de linfocitos T mediante la introducción conjunta de un anticuerpo biespecífico |
| US20160235787A1 (en) | 2012-07-13 | 2016-08-18 | The Trustees Of The University Of Pennsylvania | Epitope Spreading Associated with CAR T-Cells |
| EA028988B1 (ru) | 2012-07-13 | 2018-01-31 | Дзе Трастиз Оф Дзе Юниверсити Оф Пенсильвания | Способ in vitro анализа культуры генетически модифицированных т-клеток для детекции загрязнения |
| MX380109B (es) | 2012-08-20 | 2025-03-12 | Fred Hutchinson Cancer Center Star | Metodo y composiciones para inmunoterapia celular. |
| CN104955845B (zh) | 2012-09-27 | 2018-11-16 | 美国政府(由卫生和人类服务部的部长所代表) | 间皮素抗体和引起有效的抗肿瘤活性的方法 |
| US9365641B2 (en) | 2012-10-01 | 2016-06-14 | The Trustees Of The University Of Pennsylvania | Compositions and methods for targeting stromal cells for the treatment of cancer |
| MX370148B (es) | 2012-10-02 | 2019-12-03 | Memorial Sloan Kettering Cancer Center | Composiciones y su uso para inmunoterapia. |
| CA2892059C (en) | 2012-11-21 | 2023-02-14 | Wuhan Yzy Biopharma Co., Ltd. | Bispecific antibody |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| WO2014099671A1 (en) | 2012-12-20 | 2014-06-26 | Bluebird Bio, Inc. | Chimeric antigen receptors and immune cells targeting b cell malignancies |
| JP2016507523A (ja) | 2013-02-05 | 2016-03-10 | エンクマフ アーゲー | CD3εおよびBCMAに対する二重特異的抗体 |
| AU2014214850C1 (en) | 2013-02-06 | 2018-12-06 | Celgene Corporation | Modified T lymphocytes having improved specificity |
| KR102064230B1 (ko) | 2013-02-15 | 2020-01-13 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 키메라 항원 수용체 및 이의 이용 방법 |
| UY35340A (es) | 2013-02-20 | 2014-09-30 | Novartis Ag | Marcaje efectivo de leucemia humana usando células diseñadas con un receptor quimérico de antígeno anti-cd123 |
| EP2961773B1 (en) | 2013-02-26 | 2019-03-20 | Roche Glycart AG | Bispecific t cell activating antigen binding molecules |
| IL298125A (en) | 2013-02-26 | 2023-01-01 | Memorial Sloan Kettering Cancer Center | Compositions and methods for immunotherapy |
| ES2750550T3 (es) | 2013-03-01 | 2020-03-26 | Univ Minnesota | Corrección de gen a base de TALEN |
| AU2014225788B2 (en) | 2013-03-05 | 2018-03-29 | Baylor College Of Medicine | Engager cells for immunotherapy |
| CN105451767B (zh) | 2013-03-15 | 2019-10-18 | 泽恩格尼亚股份有限公司 | 多价和单价多特异性复合物及其用途 |
| AR095374A1 (es) | 2013-03-15 | 2015-10-14 | Amgen Res Munich Gmbh | Moléculas de unión para bcma y cd3 |
| HK1220205A1 (zh) | 2013-03-15 | 2017-04-28 | Celgene Corporation | 修饰的t淋巴细胞 |
| EP4098275A1 (en) | 2013-03-15 | 2022-12-07 | Memorial Sloan-Kettering Cancer Center | Compositions and methods for immunotherapy |
| US9446105B2 (en) | 2013-03-15 | 2016-09-20 | The Trustees Of The University Of Pennsylvania | Chimeric antigen receptor specific for folate receptor β |
| TWI654206B (zh) | 2013-03-16 | 2019-03-21 | 諾華公司 | 使用人類化抗-cd19嵌合抗原受體治療癌症 |
| WO2014165707A2 (en) | 2013-04-03 | 2014-10-09 | Memorial Sloan-Kettering Cancer Center | Effective generation of tumor-targeted t-cells derived from pluripotent stem cells |
| MX374681B (es) | 2013-05-13 | 2025-03-06 | Cellectis | Receptor quimérico de antígeno específico para cd19 y sus usos. |
