WO2021009694A1 - Functional binders synthesized and secreted by immune cells - Google Patents
Functional binders synthesized and secreted by immune cells Download PDFInfo
- Publication number
- WO2021009694A1 WO2021009694A1 PCT/IB2020/056659 IB2020056659W WO2021009694A1 WO 2021009694 A1 WO2021009694 A1 WO 2021009694A1 IB 2020056659 W IB2020056659 W IB 2020056659W WO 2021009694 A1 WO2021009694 A1 WO 2021009694A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- domain
- cells
- immune cell
- cell
- ifl
- Prior art date
Links
- 210000002865 immune cell Anatomy 0.000 title claims abstract description 51
- 239000011230 binding agent Substances 0.000 title description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 88
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 78
- 210000000822 natural killer cell Anatomy 0.000 claims abstract description 63
- 239000012634 fragment Substances 0.000 claims abstract description 22
- 102000005962 receptors Human genes 0.000 claims abstract description 17
- 108020003175 receptors Proteins 0.000 claims abstract description 17
- 238000005304 joining Methods 0.000 claims abstract description 16
- 239000003446 ligand Substances 0.000 claims abstract description 11
- 150000001413 amino acids Chemical class 0.000 claims description 38
- 108060003951 Immunoglobulin Proteins 0.000 claims description 35
- 102000018358 immunoglobulin Human genes 0.000 claims description 35
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 25
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 25
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 24
- 108700010039 chimeric receptor Proteins 0.000 claims description 21
- 102000003812 Interleukin-15 Human genes 0.000 claims description 20
- 108090000172 Interleukin-15 Proteins 0.000 claims description 20
- 230000011664 signaling Effects 0.000 claims description 16
- 230000001086 cytosolic effect Effects 0.000 claims description 14
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 claims description 10
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 claims description 10
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 claims description 10
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 claims description 10
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 10
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 9
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 9
- 230000035772 mutation Effects 0.000 claims description 7
- 102000001301 EGF receptor Human genes 0.000 claims description 6
- 108060006698 EGF receptor Proteins 0.000 claims description 6
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 6
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 6
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 5
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 5
- 101150029707 ERBB2 gene Proteins 0.000 claims description 5
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 5
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 5
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 5
- 102000003735 Mesothelin Human genes 0.000 claims description 5
- 108090000015 Mesothelin Proteins 0.000 claims description 5
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 5
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 5
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 4
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 4
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 claims description 3
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 claims description 3
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 claims description 3
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 3
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 3
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 3
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 3
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 3
- 230000004936 stimulating effect Effects 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 abstract description 137
- 239000013598 vector Substances 0.000 abstract description 51
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 abstract description 26
- 238000000034 method Methods 0.000 abstract description 23
- 230000004540 complement-dependent cytotoxicity Effects 0.000 abstract description 13
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 abstract description 9
- 206010057249 Phagocytosis Diseases 0.000 abstract description 8
- 230000008782 phagocytosis Effects 0.000 abstract description 8
- 102000004127 Cytokines Human genes 0.000 abstract description 7
- 108090000695 Cytokines Proteins 0.000 abstract description 7
- 238000001727 in vivo Methods 0.000 abstract description 7
- 230000001419 dependent effect Effects 0.000 abstract description 6
- 230000000638 stimulation Effects 0.000 abstract description 4
- 235000001014 amino acid Nutrition 0.000 description 35
- 229940024606 amino acid Drugs 0.000 description 35
- 229960004641 rituximab Drugs 0.000 description 35
- 108091008874 T cell receptors Proteins 0.000 description 30
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 30
- 239000005090 green fluorescent protein Substances 0.000 description 29
- 108020004707 nucleic acids Proteins 0.000 description 28
- 102000039446 nucleic acids Human genes 0.000 description 28
- 150000007523 nucleic acids Chemical class 0.000 description 28
- 206010028980 Neoplasm Diseases 0.000 description 27
- 239000002299 complementary DNA Substances 0.000 description 26
- 230000014509 gene expression Effects 0.000 description 24
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 22
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 22
- 108090000623 proteins and genes Proteins 0.000 description 21
- 201000011510 cancer Diseases 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 16
- 102000004196 processed proteins & peptides Human genes 0.000 description 15
- 230000000295 complement effect Effects 0.000 description 13
- 230000009261 transgenic effect Effects 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 108010087819 Fc receptors Proteins 0.000 description 10
- 108010002350 Interleukin-2 Proteins 0.000 description 10
- 102000000588 Interleukin-2 Human genes 0.000 description 10
- 239000000427 antigen Substances 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 9
- 102000009109 Fc receptors Human genes 0.000 description 9
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 210000003719 b-lymphocyte Anatomy 0.000 description 8
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 7
- 206010025323 Lymphomas Diseases 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 102000054765 polymorphisms of proteins Human genes 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 6
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 230000001177 retroviral effect Effects 0.000 description 6
- 208000003950 B-cell lymphoma Diseases 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 5
- 108010004729 Phycoerythrin Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 238000009175 antibody therapy Methods 0.000 description 5
- 239000012228 culture supernatant Substances 0.000 description 5
- 231100000433 cytotoxic Toxicity 0.000 description 5
- 230000001472 cytotoxic effect Effects 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 150000004676 glycans Chemical class 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 208000004736 B-Cell Leukemia Diseases 0.000 description 4
