TWI719946B - 使用ｃｄ１２３嵌合抗原受體治療癌症 - Google Patents
使用ｃｄ１２３嵌合抗原受體治療癌症 Download PDFInfo
- Publication number
- TWI719946B TWI719946B TW104127072A TW104127072A TWI719946B TW I719946 B TWI719946 B TW I719946B TW 104127072 A TW104127072 A TW 104127072A TW 104127072 A TW104127072 A TW 104127072A TW I719946 B TWI719946 B TW I719946B
- Authority
- TW
- Taiwan
- Prior art keywords
- seq
- amino acid
- cdr1
- cdr2
- cdr3
- Prior art date
Links
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 title claims abstract description 349
- 206010028980 Neoplasm Diseases 0.000 title claims description 115
- 201000011510 cancer Diseases 0.000 title claims description 50
- 238000011282 treatment Methods 0.000 title claims description 37
- 230000027455 binding Effects 0.000 claims abstract description 292
- 239000013598 vector Substances 0.000 claims abstract description 73
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 70
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 claims abstract description 69
- 201000010099 disease Diseases 0.000 claims abstract description 52
- 230000014509 gene expression Effects 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 210000004027 cell Anatomy 0.000 claims description 472
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 291
- 150000007523 nucleic acids Chemical class 0.000 claims description 185
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 154
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 141
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 135
- 229920001184 polypeptide Polymers 0.000 claims description 131
- 230000004068 intracellular signaling Effects 0.000 claims description 120
- 102000039446 nucleic acids Human genes 0.000 claims description 111
- 108020004707 nucleic acids Proteins 0.000 claims description 111
- 230000000139 costimulatory effect Effects 0.000 claims description 83
- 108090000623 proteins and genes Proteins 0.000 claims description 82
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 80
- 230000011664 signaling Effects 0.000 claims description 78
- 239000012642 immune effector Substances 0.000 claims description 74
- 229940121354 immunomodulator Drugs 0.000 claims description 74
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 71
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 71
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 70
- 102000004169 proteins and genes Human genes 0.000 claims description 56
- 239000002773 nucleotide Substances 0.000 claims description 53
- 125000003729 nucleotide group Chemical group 0.000 claims description 53
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 49
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 49
- 239000003112 inhibitor Substances 0.000 claims description 43
- 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 claims description 35
- -1 CD86 Proteins 0.000 claims description 32
- 241000124008 Mammalia Species 0.000 claims description 31
- 108020004999 messenger RNA Proteins 0.000 claims description 29
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical group C1C[C@@H](OCCO)[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 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 26
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 26
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 26
- 229960005167 everolimus Drugs 0.000 claims description 26
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 25
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 claims description 24
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 22
- 102100022339 Integrin alpha-L Human genes 0.000 claims description 22
- 230000000779 depleting effect Effects 0.000 claims description 22
- 102100027207 CD27 antigen Human genes 0.000 claims description 21
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 21
- 108060003951 Immunoglobulin Proteins 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 21
- 102000018358 immunoglobulin Human genes 0.000 claims description 21
- 230000019491 signal transduction Effects 0.000 claims description 21
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 20
- 102100029215 Signaling lymphocytic activation molecule Human genes 0.000 claims description 20
- 239000003446 ligand Substances 0.000 claims description 20
- 229940124302 mTOR inhibitor Drugs 0.000 claims description 20
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims description 20
- 238000002560 therapeutic procedure Methods 0.000 claims description 20
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 claims description 19
- 102100025390 Integrin beta-2 Human genes 0.000 claims description 19
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 19
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 18
- 108020004414 DNA Proteins 0.000 claims description 18
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 18
- 108091008874 T cell receptors Proteins 0.000 claims description 18
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 18
- 238000000338 in vitro Methods 0.000 claims description 18
- 102000053602 DNA Human genes 0.000 claims description 17
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 17
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 17
- 102100024263 CD160 antigen Human genes 0.000 claims description 16
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 16
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 claims description 15
- 102100032818 Integrin alpha-4 Human genes 0.000 claims description 15
- 102100032816 Integrin alpha-6 Human genes 0.000 claims description 15
- 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 claims description 15
- 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 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 101000633786 Homo sapiens SLAM family member 6 Proteins 0.000 claims description 14
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 14
- 102100029197 SLAM family member 6 Human genes 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 208000032839 leukemia Diseases 0.000 claims description 14
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 13
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 13
- 101000648507 Homo sapiens Tumor necrosis factor receptor superfamily member 14 Proteins 0.000 claims description 13
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 13
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 claims description 13
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 claims description 12
- 101000971538 Homo sapiens Killer cell lectin-like receptor subfamily F member 1 Proteins 0.000 claims description 12
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims description 12
- 102100021458 Killer cell lectin-like receptor subfamily F member 1 Human genes 0.000 claims description 12
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 230000004913 activation Effects 0.000 claims description 12
- 102100038078 CD276 antigen Human genes 0.000 claims description 11
- 101710185679 CD276 antigen Proteins 0.000 claims description 11
- 208000017604 Hodgkin disease Diseases 0.000 claims description 11
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 11
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 11
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 11
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims description 11
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 claims description 11
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 claims description 11
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 11
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 claims description 10
- 101001035237 Homo sapiens Integrin alpha-D Proteins 0.000 claims description 10
- 101001046687 Homo sapiens Integrin alpha-E Proteins 0.000 claims description 10
- 101000633780 Homo sapiens Signaling lymphocytic activation molecule Proteins 0.000 claims description 10
- 102100039904 Integrin alpha-D Human genes 0.000 claims description 10
- 102100022341 Integrin alpha-E Human genes 0.000 claims description 10
- 102100022338 Integrin alpha-M Human genes 0.000 claims description 10
- 102100022297 Integrin alpha-X Human genes 0.000 claims description 10
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 claims description 10
- 102000014128 RANK Ligand Human genes 0.000 claims description 10
- 108010025832 RANK Ligand Proteins 0.000 claims description 10
- 102100027744 Semaphorin-4D Human genes 0.000 claims description 10
- 210000001185 bone marrow Anatomy 0.000 claims description 10
- 238000002054 transplantation Methods 0.000 claims description 10
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 claims description 9
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 claims description 9
- 101001078158 Homo sapiens Integrin alpha-1 Proteins 0.000 claims description 9
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 claims description 9
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 claims description 9
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims description 9
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 9
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims description 9
- 102100025323 Integrin alpha-1 Human genes 0.000 claims description 9
- 102100025304 Integrin beta-1 Human genes 0.000 claims description 9
- 108091054437 MHC class I family Proteins 0.000 claims description 9
- 239000012270 PD-1 inhibitor Substances 0.000 claims description 9
- 239000012668 PD-1-inhibitor Substances 0.000 claims description 9
- 102100029198 SLAM family member 7 Human genes 0.000 claims description 9
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 9
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 9
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims description 9
- 210000003630 histaminocyte Anatomy 0.000 claims description 9
- 210000004698 lymphocyte Anatomy 0.000 claims description 9
- 229940121655 pd-1 inhibitor Drugs 0.000 claims description 9
- 101150013553 CD40 gene Proteins 0.000 claims description 8
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 8
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 8
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 8
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 claims description 8
- 239000000556 agonist Substances 0.000 claims description 8
- 230000001965 increasing effect Effects 0.000 claims description 8
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 7
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 7
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 7
- 102100038077 CD226 antigen Human genes 0.000 claims description 7
- 102100035793 CD83 antigen Human genes 0.000 claims description 7
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 7
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 7
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 7
- 101000884298 Homo sapiens CD226 antigen Proteins 0.000 claims description 7
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 claims description 7
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 claims description 7
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 claims description 7
- 101000914496 Homo sapiens T-cell antigen CD7 Proteins 0.000 claims description 7
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 claims description 7
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 claims description 7
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 7
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 7
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 claims description 7
- 102000043129 MHC class I family Human genes 0.000 claims description 7
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 claims description 7
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 7
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 claims description 7
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 7
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 claims description 7
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 claims description 7
- 229960005305 adenosine Drugs 0.000 claims description 7
- 230000000735 allogeneic effect Effects 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 201000005787 hematologic cancer Diseases 0.000 claims description 7
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 102000006495 integrins Human genes 0.000 claims description 7
- 108010044426 integrins Proteins 0.000 claims description 7
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 7
- 102100032937 CD40 ligand Human genes 0.000 claims description 6
- 102000004127 Cytokines Human genes 0.000 claims description 6
- 108090000695 Cytokines Proteins 0.000 claims description 6
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 6
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 6
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 6
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 6
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 6
- 229940072221 immunoglobulins Drugs 0.000 claims description 6
- 210000002706 plastid Anatomy 0.000 claims description 6
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 5
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 5
- 108010056102 CD100 antigen Proteins 0.000 claims description 5
- 108010017009 CD11b Antigen Proteins 0.000 claims description 5
- 108010062802 CD66 antigens Proteins 0.000 claims description 5
- 102100027217 CD82 antigen Human genes 0.000 claims description 5
- 101710139831 CD82 antigen Proteins 0.000 claims description 5
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 claims description 5
- 102100027816 Cytotoxic and regulatory T-cell molecule Human genes 0.000 claims description 5
- 102100025137 Early activation antigen CD69 Human genes 0.000 claims description 5
- 101000585551 Equus caballus Pregnancy-associated glycoprotein Proteins 0.000 claims description 5
- 102100022086 GRB2-related adapter protein 2 Human genes 0.000 claims description 5
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 claims description 5
- 101000900690 Homo sapiens GRB2-related adapter protein 2 Proteins 0.000 claims description 5
- 101001046683 Homo sapiens Integrin alpha-L Proteins 0.000 claims description 5
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 claims description 5
- 101001046668 Homo sapiens Integrin alpha-X Proteins 0.000 claims description 5
- 101001015037 Homo sapiens Integrin beta-7 Proteins 0.000 claims description 5
- 101001047640 Homo sapiens Linker for activation of T-cells family member 1 Proteins 0.000 claims description 5
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 claims description 5