| US11311575B2 (en) | 2013-05-13 | 2022-04-26 | Cellectis | Methods for engineering highly active T cell for immunotherapy |
| HK1223943A1 (zh) | 2013-05-24 | 2017-08-11 | Board Of Regents, The University Of Texas System | 嵌合的靶向抗原受体的单克隆抗体 |
| WO2014191128A1 (en) | 2013-05-29 | 2014-12-04 | Cellectis | Methods for engineering t cells for immunotherapy by using rna-guided cas nuclease system |
| ES2883131T3 (es) | 2013-05-29 | 2021-12-07 | Cellectis | Métodos para la modificación de células T para inmunoterapia utilizando el sistema de nucleasa CAS guiado por ARN |
| MX2016000272A (es) | 2013-07-12 | 2016-08-03 | Zymeworks Inc | Construcciones de unión a los antígenos cd19 y cd3 biespecificos. |
| US9951118B2 (en) | 2013-08-02 | 2018-04-24 | The Regents Of The University Of California | Engineering antiviral T cell immunity through stem cells and chimeric antigen receptors |
| GB201317929D0 (en) | 2013-10-10 | 2013-11-27 | Ucl Business Plc | Chimeric antigen receptor |
| CN105829349B (zh) | 2013-10-15 | 2023-02-03 | 斯克利普斯研究所 | 肽嵌合抗原受体t细胞开关和其用途 |
| WO2015057852A1 (en) | 2013-10-15 | 2015-04-23 | The California Institute For Biomedical Research | Chimeric antigen receptor t cell switches and uses thereof |
| PL3083671T3 (pl) | 2013-12-20 | 2021-03-22 | Fred Hutchinson Cancer Center | Znakowane chimeryczne cząsteczki efektorowe i ich receptory |
| US10287354B2 (en) | 2013-12-20 | 2019-05-14 | Novartis Ag | Regulatable chimeric antigen receptor |
| WO2015092024A2 (en) | 2013-12-20 | 2015-06-25 | Cellectis | Method of engineering multi-input signal sensitive t cell for immunotherapy |
| WO2015103072A1 (en) | 2013-12-30 | 2015-07-09 | Epimab Biotherapeutics | Fabs-in-tandem immunoglobulin and uses thereof |
| ES2701846T3 (es) | 2014-01-14 | 2019-02-26 | Cellectis | Receptor de antígeno quimérico que usa dominios de reconocimiento de antígenos derivados de pez cartilaginoso |
| EP4303229A3 (en) | 2014-01-21 | 2024-04-17 | Novartis AG | Enhanced antigen presenting ability of car t cells by co-introduction of costimulatory molecules |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
| EP3097123A1 (en) | 2014-01-24 | 2016-11-30 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Anti-ny-br-1 polypeptides, proteins, and chimeric antigen receptors |
| ES2989838T3 (es) | 2014-02-04 | 2024-11-27 | The United States Of America As Represented Bythe Sec Dep Of Health And Humanservices | Métodos para producir células T autólogas útiles para tratar malignidades de células B y otros cánceres y composiciones de las mismas |
| WO2015123642A1 (en) | 2014-02-14 | 2015-08-20 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors and methods of making |
| PT3105317T (pt) | 2014-02-14 | 2019-02-27 | Cellectis | Células para imunoterapia manipuladas para atuar sobre antigénios presentes tanto em células imunitárias como em células patológicas |
| WO2015124715A1 (en) | 2014-02-21 | 2015-08-27 | Cellectis | Method for in situ inhibition of regulatory t cells |
| EP3110445A4 (en) | 2014-02-25 | 2017-09-27 | Immunomedics, Inc. | Humanized rfb4 anti-cd22 antibody |
| KR101605421B1 (ko) | 2014-03-05 | 2016-03-23 | 국립암센터 | B 세포 림프종 세포를 특이적으로 인지하는 단일클론항체 및 이의 용도 |