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 4
- 108091033409 CRISPR Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 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 4
- 241000700605 Viruses Species 0.000 description 4
- 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 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000008029 eradication Effects 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000001476 gene delivery Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000006228 supernatant 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
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- -1 transposons Proteins 0.000 description 4
- 238000010354 CRISPR gene editing Methods 0.000 description 3
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 3
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 230000013595 glycosylation Effects 0.000 description 3
- 238000006206 glycosylation reaction Methods 0.000 description 3
- 238000010212 intracellular staining Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 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
- 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
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 2
- PKFBJSDMCRJYDC-GEZSXCAASA-N N-acetyl-s-geranylgeranyl-l-cysteine Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CSC[C@@H](C(O)=O)NC(C)=O PKFBJSDMCRJYDC-GEZSXCAASA-N 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 108700019146 Transgenes Proteins 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
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000005547 deoxyribonucleotide Substances 0.000 description 2
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229940027941 immunoglobulin g Drugs 0.000 description 2
- 230000001024 immunotherapeutic effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N lysine Chemical group NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 238000011272 standard treatment Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- RPROHCOBMVQVIV-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CCNC2 RPROHCOBMVQVIV-UHFFFAOYSA-N 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
- 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 1
- 101710102163 Atrial natriuretic peptide receptor 1 Proteins 0.000 description 1
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
- 201000004891 B-cell adult acute lymphocytic leukemia 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
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 238000011357 CAR T-cell therapy Methods 0.000 description 1
- 229940124292 CD20 monoclonal antibody Drugs 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102100038916 Caspase-5 Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 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
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 241000701022 Cytomegalovirus Species 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
- 102000053602 DNA Human genes 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108090000331 Firefly luciferases Proteins 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100112336 Homo sapiens CASP5 gene Proteins 0.000 description 1
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101100495232 Homo sapiens MS4A1 gene Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 102000009490 IgG Receptors Human genes 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- 206010069755 K-ras gene mutation Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 101710099301 Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 239000004472 Lysine Chemical group 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 101100273286 Mus musculus Casp4 gene Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102100038551 Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase Human genes 0.000 description 1
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 1
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010091769 Shiga Toxin 1 Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 238000010459 TALEN Methods 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 description 1
- 241000021375 Xenogenes Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 108700025316 aldesleukin Proteins 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
- 229960000723 ampicillin Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 238000002869 basic local alignment search tool Methods 0.000 description 1
- 230000008901 benefit Effects 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
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- FWDBOZPQNFPOLF-UHFFFAOYSA-N ethenyl(triethoxy)silane Chemical compound CCO[Si](OCC)(OCC)C=C FWDBOZPQNFPOLF-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229930182830 galactose Natural products 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
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 102000051442 human CD59 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 102000027596 immune receptors Human genes 0.000 description 1
- 108091008915 immune receptors Proteins 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 108040002068 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity proteins Proteins 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 229940087463 proleukin Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 108010056030 retronectin Proteins 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
- 108091005475 signaling receptors Proteins 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.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 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229950007137 tisagenlecleucel Drugs 0.000 description 1
- 108010078373 tisagenlecleucel Proteins 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus 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
- 238000011179 visual inspection Methods 0.000 description 1
- 108010065816 zeta chain antigen T cell receptor Proteins 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4613—Natural-killer cells [NK or NK-T]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464411—Immunoglobulin superfamily
- A61K39/464412—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464402—Receptors, cell surface antigens or cell surface determinants
- A61K39/464424—CD20
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/5443—IL-15
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
-
- 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
- C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
- C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0646—Natural killers cells [NK], NKT cells
-
- 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 A61K39/46
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K39/46 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 A61K39/46
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K39/46
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
- A61K2239/48—Blood cells, e.g. leukemia or lymphoma
-
- 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
- C07K2317/52—Constant or Fc region; Isotype
-
- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- 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
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
Definitions
- two nucleotide sequences, or two amino acid sequences can have at least, e.g., 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, sequence identity.