- 101001090688 Homo sapiens Lymphocyte cytosolic protein 2 Proteins 0.000 claims description 5
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims description 5
- 101000589305 Homo sapiens Natural cytotoxicity triggering receptor 2 Proteins 0.000 claims description 5
- 101000873418 Homo sapiens P-selectin glycoprotein ligand 1 Proteins 0.000 claims description 5
- 101001124867 Homo sapiens Peroxiredoxin-1 Proteins 0.000 claims description 5
- 101000692259 Homo sapiens Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 Proteins 0.000 claims description 5
- 101000702132 Homo sapiens Protein spinster homolog 1 Proteins 0.000 claims description 5
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 5
- 101000633778 Homo sapiens SLAM family member 5 Proteins 0.000 claims description 5
- 101000633782 Homo sapiens SLAM family member 8 Proteins 0.000 claims description 5
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 claims description 5
- 101000679857 Homo sapiens Tumor necrosis factor receptor superfamily member 3 Proteins 0.000 claims description 5
- 108010041100 Integrin alpha6 Proteins 0.000 claims description 5
- 108010030465 Integrin alpha6beta1 Proteins 0.000 claims description 5
- 102100033016 Integrin beta-7 Human genes 0.000 claims description 5
- 102100024032 Linker for activation of T-cells family member 1 Human genes 0.000 claims description 5
- 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 claims description 5
- 101100236305 Mus musculus Ly9 gene Proteins 0.000 claims description 5
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 claims description 5
- 108091008877 NK cell receptors Proteins 0.000 claims description 5
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims description 5
- 108010004217 Natural Cytotoxicity Triggering Receptor 1 Proteins 0.000 claims description 5
- 108010004222 Natural Cytotoxicity Triggering Receptor 3 Proteins 0.000 claims description 5
- 102100032870 Natural cytotoxicity triggering receptor 1 Human genes 0.000 claims description 5
- 102100032851 Natural cytotoxicity triggering receptor 2 Human genes 0.000 claims description 5
- 102100032852 Natural cytotoxicity triggering receptor 3 Human genes 0.000 claims description 5
- 101710141230 Natural killer cell receptor 2B4 Proteins 0.000 claims description 5
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 claims description 5
- 102100026066 Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 Human genes 0.000 claims description 5
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 claims description 5
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims description 5
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 claims description 5
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 5
- 102100029216 SLAM family member 5 Human genes 0.000 claims description 5
- 102100029214 SLAM family member 8 Human genes 0.000 claims description 5
- 102000008115 Signaling Lymphocytic Activation Molecule Family Member 1 Human genes 0.000 claims description 5
- 102100035268 T-cell surface protein tactile Human genes 0.000 claims description 5
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 claims description 5
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 claims description 5
- 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 claims description 5
- 101001038499 Yarrowia lipolytica (strain CLIB 122 / E 150) Lysine acetyltransferase Proteins 0.000 claims description 5
- 208000037833 acute lymphoblastic T-cell leukemia Diseases 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 5
- 108010072917 class-I restricted T cell-associated molecule Proteins 0.000 claims description 5
- 230000003750 conditioning effect Effects 0.000 claims description 5
- 229940126546 immune checkpoint molecule Drugs 0.000 claims description 5
- 210000005259 peripheral blood Anatomy 0.000 claims description 5
- 239000011886 peripheral blood Substances 0.000 claims description 5
- 102000005962 receptors Human genes 0.000 claims description 5
- 108020003175 receptors Proteins 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 101150051188 Adora2a gene Proteins 0.000 claims description 4
- 102100037904 CD9 antigen Human genes 0.000 claims description 4
- 102100031351 Galectin-9 Human genes 0.000 claims description 4
- 101100229077 Gallus gallus GAL9 gene Proteins 0.000 claims description 4
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 4
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 claims description 4
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims description 4
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims description 4
- 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 claims description 4
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 4
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 4
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 4
- 101000955999 Homo sapiens V-set domain-containing T-cell activation inhibitor 1 Proteins 0.000 claims description 4
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 claims description 4
- 108010043610 KIR Receptors Proteins 0.000 claims description 4
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims description 4
- 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 claims description 4
- 108091054438 MHC class II family Proteins 0.000 claims description 4
- 102000043131 MHC class II family Human genes 0.000 claims description 4
- 206010038111 Recurrent cancer Diseases 0.000 claims description 4
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 4
- 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 claims description 4
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 claims description 4
- 208000037832 acute lymphoblastic B-cell leukemia Diseases 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 102000003675 cytokine receptors Human genes 0.000 claims description 4
- 108010057085 cytokine receptors Proteins 0.000 claims description 4
- 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 claims description 4
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 claims description 4
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 4
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 4
- 229960002930 sirolimus Drugs 0.000 claims description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 102100024217 CAMPATH-1 antigen Human genes 0.000 claims description 3
- 108010065524 CD52 Antigen Proteins 0.000 claims description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
- 208000007541 Preleukemia Diseases 0.000 claims description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 201000009277 hairy cell leukemia Diseases 0.000 claims description 3
- 238000009169 immunotherapy Methods 0.000 claims description 3
- 230000001177 retroviral effect Effects 0.000 claims description 3
- 230000009870 specific binding Effects 0.000 claims description 3
- 238000011476 stem cell transplantation Methods 0.000 claims description 3
- 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 claims description 2
- 230000005809 anti-tumor immunity Effects 0.000 claims description 2
- 238000011319 anticancer therapy Methods 0.000 claims description 2
- 238000010322 bone marrow transplantation Methods 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 239000002254 cytotoxic agent Substances 0.000 claims description 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
- 201000008298 histiocytosis Diseases 0.000 claims description 2
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 claims description 2
- 230000005855 radiation Effects 0.000 claims description 2
- 230000001568 sexual effect Effects 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 230000002463 transducing effect Effects 0.000 claims description 2
- 229960005486 vaccine Drugs 0.000 claims description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 4
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims 3
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims 3
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 claims 2
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 claims 2
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 claims 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims 2
- 102000027581 NK cell receptors Human genes 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 claims 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 claims 1
- 208000012659 Joint disease Diseases 0.000 claims 1
- 102000017578 LAG3 Human genes 0.000 claims 1
- 101100341510 Mus musculus Itgal gene Proteins 0.000 claims 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims 1
- 230000002071 myeloproliferative effect Effects 0.000 claims 1
- 230000009826 neoplastic cell growth Effects 0.000 claims 1
- 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 claims 1
- 108091007433 antigens Proteins 0.000 description 105
- 102000036639 antigens Human genes 0.000 description 105
- 239000000427 antigen Substances 0.000 description 101
- 238000006467 substitution reaction Methods 0.000 description 88
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 description 56
- 241000282414 Homo sapiens Species 0.000 description 53
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 38
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 37
- 230000004048 modification Effects 0.000 description 37
- 238000012986 modification Methods 0.000 description 37
- 210000000822 natural killer cell Anatomy 0.000 description 37
- 235000018102 proteins Nutrition 0.000 description 37
- 229920002477 rna polymer Polymers 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 25
- 102000052088 human IL3RA Human genes 0.000 description 25
- 239000012634 fragment Substances 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 20
- 230000003834 intracellular effect Effects 0.000 description 20
- 235000001014 amino acid Nutrition 0.000 description 18
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 17
- 230000006870 function Effects 0.000 description 17
- 125000005647 linker group Chemical group 0.000 description 17
- 230000004044 response Effects 0.000 description 17
- 238000013518 transcription Methods 0.000 description 17
- 230000035897 transcription Effects 0.000 description 16
- 230000001086 cytosolic effect Effects 0.000 description 15
- 230000009467 reduction Effects 0.000 description 15
- 125000000539 amino acid group Chemical group 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 13
- 230000000875 corresponding effect Effects 0.000 description 13
- 108010024755 CTL019 chimeric antigen receptor Proteins 0.000 description 12
- 230000029918 bioluminescence Effects 0.000 description 12
- 238000005415 bioluminescence Methods 0.000 description 12
- 239000012636 effector Substances 0.000 description 12
- 102000040430 polynucleotide Human genes 0.000 description 12
- 108091033319 polynucleotide Proteins 0.000 description 12
- 239000002157 polynucleotide Substances 0.000 description 12
- 230000035755 proliferation Effects 0.000 description 12
- 230000004936 stimulating effect Effects 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- 108060001084 Luciferase Proteins 0.000 description 10
- 239000005089 Luciferase Substances 0.000 description 10
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 238000003384 imaging method Methods 0.000 description 10
- 230000028993 immune response Effects 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 108020001507 fusion proteins Proteins 0.000 description 9
- 102000037865 fusion proteins Human genes 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000002062 proliferating effect Effects 0.000 description 9
- 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 description 8
- 108020004705 Codon Proteins 0.000 description 8
- 229960000548 alemtuzumab Drugs 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 241000282693 Cercopithecidae Species 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 241000283984 Rodentia Species 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000008488 polyadenylation Effects 0.000 description 7
- 238000010361 transduction Methods 0.000 description 7
- 230000026683 transduction Effects 0.000 description 7
- 241000713666 Lentivirus Species 0.000 description 6
- 101800001494 Protease 2A Proteins 0.000 description 6
- 101800001066 Protein 2A Proteins 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 230000016396 cytokine production Effects 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 230000031146 intracellular signal transduction Effects 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 206010000830 Acute leukaemia Diseases 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 208000006994 Precancerous Conditions Diseases 0.000 description 5
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 5
- 201000008736 Systemic mastocytosis Diseases 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 229940090044 injection Drugs 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 210000003071 memory t lymphocyte Anatomy 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 231100000628 reference dose Toxicity 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 4
- 108010087819 Fc receptors Proteins 0.000 description 4
- 102000009109 Fc receptors Human genes 0.000 description 4
- 102000050627 Glucocorticoid-Induced TNFR-Related Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 4
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 4
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 4
- 101710187882 Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 4
- 238000002679 ablation Methods 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 239000000306 component Substances 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- 230000003463 hyperproliferative effect Effects 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229960004641 rituximab Drugs 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 108020005345 3' Untranslated Regions Proteins 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 3
- 108010067306 Fibronectins Proteins 0.000 description 3
- 102000016359 Fibronectins Human genes 0.000 description 3
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 3
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 3
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 3
- 102000002698 KIR Receptors Human genes 0.000 description 3
- 102100033467 L-selectin Human genes 0.000 description 3
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 3
- 108091036407 Polyadenylation Proteins 0.000 description 3
- 108091034057 RNA (poly(A)) Proteins 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 210000000612 antigen-presenting cell Anatomy 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 230000001461 cytolytic effect Effects 0.000 description 3