| WO2015142675A2 (en) | 2014-03-15 | 2015-09-24 | Novartis Ag | Treatment of cancer using chimeric antigen receptor |
| EP3119425B1 (en) | 2014-03-15 | 2020-09-23 | Novartis AG | Regulatable chimeric antigen receptor |
| JP6698546B2 (ja) * | 2014-04-14 | 2020-05-27 | セレクティスCellectis | 癌免疫療法のためのbcma(cd269)特異的キメラ抗原受容体 |
| EP3134095B1 (en) | 2014-04-25 | 2020-04-22 | Bluebird Bio, Inc. | Improved methods for manufacturing adoptive cell therapies |
| US10301370B2 (en) | 2014-05-02 | 2019-05-28 | The Trustees Of The University Of Pennsylvania | Compositions and methods of chimeric autoantibody receptor T cells |
| US11041021B2 (en) | 2014-05-23 | 2021-06-22 | University Of Florida Research Foundation, Incorporated | Car based immunotherapy |
| WO2015177349A1 (en) | 2014-05-23 | 2015-11-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti- egfr conformational single domain antibodies and uses thereof |
| CN111394317B (zh) * | 2014-06-06 | 2024-07-12 | 2赛文缇生物公司 | 改善的t细胞组合物 |
| EP3685842B1 (en) | 2014-06-06 | 2022-08-31 | Memorial Sloan-Kettering Cancer Center | Mesothelin-targeted chimeric antigen receptors and uses thereof |
| CN107075483A (zh) | 2014-07-15 | 2017-08-18 | 朱诺治疗学股份有限公司 | 用于过继细胞治疗的工程改造的细胞 |
| US20170226216A1 (en) * | 2014-07-24 | 2017-08-10 | Bluebird Bio, Inc. | Bcma chimeric antigen receptors |
| MX367787B (es) | 2014-07-29 | 2019-09-06 | Cellectis | Receptores de antígenos quimericos ror1 (ntrkr1) específicos para inmunoterapia del cáncer. |
| EP2982692A1 (en) | 2014-08-04 | 2016-02-10 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
| US9994817B2 (en) | 2014-08-07 | 2018-06-12 | Northwestern University | Use of ligands for the programmed cell death receptor conjugated to solid supports for cultivating human regulatory T cells |
| WO2016019969A1 (en) | 2014-08-08 | 2016-02-11 | Ludwig-Maximilians-Universität München | Subcutaneously administered bispecific antibodies for use in the treatment of cancer |
| JP6945444B2 (ja) | 2014-08-08 | 2021-10-06 | ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー | 高親和性pd−1薬剤とその使用方法 |
| SG11201701111SA (en) | 2014-08-12 | 2017-03-30 | Anthrogenesis Corp | Car-t lymphocytes engineered to home to lymph node b cell zone, skin, or gastrointestinal tract |
| DK4074735T3 (da) | 2014-08-28 | 2025-07-14 | Bioatla Inc | Betinget aktive kimæriske antigenreceptorer til modificerede t-celler |
| GB201415347D0 (en) | 2014-08-29 | 2014-10-15 | Ucl Business Plc | Signalling system |
| WO2016036678A1 (en) | 2014-09-02 | 2016-03-10 | Medimmune, Llc | Formulations of bispecific antibodies |
| SG11201701775VA (en) | 2014-09-09 | 2017-04-27 | Unum Therapeutics | Chimeric receptors and uses thereof in immune therapy |
| ES2738705T3 (es) | 2014-09-19 | 2020-01-24 | Hope City | Linfocitos T de receptor de antígeno quimérico coestimulante que se dirigen a IL13R 2 |
| WO2016054520A2 (en) | 2014-10-03 | 2016-04-07 | The California Institute For Biomedical Research | Engineered cell surface proteins and uses thereof |
| EP3204491A1 (en) | 2014-10-07 | 2017-08-16 | Cellectis | Method for modulating car-induced immune cells activity |
| AU2015336029B2 (en) | 2014-10-20 | 2021-07-22 | Juno Therapeutics, Inc. | Methods and compositions for dosing in adoptive cell therapy |