- sequences described herein are the reference sequences.
- FIG. 1 A is a schematic representation of an in vivo functional ligand (IFL) construct.
- the IFL includes a single chain variable fragment (scFv) domain, a modified fragment crystallizable (Fc) domain, and a hinge domain joining the scFv and the modified Fc domains.
- scFv single chain variable fragment
- Fc modified fragment crystallizable
- a hinge domain joining the scFv and the modified Fc domains.
- an N-terminal signal peptide leader peptide
- Signal peptides of surface proteins are generally suitable, and an example is a CD8a signal peptide.
- NK cells are large granular lymphocytes (LGL) and are known to differentiate and mature in the bone marrow from where they then enter into the circulation. NK cell can also kill tumor cells if antigens on the surface of tumor cells are bound by antibodies; the Fc portion of the antibody bind Fc receptors (CD16) on the surface of NK cells and triggers cytotoxicity, a process known as antibody-dependent cell cytotoxicity (ADCC).
- LGL large granular lymphocytes
- ADCC antibody-dependent cell cytotoxicity
- IFLs mediate CDC, ADCP and ADCC
- scFv domain binds CD19 or CD20
- the Fc domain is a human IgGl Fc domain
- the hinge domain is an IgGl hinge domain
- the peptide further comprising a CD8a signal peptide that is N-terminal to the scFv domain
- the peptide further comprising a chimeric receptor that is CD16V-4-1BB- O ⁇ 3z.
- Embodiment 24 The peptide of Embodiment 23, wherein the linker that joins IL-15 to the Fc domain is selected from the group consisting of SEQ ID NO: 51; A(EAAK) 4 ALEA(EAAAK) 4 A; (EAAAK) Z ; A(EAAAK) Z A; and (XP) W , wherein z is an integer from 1 to 100; X is any amino acid, and w is an integer from 1 to 100.
- SEQ ID NO: 5 Anti-CD20 IFL, Linker; cDNA:
- SEQ ID NO: 28 Anti-CD20 IFL-P2A-CD 16V-BB ⁇ , Immunoglobulin variable domain of rituximab heavy chain; amino acid:
- SEQ ID NO: 44 P2A amino acid: ATNF SLLKQ AGD VEENPG
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Developmental Biology & Embryology (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA3146987A CA3146987A1 (en) | 2019-07-17 | 2020-07-15 | Functional binders synthesized and secreted by immune cells |
AU2020315213A AU2020315213A1 (en) | 2019-07-17 | 2020-07-15 | Functional binders synthesized and secreted by immune cells |
CN202080058975.3A CN114286683A (en) | 2019-07-17 | 2020-07-15 | Functional conjugates synthesized and secreted by immune cells |
JP2022502230A JP2022541016A (en) | 2019-07-17 | 2020-07-15 | Functional binder synthesized and secreted by immune cells |
EP20841097.7A EP3999082A4 (en) | 2019-07-17 | 2020-07-15 | Functional binders synthesized and secreted by immune cells |
KR1020227004848A KR20220035435A (en) | 2019-07-17 | 2020-07-15 | Functional binding agent synthesized and secreted by immune cells |
US17/597,582 US20220281971A1 (en) | 2019-07-17 | 2020-07-15 | Functional Binders Synthesized and Secreted by Immune Cells |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962875455P | 2019-07-17 | 2019-07-17 | |
US62/875,455 | 2019-07-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021009694A1 true WO2021009694A1 (en) | 2021-01-21 |
Family
ID=74210274
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2020/056659 WO2021009694A1 (en) | 2019-07-17 | 2020-07-15 | Functional binders synthesized and secreted by immune cells |
Country Status (8)
Country | Link |
---|---|
US (1) | US20220281971A1 (en) |
EP (1) | EP3999082A4 (en) |
JP (1) | JP2022541016A (en) |
KR (1) | KR20220035435A (en) |
CN (1) | CN114286683A (en) |
AU (1) | AU2020315213A1 (en) |
CA (1) | CA3146987A1 (en) |
WO (1) | WO2021009694A1 (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11253547B2 (en) | 2019-03-05 | 2022-02-22 | Nkarta, Inc. | CD19-directed chimeric antigen receptors and uses thereof in immunotherapy |
US11365236B2 (en) | 2017-03-27 | 2022-06-21 | Nkarta, Inc. | Truncated NKG2D chimeric receptors and uses thereof in natural killer cell immunotherapy |
US11560548B2 (en) | 2014-05-15 | 2023-01-24 | National University Of Singapore | Immune cells expressing membrane-bound interleukin 15 (mbIL15) and uses thereof |
WO2023154890A3 (en) * | 2022-02-11 | 2023-10-26 | Fred Hutchinson Cancer Center | Chimeric antigen receptors binding steap1 |
US11896616B2 (en) | 2017-03-27 | 2024-02-13 | National University Of Singapore | Stimulatory cell lines for ex vivo expansion and activation of natural killer cells |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000023573A2 (en) * | 1998-10-20 | 2000-04-27 | City Of Hope | Cd20-specific redirected t cells and their use in cellular immunotherapy of cd20+ malignancies |
WO2002077029A2 (en) * | 2000-11-07 | 2002-10-03 | City Of Hope | Cd19-specific redirected immune cells |
WO2016142314A1 (en) * | 2015-03-06 | 2016-09-15 | Deutsches Krebsforschungszentrum | FUSION PROTEINS COMPRISING A BINDING PROTEIN AND AN INTERLEUKIN-15 POLYPEPTIDE HAVING A REDUCED AFFINITY FOR IL15Ra AND THERAPEUTIC USES THEREOF |
CN107827990A (en) * | 2017-10-30 | 2018-03-23 | 河北森朗生物科技有限公司 | A kind of polypeptide, the nucleic acid for encoding it, the T lymphocytes of its modification and its application |
WO2018103503A1 (en) * | 2016-12-05 | 2018-06-14 | 上海优卡迪生物医药科技有限公司 | Pd-l1 knockout car-t transgenic vector for suppressing immune escape, preparation method thereof, and application of same |
WO2019062817A1 (en) * | 2017-09-27 | 2019-04-04 | 亘喜生物科技(上海)有限公司 | Engineered immune cell capable of inducing secretion of anti-cd47 antibody |
WO2019129002A1 (en) * | 2017-12-28 | 2019-07-04 | 上海细胞治疗研究院 | Car-t cell specifically targeting to cd19 antigen and stably expressing pd-1 antibody with high level, and use of car-t cell |
WO2020083282A1 (en) * | 2018-10-24 | 2020-04-30 | 艾生命序公司 | Pd-l1 antibody secreting anti-mesothelin car-t cells for tumor immunotherapy |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7329745B2 (en) * | 2000-06-13 | 2008-02-12 | City Of Hope | Single-chain antibodies against human insulin-like growth factor I receptor: expression, purification, and effect on tumor growth |
CA2955154C (en) * | 2014-07-21 | 2023-10-31 | Novartis Ag | Treatment of cancer using a cd33 chimeric antigen receptor |
GB201503742D0 (en) * | 2015-03-05 | 2015-04-22 | Ucl Business Plc | Chimeric antigen receptor |
EP3340995A4 (en) * | 2015-08-28 | 2019-04-03 | The Trustees Of The University Of Pennsylvania | Methods and compositions for cells expressing a chimeric intracellular signaling molecule |
US20180371052A1 (en) * | 2015-12-22 | 2018-12-27 | Icell Gene Therapeutics Llc | Chimeric antigen receptors and enhancement of anti-tumor activity |
CA3029197A1 (en) * | 2016-06-24 | 2017-12-28 | Icell Gene Therapeutics Llc | Chimeric antigen receptors (cars), compositions and methods thereof |
US20190307799A1 (en) * | 2016-09-23 | 2019-10-10 | The Regents Of The University Of Michigan | Engineered lymphocytes |