- 239000010432 diamond Substances 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 208000000516 mast-cell leukemia Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- 108091012583 BCL2 Proteins 0.000 description 2
- 102100032412 Basigin Human genes 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 102100025466 Carcinoembryonic antigen-related cell adhesion molecule 3 Human genes 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 239000004471 Glycine Substances 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
- 102100029360 Hematopoietic cell signal transducer Human genes 0.000 description 2
- 241001272567 Hominoidea Species 0.000 description 2
- 101000914337 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 3 Proteins 0.000 description 2
- 101000990188 Homo sapiens Hematopoietic cell signal transducer Proteins 0.000 description 2
- 101000971533 Homo sapiens Killer cell lectin-like receptor subfamily G member 1 Proteins 0.000 description 2
- 101000809875 Homo sapiens TYRO protein tyrosine kinase-binding protein Proteins 0.000 description 2
- 101150106931 IFNG gene Proteins 0.000 description 2
- 108010073816 IgE Receptors Proteins 0.000 description 2
- 102000009438 IgE Receptors Human genes 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 102100021457 Killer cell lectin-like receptor subfamily G member 1 Human genes 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 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 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 102100029193 Low affinity immunoglobulin gamma Fc region receptor III-A Human genes 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 206010056450 Mastocytic leukaemia Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 2
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 2
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010070308 Refractory cancer Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000007660 Residual Neoplasm Diseases 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 102100038717 TYRO protein tyrosine kinase-binding protein Human genes 0.000 description 2
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 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
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229910003460 diamond Inorganic materials 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 210000003701 histiocyte Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000002766 immunoenhancing effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 2
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 229960004799 tryptophan Drugs 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 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
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-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
- OGHAROSJZRTIOK-KQYNXXCUSA-O 7-methylguanosine Chemical compound C1=2N=C(N)NC(=O)C=2[N+](C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OGHAROSJZRTIOK-KQYNXXCUSA-O 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 108010064528 Basigin Proteins 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
- 102000006734 Beta-Globulins Human genes 0.000 description 1
- 108010087504 Beta-Globulins Proteins 0.000 description 1
- 102100026031 Beta-glucuronidase Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 238000011357 CAR T-cell therapy Methods 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 244000205754 Colocasia esculenta Species 0.000 description 1
- 235000006481 Colocasia esculenta Nutrition 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108020004635 Complementary DNA 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
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-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
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 1
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements 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
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 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
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 101000798441 Homo sapiens Basigin Proteins 0.000 description 1
- 101000933465 Homo sapiens Beta-glucuronidase Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
- 101000914321 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 7 Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101001046677 Homo sapiens Integrin alpha-V Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001033279 Homo sapiens Interleukin-3 Proteins 0.000 description 1
- 101000960936 Homo sapiens Interleukin-5 receptor subunit alpha Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101001133056 Homo sapiens Mucin-1 Proteins 0.000 description 1
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 1
- 101000617725 Homo sapiens Pregnancy-specific beta-1-glycoprotein 2 Proteins 0.000 description 1
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 1
- 101000801433 Homo sapiens Trophoblast glycoprotein Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102000001617 Interferon Receptors Human genes 0.000 description 1
- 108010054267 Interferon Receptors Proteins 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 102100039064 Interleukin-3 Human genes 0.000 description 1
- 102000010790 Interleukin-3 Receptors Human genes 0.000 description 1
- 108010038452 Interleukin-3 Receptors Proteins 0.000 description 1
- 102100039881 Interleukin-5 receptor subunit alpha Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 229930191564 Monensin Natural products 0.000 description 1
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 1
- 102100034256 Mucin-1 Human genes 0.000 description 1
- 102100023123 Mucin-16 Human genes 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 description 1
- 238000001190 Q-PCR Methods 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010071051 Soft tissue mass Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940124675 anti-cancer drug Drugs 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001363 autoimmune Effects 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
- 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
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 201000002687 childhood acute myeloid leukemia Diseases 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000011217 control strategy Methods 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 102000006815 folate receptor Human genes 0.000 description 1
- 108020005243 folate receptor Proteins 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 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
- 230000012010 growth Effects 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
- 230000036541 health Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000000977 initiatory effect Effects 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
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 208000017830 lymphoblastoma Diseases 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 229960005358 monensin Drugs 0.000 description 1
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000007030 peptide scission Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 102220191892 rs199825512 Human genes 0.000 description 1
- 102220058139 rs372082751 Human genes 0.000 description 1
- 238000012216 screening Methods 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
- 230000008054 signal transmission Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 101150047061 tag-72 gene Proteins 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 239000000439 tumor marker Substances 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 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
- 230000003612 virological effect Effects 0.000 description 1
- 238000001262 western blot Methods 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/44—Antibodies bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/421—Immunoglobulin superfamily
- A61K40/4211—CD19 or B4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/4202—Receptors, cell surface antigens or cell surface determinants
- A61K40/4214—Receptors for cytokines
- A61K40/4217—Receptors for interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- 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
-
- 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
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/11—Antigen recognition domain
- A61K2239/13—Antibody-based
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/21—Transmembrane domain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
- A61K2239/22—Intracellular domain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
- A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
- A61K2239/48—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
- C07K2317/60—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
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- General Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Developmental Biology & Embryology (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| WOPCT/CN2014/084696 | 2014-08-09 | ||
| CN2014084696 | 2014-08-19 | ||
| CN2014090508 | 2014-11-06 | ||
| WOPCT/CN2014/090508 | 2014-11-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201617367A TW201617367A (zh) | 2016-05-16 |
| TWI719946B true TWI719946B (zh) | 2021-03-01 |
Family
ID=54011902
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW104127072A TWI719946B (zh) | 2014-08-19 | 2015-08-19 | 使用ｃｄ１２３嵌合抗原受體治療癌症 |
| TW110102298A TW202140557A (zh) | 2014-08-19 | 2015-08-19 | 使用cd123嵌合抗原受體治療癌症 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110102298A TW202140557A (zh) | 2014-08-19 | 2015-08-19 | 使用cd123嵌合抗原受體治療癌症 |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US9815901B2 (enExample) |
| EP (2) | EP3183268B1 (enExample) |
| JP (2) | JP7084138B2 (enExample) |
| KR (1) | KR102616429B1 (enExample) |
| CN (2) | CN107108744B (enExample) |
| AU (2) | AU2015305531B2 (enExample) |
| CA (1) | CA2958553A1 (enExample) |
| CO (1) | CO2017001573A2 (enExample) |
| DK (1) | DK3183268T3 (enExample) |
| ES (1) | ES2791248T3 (enExample) |
| HU (1) | HUE049218T2 (enExample) |
| IL (2) | IL250362B (enExample) |
| LT (1) | LT3183268T (enExample) |
| MX (1) | MX2017002205A (enExample) |
| MY (1) | MY189028A (enExample) |
| PL (1) | PL3183268T3 (enExample) |
| PT (1) | PT3183268T (enExample) |
| RU (2) | RU2020117196A (enExample) |
| SG (1) | SG11201700770PA (enExample) |
| TW (2) | TWI719946B (enExample) |
| WO (1) | WO2016028896A1 (enExample) |
Families Citing this family (225)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10058621B2 (en) | 2015-06-25 | 2018-08-28 | Immunomedics, Inc. | Combination therapy with anti-HLA-DR antibodies and kinase inhibitors in hematopoietic cancers |
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| IN2014DN06522A (enExample) * | 2012-02-22 | 2015-06-12 | Univ Pennsylvania | |
| ES2776698T3 (es) | 2012-12-20 | 2020-07-31 | Purdue Research Foundation | Células T que expresan un receptor antigénico quimérico como terapia contra el cáncer |
| US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
| DK2943511T3 (da) | 2013-01-14 | 2019-10-21 | Xencor Inc | Nye heterodimeriske proteiner |
| US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
| US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
| US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
| DK2958943T3 (da) | 2013-02-20 | 2019-12-09 | Univ Pennsylvania | Behandling af cancer ved anvendelse af humaniseret anti-EGFRvIII kimær antigenreceptor |
| 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 |
| ES2769574T3 (es) | 2013-03-15 | 2020-06-26 | Michael C Milone | Reconocimiento de células citotóxicas con receptores quiméricos para inmunoterapia adoptiva |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
| 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 |
| WO2015048312A1 (en) | 2013-09-26 | 2015-04-02 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
| WO2015073644A1 (en) * | 2013-11-13 | 2015-05-21 | Novartis Ag | Mtor inhibitors for enhancing the immune response |
| US10640569B2 (en) | 2013-12-19 | 2020-05-05 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
| US10287354B2 (en) | 2013-12-20 | 2019-05-14 | Novartis Ag | Regulatable chimeric antigen receptor |
| US11028143B2 (en) | 2014-01-21 | 2021-06-08 | Novartis Ag | Enhanced antigen presenting ability of RNA CAR T cells by co-introduction of costimulatory molecules |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| KR20240110004A (ko) | 2014-03-14 | 2024-07-12 | 노파르티스 아게 | Lag-3에 대한 항체 분자 및 그의 용도 |
| SI3122781T1 (sl) | 2014-03-28 | 2020-03-31 | Xencor, Inc. | Bispecifična protitelesa, ki se vežejo na CD38 in CD3 |
| KR102487608B1 (ko) | 2014-04-07 | 2023-01-12 | 노파르티스 아게 | 항-cd19 키메라 항원 수용체를 사용한 암의 치료 |
| JP6736540B2 (ja) | 2014-07-21 | 2020-08-05 | ノバルティス アーゲー | Ｃｌｌ−１キメラ抗原受容体を使用した癌の処置 |
| CN107109419B (zh) | 2014-07-21 | 2020-12-22 | 诺华股份有限公司 | 使用cd33嵌合抗原受体治疗癌症 |
| RU2751660C2 (ru) | 2014-07-21 | 2021-07-15 | Новартис Аг | Лечение злокачественного новообразования с использованием гуманизированного химерного антигенного рецептора против всма |
| US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
| SG11201700770PA (en) | 2014-08-19 | 2017-03-30 | Novartis Ag | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment |
| EP2990416B1 (en) | 2014-08-29 | 2018-06-20 | GEMoaB Monoclonals GmbH | Universal chimeric antigen receptor expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders |
| ES2771926T3 (es) | 2014-09-13 | 2020-07-07 | Novartis Ag | Terapias de combinación |
| KR102804360B1 (ko) | 2014-09-17 | 2025-05-12 | 노파르티스 아게 | 입양 면역요법을 위한 키메라 수용체에 의한 세포독성 세포의 표적화 |
| AU2015330898B2 (en) | 2014-10-08 | 2022-03-10 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
| EA037065B1 (ru) | 2014-11-26 | 2021-02-01 | Ксенкор, Инк. | Гетеродимерные антитела, связывающие cd3 и cd38 |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| HUE055115T2 (hu) | 2014-11-26 | 2021-10-28 | Xencor Inc | CD3-at és CD20-at kötõ heterodimer antitestek |
| EP3766895B1 (en) * | 2014-12-03 | 2024-07-10 | Juno Therapeutics, Inc. | Methods and compositions for adoptive cell therapy |
| EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
| EP3240803B1 (en) | 2014-12-29 | 2021-11-24 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
| US11459390B2 (en) | 2015-01-16 | 2022-10-04 | Novartis Ag | Phosphoglycerate kinase 1 (PGK) promoters and methods of use for expressing chimeric antigen receptor |
| WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