| HK1243333A1 (zh) | 2014-10-31 | 2018-07-13 | The Trustees Of The University Of Pennsylvania | 用於修饰的t细胞的方法和组合物 |
| EP3215139B1 (en) | 2014-11-03 | 2020-08-19 | Cerus Corporation | Compositions and methods for improved car-t cell therapies |
| PL3757206T3 (pl) | 2014-11-05 | 2024-07-08 | Juno Therapeutics, Inc. | Sposoby transdukcji i przetwarzania komórek |
| EP3023437A1 (en) | 2014-11-20 | 2016-05-25 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
| ES2808853T3 (es) | 2014-11-20 | 2021-03-02 | Hoffmann La Roche | Cadenas ligeras comunes y procedimientos de uso |
| EP3025719B1 (en) | 2014-11-26 | 2018-09-26 | Miltenyi Biotec GmbH | Combination immunotherapy of antigen-recognizing receptors and hematopoietic cells for the treatment of diseases |
| EP3029067A1 (en) | 2014-12-01 | 2016-06-08 | Deutsches Krebsforschungszentrum | Use of blocking-reagents for reducing unspecific T cell-activation |
| US11266739B2 (en) | 2014-12-03 | 2022-03-08 | Juno Therapeutics, Inc. | Methods and compositions for adoptive cell therapy |
| WO2016090034A2 (en) | 2014-12-03 | 2016-06-09 | Novartis Ag | Methods for b cell preconditioning in car therapy |
| EP3029068A1 (en) | 2014-12-03 | 2016-06-08 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases |
| SI3227339T1 (sl) | 2014-12-05 | 2022-02-28 | Memorial Sloan-Kettering Cancer Center | Himerni antigenski receptorji, ki ciljajo na receptor, povezan z G-proteinom, in njihova uporaba |
| SG11201704549UA (en) | 2014-12-05 | 2017-07-28 | Memorial Sloan Kettering Cancer Center | Chimeric antigen receptors targeting b-cell maturation antigen and uses thereof |
| CN113388036A (zh) | 2014-12-05 | 2021-09-14 | 纪念斯隆-凯特琳癌症中心 | 靶向b-细胞成熟抗原的抗体及其用途 |
| AU2015367317A1 (en) | 2014-12-17 | 2017-06-01 | Cellectis | Inhibitory chimeric antigen receptor (iCAR or N-CAR) expressing non-T cell transduction domain |
| EP3037170A1 (en) | 2014-12-27 | 2016-06-29 | Miltenyi Biotec GmbH | Multisort cell separation method |
| KR20250075716A (ko) | 2014-12-29 | 2025-05-28 | 노파르티스 아게 | 키메라 항원 수용체-발현 세포를 제조하는 방법 |
| BR112017015136A2 (pt) | 2015-01-14 | 2018-01-30 | Compass Therapeutics Llc | polipeptídeo de construto de ligação ao antígeno imunomodulador multiespecífico, construto de ligação ao antígeno imunomodulador multiespecífico, conjugado, composição farmacêutica, método para tratar um indivíduo com câncer, método para inibir ou reduzir o crescimento de câncer, composição, célula, método de fazer um polipeptídeo de construto de ligação ao antígeno imunomodulador multiespecífico, vetor ou conjunto de vetores e kit |
| WO2016115482A1 (en) | 2015-01-16 | 2016-07-21 | Novartis Pharma Ag | Phosphoglycerate kinase 1 (pgk) promoters and methods of use for expressing chimeric antigen receptor |
| US20160208018A1 (en) | 2015-01-16 | 2016-07-21 | Juno Therapeutics, Inc. | Antibodies and chimeric antigen receptors specific for ror1 |
| GB201501175D0 (en) | 2015-01-23 | 2015-03-11 | Univ Oslo Hf | A universal T-cell for personalised medicine |
| WO2016123143A1 (en) | 2015-01-26 | 2016-08-04 | The University Of Chicago | CAR T-CELLS RECOGNIZING CANCER-SPECIFIC IL 13Rα2 |
| WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