JP2021505131A (en) * | 2017-12-08 | 2021-02-18 | フェイト セラピューティクス,インコーポレイテッド | Immunotherapy with enhanced iPSC-derived effector cells |
EP3781176A4 (en) * | 2018-04-09 | 2022-05-25 | The Trustees of the University of Pennsylvania | Methods and compositions comprising a viral vector for expression of a transgene and an effector |
CN108840930B (en) * | 2018-06-29 | 2021-01-26 | 浙江生研生物科技有限公司 | anti-CD 19 monoclonal antibody, preparation method and application thereof |
-
2020
- 2020-07-15 EP EP20841097.7A patent/EP3999082A4/en active Pending
- 2020-07-15 WO PCT/IB2020/056659 patent/WO2021009694A1/en unknown
- 2020-07-15 AU AU2020315213A patent/AU2020315213A1/en active Pending
- 2020-07-15 CN CN202080058975.3A patent/CN114286683A/en active Pending
- 2020-07-15 CA CA3146987A patent/CA3146987A1/en active Pending
- 2020-07-15 JP JP2022502230A patent/JP2022541016A/en active Pending
- 2020-07-15 KR KR1020227004848A patent/KR20220035435A/en unknown
- 2020-07-15 US US17/597,582 patent/US20220281971A1/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000023573A2 (en) * | 1998-10-20 | 2000-04-27 | City Of Hope | Cd20-specific redirected t cells and their use in cellular immunotherapy of cd20+ malignancies |
WO2002077029A2 (en) * | 2000-11-07 | 2002-10-03 | City Of Hope | Cd19-specific redirected immune cells |
WO2016142314A1 (en) * | 2015-03-06 | 2016-09-15 | Deutsches Krebsforschungszentrum | FUSION PROTEINS COMPRISING A BINDING PROTEIN AND AN INTERLEUKIN-15 POLYPEPTIDE HAVING A REDUCED AFFINITY FOR IL15Ra AND THERAPEUTIC USES THEREOF |
WO2018103503A1 (en) * | 2016-12-05 | 2018-06-14 | 上海优卡迪生物医药科技有限公司 | Pd-l1 knockout car-t transgenic vector for suppressing immune escape, preparation method thereof, and application of same |
WO2019062817A1 (en) * | 2017-09-27 | 2019-04-04 | 亘喜生物科技(上海)有限公司 | Engineered immune cell capable of inducing secretion of anti-cd47 antibody |
CN107827990A (en) * | 2017-10-30 | 2018-03-23 | 河北森朗生物科技有限公司 | A kind of polypeptide, the nucleic acid for encoding it, the T lymphocytes of its modification and its application |
WO2019129002A1 (en) * | 2017-12-28 | 2019-07-04 | 上海细胞治疗研究院 | Car-t cell specifically targeting to cd19 antigen and stably expressing pd-1 antibody with high level, and use of car-t cell |
WO2020083282A1 (en) * | 2018-10-24 | 2020-04-30 | 艾生命序公司 | Pd-l1 antibody secreting anti-mesothelin car-t cells for tumor immunotherapy |
Non-Patent Citations (3)
Title |
---|
KOBER JOHANNA, LEITNER JUDITH, KLAUSER CHRISTOPH, WOITEK RAMONA, MAJDIC OTTO, STÖCKL JOHANNES, HERNDLER-BRANDSTETTER DIETMAR, GRUB: "The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells", EUROPEAN JOURNAL OF IMMUNOLOGY, WILEY VCH, WEINHEIM, vol. 38, no. 10, 1 October 2008 (2008-10-01), Weinheim, pages 2678 - 2688, XP055783980, ISSN: 0014-2980, DOI: 10.1002/eji.200838250 * |
SARA CARATELLI, TOMMASO SCONOCCHIA, ROBERTO ARRIGA, ANDREA COPPOLA, GIULIA LANZILLI, DAVIDE LAURO, ADRIANO VENDITTI, MARIA ILARIA : "FCγ Chimeric Receptor-Engineered T Cells: Methodology, Advantages, Limitations, and Clinical Relevance", FRONTIERS IN IMMUNOLOGY, vol. 8, XP055688148, DOI: 10.3389/fimmu.2017.00457 * |
See also references of EP3999082A4 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11560548B2 (en) | 2014-05-15 | 2023-01-24 | National University Of Singapore | Immune cells expressing membrane-bound interleukin 15 (mbIL15) and uses thereof |
US11365236B2 (en) | 2017-03-27 | 2022-06-21 | Nkarta, Inc. | Truncated NKG2D chimeric receptors and uses thereof in natural killer cell immunotherapy |
US11896616B2 (en) | 2017-03-27 | 2024-02-13 | National University Of Singapore | Stimulatory cell lines for ex vivo expansion and activation of natural killer cells |
US11253547B2 (en) | 2019-03-05 | 2022-02-22 | Nkarta, Inc. | CD19-directed chimeric antigen receptors and uses thereof in immunotherapy |
WO2023154890A3 (en) * | 2022-02-11 | 2023-10-26 | Fred Hutchinson Cancer Center | Chimeric antigen receptors binding steap1 |
Also Published As
Publication number | Publication date |
---|---|
KR20220035435A (en) | 2022-03-22 |
JP2022541016A (en) | 2022-09-21 |
US20220281971A1 (en) | 2022-09-08 |
AU2020315213A1 (en) | 2022-02-03 |
EP3999082A1 (en) | 2022-05-25 |
CN114286683A (en) | 2022-04-05 |
CA3146987A1 (en) | 2021-01-21 |
EP3999082A4 (en) | 2022-11-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20220281971A1 (en) | Functional Binders Synthesized and Secreted by Immune Cells | |
US11253546B2 (en) | Bispecific OR-gate chimeric antigen receptor responsive to CD19 and CD20 | |
AU2015315199A1 (en) | Chimeric receptors and uses thereof in immune therapy | |
US20200017588A1 (en) | Modular tetravalent bispecific antibody platform | |
KR102412805B1 (en) | Compositions and methods for cellular immunotherapy | |
KR102316091B1 (en) | Chimeric antigen receptor targeting BCMA and use thereof | |
US20190345218A1 (en) | Targeted t cells with cytotoxicity toward immunosuppressive cells | |
US20200181226A1 (en) | Antibody-coupled t cell receptor constructs and therapeutic uses thereof | |
CA3100349A1 (en) | Receptor inhibition by phosphatase recruitment | |
KR20210143096A (en) | Antibody specific for CD22 and uses thereof | |
EP3230311B1 (en) | Soluble universal adcc-enhancing synthetic fusion gene and peptide technology and its use thereof | |
WO2023056429A1 (en) | Anti-nmdar2b antibodies, antibody-drug conjugates, and chimeric antigen receptors, and compositions and methods of use | |
WO2022232016A2 (en) | Chimeric receptors targeting adgre2 and/or clec12a and uses thereof | |
EP3769816A1 (en) | Car-cd123 vector and uses thereof | |
JP2022513099A (en) | Suicide gene | |
Nagashima et al. | Tandemly repeated Fc domain augments binding avidities of antibodies for Fcγ receptors, resulting in enhanced antibody-dependent cellular cytotoxicity | |
WO2024111635A1 (en) | Antibody against hematological cancer | |
WO2023133424A2 (en) | Compositions and methods for tcr reprogramming using fusion proteins and anti-pd-1 fusion peptides | |
JP2023527462A (en) | Antibodies specific for CD22 and uses thereof | |
CA3217614A1 (en) | Chimeric receptors and methods of use thereof | |
CN111218448A (en) | Preparation and use of engineered immune cells | |
Moritz | Blocking the" Don't Eat Me" Checkpoint in Acute Myeloid Leukemia: Development of a Novel Antibody Format |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20841097 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 3146987 Country of ref document: CA |
|
ENP | Entry into the national phase |
Ref document number: 2022502230 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2020315213 Country of ref document: AU Date of ref document: 20200715 Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 20227004848 Country of ref document: KR Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2020841097 Country of ref document: EP Effective date: 20220217 |