| US20170151281A1 (en) | 2015-02-19 | 2017-06-01 | Batu Biologics, Inc. | Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer |
| US10227411B2 (en) | 2015-03-05 | 2019-03-12 | Xencor, Inc. | Modulation of T cells with bispecific antibodies and FC fusions |
| CN107708710A (zh) | 2015-03-17 | 2018-02-16 | 嵌合体生物工程公司 | Smart CAR装置,DE CAR多肽,Side CAR及其使用 |
| CA2981751A1 (en) * | 2015-04-08 | 2016-10-13 | Novartis Ag | Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car)- expressing cell |
| SG11201708516YA (en) | 2015-04-17 | 2017-11-29 | David Maxwell Barrett | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
| WO2016172583A1 (en) | 2015-04-23 | 2016-10-27 | Novartis Ag | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
| US10576076B2 (en) | 2015-05-20 | 2020-03-03 | Novartis Ag | Pharmaceutical combination of everolimus with dactolisib |
| IL287718B2 (en) * | 2015-06-25 | 2025-05-01 | Icell Gene Therapeutics Llc | Chimeric antigen receptors (CARs), compositions and methods for using them |
| US10829735B2 (en) | 2015-07-21 | 2020-11-10 | The Trustees Of The University Of Pennsylvania | Methods for improving the efficacy and expansion of immune cells |
| US11667691B2 (en) | 2015-08-07 | 2023-06-06 | Novartis Ag | Treatment of cancer using chimeric CD3 receptor proteins |
| CN108780084B (zh) | 2015-09-03 | 2022-07-22 | 诺华股份有限公司 | 预测细胞因子释放综合征的生物标志物 |
| MX2018005825A (es) * | 2015-11-09 | 2019-07-04 | Aperisys Inc | Celulas inmunes modificadas y usos de las mismas. |
| MA43380A (fr) | 2015-12-03 | 2018-10-10 | Juno Therapeutics Inc | Récepteurs chimériques modifiés et compositions et procédés associés |
| SG11201804373VA (en) | 2015-12-04 | 2018-06-28 | Novartis Ag | Compositions and methods for immunooncology |
| CA3007030A1 (en) | 2015-12-07 | 2017-06-15 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and psma |
| US11052111B2 (en) | 2015-12-08 | 2021-07-06 | Chimera Bioengineering, Inc. | Smart CAR devices and DE CAR polypeptides for treating disease and methods for enhancing immune responses |
| US11413340B2 (en) | 2015-12-22 | 2022-08-16 | Novartis Ag | Mesothelin chimeric antigen receptor (CAR) and antibody against PD-L1 inhibitor for combined use in anticancer therapy |
| CN109153975A (zh) | 2015-12-28 | 2019-01-04 | 诺华股份有限公司 | 制备嵌合抗原受体表达细胞的方法 |
| EP3397756B1 (en) | 2015-12-30 | 2023-03-08 | Novartis AG | Immune effector cell therapies with enhanced efficacy |
| AU2017225733A1 (en) | 2016-03-04 | 2018-09-27 | Novartis Ag | Cells expressing multiple chimeric antigen receptor (CAR) molecules and uses therefore |
| EP3432924A1 (en) | 2016-03-23 | 2019-01-30 | Novartis AG | Cell secreted minibodies and uses thereof |
| WO2017177149A2 (en) | 2016-04-08 | 2017-10-12 | Purdue Research Foundation | Methods and compositions for car t cell therapy |
| US11446398B2 (en) | 2016-04-11 | 2022-09-20 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
| WO2017180565A1 (en) * | 2016-04-14 | 2017-10-19 | Immunomedics, Inc. | Combination therapy with anti-hla-dr antibodies and kinase inhibitors in hematopoietic cancers |
| MX2018012615A (es) | 2016-04-15 | 2019-05-30 | Novartis Ag | Composiciones y metodos para la expresion selectiva de proteinas. |
| WO2017201019A1 (en) | 2016-05-17 | 2017-11-23 | Chimera Bioengineering, Inc. | Methods for making novel antigen binding domains |
| US11191771B2 (en) | 2016-06-09 | 2021-12-07 | Seagen Inc. | Combinations of PBD-based antibody drug conjugates with FLT3 inhibitors |
| EP4257613A3 (en) | 2016-06-14 | 2023-12-13 | Xencor, Inc. | Bispecific checkpoint inhibitor antibodies |
| EP4353750A3 (en) * | 2016-06-24 | 2024-07-24 | iCell Gene Therapeutics LLC | Chimeric antigen receptors (cars), compositions and methods thereof |
| AU2017290086A1 (en) | 2016-06-28 | 2019-01-24 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| JP7219376B2 (ja) * | 2016-07-15 | 2023-02-08 | ノバルティス アーゲー | キメラ抗原受容体をキナーゼ阻害薬と併用して使用したサイトカイン放出症候群の治療及び予防 |
| EP3487525A4 (en) * | 2016-07-22 | 2020-03-18 | Seattle Genetics, Inc. | COMBINATION THERAPY WITH CD19-ADC AND RCHP |
| CN110035768A (zh) * | 2016-07-26 | 2019-07-19 | 泰莎治疗私人有限公司 | 嵌合抗原受体 |
| EP3491016A1 (en) | 2016-07-28 | 2019-06-05 | Novartis AG | Combination therapies of chimeric antigen receptors and pd-1 inhibitors |
| RU2019105693A (ru) * | 2016-08-01 | 2020-09-01 | Новартис Аг | Лечение рака с применением химерного антигенного рецептора в комбинации с ингибитором молекулы, способствующей фенотипу m2 макрофага |
| US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| CN107793481A (zh) * | 2016-08-31 | 2018-03-13 | 南京传奇生物科技有限公司 | 一种靶向人cd123的嵌合受体配体及其应用 |
| US10323248B2 (en) | 2016-09-01 | 2019-06-18 | Chimera Bioengineering, Inc. | Gold optimized CAR T-cells |
| AU2017331275A1 (en) * | 2016-09-23 | 2019-05-16 | Oncosec Medical Incorporated | Modulating responses to checkpoint inhibitor therapy |
| EP3519577A1 (en) | 2016-09-28 | 2019-08-07 | Novartis AG | Porous membrane-based macromolecule delivery system |
| MX2019003886A (es) | 2016-10-07 | 2019-08-05 | Novartis Ag | Receptores de antigenos quimericos para el tratamiento del cancer. |
| US10501543B2 (en) | 2016-10-14 | 2019-12-10 | Xencor, Inc. | IL15/IL15Rα heterodimeric Fc-fusion proteins |
| IL317416A (en) * | 2016-11-16 | 2025-02-01 | Ablynx Nv | T cell-recruiting polypeptides capable of binding CD123 and TCR alpha/beta |
| AU2017363970A1 (en) | 2016-11-23 | 2019-06-20 | Novartis Ag | Methods of enhancing immune response with everolimus, dactolisib or both |
| KR20190104528A (ko) | 2016-12-03 | 2019-09-10 | 주노 쎄러퓨티크스 인코퍼레이티드 | Car-t 세포들 투여를 결정하는 방법 |
| EP3548611A1 (en) | 2016-12-05 | 2019-10-09 | Juno Therapeutics, Inc. | Production of engineered cells for adoptive cell therapy |
| CN107058390A (zh) * | 2017-01-17 | 2017-08-18 | 上海交通大学医学院附属第九人民医院 | 一种慢病毒载体、重组慢病毒质粒、病毒及病毒的应用 |
| EP3570850A4 (en) * | 2017-01-18 | 2020-10-14 | Thalia Papayannopoulou | PACKAGING COMPOSITIONS AND METHODS FOR A TRANSPLANT RECEIVER |
| ES2912408T3 (es) | 2017-01-26 | 2022-05-25 | Novartis Ag | Composiciones de CD28 y métodos para terapia con receptores quiméricos para antígenos |
| WO2018148224A1 (en) | 2017-02-07 | 2018-08-16 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Phospholipid ether (ple) car t cell tumor targeting (ctct) agents |
| BR112019017767A2 (pt) | 2017-02-27 | 2020-04-07 | Juno Therapeutics Inc | composições, artigos de fabricação e métodos relacionados à dosagem em terapia celular |
| CN110582288B (zh) | 2017-02-28 | 2024-09-20 | 恩多塞特公司 | 用于car t细胞疗法的组合物和方法 |
| RU2019133280A (ru) | 2017-03-22 | 2021-04-22 | Новартис Аг | Композиции и способы для иммуноонкологии |
| US11104737B2 (en) | 2017-03-28 | 2021-08-31 | Rigel Pharmaceuticals, Inc. | ACVR2A-specific antibody and method of treatment of muscle atrophy |
| CN110582280B (zh) | 2017-03-31 | 2024-03-19 | 小利兰·斯坦福大学托管委员会 | 通过抑制或调节t细胞受体信号传导来治疗t细胞耗竭的方法 |
| AU2018256436B2 (en) | 2017-04-19 | 2024-12-05 | Board Of Regents, The University Of Texas System | Immune cells expressing engineered antigen receptors |
| CA3062433A1 (en) | 2017-05-15 | 2018-11-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bicistronic chimeric antigen receptors and their uses |
| AU2018275109A1 (en) * | 2017-06-01 | 2020-01-02 | Xencor, Inc. | Bispecific antibodies that bind CD 123 CD3 |
| AU2018275894B2 (en) * | 2017-06-02 | 2025-04-24 | Juno Therapeutics, Inc. | Articles of manufacture and methods for treatment using adoptive cell therapy |
| US11434290B2 (en) | 2017-06-08 | 2022-09-06 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Chimeric antigen receptors with enhanced NFκB signaling |
| US12275787B2 (en) | 2017-06-21 | 2025-04-15 | Icell Gene Therapeutics Llc | Chimeric antigen receptors (CARs), compositions and methods thereof |
| CN111132733A (zh) | 2017-06-30 | 2020-05-08 | Xencor股份有限公司 | 含有IL-15/IL-15Rα和抗原结合结构域的靶向异源二聚体Fc融合蛋白 |
| US11976121B2 (en) | 2017-07-20 | 2024-05-07 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | CD123-binding chimeric antigen receptors |
| CN109423495A (zh) * | 2017-08-24 | 2019-03-05 | 上海恒润达生生物科技有限公司 | 一种双靶向嵌合抗原受体及其用途 |
| AU2018335266A1 (en) * | 2017-09-22 | 2020-02-06 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Chimeric antigen receptors with enhanced NFκB signaling |
| JP2020536531A (ja) * | 2017-09-26 | 2020-12-17 | ロングウッド ユニバーシティーＬｏｎｇｗｏｏｄ Ｕｎｉｖｅｒｓｉｔｙ | 免疫療法としてのｐｄ１特異的キメラ抗原受容体 |
| WO2019072824A1 (en) * | 2017-10-09 | 2019-04-18 | Cellectis | IMPROVED ANTI-CD123 CAR IN UNIVERSAL MODIFIED IMMUNE T LYMPHOCYTES |
| KR20200086278A (ko) | 2017-10-18 | 2020-07-16 | 노파르티스 아게 | 선택적 단백질 분해를 위한 조성물 및 방법 |
| CN109694854B (zh) * | 2017-10-20 | 2023-11-21 | 亘喜生物科技（上海）有限公司 | 通用型嵌合抗原受体t细胞制备技术 |
| AU2018355427A1 (en) | 2017-10-25 | 2020-04-30 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| US12258580B2 (en) | 2017-11-01 | 2025-03-25 | Juno Therapeutics, Inc. | Process for generating therapeutic compositions of engineered cells |
| US12031975B2 (en) | 2017-11-01 | 2024-07-09 | Juno Therapeutics, Inc. | Methods of assessing or monitoring a response to a cell therapy |
| US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
| KR20200085828A (ko) | 2017-11-08 | 2020-07-15 | 젠코어 인코포레이티드 | 신규의 항-pd-1 서열을 사용한 이중특이적 및 단일특이적 항체 |
| KR20200096253A (ko) * | 2017-11-30 | 2020-08-11 | 노파르티스 아게 | Bcma-표적화 키메라 항원 수용체, 및 이의 용도 |
| WO2019109053A1 (en) | 2017-12-01 | 2019-06-06 | Juno Therapeutics, Inc. | Methods for dosing and for modulation of genetically engineered cells |
| AU2018379094B2 (en) | 2017-12-08 | 2025-09-25 | Juno Therapeutics, Inc. | Phenotypic markers for cell therapy and related methods |
| MA51291A (fr) | 2017-12-19 | 2020-10-28 | Xencor Inc | Protéines de fusion il-2 fc modifiées |
| CN111247429B (zh) | 2017-12-21 | 2025-03-28 | 豪夫迈·罗氏有限公司 | 用于新颖抗原结合模块的特异性测试的通用报告细胞测定法 |
| CN111492243B (zh) | 2017-12-21 | 2024-11-01 | 豪夫迈·罗氏有限公司 | 用于新颖抗原结合模块的特异性测试的car-t细胞测定法 |
| WO2019134950A1 (en) * | 2018-01-04 | 2019-07-11 | Miltenyi Biotec Gmbh | Chimeric antigen receptor specific for bdca2 antigen |
| WO2019144091A1 (en) | 2018-01-22 | 2019-07-25 | Endocyte, Inc. | Methods of use for car t cells |
| WO2019156795A1 (en) | 2018-02-06 | 2019-08-15 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Fluorescein-specific cars exhibiting optimal t cell function against fl-ple labelled tumors |
| JP2021518747A (ja) | 2018-02-13 | 2021-08-05 | キメラ・バイオエンジニアリング，インコーポレーテッド | Ｒｎａ不安定化エレメントを使用した遺伝子発現の調整 |
| EP3755349A4 (en) | 2018-02-21 | 2021-11-17 | Board of Regents, The University of Texas System | PROCESS FOR ACTIVATION AND EXPANSION OF NATURAL KILLER CELLS AND THEIR USES |
| JP7568224B2 (ja) | 2018-02-23 | 2024-10-16 | エンドサイト・インコーポレイテッド | Ｃａｒ ｔ細胞療法のための配列決定法 |
| WO2019166453A1 (en) * | 2018-03-01 | 2019-09-06 | F. Hoffmann-La Roche Ag | Specificity assay for novel target antigen binding moieties |
| EP3768281B1 (en) * | 2018-03-19 | 2023-07-05 | The Regents Of The University Of Michigan | Compositions and methods for t-cell and cytokine activation |
| CN112469477A (zh) | 2018-04-04 | 2021-03-09 | Xencor股份有限公司 | 与成纤维细胞活化蛋白结合的异源二聚体抗体 |
| US12090170B2 (en) | 2018-04-06 | 2024-09-17 | The Regents Of The University Of California | Methods of treating glioblastomas |
| US12144826B2 (en) | 2018-04-06 | 2024-11-19 | The Regents Of The University Of California | Methods of treating EGFRvIII expressing glioblastomas |
| AU2019256539A1 (en) | 2018-04-18 | 2020-11-26 | Xencor, Inc. | PD-1 targeted heterodimeric fusion proteins containing IL-15/IL-15Ra Fc-fusion proteins and PD-1 antigen binding domains and uses thereof |
| WO2019204655A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
| EP3784351A1 (en) | 2018-04-27 | 2021-03-03 | Novartis AG | Car t cell therapies with enhanced efficacy |
| EP3788369A1 (en) | 2018-05-01 | 2021-03-10 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
| US20210213063A1 (en) | 2018-05-25 | 2021-07-15 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
| WO2019237035A1 (en) | 2018-06-08 | 2019-12-12 | Intellia Therapeutics, Inc. | Compositions and methods for immunooncology |
| WO2019241315A1 (en) | 2018-06-12 | 2019-12-19 | Obsidian Therapeutics, Inc. | Pde5 derived regulatory constructs and methods of use in immunotherapy |
| SG11202011830SA (en) | 2018-06-13 | 2020-12-30 | Novartis Ag | Bcma chimeric antigen receptors and uses thereof |
| EP3817767A1 (en) * | 2018-07-02 | 2021-05-12 | Cellectis | Chimeric antigen receptors (car)-expressing cells and combination treatment for immunotherapy of patients with relapse refractory adverse genetic risk aml |
| AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
| KR20210031898A (ko) * | 2018-07-13 | 2021-03-23 | 난징 레전드 바이오테크 씨오., 엘티디. | 전염병을 치료하기 위한 공동수용체 시스템 |
| EP3831936A4 (en) | 2018-07-31 | 2022-04-13 | Thyas Co. Ltd. | METHOD FOR PRODUCING A REGENERATED T LYMPHOCYTE POPULATION USING IPS CELLS |
| IL314189A (en) * | 2018-08-01 | 2024-09-01 | Immunitybio Inc | A QUADRICISTRONIC SYSTEM COMPRISING A HOMING RECEPTOR OR A CYTOKINE, AND CHIMERIC ANTIGEN RECEPTOR FOR GENETIC MODIFICATION OF IMMUNOTHERAPIES- Expedited Examination |
| CN112513069A (zh) * | 2018-08-01 | 2021-03-16 | 南克维斯特公司 | 具有对于验证的靶标的二次归巢激活的趋化因子反应性激活的自然杀伤细胞 |
| US20210171909A1 (en) | 2018-08-31 | 2021-06-10 | Novartis Ag | Methods of making chimeric antigen receptor?expressing cells |
| CN112639083A (zh) | 2018-08-31 | 2021-04-09 | 诺华股份有限公司 | 制备表达嵌合抗原受体的细胞的方法 |
| US20210338727A1 (en) * | 2018-09-13 | 2021-11-04 | Nkarta, Inc. | Natural killer cell compositions and immunotherapy methods for treating tumors |
| WO2020061048A1 (en) * | 2018-09-17 | 2020-03-26 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Bicistronic chimeric antigen receptors targeting cd19 and cd20 and their uses |
| CN118291501A (zh) | 2018-09-20 | 2024-07-05 | 莱蒂恩技术公司 | 用于用抗cd123免疫治疗来治疗癌症的组合物和方法 |
| CN110950954B (zh) * | 2018-09-26 | 2021-06-25 | 重庆精准生物技术有限公司 | 抗cd123人源化单链抗体及其应用 |
| AU2019355971B2 (en) | 2018-10-03 | 2025-05-08 | Xencor, Inc. | IL-12 heterodimeric Fc-fusion proteins |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| EP3870600A1 (en) | 2018-10-24 | 2021-09-01 | Obsidian Therapeutics, Inc. | Er tunable protein regulation |
| US12257286B2 (en) | 2018-10-31 | 2025-03-25 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
| EP3873500A4 (en) | 2018-10-31 | 2023-01-11 | Mayo Foundation for Medical Education and Research | METHODS AND MATERIALS FOR THE TREATMENT OF CANCER |
| WO2020125806A1 (en) | 2018-12-17 | 2020-06-25 | Shanghai United Imaging Intelligence Co., Ltd. | Systems and methods for image segmentation |
| CN109754394B (zh) * | 2018-12-28 | 2021-02-23 | 上海联影智能医疗科技有限公司 | 三维医学图像处理装置及方法 |