| WO2016127043A1 (en) | 2015-02-05 | 2016-08-11 | Stc.Unm | Anti-pre-bcr antagonists and methods |
| US20180016352A1 (en) | 2015-02-05 | 2018-01-18 | The University Of Queensland | Targeting constructs for delivery of payloads |
| US20160228547A1 (en) | 2015-02-06 | 2016-08-11 | Batu Biologics, Inc. | Chimeric antigen receptor targeting of tumor endothelium |
| KR102607152B1 (ko) | 2015-02-12 | 2023-11-27 | 유니버시티 헬스 네트워크 | 키메라 항원 수용체 |
| US20160237407A1 (en) | 2015-02-17 | 2016-08-18 | Batu Biologics, Inc. | Universal donor chimeric antigen receptor cells |
| AU2016221305B2 (en) | 2015-02-18 | 2021-05-27 | Enlivex Therapeutics Rdo Ltd | Combination immune therapy and cytokine control therapy for cancer treatment |
| JP6784687B2 (ja) | 2015-02-24 | 2020-11-11 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 結合誘発型転写スイッチ及びその使用方法 |
| EP3089761B1 (en) | 2015-03-02 | 2019-06-12 | Innovative Cellular Therapeutics Co., Ltd. | Reducing immune tolerance induced by pd l1 |
| GB201504840D0 (en) | 2015-03-23 | 2015-05-06 | Ucl Business Plc | Chimeric antigen receptor |
| CA2981304C (en) | 2015-04-02 | 2024-01-02 | Memorial Sloan Kettering Cancer Center | Tnfrsf14/hvem proteins and methods of use thereof |
| CA2989949A1 (en) | 2015-06-19 | 2016-12-22 | Sebastian KOBOLD | Pd-1-cd28 fusion proteins and their use in medicine |
| AU2016333898B2 (en) | 2015-10-05 | 2020-11-12 | Precision Biosciences, Inc. | Genetically-modified cells comprising a modified human T cell receptor alpha constant region gene |
| EP4643874A2 (en) | 2015-12-22 | 2025-11-05 | Novartis AG | Mesothelin chimeric antigen receptor (car) and antibody against pd-l1 inhibitor for combined use in anticancer therapy |
| SG10201912489QA (en) | 2016-04-01 | 2020-02-27 | Kite Pharma Inc | Chimeric antigen and t cell receptors and methods of use |
| EP4371570A3 (en) | 2016-06-08 | 2024-07-17 | Xencor, Inc. | Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b |
| AU2017306432A1 (en) | 2016-08-02 | 2019-03-21 | TCR2 Therapeutics Inc. | Compositions and methods for TCR reprogramming using fusion proteins |
| CA3036745A1 (en) | 2016-10-07 | 2018-04-12 | TCR2 Therapeutics Inc. | Compositions and methods for t-cell receptors reprogramming using fusion proteins |
| CA3044593A1 (en) | 2016-11-22 | 2018-05-31 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
| JP2020513754A (ja) | 2016-12-21 | 2020-05-21 | ティーシーアール2 セラピューティクス インク. | がん治療用に操作されたt細胞 |
| WO2018200583A1 (en) | 2017-04-26 | 2018-11-01 | Eureka Therapeutics, Inc. | Cells expressing chimeric activating receptors and chimeric stimulating receptors and uses thereof |
| US20210079057A1 (en) | 2017-06-13 | 2021-03-18 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
| JP2021515598A (ja) | 2018-03-09 | 2021-06-24 | ティーシーアール2 セラピューティクス インク. | 融合タンパク質を用いたtcrリプログラミングのための組成物及び方法 |
| WO2019222275A2 (en) | 2018-05-14 | 2019-11-21 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using inducible fusion proteins |
| CN113039197A (zh) | 2018-07-26 | 2021-06-25 | T细胞受体治疗公司 | 使用靶特异性融合蛋白进行tcr重编程的组合物和方法 |
| EP3844192A1 (en) | 2018-08-30 | 2021-07-07 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
-
2017
- 2017-08-02 AU AU2017306432A patent/AU2017306432A1/en not_active Abandoned