| AU2019402189B2 (en) | 2018-12-20 | 2023-04-13 | Novartis Ag | Dosing regimen and pharmaceutical combination comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| BR112021015783A2 (pt) | 2019-02-15 | 2021-10-05 | Novartis Ag | Derivados de 3-(1-oxo-5-(piperidin-4-il)isoindolin-2-il)piperidina-2,6-diona e usos dos mesmos |
| CN113329792B (zh) | 2019-02-15 | 2024-06-28 | 诺华股份有限公司 | 取代的3-(1-氧代异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途 |
| CN109777783B (zh) * | 2019-02-20 | 2023-07-04 | 上海尚泰生物技术有限公司 | 表达cxcr2的car-nk92细胞、制备方法及其应用 |
| US20220088075A1 (en) | 2019-02-22 | 2022-03-24 | The Trustees Of The University Of Pennsylvania | Combination therapies of egfrviii chimeric antigen receptors and pd-1 inhibitors |
| CA3126087A1 (en) | 2019-02-25 | 2020-09-03 | Novartis Ag | Mesoporous silica particles compositions for viral delivery |
| BR112021016955A2 (pt) | 2019-03-01 | 2021-11-23 | Xencor Inc | Composição, composição de ácido nucleico, composição de vetor de expressão, vetor de expressão, célula hospedeira, métodos de produção de um domínio de ligação de membro de família 3 de pirofosfatase/fosfodiesterase de ectonucleotídeo e de tratamento de um câncer, anticorpo anti-enpp3, e, anticorpo heterodimérico |
| US20220175836A1 (en) * | 2019-03-27 | 2022-06-09 | University Of Virginia Patent Foundation | Priming with targeted activated t cells can enhance chemo responsiveness of cancer cells |
| CA3136618A1 (en) | 2019-04-10 | 2020-10-15 | Elevatebio Technologies, Inc. | Flt3-specific chimeric antigen receptors and methods of using the same |
| US20220168389A1 (en) | 2019-04-12 | 2022-06-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| WO2020210665A1 (en) * | 2019-04-12 | 2020-10-15 | St. Jude Children's Research Hospital, Inc. | Chimeric antigen receptors with cd20 safety switch |
| US20220251152A1 (en) | 2019-04-24 | 2022-08-11 | Novartis Ag | Compositions and methods for selective protein degradation |
| KR20220004076A (ko) * | 2019-04-26 | 2022-01-11 | 알로젠 테라퓨틱스 인코포레이티드 | 리툭시맙-내성 키메라 항원 수용체 및 이의 용도 |
| US11434297B2 (en) | 2019-05-04 | 2022-09-06 | Inhibrx, Inc. | CD123-binding polypeptides and uses thereof |
| UY38701A (es) | 2019-05-21 | 2020-12-31 | Novartis Ag | Moléculas de unión a cd19, conjugados, composiciones que las comprenden y usos de las mismas |
| WO2020251046A1 (ja) | 2019-06-14 | 2020-12-17 | サイアス株式会社 | 医薬組成物 |
| EP4013431A4 (en) | 2019-08-18 | 2024-05-01 | Chimera Bioengineering, Inc. | Combination therapy with gold controlled transgenes |
| AU2020337428A1 (en) * | 2019-08-27 | 2022-03-17 | Janssen Biotech, Inc. | Chimeric antigen receptor system and uses thereof |
| WO2021046451A1 (en) | 2019-09-06 | 2021-03-11 | Obsidian Therapeutics, Inc. | Compositions and methods for dhfr tunable protein regulation |
| TW202134278A (zh) | 2019-11-08 | 2021-09-16 | 美商胡曼尼根公司 | 用於治療腫瘤之ｅｐｈａ３導向ｃａｒ－ｔ細胞 |
| AU2020394441B2 (en) | 2019-11-26 | 2025-11-13 | Novartis Ag | CD19 and CD22 chimeric antigen receptors and uses thereof |
| TW202134264A (zh) | 2019-11-26 | 2021-09-16 | 瑞士商諾華公司 | 嵌合抗原受體及其用途 |
| US10980836B1 (en) | 2019-12-11 | 2021-04-20 | Myeloid Therapeutics, Inc. | Therapeutic cell compositions and methods of manufacturing and use thereof |
| AU2020406350A1 (en) | 2019-12-20 | 2022-08-11 | Novartis Ag | Uses of anti-TGF-beta antibodies and checkpoint inhibitors for the treatment of proliferative diseases |
| CA3165414A1 (en) * | 2020-01-17 | 2021-07-22 | Aetio Biotherapy, Inc. | Pro-antibody that reduces off-target toxicity |
| US11230699B2 (en) | 2020-01-28 | 2022-01-25 | Immunitybio, Inc. | Chimeric antigen receptor-modified NK-92 cells targeting EGFR super-family receptors |
| WO2021173985A2 (en) | 2020-02-27 | 2021-09-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| MX2022010685A (es) | 2020-02-27 | 2022-09-23 | Novartis Ag | Metodos de produccion de celulas que expresan receptores de antigeno quimericos. |
| US20210277149A1 (en) * | 2020-03-06 | 2021-09-09 | Mustang Bio, Inc. | Anti-idiotype antibodies and methods of using the same |
| CN113493521B (zh) * | 2020-04-03 | 2023-05-05 | 重庆精准生物技术有限公司 | 靶向cd19和cd123的双靶点嵌合抗原受体及其应用 |
| CN113493522B (zh) * | 2020-04-03 | 2023-04-28 | 重庆精准生物技术有限公司 | 双特异性嵌合抗原受体及其应用 |
| US11919956B2 (en) | 2020-05-14 | 2024-03-05 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3 |
| BR112022025026A2 (pt) | 2020-06-08 | 2023-02-14 | Janssen Biotech Inc | Ensaio baseado em células para determinar atividade de morte tumoral in vitro de células imunitárias que expressam antigénio quimérico |
| EP4165169A1 (en) | 2020-06-11 | 2023-04-19 | Novartis AG | Zbtb32 inhibitors and uses thereof |
| TW202216768A (zh) | 2020-06-22 | 2022-05-01 | 美商恩格姆生物製藥公司 | Ｌａｉｒ－１結合劑及其使用方法 |
| CA3182346A1 (en) | 2020-06-23 | 2021-12-30 | Novartis Ag | Dosing regimen comprising 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives |
| WO2022010847A1 (en) | 2020-07-07 | 2022-01-13 | Cancure, Llc | Mic antibodies and binding agents and methods of using the same |
| JP2023536164A (ja) | 2020-08-03 | 2023-08-23 | ノバルティス アーゲー | ヘテロアリール置換３－（１－オキソイソインドリン－２－イル）ピペリジン－２，６－ジオン誘導体及びその使用 |
| CN111995688B (zh) * | 2020-08-13 | 2024-01-16 | 金鑫 | 靶向cd123和nkg2d配体的双特异嵌合抗原受体及应用 |
| EP4200332A1 (en) | 2020-08-19 | 2023-06-28 | Xencor, Inc. | Anti-cd28 and/or anti-b7h3 compositions |
| MX2023002017A (es) * | 2020-08-20 | 2023-04-28 | A2 Biotherapeutics Inc | Composiciones y métodos para tratar cánceres positivos para ceacam. |
| CA3188978A1 (en) | 2020-08-21 | 2022-02-24 | Sandeep Tharian Koshy | Compositions and methods for in vivo generation of car expressing cells |
| CA3197423A1 (en) | 2020-11-04 | 2022-05-12 | Daniel Getts | Engineered chimeric fusion protein compositions and methods of use thereof |
| AU2021378316A1 (en) | 2020-11-13 | 2023-06-01 | Novartis Ag | Combination therapies with chimeric antigen receptor (car)-expressing cells |
| EP4263600A1 (en) | 2020-12-18 | 2023-10-25 | Century Therapeutics, Inc. | Chimeric antigen receptor systems with adaptable receptor specificity |
| JP2024504728A (ja) | 2021-01-26 | 2024-02-01 | サイトケアズ （シャンハイ） インコーポレイテッド | キメラ抗原受容体（ｃａｒ）構築物およびｃａｒ構築物を発現するｎｋ細胞 |
| MX2023010499A (es) | 2021-03-09 | 2023-09-18 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cldn6. |
| JP2024509274A (ja) | 2021-03-10 | 2024-02-29 | ゼンコア インコーポレイテッド | Ｃｄ３及びｇｐｃ３に結合するヘテロ二量体抗体 |
| MX2023010916A (es) | 2021-03-17 | 2023-12-14 | Myeloid Therapeutics Inc | Composiciones de proteinas de fusion quimericas modificadas por ingenieria y metodos de uso de las mismas. |
| TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途 |
| AU2022267891A1 (en) | 2021-04-27 | 2023-11-09 | Novartis Ag | Viral vector production system |
| WO2022241029A1 (en) | 2021-05-11 | 2022-11-17 | Myeloid Therapeutics, Inc. | Methods and compositions for genomic integration |
| EP4349857A4 (en) | 2021-05-25 | 2025-06-11 | Vaxcell-Bio | Monobody-based chimeric antigen receptor and immune cell including same |
| WO2022267843A1 (en) * | 2021-06-21 | 2022-12-29 | Westlake University | Library construction method based on long overhang sequence ligation |
| JP2024528086A (ja) * | 2021-07-29 | 2024-07-26 | ブイオーアール バイオファーマ インコーポレーテッド | がん治療用キメラ抗原受容体 |
| CN114933654B (zh) * | 2021-08-16 | 2024-09-06 | 上海优替济生生物医药有限公司 | 靶向cd123的抗体、嵌合抗原受体及其用途 |
| AR126838A1 (es) | 2021-08-20 | 2023-11-22 | Novartis Ag | Métodos para preparar células que expresan receptores de antígeno quiméricos |
| US20230338424A1 (en) * | 2022-03-02 | 2023-10-26 | Lentigen Technology, Inc. | Compositions and Methods for Treating Cancer with Anti-CD123 Immunotherapy |
| WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
| AU2023369684A1 (en) | 2022-10-26 | 2025-04-17 | Novartis Ag | Lentiviral formulations |
| WO2024094004A1 (zh) * | 2022-11-03 | 2024-05-10 | 重庆精准生物技术有限公司 | 靶向cd123的全人源抗体及其应用 |
| CN121002061A (zh) * | 2023-01-12 | 2025-11-21 | 弗吉尼亚大学专利基金委员会 | 抗cith3抗体及其用途 |
| CN116836282B (zh) * | 2023-02-13 | 2024-03-29 | 北京艺妙神州医药科技有限公司 | 抗体、嵌合抗原受体及其用途 |
| CN120981456A (zh) | 2023-05-24 | 2025-11-18 | 金橘生物科技公司 | 杂环化合物及其用途 |
| CN116990504B (zh) * | 2023-09-27 | 2023-12-01 | 苏州旭光科星抗体生物科技有限公司 | 检测人可溶性cd4的双抗体夹心酶联免疫试剂盒 |
Family Cites Families (410)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA737247B (en) | 1972-09-29 | 1975-04-30 | Ayerst Mckenna & Harrison | Rapamycin and process of preparation |
| US4433059A (en) | 1981-09-08 | 1984-02-21 | Ortho Diagnostic Systems Inc. | Double antibody conjugate |
| US4444878A (en) | 1981-12-21 | 1984-04-24 | Boston Biomedical Research Institute, Inc. | Bispecific antibody determinants |
| EP0090505B1 (en) | 1982-03-03 | 1990-08-08 | Genentech, Inc. | Human antithrombin iii, dna sequences therefor, expression vehicles and cloning vectors containing such sequences and cell cultures transformed thereby, a process for expressing human antithrombin iii, and pharmaceutical compositions comprising it |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| US5869620A (en) | 1986-09-02 | 1999-02-09 | Enzon, Inc. | Multivalent antigen-binding proteins |
| US5906936A (en) | 1988-05-04 | 1999-05-25 | Yeda Research And Development Co. Ltd. | Endowing lymphocytes with antibody specificity |
| JPH021556A (ja) | 1988-06-09 | 1990-01-05 | Snow Brand Milk Prod Co Ltd | ハイブリッド抗体及びその作製方法 |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| AU4308689A (en) | 1988-09-02 | 1990-04-02 | Protein Engineering Corporation | Generation and selection of recombinant varied binding proteins |
| US6303121B1 (en) | 1992-07-30 | 2001-10-16 | Advanced Research And Technology | Method of using human receptor protein 4-1BB |
| 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 |
| 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 |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
| 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 |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
| AU6290090A (en) | 1989-08-29 | 1991-04-08 | University Of Southampton | Bi-or trispecific (fab)3 or (fab)4 conjugates |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| US5273743A (en) | 1990-03-09 | 1993-12-28 | Hybritech Incorporated | Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9012995D0 (en) | 1990-06-11 | 1990-08-01 | Celltech Ltd | Multivalent antigen-binding proteins |
| JPH06508511A (ja) | 1990-07-10 | 1994-09-29 | ケンブリッジ アンティボディー テクノロジー リミティド | 特異的な結合ペアーの構成員の製造方法 |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| DK0564531T3 (da) | 1990-12-03 | 1998-09-28 | Genentech Inc | Berigelsesfremgangsmåde for variantproteiner med ændrede bindingsegenskaber |
| US5582996A (en) | 1990-12-04 | 1996-12-10 | The Wistar Institute Of Anatomy & Biology | Bifunctional antibodies and method of preparing same |
| KR100246529B1 (ko) | 1990-12-14 | 2000-04-01 | 스티븐 에이. 서윈. 엠.디. | 수용체 관련된 신호 변환 경로를 위한 키메라 사슬 |
| US6319494B1 (en) | 1990-12-14 | 2001-11-20 | Cell Genesys, Inc. | Chimeric chains for receptor-associated signal transduction pathways |
| JP4146512B2 (ja) | 1991-03-01 | 2008-09-10 | ダイアックス コープ． | 小型タンパク質 |
| IL101147A (en) | 1991-03-07 | 2004-06-20 | Gen Hospital Corp | Redirection of cellular immunity by receptor chimeras |
| US7049136B2 (en) | 1991-03-07 | 2006-05-23 | The General Hospital Corporation | Redirection of cellular immunity by receptor chimeras |
| US6004811A (en) | 1991-03-07 | 1999-12-21 | The Massachussetts General Hospital | Redirection of cellular immunity by protein tyrosine kinase chimeras |
| ES2223040T3 (es) | 1991-04-10 | 2005-02-16 | The Scripps Research Institute | Bibliotecas de receptor heterodimerilo que usan fagemidos. |
| WO1992018628A1 (en) | 1991-04-19 | 1992-10-29 | Schering Corporation | Subunit of the human interleukin-3 receptor |
| EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
| DE4118120A1 (de) | 1991-06-03 | 1992-12-10 | Behringwerke Ag | Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung |
| US5199942A (en) | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
| US6511663B1 (en) | 1991-06-11 | 2003-01-28 | Celltech R&D Limited | Tri- and tetra-valent monospecific antigen-binding proteins |
| CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
| US5637481A (en) | 1993-02-01 | 1997-06-10 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
| DE4122599C2 (de) | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5932448A (en) | 1991-11-29 | 1999-08-03 | Protein Design Labs., Inc. | Bispecific antibody heterodimers |
| EP0571613B1 (en) | 1991-12-13 | 2003-09-17 | Xoma Corporation | Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof |
| KR100254759B1 (ko) | 1992-01-23 | 2000-05-01 | 플레믹 크리스티안 | 단량체 및 이량체 항체-단편 융합 단백질 |
| EP1514934B1 (en) | 1992-02-06 | 2008-12-31 | Novartis Vaccines and Diagnostics, Inc. | Biosynthetic binding protein for cancer marker |
| GB9203459D0 (en) | 1992-02-19 | 1992-04-08 | Scotgen Ltd | Antibodies with germ-line variable regions |
| US8211422B2 (en) | 1992-03-18 | 2012-07-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric receptor genes and cells transformed therewith |
| IL104570A0 (en) | 1992-03-18 | 1993-05-13 | Yeda Res & Dev | Chimeric genes and cells transformed therewith |
| ATE165113T1 (de) | 1992-05-08 | 1998-05-15 | Creative Biomolecules Inc | Mehrwertige chimäre proteine anologe und verfahren zu deren anwendungen |
| US6005079A (en) | 1992-08-21 | 1999-12-21 | Vrije Universiteit Brussels | Immunoglobulins devoid of light chains |
| DE69330523T4 (de) | 1992-08-21 | 2012-08-23 | Vrije Universiteit Brussel | Immunoglobuline ohne leichte ketten |
| 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 |
| DE69334287D1 (de) | 1992-09-25 | 2009-07-09 | Avipep Pty Ltd | Zielmoleküle-bindende Polypeptide bestehend aus einer IG-artigen VL Domäne die an eine IG-artige VH Domäne gebunden ist |
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| GB9221657D0 (en) | 1992-10-15 | 1992-11-25 | Scotgen Ltd | Recombinant bispecific antibodies |
| EP0627932B1 (en) | 1992-11-04 | 2002-05-08 | City Of Hope | Antibody construct |
| GB9323648D0 (en) | 1992-11-23 | 1994-01-05 | Zeneca Ltd | Proteins |
| JP3720353B2 (ja) | 1992-12-04 | 2005-11-24 | メディカル リサーチ カウンシル | 多価および多重特異性の結合タンパク質、それらの製造および使用 |
| US7211259B1 (en) | 1993-05-07 | 2007-05-01 | Immunex Corporation | 4-1BB polypeptides and DNA encoding 4-1BB polypeptides |
| US6476198B1 (en) | 1993-07-13 | 2002-11-05 | The Scripps Research Institute | Multispecific and multivalent antigen-binding polypeptide molecules |
| US5635602A (en) | 1993-08-13 | 1997-06-03 | The Regents Of The University Of California | Design and synthesis of bispecific DNA-antibody conjugates |
| WO1995009917A1 (en) | 1993-10-07 | 1995-04-13 | The Regents Of The University Of California | Genetically engineered bispecific tetravalent antibodies |
| JP4105761B2 (ja) | 1993-11-19 | 2008-06-25 | アボット・ラボラトリーズ | ラパミシン（マクロライド）の半合成類似体免疫調節剤 |
| JP3745772B2 (ja) | 1993-12-17 | 2006-02-15 | ノバルティス アクチエンゲゼルシャフト | 免疫抑制剤として有用なラパマイシン誘導体 |
| US5362718A (en) | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| AU694222B2 (en) | 1994-05-02 | 1998-07-16 | Bernd Groner | Bifunctional protein, preparation and use |
| US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
| US5786464C1 (en) | 1994-09-19 | 2012-04-24 | Gen Hospital Corp | Overexpression of mammalian and viral proteins |
| EP0787185A2 (en) | 1994-10-20 | 1997-08-06 | MorphoSys AG | Targeted hetero-association of recombinant proteins to multi-functional complexes |
| US5712149A (en) | 1995-02-03 | 1998-01-27 | Cell Genesys, Inc. | Chimeric receptor molecules for delivery of co-stimulatory signals |
| US6103521A (en) | 1995-02-06 | 2000-08-15 | Cell Genesys, Inc. | Multispecific chimeric receptors |
| WO1996025953A1 (en) | 1995-02-24 | 1996-08-29 | The General Hospital Corporation | Redirection of cellular immunity by receptor chimeras |
| 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 |
| JPH11508126A (ja) | 1995-05-23 | 1999-07-21 | モルフォシス ゲゼルシャフト ファー プロテインオプティマイルング エムベーハー | 多量体タンパク質 |
| JP3226545B2 (ja) | 1995-06-09 | 2001-11-05 | ノバルティス・アクチエンゲゼルシャフト | ラパマイシン誘導体 |
| BE1009856A5 (fr) | 1995-07-14 | 1997-10-07 | Sandoz Sa | Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule. |
| EP0799244A1 (en) | 1995-10-16 | 1997-10-08 | Unilever N.V. | A bifunctional or bivalent antibody fragment analogue |
| GB9526131D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Recombinant chimeric receptors |
| US6177078B1 (en) | 1995-12-29 | 2001-01-23 | Medvet Science Pty Limited | Monoclonal antibody antagonists to IL-3 |
| US5874240A (en) | 1996-03-15 | 1999-02-23 | Human Genome Sciences, Inc. | Human 4-1BB receptor splicing variant |
| JP2000508892A (ja) | 1996-04-04 | 2000-07-18 | ユニリーバー・ナームローゼ・ベンノートシャープ | 多価および多特異的抗原結合タンパク |
| WO1998002441A2 (en) | 1996-07-12 | 1998-01-22 | Ariad Pharmaceuticals, Inc. | Non immunosuppressive antifungal rapalogs |
| US6111090A (en) | 1996-08-16 | 2000-08-29 | Schering Corporation | Mammalian cell surface antigens; related reagents |
| JP4440344B2 (ja) | 1996-08-16 | 2010-03-24 | シェーリング コーポレイション | 哺乳動物細胞表面抗原；関連試薬 |
| US6114148C1 (en) | 1996-09-20 | 2012-05-01 | Gen Hospital Corp | High level expression of proteins |
| WO1998018809A1 (en) | 1996-10-25 | 1998-05-07 | Cell Genesys, Inc. | Targeted cytolysis of cancer cells |
| WO1998031700A1 (en) | 1997-01-21 | 1998-07-23 | The General Hospital Corporation | Selection of proteins using rna-protein fusions |
| JP2002505574A (ja) | 1997-04-30 | 2002-02-19 | エンゾン，インコーポレイテッド | ポリアルキレンオキシド修飾された単鎖ポリペプチド |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| US20030207346A1 (en) | 1997-05-02 | 2003-11-06 | William R. Arathoon | Method for making multispecific antibodies having heteromultimeric and common components |
| ES2231991T3 (es) | 1997-06-11 | 2005-05-16 | Borean Pharma A/S | Modulo de trimerizacion. |
| CA2293632C (en) | 1997-06-12 | 2011-11-29 | Research Corporation Technologies, Inc. | Artificial antibody polypeptides |
| GB9713473D0 (en) | 1997-06-25 | 1997-09-03 | Celltech Therapeutics Ltd | Biological products |
| US20030060444A1 (en) | 1997-06-25 | 2003-03-27 | Celltech Therapeutics, Ltd. | Cell activation process and reagents therefor |
| US6015815A (en) | 1997-09-26 | 2000-01-18 | Abbott Laboratories | Tetrazole-containing rapamycin analogs with shortened half-lives |
| TW557297B (en) | 1997-09-26 | 2003-10-11 | Abbott Lab | Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same |
| CA2308114A1 (en) | 1997-10-21 | 1999-04-29 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like proteins tr11, tr11sv1, and tr11sv2 |
| US6670453B2 (en) | 1997-10-27 | 2003-12-30 | Unilever Patent Holdings B.V. | Multivalent antigen-binding proteins |
| WO1999037791A1 (en) | 1998-01-23 | 1999-07-29 | Vlaams Interuniversitair Instituut Voor Biotechnologie | Multipurpose antibody derivatives |
| JP2002502607A (ja) | 1998-02-09 | 2002-01-29 | ジェネンテク・インコーポレイテッド | 新規な腫瘍壊死因子レセプター相同体及びそれをコードする核酸 |
| CZ121599A3 (cs) | 1998-04-09 | 1999-10-13 | Aventis Pharma Deutschland Gmbh | Jednořetězcová molekula vázající několik antigenů, způsob její přípravy a léčivo obsahující tuto molekulu |
| DE69925909T2 (de) | 1998-04-15 | 2006-05-11 | Brigham & Women's Hospital, Inc., Boston | T-zell inhibierende rezeptorzusammensetzungen sowie deren verwendung |
| DE19819846B4 (de) | 1998-05-05 | 2016-11-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Multivalente Antikörper-Konstrukte |
| GB9809658D0 (en) | 1998-05-06 | 1998-07-01 | Celltech Therapeutics Ltd | Biological products |
| GB9812545D0 (en) | 1998-06-10 | 1998-08-05 | Celltech Therapeutics Ltd | Biological products |
| AU5728999A (en) | 1998-07-28 | 2000-02-21 | Micromet Ag | Heterominibodies |
| JP2002524081A (ja) | 1998-09-04 | 2002-08-06 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | 前立腺−特異的膜抗原に特異的な融合受容体およびその使用 |
| US6410319B1 (en) | 1998-10-20 | 2002-06-25 | City Of Hope | CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies |
| US6333396B1 (en) | 1998-10-20 | 2001-12-25 | Enzon, Inc. | Method for targeted delivery of nucleic acids |
| JP2002541845A (ja) | 1999-04-16 | 2002-12-10 | セルテック セラピューティックス リミテッド | 合成膜貫通成分 |
| US7527787B2 (en) | 2005-10-19 | 2009-05-05 | Ibc Pharmaceuticals, Inc. | Multivalent immunoglobulin-based bioactive assemblies |
| US7534866B2 (en) | 2005-10-19 | 2009-05-19 | Ibc Pharmaceuticals, Inc. | Methods and compositions for generating bioactive assemblies of increased complexity and uses |
| DK1196186T3 (da) | 1999-07-12 | 2008-03-03 | Genentech Inc | Stimulering eller inhibering af angiogenese og kardiovaskularisation med tumornekrosefaktorligand/receptorhomologer |
| EP1212331B1 (en) | 1999-08-24 | 2004-04-21 | Ariad Gene Therapeutics, Inc. | 28-epirapalogs |
| WO2001029058A1 (en) | 1999-10-15 | 2001-04-26 | University Of Massachusetts | Rna interference pathway genes as tools for targeted genetic interference |
| GB9925848D0 (en) | 1999-11-01 | 1999-12-29 | Celltech Therapeutics Ltd | Biological products |
| US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
| US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| EP1257632B1 (en) | 2000-02-24 | 2007-09-12 | 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 |
| AU5003001A (en) | 2000-03-06 | 2001-09-17 | Univ Kentucky Res Found | Methods to impair hematologic cancer progenitor cells and compounds related thereto |
| US20020004587A1 (en) | 2000-04-11 | 2002-01-10 | Genentech, Inc. | Multivalent antibodies and uses therefor |
| EP1299419A2 (en) | 2000-05-24 | 2003-04-09 | Imclone Systems, Inc. | Bispecific immunoglobulin-like antigen binding proteins and method of production |
| IL136511A0 (en) | 2000-06-01 | 2001-06-14 | Gavish Galilee Bio Appl Ltd | Genetically engineered mhc molecules |
| WO2001096584A2 (en) | 2000-06-12 | 2001-12-20 | Akkadix Corporation | Materials and methods for the control of nematodes |
| CA2410551A1 (en) | 2000-06-30 | 2002-01-10 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw (Vib) | Heterodimeric fusion proteins |
| ATE545703T1 (de) | 2000-07-25 | 2012-03-15 | Immunomedics Inc | Multivalentes zielbindendes protein |
| GB0025307D0 (en) | 2000-10-16 | 2000-11-29 | Celltech Chiroscience Ltd | Biological products |
| US20040242847A1 (en) | 2000-10-20 | 2004-12-02 | Naoshi Fukushima | Degraded agonist antibody |
| CA2427858A1 (en) * | 2000-11-03 | 2002-05-10 | University Of Vermont And State Agricultural College | Compositions for inhibiting grb7 |
| US7446179B2 (en) | 2000-11-07 | 2008-11-04 | City Of Hope | CD19-specific chimeric T cell receptor |
| US7829084B2 (en) | 2001-01-17 | 2010-11-09 | Trubion Pharmaceuticals, Inc. | Binding constructs and methods for use thereof |
| AU2002247826A1 (en) | 2001-03-13 | 2002-09-24 | University College London | Specific binding members |
| 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 |
| US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
| US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
| AU2002256390B2 (en) | 2001-04-30 | 2007-08-30 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
| US7514537B2 (en) | 2001-04-30 | 2009-04-07 | City Of Hope | Chimeric immunoreceptor useful in treating human gliomas |
| EP1399484B1 (en) | 2001-06-28 | 2010-08-11 | Domantis Limited | Dual-specific ligand and its use |
| US6833441B2 (en) | 2001-08-01 | 2004-12-21 | Abmaxis, Inc. | Compositions and methods for generating chimeric heteromultimers |
| JP5133494B2 (ja) | 2001-08-10 | 2013-01-30 | アバディーン ユニバーシティ | 抗原結合ドメイン |
| EP1293514B1 (en) | 2001-09-14 | 2006-11-29 | Affimed Therapeutics AG | Multimeric single chain tandem Fv-antibodies |
| JP4578098B2 (ja) | 2001-10-01 | 2010-11-10 | ダイアックス、コープ | 多重鎖真核ディスプレイベクターとその使用 |
| US20030148982A1 (en) | 2001-11-13 | 2003-08-07 | Brenner Malcolm K. | Bi-spcific chimeric T cells |
| WO2003049684A2 (en) | 2001-12-07 | 2003-06-19 | Centocor, Inc. | Pseudo-antibody constructs |
| US7638326B2 (en) | 2002-01-03 | 2009-12-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform |
| US7670781B2 (en) | 2002-01-03 | 2010-03-02 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an agent that provides a primary activation signal and another agent that provides a co-stimulatory signal |
| US7745140B2 (en) | 2002-01-03 | 2010-06-29 | The Trustees Of The University Of Pennsylvania | Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool |
| ES2485841T3 (es) | 2002-02-01 | 2014-08-14 | Ariad Pharmaceuticals, Inc | Compuestos que contienen fósforo y usos de los mismos |
| EP1487879B1 (en) | 2002-03-01 | 2012-12-26 | Immunomedics, Inc. | Bispecific antibody point mutations for enhancing rate of clearance |
| GB0208104D0 (en) | 2002-04-09 | 2002-05-22 | Univ Dundee | Method |
| JP4386741B2 (ja) | 2002-04-15 | 2009-12-16 | 中外製薬株式会社 | ｓｃＤｂライブラリーの作成方法 |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| US20040047858A1 (en) | 2002-09-11 | 2004-03-11 | Blumberg Richard S. | Therapeutic anti-BGP(C-CAM1) antibodies and uses thereof |
| MXPA05006828A (es) | 2002-12-23 | 2005-09-08 | Wyeth Corp | Anticuerpos contra pd-1, y sus usos. |
| GB0230203D0 (en) | 2002-12-27 | 2003-02-05 | Domantis Ltd | Fc fusion |
| US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
| GB0305702D0 (en) | 2003-03-12 | 2003-04-16 | Univ Birmingham | Bispecific antibodies |
| US20050003403A1 (en) | 2003-04-22 | 2005-01-06 | Rossi Edmund A. | Polyvalent protein complex |
| MXPA05012475A (es) | 2003-05-23 | 2006-05-25 | Wyeth Corp | Anticuerpos y moleculas relacionadas con el ligando para el receptor tnf inducido por glucorticoides (gitr) y el ligando (gitr) y usos de los mismos. |
| US20050163782A1 (en) | 2003-06-27 | 2005-07-28 | Biogen Idec Ma Inc. | Modified binding molecules comprising connecting peptides |
| US20050100543A1 (en) | 2003-07-01 | 2005-05-12 | Immunomedics, Inc. | Multivalent carriers of bi-specific antibodies |
| WO2005007190A1 (en) | 2003-07-11 | 2005-01-27 | Schering Corporation | Agonists or antagonists of the clucocorticoid-induced tumour necrosis factor receptor (gitr) or its ligand for the treatment of immune disorders, infections and cancer |
| US7696322B2 (en) | 2003-07-28 | 2010-04-13 | Catalent Pharma Solutions, Inc. | Fusion antibodies |
| ES2458636T3 (es) | 2003-08-18 | 2014-05-06 | Medimmune, Llc | Humanización de anticuerpos |
| WO2005019429A2 (en) | 2003-08-22 | 2005-03-03 | Potentia Pharmaceuticals, Inc. | Compositions and methods for enhancing phagocytosis or phagocyte activity |
| AU2004280333A1 (en) | 2003-08-22 | 2005-04-21 | Medimmune, Llc | Humanization of antibodies |
| CA2542046A1 (en) | 2003-10-08 | 2005-04-21 | Kyowa Hakko Kogyo Co., Ltd. | Fused protein composition |
| US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
| US20050113564A1 (en) | 2003-11-05 | 2005-05-26 | St. Jude Children's Research Hospital | Chimeric receptors with 4-1BB stimulatory signaling domain |
| US7220755B2 (en) | 2003-11-12 | 2007-05-22 | Biosensors International Group, Ltd. | 42-O-alkoxyalkyl rapamycin derivatives and compositions comprising same |
| EP1692318A4 (en) | 2003-12-02 | 2008-04-02 | Genzyme Corp | COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF LUNG CANCER |
| AU2004308439A1 (en) | 2003-12-22 | 2005-07-14 | Centocor, Inc. | Methods for generating multimeric molecules |
| GB0329825D0 (en) | 2003-12-23 | 2004-01-28 | Celltech R&D Ltd | Biological products |
| US20050266425A1 (en) | 2003-12-31 | 2005-12-01 | Vaccinex, Inc. | Methods for producing and identifying multispecific antibodies |
| US8383575B2 (en) | 2004-01-30 | 2013-02-26 | Paul Scherrer Institut | (DI)barnase-barstar complexes |
| GB0409799D0 (en) | 2004-04-30 | 2004-06-09 | Isis Innovation | Method of generating improved immune response |
| US7754482B2 (en) | 2004-05-27 | 2010-07-13 | The Trustees Of The University Of Pennsylvania | Artificial antigen presenting cells and uses therefor |
| WO2006083289A2 (en) | 2004-06-04 | 2006-08-10 | Duke University | Methods and compositions for enhancement of immunity by in vivo depletion of immunosuppressive cell activity |
| EP1786918A4 (en) | 2004-07-17 | 2009-02-11 | Imclone Systems Inc | NEW BISPECIFIC ANTIBODY TETRAVALENT |
| AU2005282700A1 (en) | 2004-09-02 | 2006-03-16 | Genentech, Inc. | Heteromultimeric molecules |
| WO2006036445A2 (en) | 2004-09-24 | 2006-04-06 | Trustees Of Dartmouth College | Chimeric nk receptor and methods for treating cancer |
| EP1827604B1 (en) | 2004-12-10 | 2019-11-20 | Peter MacCallum Cancer Institute | Methods and compositions for adoptive immunotherapy |
| DK1866339T3 (da) | 2005-03-25 | 2013-09-02 | Gitr Inc | GTR-bindende molekyler og anvendelser heraf |
| EP3050963B1 (en) | 2005-03-31 | 2019-09-18 | Chugai Seiyaku Kabushiki Kaisha | Process for production of polypeptide by regulation of assembly |
| CN101484182B (zh) | 2005-04-06 | 2014-06-11 | Ibc药品公司 | 由同二聚体、同四聚体或二聚体的二聚体组成的稳定连接复合体的生产方法及用途 |
| JP5838021B2 (ja) | 2005-04-15 | 2015-12-24 | マクロジェニクス，インコーポレーテッド | 共有結合型ダイアボディとその使用 |
| JP4361545B2 (ja) | 2005-05-09 | 2009-11-11 | 小野薬品工業株式会社 | ＰｒｏｇｒａｍｍｅｄＤｅａｔｈ１（ＰＤ−１）に対するヒトモノクローナル抗体および抗ＰＤ−１抗体単独または他の免疫療法と併用した癌治療方法 |
| PT1899364T (pt) | 2005-05-17 | 2020-05-20 | Univ Connecticut | Composições e métodos para imunomodulação num organismo |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| US20060263367A1 (en) | 2005-05-23 | 2006-11-23 | Fey Georg H | Bispecific antibody devoid of Fc region and method of treatment using same |
| HRP20151102T1 (xx) | 2005-07-01 | 2015-11-20 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska antitijela za ligand programirane smrti 1 (pd-l1) |
| US20070036773A1 (en) | 2005-08-09 | 2007-02-15 | City Of Hope | Generation and application of universal T cells for B-ALL |
| US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
| CA2618482C (en) | 2005-08-19 | 2014-10-07 | Abbott Laboratories | Dual variable domain immunoglobin and uses thereof |
| EP1757622B1 (en) | 2005-08-26 | 2009-12-23 | PLS Design GmbH | Bivalent IgY antibody constructs for diagnostic and therapeutic applications |
| RS53627B1 (sr) | 2005-10-07 | 2015-04-30 | Exelixis Inc. | Derivati n-(3-amino-hinoksalin-2-il)-sulfonamida i njihova upotreba kao inhibitora fosfatidilinozitol3-kinaze |
| WO2007044887A2 (en) | 2005-10-11 | 2007-04-19 | Transtarget, Inc. | Method for producing a population of homogenous tetravalent bispecific antibodies |
| EP1962961B1 (en) | 2005-11-29 | 2013-01-09 | The University Of Sydney | Demibodies: dimerisation-activated therapeutic agents |
| ES2668464T3 (es) | 2005-12-02 | 2018-05-18 | Icahn School Of Medicine At Mount Sinai | Virus quiméricos de la enfermedad de Newcastle que presentan proteínas de superficie no naturales y sus usos |
| MX357691B (es) | 2006-01-13 | 2018-07-19 | The Government Of The United States As Represented By The Secretary Of The Department Of Health And | Il-15 y il-15r-alfa mejoradas para expresion en celulas mamiferas. |
| EP1981969A4 (en) | 2006-01-19 | 2009-06-03 | Genzyme Corp | ANTI-GITRANT ANTIBODIES FOR THE TREATMENT OF CANCER |
| EP1986684A2 (en) | 2006-02-15 | 2008-11-05 | ImClone Systems Incorporated | Functional antibodies |
| CN103073639A (zh) | 2006-03-17 | 2013-05-01 | 比奥根艾迪克Ma公司 | 稳定的多肽组合物 |
| WO2007112362A2 (en) | 2006-03-24 | 2007-10-04 | The Regents Of The University Of California | Construction of a multivalent scfv through alkyne-azide 1,3-dipolar cycloaddition |
| AR060070A1 (es) | 2006-03-24 | 2008-05-21 | Merck Patent Gmbh | Dominios proteicos heterodimericos obtenidos por ingenieria |
| ES2654040T3 (es) | 2006-03-31 | 2018-02-12 | Chugai Seiyaku Kabushiki Kaisha | Método de modificación de anticuerpos para la purificación de anticuerpos biespecíficos |
| EP2799449A1 (en) | 2006-05-25 | 2014-11-05 | Bayer Intellectual Property GmbH | Dimeric molecular complexes |
| US20070274985A1 (en) | 2006-05-26 | 2007-11-29 | Stefan Dubel | Antibody |
| MX363905B (es) | 2006-06-12 | 2019-04-08 | Aptevo Res & Development Llc | Proteinas de union multivalentes monocatenarias con funcion efectora. |
| US8497246B2 (en) | 2006-08-18 | 2013-07-30 | Armagen Technologies, Inc. | Methods for diagnosing and treating CNS disorders by trans-blood-brain barrier delivery of protein compositions |
| US10118970B2 (en) | 2006-08-30 | 2018-11-06 | Genentech, Inc. | Multispecific antibodies |
| US20100105136A1 (en) | 2006-10-09 | 2010-04-29 | The General Hospital Corporation | Chimeric t-cell receptors and t-cells targeting egfrviii on tumors |
| BRPI0716680A2 (pt) | 2006-11-02 | 2013-09-24 | Daniel J Capon | "composto, multÍmero, composiÇço, mÉtodo de afetar a atividade de um alvo, complexo, processo de produÇço do composto, mÉtodo de produÇço de um extensço de aminoÁcidos consecutivos, processo de produÇço de uma extensço de aminoacidos consecutivos , processo para a produÇço de um composto , mÉtodo de produÇço de uma proteina e polipeptÍdeo" |
| US20080131415A1 (en) | 2006-11-30 | 2008-06-05 | Riddell Stanley R | Adoptive transfer of cd8 + t cell clones derived from central memory cells |
| WO2008140621A2 (en) | 2006-12-21 | 2008-11-20 | Mount Sinai School Of Medicine Of New York University | Transgenic oncolytic viruses and uses thereof |
| EP2139924B1 (en) | 2007-03-29 | 2016-07-06 | Genmab A/S | Bispecific antibodies and methods for production thereof |
| NO2856876T3 (enExample) | 2007-03-30 | 2018-06-30 | ||
| US8163279B2 (en) | 2007-04-13 | 2012-04-24 | Stemline Therapeutics, Inc. | IL3Rα antibody conjugates and uses thereof |
| WO2008131242A1 (en) | 2007-04-18 | 2008-10-30 | Zymogenetics, Inc. | Single chain fc, methods of making and methods of treatment |
| NZ582150A (en) | 2007-06-18 | 2012-08-31 | Msd Oss Bv | Antibodies to human programmed death receptor pd-1 |
| JP2010531878A (ja) | 2007-06-27 | 2010-09-30 | マリン ポリマー テクノロジーズ，インコーポレーテッド | ＩＬ‐１５とＩＬ‐１５Ｒαとの複合体及びその使用 |
| PT2175884T (pt) | 2007-07-12 | 2016-09-21 | Gitr Inc | Terapias de combinação empregando moléculas de ligação a gitr |
| EP2069401A4 (en) | 2007-07-31 | 2011-02-23 | Medimmune Llc | MULTISPECIENT EPITOP BINDING PROTEINS AND THEIR USE |
| EP2178914A2 (en) | 2007-08-15 | 2010-04-28 | Bayer Schering Pharma Aktiengesellschaft | Monospecific and multispecific antibodies and method of use |
| US9416165B2 (en) | 2007-10-26 | 2016-08-16 | The Regents Of The University Of California | Methods of inhibiting viral replication and improving T cell function employing soluble Tim-3 inhibitors |
| EP2215123A1 (en) | 2007-11-27 | 2010-08-11 | Ablynx N.V. | Immunoglobulin constructs |
| AR069495A1 (es) | 2007-11-30 | 2010-01-27 | Glaxo Group Ltd | Construcciones de union de antigenos para el tratamiento de cancer o enfermedades inflamatorias (asma, artritis o artrosis) |
| EA201070687A1 (ru) | 2007-12-06 | 2010-12-30 | Си Эс Эл ЛИМИТЕД | Способ ингибирования лейкозных стволовых клеток |
| US9266967B2 (en) | 2007-12-21 | 2016-02-23 | Hoffmann-La Roche, Inc. | Bivalent, bispecific antibodies |
| US8242247B2 (en) | 2007-12-21 | 2012-08-14 | Hoffmann-La Roche Inc. | Bivalent, bispecific antibodies |
| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US8227577B2 (en) | 2007-12-21 | 2012-07-24 | Hoffman-La Roche Inc. | Bivalent, bispecific antibodies |
| EP3663318A1 (en) | 2008-01-07 | 2020-06-10 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| US10059923B2 (en) | 2008-01-30 | 2018-08-28 | Memorial Sloan Kettering Cancer Center | Methods for off-the-shelf tumor immunotherapy using allogeneic T-cell precursors |
| CA2715166C (en) | 2008-02-11 | 2017-05-16 | Curetech Ltd. | Monoclonal antibodies for tumor treatment |
| EP2262504A1 (en) | 2008-02-21 | 2010-12-22 | AstraZeneca AB | Combination therapy 238 |
| US8379824B2 (en) | 2008-03-06 | 2013-02-19 | At&T Intellectual Property I, Lp | Methods and apparatus to provide a network-based caller identification service in a voice over internet protocol network |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| MX2011000039A (es) | 2008-07-02 | 2011-05-31 | Emergent Product Dev Seattle | Proteinas antagonistas del factor-beta de crecimiento transformante (tgf-beta), que se unen a multiples objetivos. |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| CN102203132A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂的组合物和使用方法 |
| JP2012510429A (ja) | 2008-08-25 | 2012-05-10 | アンプリミューン、インコーポレーテッド | Ｐｄ−１アンタゴニストおよびその使用方法 |
| PT3006459T (pt) | 2008-08-26 | 2021-11-26 | Hope City | Método e composições para funcionamento melhorado de efetores antitumorais de células t |
| CN102149820B (zh) | 2008-09-12 | 2014-07-23 | 国立大学法人三重大学 | 能够表达外源gitr配体的细胞 |
| US8476282B2 (en) | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
| KR20250091300A (ko) | 2008-12-09 | 2025-06-20 | 제넨테크, 인크. | 항-ｐｄ-ｌ１ 항체 및 ｔ 세포 기능을 향상시키기 위한 그의 용도 |
| WO2010085660A2 (en) | 2009-01-23 | 2010-07-29 | Roger Williams Hospital | Viral vectors encoding multiple highly homologous non-viral polypeptides and the use of same |
| EP2393921B1 (en) | 2009-02-05 | 2015-07-15 | Icahn School of Medicine at Mount Sinai | Chimeric newcastle disease viruses and uses thereof |
| JP5844159B2 (ja) | 2009-02-09 | 2016-01-13 | ユニヴェルシテ デクス−マルセイユＵｎｉｖｅｒｓｉｔｅ Ｄ’Ａｉｘ−Ｍａｒｓｅｉｌｌｅ | Ｐｄ−１抗体およびｐｄ−ｌ１抗体ならびにその使用 |
| WO2010110346A1 (ja) | 2009-03-24 | 2010-09-30 | 独立行政法人理化学研究所 | 白血病幹細胞マーカー |
| CA2950529C (en) | 2009-04-03 | 2019-04-30 | Verastem, Inc. | Pyrimidine substituted purine compounds as kinase (s) inhibitors |
| AU2010245011B2 (en) | 2009-04-27 | 2015-09-03 | Oncomed Pharmaceuticals, Inc. | Method for making heteromultimeric molecules |
| WO2010126066A1 (ja) | 2009-04-27 | 2010-11-04 | 協和発酵キリン株式会社 | 血液腫瘍治療を目的とした抗IL-3Rα抗体 |
| ES2668874T3 (es) | 2009-04-30 | 2018-05-22 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | Anticuerpos anti-CEACAM1 y métodos de uso de los mismos |
| NZ714757A (en) | 2009-08-14 | 2018-07-27 | Us Gov Health & Human Services | Use of il-15 to increase thymic output and to treat lymphopenia |
| CN103951753B (zh) | 2009-09-03 | 2018-01-12 | 默沙东公司 | 抗‑gitr抗体 |
| CA2775155A1 (en) | 2009-10-01 | 2011-04-07 | Csl Limited | Method of treatment of philadelphia chromosome positive leukemia |
| JP5934099B2 (ja) | 2009-10-01 | 2016-06-15 | アメリカ合衆国 | 抗血管内皮増殖因子受容体−２キメラ抗原受容体及び癌の治療のためのその使用 |
| US9181527B2 (en) | 2009-10-29 | 2015-11-10 | The Trustees Of Dartmouth College | T cell receptor-deficient T cell compositions |
| GB0919054D0 (en) | 2009-10-30 | 2009-12-16 | Isis Innovation | Treatment of obesity |
| EP4049674A1 (en) | 2009-11-03 | 2022-08-31 | City of Hope | Truncated epidermal growth factor receptor (egfrt) for transduced t cell selection |
| US8956828B2 (en) | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Ｐｄ−ｌ１／ｐｄ−ｌ２の同時阻害 |
| EP2332994A1 (en) | 2009-12-09 | 2011-06-15 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Trispecific therapeutics against acute myeloid leukaemia |
| WO2011090762A1 (en) | 2009-12-29 | 2011-07-28 | Emergent Product Development Seattle, Llc | Heterodimer binding proteins and uses thereof |
| EP2531216B1 (en) | 2010-02-04 | 2019-03-27 | The Trustees Of The University Of Pennsylvania | Icos critically regulates the expansion and function of inflammatory human th17 cells |
| HUE068268T2 (hu) | 2010-04-20 | 2024-12-28 | Genmab As | Heterodimer antitest Fc-t tartalmazó fehérjék és azok elõállítási eljárásai |
| EP2582390B1 (en) | 2010-06-15 | 2014-11-19 | CSL Limited | Immunotherapeutic method involving cd123 (il-3r ) antibodies and immunostimulating complex |
| CA2802344C (en) | 2010-06-18 | 2023-06-13 | The Brigham And Women's Hospital, Inc. | Bi-specific antibodies against tim-3 and pd-1 for immunotherapy in chronic immune conditions |
| CA2803900A1 (en) | 2010-07-09 | 2012-01-12 | Exelixis, Inc. | Combinations of kinase inhibitors for the treatment of cancer |
| US9062046B2 (en) | 2010-07-16 | 2015-06-23 | Piramal Enterprises Limited | Substituted imidazoquinoline derivatives as kinase inhibitors |
| EP2596011B1 (en) | 2010-07-21 | 2018-10-03 | Sangamo Therapeutics, Inc. | Methods and compositions for modification of a hla locus |
| WO2012033885A1 (en) | 2010-09-08 | 2012-03-15 | Baylor College Of Medicine | Immunotherapy of cancer using genetically engineered gd2-specific t cells |
| NZ706016A (en) | 2010-10-27 | 2016-10-28 | Baylor College Medicine | Chimeric cd27 receptors for redirecting t cells to cd70-positive malignancies |
| PH12013501201A1 (en) | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| JP5897035B2 (ja) | 2010-12-14 | 2016-03-30 | ユニバーシティ オブ メリーランド，ボルチモア | 汎用の抗タグキメラ抗原受容体発現ｔ細胞及びがんを治療する方法 |
| EP2665521A4 (en) | 2011-01-18 | 2014-09-03 | Univ Pennsylvania | COMPOSITIONS AND METHOD FOR THE TREATMENT OF CANCER |
| ES2841983T3 (es) | 2011-03-23 | 2021-07-12 | Hutchinson Fred Cancer Res | Método y composiciones para inmunoterapia celular |
| WO2012127464A2 (en) | 2011-03-23 | 2012-09-27 | Gavish-Galilee Bio Applications Ltd | Constitutively activated t cells for use in adoptive cell therapy |
| MY160662A (en) | 2011-04-01 | 2017-03-15 | Memorial Sloan Kettering Cancer Center | T cell receptor-like antibodies specific for a wt1 peptide presented by hla-a2 |
| DK2694640T3 (da) | 2011-04-08 | 2017-11-20 | Baylor College Medicine | Reversion af effekterne af tumormikromiljø ved anvendelse af kimæriske cytokinreceptorer |
| US20130071414A1 (en) | 2011-04-27 | 2013-03-21 | Gianpietro Dotti | Engineered cd19-specific t lymphocytes that coexpress il-15 and an inducible caspase-9 based suicide gene for the treatment of b-cell malignancies |
| CN102796198A (zh) | 2011-05-26 | 2012-11-28 | 中国医学科学院血液病医院 | 抗CD3抗体Fv片段与白介素3的融合蛋白、制备方法及其用途 |
| US8841418B2 (en) | 2011-07-01 | 2014-09-23 | Cellerant Therapeutics, Inc. | Antibodies that specifically bind to TIM3 |
| ES2990023T3 (es) | 2011-07-25 | 2024-11-28 | Nationwide Childrens Hospital Inc | Productos de virus recombinantes y métodos para inhibición de la expresión de DUX4 |
| CN114835823A (zh) | 2011-07-29 | 2022-08-02 | 宾夕法尼亚大学董事会 | 转换共刺激受体 |
| WO2013023184A1 (en) | 2011-08-11 | 2013-02-14 | Intellikine, Llc | Kinase inhibitor polymorphs |
| US9833476B2 (en) | 2011-08-31 | 2017-12-05 | The Trustees Of Dartmouth College | NKP30 receptor targeted therapeutics |
| US20130108641A1 (en) | 2011-09-14 | 2013-05-02 | Sanofi | Anti-gitr antibodies |
| EP2756521A4 (en) | 2011-09-16 | 2015-04-22 | Univ Pennsylvania | RNA-MANIPULATED T-CELLS FOR THE TREATMENT OF CANCER |
| DK2755487T3 (en) | 2011-09-16 | 2019-04-08 | Baylor College Medicine | TARGETATION OF THE TUMORMICROMY ENVIRONMENT USING MANIPULATED NKT CELLS |
| WO2013054320A1 (en) | 2011-10-11 | 2013-04-18 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | Antibodies to carcinoembryonic antigen-related cell adhesion molecule (ceacam) |
| AU2012325915A1 (en) | 2011-10-20 | 2014-04-24 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-CD22 chimeric antigen receptors |
| EP3674320A3 (en) | 2011-10-27 | 2020-08-12 | Genmab A/S | Production of heterodimeric proteins |
| WO2013082366A1 (en) | 2011-12-01 | 2013-06-06 | The Brigham And Women's Hospital, Inc. | Anti-ceacam1 recombinant antibodies for cancer therapy |
| DK2794658T3 (en) | 2011-12-19 | 2017-06-19 | Synimmune Gmbh | BISPECIFIC ANTIBODY MOLECULE |
| IN2014DN06522A (enExample) | 2012-02-22 | 2015-06-12 | Univ Pennsylvania | |
| AU2013222288A1 (en) | 2012-02-22 | 2014-08-14 | The Trustees Of The University Of Pennsylvania | Use of ICOS-based CARs to enhance antitumor activity and CAR persistence |
| AU2013222267A1 (en) | 2012-02-22 | 2014-07-31 | The Trustees Of The University Of Pennsylvania | Compositions and methods for generating a persisting population of T cells useful for the treatment of cancer |
| WO2013126726A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Double transgenic t cells comprising a car and a tcr and their methods of use |
| EP4053162A1 (en) | 2012-05-18 | 2022-09-07 | Aptevo Research and Development LLC | Bispecific scfv immunofusion (bif) binding to cd123 and cd3 |
| US20160046961A1 (en) | 2012-05-25 | 2016-02-18 | Emmanuelle Charpentier | Methods and Compositions for RNA-Directed Target DNA Modification and For RNA-Directed Modulation of Transcription |
| EP2872171B1 (en) | 2012-07-13 | 2021-01-06 | The Trustees Of The University Of Pennsylvania | Toxicity management for anti-tumor activity of cars |
| CA2878862C (en) | 2012-07-13 | 2023-01-10 | The Trustees Of The University Of Pennsylvania | Methods of assessing the suitability of transduced t cells for administration |
| HK1207090A1 (en) | 2012-07-13 | 2016-01-22 | 宾夕法尼亚大学董事会 | Enhancing activity of car t cells by co-introducing a bispecific antibody |
| WO2014012001A2 (en) | 2012-07-13 | 2014-01-16 | The Trustees Of The University Of Pennsylvania | Use of cart19 to deplete normal b cells to induce tolerance |
| EP2872617A4 (en) | 2012-07-13 | 2015-12-09 | Univ Pennsylvania | EPITOP SPREADING IN CONNECTION WITH CAR T CELLS |
| CN104507537A (zh) | 2012-07-13 | 2015-04-08 | 宾夕法尼亚大学董事会 | 用于调节car t细胞的组合物和方法 |
| WO2014022332A1 (en) | 2012-07-31 | 2014-02-06 | The Brigham And Women's Hospital, Inc. | Modulation of the immune response |
| IL269270B (en) | 2012-08-20 | 2022-07-01 | Hutchinson Fred Cancer Res | Method and preparations for cellular immunotherapy |
| US9937205B2 (en) | 2012-09-04 | 2018-04-10 | The Trustees Of The University Of Pennsylvania | Inhibition of diacylglycerol kinase to augment adoptive T cell transfer |
| WO2014055442A2 (en) | 2012-10-01 | 2014-04-10 | The Trustees Of The University Of Pennsylvania | Compositions and methods for targeting stromal cells for the treatment of cancer |
| WO2014055657A1 (en) | 2012-10-05 | 2014-04-10 | The Trustees Of The University Of Pennsylvania | Use of a trans-signaling approach in chimeric antigen receptors |
| JP6401704B2 (ja) * | 2012-10-10 | 2018-10-10 | サンガモ セラピューティクス， インコーポレイテッド | Ｔ細胞を修飾する化合物およびその使用 |
| JP6356134B2 (ja) | 2012-10-12 | 2018-07-11 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドＴｈｅ Ｂｒｉｇｈａｍ ａｎｄ Ｗｏｍｅｎ’ｓ Ｈｏｓｐｉｔａｌ， Ｉｎｃ． | 免疫応答の増強 |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| CA2894668A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas systems and methods for altering expression of gene products in eukaryotic cells |
| CN105209621B (zh) | 2012-12-12 | 2021-05-25 | 布罗德研究所有限公司 | 对用于序列操纵的改进的系统、方法和酶组合物进行的工程化和优化 |
| WO2014110591A1 (en) | 2013-01-14 | 2014-07-17 | Fred Hutchinson Cancer Research Center | Compositions and methods for delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse |
| DK2958943T3 (da) | 2013-02-20 | 2019-12-09 | Univ Pennsylvania | Behandling af cancer ved anvendelse af humaniseret anti-EGFRvIII kimær antigenreceptor |
| 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 |
| US20160031996A1 (en) | 2013-03-14 | 2016-02-04 | Csl Limited | Anti il-3r alpha agents and uses thereof |
| WO2014138819A1 (en) | 2013-03-14 | 2014-09-18 | Csl Limited | Agents that neutralize il-3 signaling and uses thereof |
| MX375431B (es) | 2013-03-14 | 2025-03-06 | Icahn School Med Mount Sinai | Virus de la enfermedad de newcastle y usos de los mismos. |
| US9657105B2 (en) | 2013-03-15 | 2017-05-23 | City Of Hope | CD123-specific chimeric antigen receptor redirected T cells and methods of their use |
| ES2769574T3 (es) | 2013-03-15 | 2020-06-26 | Michael C Milone | Reconocimiento de células citotóxicas con receptores quiméricos para inmunoterapia adoptiva |
| 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 |
| US9701758B2 (en) | 2013-05-24 | 2017-07-11 | Board Of Regents, The University Of Texas System | Anti-CD19 scFv (FMC63) polypeptide |
| AU2014326674B2 (en) | 2013-09-26 | 2020-03-12 | Ablynx Nv | Bispecific nanobodies |
| US9512084B2 (en) | 2013-11-29 | 2016-12-06 | Novartis Ag | Amino pyrimidine derivatives |
| US10640569B2 (en) | 2013-12-19 | 2020-05-05 | Novartis Ag | Human mesothelin chimeric antigen receptors and uses thereof |
| US10287354B2 (en) | 2013-12-20 | 2019-05-14 | Novartis Ag | Regulatable chimeric antigen receptor |
| CN113307880B (zh) * | 2014-01-13 | 2025-07-04 | 希望之城公司 | 在Fc间隔物区中具有突变的嵌合抗原受体(CAR)及其使用方法 |
| US11028143B2 (en) | 2014-01-21 | 2021-06-08 | Novartis Ag | Enhanced antigen presenting ability of RNA CAR T cells by co-introduction of costimulatory molecules |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
| CA2939711C (en) | 2014-02-21 | 2020-09-29 | Cellectis | Method for in situ inhibition of regulatory t cells |
| EP3811970A1 (en) | 2014-03-15 | 2021-04-28 | Novartis AG | Regulatable chimeric antigen receptor |
| EP3593812A3 (en) | 2014-03-15 | 2020-05-27 | Novartis AG | Treatment of cancer using chimeric antigen receptor |
| AU2015233461B2 (en) | 2014-03-19 | 2020-03-19 | Cellectis | CD123 specific chimeric antigen receptors for cancer immunotherapy |
| KR102487608B1 (ko) | 2014-04-07 | 2023-01-12 | 노파르티스 아게 | 항-cd19 키메라 항원 수용체를 사용한 암의 치료 |
| EP3193915A1 (en) | 2014-07-21 | 2017-07-26 | Novartis AG | Combinations of low, immune enhancing. doses of mtor inhibitors and cars |
| US11542488B2 (en) | 2014-07-21 | 2023-01-03 | Novartis Ag | Sortase synthesized chimeric antigen receptors |
| US20170226495A1 (en) | 2014-07-21 | 2017-08-10 | Novartis Ag | Sortase molecules and uses thereof |
| CN107109419B (zh) | 2014-07-21 | 2020-12-22 | 诺华股份有限公司 | 使用cd33嵌合抗原受体治疗癌症 |
| RU2751660C2 (ru) | 2014-07-21 | 2021-07-15 | Новартис Аг | Лечение злокачественного новообразования с использованием гуманизированного химерного антигенного рецептора против всма |
| JP6736540B2 (ja) | 2014-07-21 | 2020-08-05 | ノバルティス アーゲー | Ｃｌｌ−１キメラ抗原受容体を使用した癌の処置 |
| US20170274014A1 (en) | 2014-07-21 | 2017-09-28 | Jennifer Brogdon | Combinations of low, immune enhancing, doses of mtor inhibitors and cars |
| EP4205749A1 (en) | 2014-07-31 | 2023-07-05 | Novartis AG | Subset-optimized chimeric antigen receptor-containing cells |
| EP3180359A1 (en) | 2014-08-14 | 2017-06-21 | Novartis AG | Treatment of cancer using gfr alpha-4 chimeric antigen receptor |
| SG11201700770PA (en) | 2014-08-19 | 2017-03-30 | Novartis Ag | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment |
| KR102804360B1 (ko) | 2014-09-17 | 2025-05-12 | 노파르티스 아게 | 입양 면역요법을 위한 키메라 수용체에 의한 세포독성 세포의 표적화 |
| AU2015330898B2 (en) | 2014-10-08 | 2022-03-10 | Novartis Ag | Biomarkers predictive of therapeutic responsiveness to chimeric antigen receptor therapy and uses thereof |
| WO2016061368A1 (en) | 2014-10-15 | 2016-04-21 | The Children's Hospital Of Philadelphia | Compositions and methods for treating b-lymphoid malignancies |
| EP3240803B1 (en) | 2014-12-29 | 2021-11-24 | Novartis AG | Methods of making chimeric antigen receptor-expressing cells |
| US11459390B2 (en) | 2015-01-16 | 2022-10-04 | Novartis Ag | Phosphoglycerate kinase 1 (PGK) promoters and methods of use for expressing chimeric antigen receptor |
| WO2016126608A1 (en) | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
| US20180140602A1 (en) | 2015-04-07 | 2018-05-24 | Novartis Ag | Combination of chimeric antigen receptor therapy and amino pyrimidine derivatives |
| CA2981751A1 (en) | 2015-04-08 | 2016-10-13 | Novartis Ag | Cd20 therapies, cd22 therapies, and combination therapies with a cd19 chimeric antigen receptor (car)- expressing cell |
| SG11201708516YA (en) | 2015-04-17 | 2017-11-29 | David Maxwell Barrett | Methods for improving the efficacy and expansion of chimeric antigen receptor-expressing cells |
| WO2016172583A1 (en) | 2015-04-23 | 2016-10-27 | Novartis Ag | Treatment of cancer using chimeric antigen receptor and protein kinase a blocker |
| US10829735B2 (en) | 2015-07-21 | 2020-11-10 | The Trustees Of The University Of Pennsylvania | Methods for improving the efficacy and expansion of immune cells |
| US11667691B2 (en) | 2015-08-07 | 2023-06-06 | Novartis Ag | Treatment of cancer using chimeric CD3 receptor proteins |
| CN108780084B (zh) | 2015-09-03 | 2022-07-22 | 诺华股份有限公司 | 预测细胞因子释放综合征的生物标志物 |
| JP7530702B2 (ja) | 2015-09-17 | 2024-08-08 | ノバルティス アーゲー | 有効性が増強されたｃａｒ ｔ細胞療法 |
| US11413340B2 (en) | 2015-12-22 | 2022-08-16 | Novartis Ag | Mesothelin chimeric antigen receptor (CAR) and antibody against PD-L1 inhibitor for combined use in anticancer therapy |
| EP3397756B1 (en) | 2015-12-30 | 2023-03-08 | Novartis AG | Immune effector cell therapies with enhanced efficacy |
| AU2017225733A1 (en) | 2016-03-04 | 2018-09-27 | Novartis Ag | Cells expressing multiple chimeric antigen receptor (CAR) molecules and uses therefore |
| EP3432924A1 (en) | 2016-03-23 | 2019-01-30 | Novartis AG | Cell secreted minibodies and uses thereof |
| EP3464375A2 (en) | 2016-06-02 | 2019-04-10 | Novartis AG | Therapeutic regimens for chimeric antigen receptor (car)- expressing cells |
| JP7219376B2 (ja) | 2016-07-15 | 2023-02-08 | ノバルティス アーゲー | キメラ抗原受容体をキナーゼ阻害薬と併用して使用したサイトカイン放出症候群の治療及び予防 |
| EP3491016A1 (en) | 2016-07-28 | 2019-06-05 | Novartis AG | Combination therapies of chimeric antigen receptors and pd-1 inhibitors |
| RU2019105693A (ru) | 2016-08-01 | 2020-09-01 | Новартис Аг | Лечение рака с применением химерного антигенного рецептора в комбинации с ингибитором молекулы, способствующей фенотипу m2 макрофага |
| US20190298715A1 (en) | 2016-09-30 | 2019-10-03 | Novartis Ag | Immune effector cell therapies with enhanced efficacy |
| MX2019003886A (es) | 2016-10-07 | 2019-08-05 | Novartis Ag | Receptores de antigenos quimericos para el tratamiento del cancer. |
| US20190375815A1 (en) | 2017-01-31 | 2019-12-12 | Novartis Ag | Treatment of cancer using chimeric t cell receptor proteins having multiple specificities |
| EP3589647A1 (en) | 2017-02-28 | 2020-01-08 | Novartis AG | Shp inhibitor compositions and uses for chimeric antigen receptor therapy |
| BR112019019426A2 (pt) | 2017-03-22 | 2020-05-26 | Novartis Ag | Biomarcadores e terapias com células t car com eficácia intensificada |
| US20200055948A1 (en) | 2017-04-28 | 2020-02-20 | Novartis Ag | Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor |
| EP3615068A1 (en) | 2017-04-28 | 2020-03-04 | Novartis AG | Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor |
| KR20200086278A (ko) | 2017-10-18 | 2020-07-16 | 노파르티스 아게 | 선택적 단백질 분해를 위한 조성물 및 방법 |
| AU2018355427A1 (en) | 2017-10-25 | 2020-04-30 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| JP2021502979A (ja) | 2017-11-15 | 2021-02-04 | ノバルティス アーゲー | Ｂｃｍａターゲティングキメラ抗原受容体、ｃｄ１９ターゲティングキメラ抗原受容体及び併用療法 |
| KR20200096253A (ko) | 2017-11-30 | 2020-08-11 | 노파르티스 아게 | Bcma-표적화 키메라 항원 수용체, 및 이의 용도 |
| WO2019160956A1 (en) | 2018-02-13 | 2019-08-22 | Novartis Ag | Chimeric antigen receptor therapy in combination with il-15r and il15 |
| US20200061113A1 (en) | 2018-04-12 | 2020-02-27 | Novartis Ag | Chimeric antigen receptor therapy characterization assays and uses thereof |
| EP3784351A1 (en) | 2018-04-27 | 2021-03-03 | Novartis AG | Car t cell therapies with enhanced efficacy |
| EP3788369A1 (en) | 2018-05-01 | 2021-03-10 | Novartis Ag | Biomarkers for evaluating car-t cells to predict clinical outcome |
| US20200085869A1 (en) | 2018-05-16 | 2020-03-19 | Novartis Ag | Therapeutic regimens for chimeric antigen receptor therapies |
| US20210213063A1 (en) | 2018-05-25 | 2021-07-15 | Novartis Ag | Combination therapy with chimeric antigen receptor (car) therapies |
| SG11202011830SA (en) | 2018-06-13 | 2020-12-30 | Novartis Ag | Bcma chimeric antigen receptors and uses thereof |
| US20210171909A1 (en) | 2018-08-31 | 2021-06-10 | Novartis Ag | Methods of making chimeric antigen receptor?expressing cells |
| EP3856779A1 (en) | 2018-09-28 | 2021-08-04 | Novartis AG | Cd22 chimeric antigen receptor (car) therapies |
| EP3856782A1 (en) | 2018-09-28 | 2021-08-04 | Novartis AG | Cd19 chimeric antigen receptor (car) and cd22 car combination therapies |
| CA3126087A1 (en) | 2019-02-25 | 2020-09-03 | Novartis Ag | Mesoporous silica particles compositions for viral delivery |
| US20220168389A1 (en) | 2019-04-12 | 2022-06-02 | Novartis Ag | Methods of making chimeric antigen receptor-expressing cells |
| TW202134264A (zh) | 2019-11-26 | 2021-09-16 | 瑞士商諾華公司 | 嵌合抗原受體及其用途 |
| AU2020394441B2 (en) | 2019-11-26 | 2025-11-13 | Novartis Ag | CD19 and CD22 chimeric antigen receptors and uses thereof |
-
2015
- 2015-08-19 SG SG11201700770PA patent/SG11201700770PA/en unknown
- 2015-08-19 US US14/830,392 patent/US9815901B2/en active Active
- 2015-08-19 LT LTEP15756525.0T patent/LT3183268T/lt unknown
- 2015-08-19 CA CA2958553A patent/CA2958553A1/en active Pending
- 2015-08-19 EP EP15756525.0A patent/EP3183268B1/en active Active
- 2015-08-19 RU RU2020117196A patent/RU2020117196A/ru unknown
- 2015-08-19 CN CN201580056515.6A patent/CN107108744B/zh active Active
- 2015-08-19 EP EP19219069.2A patent/EP3712171A1/en not_active Withdrawn
- 2015-08-19 RU RU2017108903A patent/RU2724999C2/ru active
- 2015-08-19 WO PCT/US2015/045898 patent/WO2016028896A1/en not_active Ceased
- 2015-08-19 TW TW104127072A patent/TWI719946B/zh active
- 2015-08-19 TW TW110102298A patent/TW202140557A/zh unknown
- 2015-08-19 AU AU2015305531A patent/AU2015305531B2/en active Active
- 2015-08-19 MX MX2017002205A patent/MX2017002205A/es unknown
- 2015-08-19 HU HUE15756525A patent/HUE049218T2/hu unknown
- 2015-08-19 MY MYPI2017700355A patent/MY189028A/en unknown
- 2015-08-19 CN CN202010892861.0A patent/CN112410363A/zh active Pending
- 2015-08-19 PT PT157565250T patent/PT3183268T/pt unknown
- 2015-08-19 ES ES15756525T patent/ES2791248T3/es active Active
- 2015-08-19 PL PL15756525T patent/PL3183268T3/pl unknown
- 2015-08-19 KR KR1020177007130A patent/KR102616429B1/ko active Active
- 2015-08-19 DK DK15756525.0T patent/DK3183268T3/da active
- 2015-08-19 JP JP2017509621A patent/JP7084138B2/ja active Active
-
2017
- 2017-01-30 IL IL250362A patent/IL250362B/en active IP Right Grant
- 2017-02-17 CO CONC2017/0001573A patent/CO2017001573A2/es unknown
- 2017-10-06 US US15/726,703 patent/US10703819B2/en active Active
-
2020
- 2020-05-27 US US16/884,867 patent/US11591404B2/en active Active
-
2021
- 2021-01-14 IL IL280204A patent/IL280204A/en unknown
- 2021-07-26 JP JP2021121574A patent/JP2021184715A/ja active Pending
- 2021-08-20 AU AU2021218185A patent/AU2021218185A1/en not_active Abandoned
-
2022
- 2022-12-30 US US18/148,807 patent/US20230220090A1/en active Pending
Non-Patent Citations (7)
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230220090A1 (en) | Treatment of cancer using a cd123 chimeric antigen receptor | |
| US20250353916A1 (en) | Treatment of cancer using a cd33 chimeric antigen receptor | |
| TWI746437B (zh) | Ｃｄ２０療法、ｃｄ２２療法及與表現ｃｄ１９嵌合抗原受體（ｃａｒ）之細胞的組合療法 | |
| TWI718992B (zh) | 使用cll-1嵌合抗原受體治療癌症 | |
| HK40035924A (en) | Treatment of cancer using a cd123 chimeric antigen receptor | |
| HK1238262B (en) | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment | |
| HK1238262A1 (en) | Anti-cd123 chimeric antigen receptor (car) for use in cancer treatment | |
| BR112017003104B1 (pt) | Molécula de ácido nucleico isolada que codifica um receptor de antígeno quimérico (car), polipeptídeo do car isolado, domínio de ligação a cd123, vetor, método in vitro ou ex vivo para preparação de uma célula ou para geração de uma população de células, usos de uma célula, e composição farmacêutica | |
| HK1231901B (en) | Treatment of cancer using a cd33 chimeric antigen receptor | |
| HK1231901A1 (en) | Treatment of cancer using a cd33 chimeric antigen receptor |