- 2017-08-02 US US16/322,897 patent/US11242376B2/en active Active
- 2017-08-02 CN CN201780057921.3A patent/CN109715668A/zh active Pending
- 2017-08-02 CA CA3032498A patent/CA3032498A1/en not_active Abandoned
- 2017-08-02 JP JP2019505451A patent/JP7109789B2/ja active Active
- 2017-08-02 EP EP17754238.8A patent/EP3494138A1/en not_active Withdrawn
- 2017-08-02 WO PCT/US2017/045159 patent/WO2018026953A1/en not_active Ceased
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016014565A2 (en) | 2014-07-21 | 2016-01-28 | Novartis Ag | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
| JP2018515123A (ja) | 2015-05-18 | 2018-06-14 | ティーシーアール2 セラピューティクス インク. | 融合タンパク質を用いたtcrの再プログラミングのための組成物及び方法 |
Non-Patent Citations (1)
| Title |
|---|
| 産業医科大学雑誌,1998年,Vol.20, No.2, p.153-162 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3032498A1 (en) | 2018-02-08 |
| EP3494138A1 (en) | 2019-06-12 |
| JP2019531056A (ja) | 2019-10-31 |
| WO2018026953A1 (en) | 2018-02-08 |
| US11242376B2 (en) | 2022-02-08 |
| CN109715668A (zh) | 2019-05-03 |
| AU2017306432A1 (en) | 2019-03-21 |
| US20190256571A1 (en) | 2019-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7262535B2 (ja) | 融合タンパク質を用いたtcrの再プログラミングのための組成物及び方法 | |
| JP7109789B2 (ja) | 融合タンパク質を使用したtcrの再プログラム化のための組成物及び方法 | |
| US20220298478A1 (en) | Compositions and methods for tcr reprogramming using fusion proteins | |
| JP7291396B2 (ja) | 融合タンパク質を用いたtcrの再プログラミングのための組成物及び方法 | |
| JP2022188163A (ja) | がん治療用に操作されたt細胞 | |
| CN113039209A (zh) | 用于使用融合蛋白进行tcr重编程的组合物和方法 | |
| HK40076914A (en) | Compositions and methods for tcr reprogramming using fusion proteins | |
| HK40045811A (en) | Compositions and methods for tcr reprogramming using fusion proteins | |
| HK40008051A (en) | Compositions and methods for tcr reprogramming using fusion proteins | |
| HK40004389A (en) | Compositions and methods for tcr reprogramming using fusion proteins | |
| EA043737B1 (ru) | Композиции и способы репрограммирования т-клеточных рецепторов с помощью гибридных белков | |
| HK1252643B (en) | Compositions and medical uses for tcr reprogramming using fusion proteins | |
| HK40010509A (en) | Engineered t cells for the treatment of cancer | |
| HK40007902A (en) | Compositions and methods for tcr reprogramming using fusion proteins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190408 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200728 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200729 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210506 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20210428 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20210615 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20210616 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210721 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211006 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220127 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220427 |
|
| 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: 20220614 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220712 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7109789 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |