CA3129140A1 - Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers - Google Patents
Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers Download PDFInfo
- Publication number
- CA3129140A1 CA3129140A1 CA3129140A CA3129140A CA3129140A1 CA 3129140 A1 CA3129140 A1 CA 3129140A1 CA 3129140 A CA3129140 A CA 3129140A CA 3129140 A CA3129140 A CA 3129140A CA 3129140 A1 CA3129140 A1 CA 3129140A1
- Authority
- CA
- Canada
- Prior art keywords
- cells
- cell
- car
- cldn6
- immune effector
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108091007433 antigens Proteins 0.000 title claims description 269
- 102000036639 antigens Human genes 0.000 title claims description 269
- 239000000427 antigen Substances 0.000 title claims description 263
- 206010028980 Neoplasm Diseases 0.000 title claims description 152
- 238000011282 treatment Methods 0.000 title claims description 32
- 210000004027 cell Anatomy 0.000 claims abstract description 415
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims abstract description 197
- 102100038449 Claudin-6 Human genes 0.000 claims abstract 16
- 101000882898 Homo sapiens Claudin-6 Proteins 0.000 claims abstract 16
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 253
- 230000027455 binding Effects 0.000 claims description 134
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 126
- 239000012642 immune effector Substances 0.000 claims description 115
- 229940121354 immunomodulator Drugs 0.000 claims description 115
- 230000014509 gene expression Effects 0.000 claims description 98
- 150000007523 nucleic acids Chemical class 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 94
- 102000039446 nucleic acids Human genes 0.000 claims description 87
- 108020004707 nucleic acids Proteins 0.000 claims description 87
- 108090000623 proteins and genes Proteins 0.000 claims description 82
- 239000013598 vector Substances 0.000 claims description 71
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
- 239000012634 fragment Substances 0.000 claims description 60
- -1 CD86 Proteins 0.000 claims description 57
- 102000004169 proteins and genes Human genes 0.000 claims description 56
- 201000010099 disease Diseases 0.000 claims description 52
- 201000011510 cancer Diseases 0.000 claims description 40
- 238000001727 in vivo Methods 0.000 claims description 40
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 33
- 239000002245 particle Substances 0.000 claims description 32
- 230000011664 signaling Effects 0.000 claims description 31
- 108091008874 T cell receptors Proteins 0.000 claims description 30
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 30
- 150000002632 lipids Chemical class 0.000 claims description 30
- 230000004913 activation Effects 0.000 claims description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 25
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims description 24
- 210000004443 dendritic cell Anatomy 0.000 claims description 23
- 210000001519 tissue Anatomy 0.000 claims description 23
- 206010033128 Ovarian cancer Diseases 0.000 claims description 20
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 19
- 230000000139 costimulatory effect Effects 0.000 claims description 19
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims description 18
- 210000000952 spleen Anatomy 0.000 claims description 18
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 17
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 17
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 15
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 14
- 239000002502 liposome Substances 0.000 claims description 13
- 230000003834 intracellular effect Effects 0.000 claims description 12
- 208000020816 lung neoplasm Diseases 0.000 claims description 12
- 210000002540 macrophage Anatomy 0.000 claims description 12
- 239000013612 plasmid Substances 0.000 claims description 12
- 238000007910 systemic administration Methods 0.000 claims description 12
- 102000004127 Cytokines Human genes 0.000 claims description 11
- 108090000695 Cytokines Proteins 0.000 claims description 11
- 241000713666 Lentivirus Species 0.000 claims description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 206010039491 Sarcoma Diseases 0.000 claims description 10
- 201000005202 lung cancer Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 201000001441 melanoma Diseases 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 8
- 230000007423 decrease Effects 0.000 claims description 8
- 241001430294 unidentified retrovirus Species 0.000 claims description 8
- 102100038080 B-cell receptor CD22 Human genes 0.000 claims description 7
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 claims description 7
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 7
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 7
- 201000002528 pancreatic cancer Diseases 0.000 claims description 7
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 7
- 239000003981 vehicle Substances 0.000 claims description 7
- 206010004593 Bile duct cancer Diseases 0.000 claims description 6
- 102100024263 CD160 antigen Human genes 0.000 claims description 6
- 101000761938 Homo sapiens CD160 antigen Proteins 0.000 claims description 6
- 101001078158 Homo sapiens Integrin alpha-1 Proteins 0.000 claims description 6
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 claims description 6
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 6
- 102100025323 Integrin alpha-1 Human genes 0.000 claims description 6
- 102100022339 Integrin alpha-L Human genes 0.000 claims description 6
- 102100025390 Integrin beta-2 Human genes 0.000 claims description 6
- 102100029215 Signaling lymphocytic activation molecule Human genes 0.000 claims description 6
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 6
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 206010017758 gastric cancer Diseases 0.000 claims description 6
- 201000007270 liver cancer Diseases 0.000 claims description 6
- 208000014018 liver neoplasm Diseases 0.000 claims description 6
- 230000002062 proliferating effect Effects 0.000 claims description 6
- 201000000849 skin cancer Diseases 0.000 claims description 6
- 230000004936 stimulating effect Effects 0.000 claims description 6
- 201000011549 stomach cancer Diseases 0.000 claims description 6
- 206010073069 Hepatic cancer Diseases 0.000 claims description 5
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 5
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 claims description 5
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 claims description 5
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 claims description 5
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 5
- 102100032816 Integrin alpha-6 Human genes 0.000 claims description 5
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 claims description 5
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 claims description 5
- 230000000735 allogeneic effect Effects 0.000 claims description 5
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 5
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 5
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 210000003289 regulatory T cell Anatomy 0.000 claims description 5
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 claims description 4
- 101001046687 Homo sapiens Integrin alpha-E Proteins 0.000 claims description 4
- 101000971538 Homo sapiens Killer cell lectin-like receptor subfamily F member 1 Proteins 0.000 claims description 4
- 102100032818 Integrin alpha-4 Human genes 0.000 claims description 4
- 102100022341 Integrin alpha-E Human genes 0.000 claims description 4
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims description 4
- 102100021458 Killer cell lectin-like receptor subfamily F member 1 Human genes 0.000 claims description 4
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 4
- 102100038082 Natural killer cell receptor 2B4 Human genes 0.000 claims description 4
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 claims description 4
- 108010074687 Signaling Lymphocytic Activation Molecule Family Member 1 Proteins 0.000 claims description 4
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims description 4
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 claims description 4
- 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 claims description 4
- 230000009149 molecular binding Effects 0.000 claims description 4
- 102100037904 CD9 antigen Human genes 0.000 claims description 3
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 claims description 3
- 101000738354 Homo sapiens CD9 antigen Proteins 0.000 claims description 3
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 claims description 3
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 claims description 3
- 101000777628 Homo sapiens Leukocyte antigen CD37 Proteins 0.000 claims description 3
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 3
- 101000633786 Homo sapiens SLAM family member 6 Proteins 0.000 claims description 3
- 101000633784 Homo sapiens SLAM family member 7 Proteins 0.000 claims description 3
- 101000934341 Homo sapiens T-cell surface glycoprotein CD5 Proteins 0.000 claims description 3
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 claims description 3
- 102100022338 Integrin alpha-M Human genes 0.000 claims description 3
- 102100031586 Leukocyte antigen CD37 Human genes 0.000 claims description 3
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 3
- 102100029197 SLAM family member 6 Human genes 0.000 claims description 3
- 102100029198 SLAM family member 7 Human genes 0.000 claims description 3
- 102100027744 Semaphorin-4D Human genes 0.000 claims description 3
- 102100025244 T-cell surface glycoprotein CD5 Human genes 0.000 claims description 3
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 208000026037 malignant tumor of neck Diseases 0.000 claims description 3
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 2
- 108010056102 CD100 antigen Proteins 0.000 claims description 2
- 108010017009 CD11b Antigen Proteins 0.000 claims description 2
- 102100027207 CD27 antigen Human genes 0.000 claims description 2
- 108010062802 CD66 antigens Proteins 0.000 claims description 2
- 102100027217 CD82 antigen Human genes 0.000 claims description 2
- 101710139831 CD82 antigen Proteins 0.000 claims description 2
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 claims description 2
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 2
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 claims description 2
- 101001035237 Homo sapiens Integrin alpha-D Proteins 0.000 claims description 2
- 101001046683 Homo sapiens Integrin alpha-L Proteins 0.000 claims description 2
- 101001046668 Homo sapiens Integrin alpha-X Proteins 0.000 claims description 2
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 claims description 2
- 101001015037 Homo sapiens Integrin beta-7 Proteins 0.000 claims description 2
- 101001109503 Homo sapiens NKG2-C type II integral membrane protein Proteins 0.000 claims description 2
- 101001109501 Homo sapiens NKG2-D type II integral membrane protein Proteins 0.000 claims description 2
- 101000589305 Homo sapiens Natural cytotoxicity triggering receptor 2 Proteins 0.000 claims description 2
- 101000873418 Homo sapiens P-selectin glycoprotein ligand 1 Proteins 0.000 claims description 2
- 101000633778 Homo sapiens SLAM family member 5 Proteins 0.000 claims description 2
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 claims description 2
- 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 claims description 2
- 101000648507 Homo sapiens Tumor necrosis factor receptor superfamily member 14 Proteins 0.000 claims description 2
- 101000679857 Homo sapiens Tumor necrosis factor receptor superfamily member 3 Proteins 0.000 claims description 2
- 101150102264 IE gene Proteins 0.000 claims description 2
- 102100039904 Integrin alpha-D Human genes 0.000 claims description 2
- 102100022297 Integrin alpha-X Human genes 0.000 claims description 2
- 108010041100 Integrin alpha6 Proteins 0.000 claims description 2
- 108010030465 Integrin alpha6beta1 Proteins 0.000 claims description 2
- 102100025304 Integrin beta-1 Human genes 0.000 claims description 2
- 102100033016 Integrin beta-7 Human genes 0.000 claims description 2
- 101001043810 Macaca fascicularis Interleukin-7 receptor subunit alpha Proteins 0.000 claims description 2
- 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 claims description 2
- 102100022683 NKG2-C type II integral membrane protein Human genes 0.000 claims description 2
- 102100022680 NKG2-D type II integral membrane protein Human genes 0.000 claims description 2
- 108010004217 Natural Cytotoxicity Triggering Receptor 1 Proteins 0.000 claims description 2
- 108010004222 Natural Cytotoxicity Triggering Receptor 3 Proteins 0.000 claims description 2
- 102100032870 Natural cytotoxicity triggering receptor 1 Human genes 0.000 claims description 2
- 102100032851 Natural cytotoxicity triggering receptor 2 Human genes 0.000 claims description 2
- 102100032852 Natural cytotoxicity triggering receptor 3 Human genes 0.000 claims description 2
- 101710141230 Natural killer cell receptor 2B4 Proteins 0.000 claims description 2
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 claims description 2
- 102100037935 Polyubiquitin-C Human genes 0.000 claims description 2
- 208000006994 Precancerous Conditions Diseases 0.000 claims description 2
- 229940116193 Protein phosphatase inhibitor Drugs 0.000 claims description 2
- 102100029216 SLAM family member 5 Human genes 0.000 claims description 2
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 claims description 2
- 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 claims description 2
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 claims description 2
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 claims description 2
- 102100022156 Tumor necrosis factor receptor superfamily member 3 Human genes 0.000 claims description 2
- 108010056354 Ubiquitin C Proteins 0.000 claims description 2
- 230000005809 anti-tumor immunity Effects 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 229940043355 kinase inhibitor Drugs 0.000 claims description 2
- 239000003934 phosphoprotein phosphatase inhibitor Substances 0.000 claims description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 2
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims 1
- 101150013553 CD40 gene Proteins 0.000 claims 1
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 claims 1
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 claims 1
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 claims 1
- 102100035268 T-cell surface protein tactile Human genes 0.000 claims 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims 1
- 125000003473 lipid group Chemical group 0.000 claims 1
- 108091007741 Chimeric antigen receptor T cells Proteins 0.000 abstract description 30
- 230000000638 stimulation Effects 0.000 abstract description 12
- 230000003252 repetitive effect Effects 0.000 abstract description 8
- 230000004083 survival effect Effects 0.000 abstract description 3
- 102000003859 Claudin-6 Human genes 0.000 description 162
- 108090000229 Claudin-6 Proteins 0.000 description 162
- 235000001014 amino acid Nutrition 0.000 description 96
- 229940024606 amino acid Drugs 0.000 description 87
- 150000001413 amino acids Chemical class 0.000 description 81
- 108090000765 processed proteins & peptides Proteins 0.000 description 69
- 235000018102 proteins Nutrition 0.000 description 52
- 102000004196 processed proteins & peptides Human genes 0.000 description 41
- 229920001184 polypeptide Polymers 0.000 description 32
- 241000699670 Mus sp. Species 0.000 description 31
- 230000006870 function Effects 0.000 description 30
- 230000000259 anti-tumor effect Effects 0.000 description 26
- 238000000684 flow cytometry Methods 0.000 description 26
- 238000000338 in vitro Methods 0.000 description 26
- 125000003729 nucleotide group Chemical group 0.000 description 24
- 210000004881 tumor cell Anatomy 0.000 description 24
- 102100035360 Cerebellar degeneration-related antigen 1 Human genes 0.000 description 23
- 239000002479 lipoplex Substances 0.000 description 23
- 210000004698 lymphocyte Anatomy 0.000 description 23
- 239000002773 nucleotide Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 108091033319 polynucleotide Proteins 0.000 description 22
- 102000040430 polynucleotide Human genes 0.000 description 22
- 239000002157 polynucleotide Substances 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 21
- 238000012546 transfer Methods 0.000 description 21
- 108020004414 DNA Proteins 0.000 description 20
- 108020004999 messenger RNA Proteins 0.000 description 20
- 239000008194 pharmaceutical composition Substances 0.000 description 20
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 19
- 230000001404 mediated effect Effects 0.000 description 19
- 230000002688 persistence Effects 0.000 description 19
- 238000013518 transcription Methods 0.000 description 18
- 230000035897 transcription Effects 0.000 description 18
- 239000012636 effector Substances 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 16
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 15
- 230000001086 cytosolic effect Effects 0.000 description 15
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 14
- 230000028993 immune response Effects 0.000 description 14
- 239000011324 bead Substances 0.000 description 13
- 230000009089 cytolysis Effects 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 13
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 12
- 108060003951 Immunoglobulin Proteins 0.000 description 12
- 102000018358 immunoglobulin Human genes 0.000 description 12
- 230000035755 proliferation Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 208000009956 adenocarcinoma Diseases 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 230000007774 longterm Effects 0.000 description 11
- VDABVNMGKGUPEY-UHFFFAOYSA-N 6-carboxyfluorescein succinimidyl ester Chemical compound C=1C(O)=CC=C2C=1OC1=CC(O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O VDABVNMGKGUPEY-UHFFFAOYSA-N 0.000 description 10
- 201000009030 Carcinoma Diseases 0.000 description 10
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 10
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 10
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 10
- 210000002443 helper t lymphocyte Anatomy 0.000 description 10
- 238000003384 imaging method Methods 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 230000001177 retroviral effect Effects 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 238000010361 transduction Methods 0.000 description 10
- 230000026683 transduction Effects 0.000 description 10
- 102100035361 Cerebellar degeneration-related protein 2 Human genes 0.000 description 9
- 101000737793 Homo sapiens Cerebellar degeneration-related antigen 1 Proteins 0.000 description 9
- 101000737796 Homo sapiens Cerebellar degeneration-related protein 2 Proteins 0.000 description 9
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 239000002671 adjuvant Substances 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000029918 bioluminescence Effects 0.000 description 9
- 238000005415 bioluminescence Methods 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 210000005259 peripheral blood Anatomy 0.000 description 9
- 239000011886 peripheral blood Substances 0.000 description 9
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000002255 vaccination Methods 0.000 description 9
- LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 8
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 8
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 8
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 8
- 241001529936 Murinae Species 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 108700026244 Open Reading Frames Proteins 0.000 description 8
- 238000003501 co-culture Methods 0.000 description 8
- 125000005647 linker group Chemical group 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 125000006850 spacer group Chemical group 0.000 description 8
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 7
- 108700008625 Reporter Genes Proteins 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 230000010354 integration Effects 0.000 description 7
- 230000002147 killing effect Effects 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 210000000130 stem cell Anatomy 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- 108020005345 3' Untranslated Regions Proteins 0.000 description 6
- 102000002029 Claudin Human genes 0.000 description 6
- 108050009302 Claudin Proteins 0.000 description 6
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 6
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000011529 RT qPCR Methods 0.000 description 6
- 208000024313 Testicular Neoplasms Diseases 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 6
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000004068 intracellular signaling Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 230000037452 priming Effects 0.000 description 6
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 238000013519 translation Methods 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 108020003589 5' Untranslated Regions Proteins 0.000 description 5
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group 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 5
- 108010002586 Interleukin-7 Proteins 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000006044 T cell activation Effects 0.000 description 5
- 108091023045 Untranslated Region Proteins 0.000 description 5
- 238000002617 apheresis Methods 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 230000002596 correlated effect Effects 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 5
- 239000005090 green fluorescent protein Substances 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 210000000987 immune system Anatomy 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 210000004324 lymphatic system Anatomy 0.000 description 5
- 230000001394 metastastic effect Effects 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 210000000822 natural killer cell Anatomy 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000004043 responsiveness Effects 0.000 description 5
- 125000002652 ribonucleotide group Chemical group 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 201000003120 testicular cancer Diseases 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 210000001541 thymus gland Anatomy 0.000 description 5
- 241000701161 unidentified adenovirus Species 0.000 description 5
- 206010008342 Cervix carcinoma Diseases 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 241000702421 Dependoparvovirus Species 0.000 description 4
- 241000126130 Ganymedes Species 0.000 description 4
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- 108010052285 Membrane Proteins Proteins 0.000 description 4
- 102000015636 Oligopeptides Human genes 0.000 description 4
- 108010038807 Oligopeptides Proteins 0.000 description 4
- 102000004503 Perforin Human genes 0.000 description 4
- 108010056995 Perforin Proteins 0.000 description 4
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 108091034057 RNA (poly(A)) Proteins 0.000 description 4
- 206010041067 Small cell lung cancer Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000024932 T cell mediated immunity Effects 0.000 description 4
- 206010057644 Testis cancer Diseases 0.000 description 4
- 108700019146 Transgenes Proteins 0.000 description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 125000002091 cationic group Chemical group 0.000 description 4
- 230000032823 cell division Effects 0.000 description 4
- 201000010881 cervical cancer Diseases 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 210000001616 monocyte Anatomy 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 229930192851 perforin Natural products 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 235000013849 propane Nutrition 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 description 4
- 208000001608 teratocarcinoma Diseases 0.000 description 4
- 102000035160 transmembrane proteins Human genes 0.000 description 4
- 108091005703 transmembrane proteins Proteins 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
- 206010004146 Basal cell carcinoma Diseases 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 101150029707 ERBB2 gene Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 3
- 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 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 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 206010038389 Renal cancer Diseases 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 102100037906 T-cell surface glycoprotein CD3 zeta chain Human genes 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000035508 accumulation Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000006023 anti-tumor response Effects 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000006037 cell lysis Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 3
- 230000001461 cytolytic effect Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 238000002784 cytotoxicity assay Methods 0.000 description 3
- 231100000263 cytotoxicity test Toxicity 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- REZZEXDLIUJMMS-UHFFFAOYSA-M dimethyldioctadecylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC REZZEXDLIUJMMS-UHFFFAOYSA-M 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 239000002955 immunomodulating agent Substances 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 201000010982 kidney cancer Diseases 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000010859 live-cell imaging Methods 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000007758 minimum essential medium Substances 0.000 description 3
- 238000009126 molecular therapy Methods 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000002611 ovarian Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 201000010198 papillary carcinoma Diseases 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000001294 propane Substances 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 229940054269 sodium pyruvate Drugs 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 206010042863 synovial sarcoma Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000001578 tight junction Anatomy 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 210000003932 urinary bladder Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 2
- 239000012114 Alexa Fluor 647 Substances 0.000 description 2
- 102000006306 Antigen Receptors Human genes 0.000 description 2
- 108010083359 Antigen Receptors Proteins 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- NALWOULWGHTVDA-UWVGGRQHSA-N Asp-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NALWOULWGHTVDA-UWVGGRQHSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 108091008875 B cell receptors Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 2
- 108700012439 CA9 Proteins 0.000 description 2
- 238000011357 CAR T-cell therapy Methods 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 108091033409 CRISPR Proteins 0.000 description 2
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 2
- 201000000274 Carcinosarcoma Diseases 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- 102100038423 Claudin-3 Human genes 0.000 description 2
- 102100038447 Claudin-4 Human genes 0.000 description 2
- 102100026097 Claudin-9 Human genes 0.000 description 2
- 208000019487 Clear cell papillary renal cell carcinoma Diseases 0.000 description 2
- 208000030808 Clear cell renal carcinoma Diseases 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- 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 2
- 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 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- XULFJDKZVHTRLG-JDVCJPALSA-N DOSPA trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)CCNC(=O)C(CCCNCCCN)NCCCN)OCCCCCCCC\C=C/CCCCCCCC XULFJDKZVHTRLG-JDVCJPALSA-N 0.000 description 2
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 108090000331 Firefly luciferases Proteins 0.000 description 2
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 239000012571 GlutaMAX medium Substances 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 101710168479 Granulysin Proteins 0.000 description 2
- 102100021186 Granulysin Human genes 0.000 description 2
- 102000001398 Granzyme Human genes 0.000 description 2
- 108060005986 Granzyme Proteins 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101000882908 Homo sapiens Claudin-3 Proteins 0.000 description 2
- 101000882890 Homo sapiens Claudin-4 Proteins 0.000 description 2
- 101000912661 Homo sapiens Claudin-9 Proteins 0.000 description 2
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 2
- 108010002616 Interleukin-5 Proteins 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 206010050017 Lung cancer metastatic Diseases 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
- 206010025598 Malignant hydatidiform mole Diseases 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000714177 Murine leukemia virus Species 0.000 description 2
- 208000009869 Neu-Laxova syndrome Diseases 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 101100309040 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) lea-1 gene Proteins 0.000 description 2
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 2
- 206010061328 Ovarian epithelial cancer 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
- 108091036407 Polyadenylation Proteins 0.000 description 2
- RWCOTTLHDJWHRS-YUMQZZPRSA-N Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 RWCOTTLHDJWHRS-YUMQZZPRSA-N 0.000 description 2
- RTQKBZIRDWZLDF-BZSNNMDCSA-N Pro-Pro-Trp Chemical compound C([C@H]1C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)O)CCN1C(=O)[C@@H]1CCCN1 RTQKBZIRDWZLDF-BZSNNMDCSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 101710156660 T-cell surface glycoprotein CD3 zeta chain Proteins 0.000 description 2
- 208000033133 Testicular seminomatous germ cell tumor Diseases 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
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 2
- SAZUGELZHZOXHB-UHFFFAOYSA-N acecarbromal Chemical compound CCC(Br)(CC)C(=O)NC(=O)NC(C)=O SAZUGELZHZOXHB-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000006229 amino acid addition Effects 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 108010068265 aspartyltyrosine Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 208000003373 basosquamous carcinoma Diseases 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 238000002659 cell therapy Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 239000013626 chemical specie Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 206010073251 clear cell renal cell carcinoma Diseases 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 210000003162 effector t lymphocyte Anatomy 0.000 description 2
- 230000009881 electrostatic interaction Effects 0.000 description 2
- 201000011025 embryonal testis carcinoma Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229950010640 ensituximab Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 229940029575 guanosine Drugs 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 201000002312 ileal neoplasm Diseases 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 230000005965 immune activity Effects 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 201000002313 intestinal cancer Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 210000001365 lymphatic vessel Anatomy 0.000 description 2
- 210000005210 lymphoid organ Anatomy 0.000 description 2
- 230000002934 lysing effect Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 2
- 102000006240 membrane receptors Human genes 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 201000011330 nonpapillary renal cell carcinoma Diseases 0.000 description 2
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 2
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 2
- 229950003709 oxelumab Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000001539 phagocyte Anatomy 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 201000008824 placental choriocarcinoma Diseases 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 208000004333 pleomorphic adenoma Diseases 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 108010077112 prolyl-proline Proteins 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 206010073373 small intestine adenocarcinoma Diseases 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 206010062123 testicular embryonal carcinoma Diseases 0.000 description 2
- 208000024662 testicular seminoma Diseases 0.000 description 2
- 208000004238 testicular teratoma Diseases 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 206010044412 transitional cell carcinoma Diseases 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
- 206010046766 uterine cancer Diseases 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- MFZSNESUTRVBQX-XEURHVNRSA-N (2S)-2-amino-6-[4-[[3-[[(2S)-1-[[(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]disulfanyl]pentanoylamino]hexanoic acid Chemical compound CO[C@@H]1\C=C\C=C(C)\Cc2cc(OC)c(Cl)c(c2)N(C)C(=O)C[C@H](OC(=O)[C@H](C)N(C)C(=O)CCSSC(C)CCC(=O)NCCCC[C@H](N)C(O)=O)[C@]2(C)O[C@H]2[C@H](C)[C@@H]2C[C@@]1(O)NC(=O)O2 MFZSNESUTRVBQX-XEURHVNRSA-N 0.000 description 1
- JSPNNZKWADNWHI-PNANGNLXSA-N (2r)-2-hydroxy-n-[(2s,3r,4e,8e)-3-hydroxy-9-methyl-1-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]heptadecanamide Chemical compound CCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CC\C=C(/C)CCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O JSPNNZKWADNWHI-PNANGNLXSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- UVBYMVOUBXYSFV-XUTVFYLZSA-N 1-methylpseudouridine Chemical compound O=C1NC(=O)N(C)C=C1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UVBYMVOUBXYSFV-XUTVFYLZSA-N 0.000 description 1
- UVBYMVOUBXYSFV-UHFFFAOYSA-N 1-methylpseudouridine Natural products O=C1NC(=O)N(C)C=C1C1C(O)C(O)C(CO)O1 UVBYMVOUBXYSFV-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- UZLHBUQJHDTDRD-UHFFFAOYSA-N 2,3-di(tetradecoxy)propyl-(2-hydroxyethyl)-dimethylazanium Chemical compound CCCCCCCCCCCCCCOCC(C[N+](C)(C)CCO)OCCCCCCCCCCCCCC UZLHBUQJHDTDRD-UHFFFAOYSA-N 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 1
- ZAYHVCMSTBRABG-UHFFFAOYSA-N 5-Methylcytidine Natural products O=C1N=C(N)C(C)=CN1C1C(O)C(O)C(CO)O1 ZAYHVCMSTBRABG-UHFFFAOYSA-N 0.000 description 1
- ZAYHVCMSTBRABG-JXOAFFINSA-N 5-methylcytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZAYHVCMSTBRABG-JXOAFFINSA-N 0.000 description 1
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 1
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100023635 Alpha-fetoprotein Human genes 0.000 description 1
- 241000024188 Andala Species 0.000 description 1
- 108010031480 Artificial Receptors Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000714230 Avian leukemia virus Species 0.000 description 1
- 230000003844 B-cell-activation Effects 0.000 description 1
- 108010074708 B7-H1 Antigen 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
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 206010006143 Brain stem glioma Diseases 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 101150117674 Cd247 gene Proteins 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
- 229940126626 Ektomab Drugs 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102100039328 Endoplasmin Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010051841 Exposure to allergen Diseases 0.000 description 1
- 229940126611 FBTA05 Drugs 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 102000010451 Folate receptor alpha Human genes 0.000 description 1
- 108050001931 Folate receptor alpha Proteins 0.000 description 1
- 108091092584 GDNA Proteins 0.000 description 1
- 208000000527 Germinoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- OPINTGHFESTVAX-BQBZGAKWSA-N Gln-Arg Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N OPINTGHFESTVAX-BQBZGAKWSA-N 0.000 description 1
- NKCZYEDZTKOFBG-GUBZILKMSA-N Gln-Gln-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O NKCZYEDZTKOFBG-GUBZILKMSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 101000773083 Homo sapiens 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101100005238 Homo sapiens CARTPT gene Proteins 0.000 description 1
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
- 101000812663 Homo sapiens Endoplasmin Proteins 0.000 description 1
- 101000896557 Homo sapiens Eukaryotic translation initiation factor 3 subunit B 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
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 1
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
- 101000988834 Homo sapiens Hypoxanthine-guanine phosphoribosyltransferase Proteins 0.000 description 1
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M 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
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000797623 Homo sapiens Protein AMBP Proteins 0.000 description 1
- 101000874179 Homo sapiens Syndecan-1 Proteins 0.000 description 1
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 1
- 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 108091058560 IL8 Proteins 0.000 description 1
- 208000001718 Immediate Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 102000003816 Interleukin-13 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 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
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-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
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 108010028921 Lipopeptides Proteins 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 102000043129 MHC class I family Human genes 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000004658 Medicago sativa Species 0.000 description 1
- 235000010624 Medicago sativa Nutrition 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 108010050619 Monokines Proteins 0.000 description 1
- 102000013967 Monokines Human genes 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- SUHQNCLNRUAGOO-UHFFFAOYSA-N N-glycoloyl-neuraminic acid Natural products OCC(O)C(O)C(O)C(NC(=O)CO)C(O)CC(=O)C(O)=O SUHQNCLNRUAGOO-UHFFFAOYSA-N 0.000 description 1
- FDJKUWYYUZCUJX-UHFFFAOYSA-N N-glycolyl-beta-neuraminic acid Natural products OCC(O)C(O)C1OC(O)(C(O)=O)CC(O)C1NC(=O)CO FDJKUWYYUZCUJX-UHFFFAOYSA-N 0.000 description 1
- FDJKUWYYUZCUJX-KVNVFURPSA-N N-glycolylneuraminic acid Chemical compound OC[C@H](O)[C@H](O)[C@@H]1O[C@](O)(C(O)=O)C[C@H](O)[C@H]1NC(=O)CO FDJKUWYYUZCUJX-KVNVFURPSA-N 0.000 description 1
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000577979 Peromyscus spicilegus Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 238000010806 PrimeScriptTM RT Reagent kit Methods 0.000 description 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 1
- 102100032859 Protein AMBP Human genes 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 229930185560 Pseudouridine Natural products 0.000 description 1
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 description 1
- 238000011531 Quantitect SYBR Green PCR kit Methods 0.000 description 1
- 102000014128 RANK Ligand Human genes 0.000 description 1
- 108010025832 RANK Ligand Proteins 0.000 description 1
- 238000011530 RNeasy Mini Kit Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101900083372 Rabies virus Glycoprotein Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 241000714474 Rous sarcoma virus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101100225046 Schizosaccharomyces pombe (strain 972 / ATCC 24843) ecl2 gene Proteins 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- PFNFFQXMRSDOHW-UHFFFAOYSA-N Spermine Natural products NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 102100035721 Syndecan-1 Human genes 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 210000000173 T-lymphoid precursor cell Anatomy 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 229940126624 Tacatuzumab tetraxetan Drugs 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 102000008579 Transposases Human genes 0.000 description 1
- 108010020764 Transposases Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 1
- 206010045240 Type I hypersensitivity Diseases 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 102000013127 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 241001441550 Zeiformes Species 0.000 description 1
- XYVNHPYNSPGYLI-UUOKFMHZSA-N [(2r,3s,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-4-hydroxy-2-(phosphonooxymethyl)oxolan-3-yl] dihydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O XYVNHPYNSPGYLI-UUOKFMHZSA-N 0.000 description 1
- NYDLOCKCVISJKK-WRBBJXAJSA-N [3-(dimethylamino)-2-[(z)-octadec-9-enoyl]oxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(CN(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC NYDLOCKCVISJKK-WRBBJXAJSA-N 0.000 description 1
- PRSMTOHTFYVJSQ-UHFFFAOYSA-N [Ca].[Pb] Chemical compound [Ca].[Pb] PRSMTOHTFYVJSQ-UHFFFAOYSA-N 0.000 description 1
- 229950005186 abagovomab Drugs 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 229950009084 adecatumumab Drugs 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229950008459 alacizumab pegol Drugs 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 229950009106 altumomab Drugs 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 229950001537 amatuximab Drugs 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 238000009175 antibody therapy Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229950003145 apolizumab Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- SCJNCDSAIRBRIA-DOFZRALJSA-N arachidonyl-2'-chloroethylamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCCl SCJNCDSAIRBRIA-DOFZRALJSA-N 0.000 description 1
- 229950005725 arcitumomab Drugs 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960003852 atezolizumab Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 229950007843 bavituximab Drugs 0.000 description 1
- 229950003269 bectumomab Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 229960003270 belimumab Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 201000007180 bile duct carcinoma Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 229960005522 bivatuzumab mertansine Drugs 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 229960003008 blinatumomab Drugs 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 229960005520 bryostatin Drugs 0.000 description 1
- MJQUEDHRCUIRLF-TVIXENOKSA-N bryostatin 1 Chemical compound C([C@@H]1CC(/[C@@H]([C@@](C(C)(C)/C=C/2)(O)O1)OC(=O)/C=C/C=C/CCC)=C\C(=O)OC)[C@H]([C@@H](C)O)OC(=O)C[C@H](O)C[C@@H](O1)C[C@H](OC(C)=O)C(C)(C)[C@]1(O)C[C@@H]1C\C(=C\C(=O)OC)C[C@H]\2O1 MJQUEDHRCUIRLF-TVIXENOKSA-N 0.000 description 1
- MUIWQCKLQMOUAT-AKUNNTHJSA-N bryostatin 20 Natural products COC(=O)C=C1C[C@@]2(C)C[C@]3(O)O[C@](C)(C[C@@H](O)CC(=O)O[C@](C)(C[C@@]4(C)O[C@](O)(CC5=CC(=O)O[C@]45C)C(C)(C)C=C[C@@](C)(C1)O2)[C@@H](C)O)C[C@H](OC(=O)C(C)(C)C)C3(C)C MUIWQCKLQMOUAT-AKUNNTHJSA-N 0.000 description 1
- 210000004900 c-terminal fragment Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000003710 calcium ionophore Substances 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229950011547 cantuzumab ravtansine Drugs 0.000 description 1
- 229940034605 capromab pendetide Drugs 0.000 description 1
- 101150058049 car gene Proteins 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- JGPOSNWWINVNFV-UHFFFAOYSA-N carboxyfluorescein diacetate succinimidyl ester Chemical compound C=1C(OC(=O)C)=CC=C2C=1OC1=CC(OC(C)=O)=CC=C1C2(C1=C2)OC(=O)C1=CC=C2C(=O)ON1C(=O)CCC1=O JGPOSNWWINVNFV-UHFFFAOYSA-N 0.000 description 1
- 229950000771 carlumab Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 238000009172 cell transfer therapy Methods 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 229930183167 cerebroside Natural products 0.000 description 1
- RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
- 208000012191 childhood neoplasm Diseases 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229950010905 citatuzumab bogatox Drugs 0.000 description 1
- 229950006647 cixutumumab Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 229950002595 clivatuzumab tetraxetan Drugs 0.000 description 1
- 238000011198 co-culture assay Methods 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 108700032673 cocaine- and amphetamine-regulated transcript Proteins 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 229950007276 conatumumab Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect 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
- 230000009260 cross reactivity Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 229950007409 dacetuzumab Drugs 0.000 description 1
- 229960002482 dalotuzumab Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 229950008962 detumomab Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- UMGXUWVIJIQANV-UHFFFAOYSA-M didecyl(dimethyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC UMGXUWVIJIQANV-UHFFFAOYSA-M 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 229950009964 drozitumab Drugs 0.000 description 1
- 101150058725 ecl1 gene Proteins 0.000 description 1
- 229950000006 ecromeximab Drugs 0.000 description 1
- 229960001776 edrecolomab Drugs 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229960004137 elotuzumab Drugs 0.000 description 1
- 210000002242 embryoid body Anatomy 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229950003048 enavatuzumab Drugs 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229950009760 epratuzumab Drugs 0.000 description 1
- 229950008579 ertumaxomab Drugs 0.000 description 1
- 229950009569 etaracizumab Drugs 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 229950009929 farletuzumab Drugs 0.000 description 1
- 210000004700 fetal blood Anatomy 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 229950002846 ficlatuzumab Drugs 0.000 description 1
- 229950008085 figitumumab Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229950010320 flanvotumab Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229950004003 fresolimumab Drugs 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229950001109 galiximab Drugs 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 229950004896 ganitumab Drugs 0.000 description 1
- 201000006585 gastric adenocarcinoma Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 201000003115 germ cell cancer Diseases 0.000 description 1
- 229950003717 gevokizumab Drugs 0.000 description 1
- 229950002026 girentuximab Drugs 0.000 description 1
- 229950009672 glembatumumab vedotin Drugs 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960004956 glycerylphosphorylcholine Drugs 0.000 description 1
- 150000002337 glycosamines Chemical group 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 229950006359 icrucumab Drugs 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 210000003297 immature b lymphocyte Anatomy 0.000 description 1
- 210000002861 immature t-cell Anatomy 0.000 description 1
- 230000037189 immune system physiology Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000002847 impedance measurement Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000002743 insertional mutagenesis Methods 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 229950001014 intetumumab Drugs 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 229950010939 iratumumab Drugs 0.000 description 1
- 229950000518 labetuzumab Drugs 0.000 description 1
- 238000002789 length control Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229950002884 lexatumumab Drugs 0.000 description 1
- 229950005173 libivirumab Drugs 0.000 description 1
- 229950002950 lintuzumab Drugs 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229950003526 lorvotuzumab mertansine Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229950004563 lucatumumab Drugs 0.000 description 1
- 229950000128 lumiliximab Drugs 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- FVVLHONNBARESJ-NTOWJWGLSA-H magnesium;potassium;trisodium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;acetate;tetrachloride;nonahydrate Chemical compound O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Mg+2].[Cl-].[Cl-].[Cl-].[Cl-].[K+].CC([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O FVVLHONNBARESJ-NTOWJWGLSA-H 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229950001869 mapatumumab Drugs 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 229950008001 matuzumab Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 229960005108 mepolizumab Drugs 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 239000013586 microbial product Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 229950003734 milatuzumab Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 229950003063 mitumomab Drugs 0.000 description 1
- 201000004058 mixed glioma Diseases 0.000 description 1
- 229950007699 mogamulizumab Drugs 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000011294 monotherapeutic Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229950000720 moxetumomab pasudotox Drugs 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 229950003027 nacolomab tafenatox Drugs 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 229950009793 naptumomab estafenatox Drugs 0.000 description 1
- 229960000513 necitumumab Drugs 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 201000002120 neuroendocrine carcinoma Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229950010203 nimotuzumab Drugs 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229960003347 obinutuzumab Drugs 0.000 description 1
- 229960002450 ofatumumab Drugs 0.000 description 1
- 229950008516 olaratumab Drugs 0.000 description 1
- 229950000846 onartuzumab Drugs 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 229950009057 oportuzumab monatox Drugs 0.000 description 1
- 229950007283 oregovomab Drugs 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229950007318 ozogamicin Drugs 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229950010966 patritumab Drugs 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940067082 pentetate Drugs 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229940126620 pintumomab Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 108010058237 plasma protein fraction Proteins 0.000 description 1
- 229940002993 plasmanate Drugs 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 210000004986 primary T-cell Anatomy 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 210000005211 primary lymphoid organ Anatomy 0.000 description 1
- 229950009904 pritumumab Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229950011613 racotumomab Drugs 0.000 description 1
- 229950011639 radretumab Drugs 0.000 description 1
- 229950002786 rafivirumab Drugs 0.000 description 1
- 229960002633 ramucirumab Drugs 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 108010056030 retronectin Proteins 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 229950003238 rilotumumab Drugs 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 229950001808 robatumumab Drugs 0.000 description 1
- HNMATTJJEPZZMM-BPKVFSPJSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2s,5z,9r,13e)-13-[2-[[4-[(2e)-2-[1-[4-(4-amino-4-oxobutoxy)phenyl]ethylidene]hydrazinyl]-2-methyl-4-oxobutan-2-yl]disulfanyl]ethylidene]-9-hydroxy-12-(m Chemical compound C1[C@H](OC)[C@@H](N(CC)C(C)=O)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSC(C)(C)CC(=O)N\N=C(/C)C=3C=CC(OCCCC(N)=O)=CC=3)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HNMATTJJEPZZMM-BPKVFSPJSA-N 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229950000106 samalizumab Drugs 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 210000005212 secondary lymphoid organ Anatomy 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique 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
- 229950008684 sibrotuzumab Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229960003323 siltuximab Drugs 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 210000001845 splenic macrophage Anatomy 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229950010265 tabalumab Drugs 0.000 description 1
- 101150047061 tag-72 gene Proteins 0.000 description 1
- 229950001603 taplitumomab paptox Drugs 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229950001289 tenatumomab Drugs 0.000 description 1
- 229950010259 teprotumumab Drugs 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 239000012749 thinning agent Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
- 229950004742 tigatuzumab Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 210000002105 tongue Anatomy 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 229950003364 tucotuzumab celmoleukin Drugs 0.000 description 1
- 108700008509 tucotuzumab celmoleukin Proteins 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- 229950004593 ublituximab Drugs 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000003827 upregulation Effects 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
- 229950005972 urelumab Drugs 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 229950001212 volociximab Drugs 0.000 description 1
- 229950003511 votumumab Drugs 0.000 description 1
- JFCFGYGEYRIEBE-YVLHJLIDSA-N wob38vs2ni Chemical compound CO[C@@H]([C@@]1(O)C[C@H](OC(=O)N1)[C@@H](C)[C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(=O)CCC(C)(C)S)CC(=O)N1C)\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 JFCFGYGEYRIEBE-YVLHJLIDSA-N 0.000 description 1
- 229950008250 zalutumumab Drugs 0.000 description 1
- 229950009002 zanolimumab Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
- A61K40/4264—Cancer antigens from embryonic or fetal origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
- C12N15/867—Retroviral vectors
-
- 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
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- 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
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- C07K2319/00—Fusion polypeptide
-
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EPPCT/EP2019/053156 | 2019-02-08 | ||
| EP2019053156 | 2019-02-08 | ||
| PCT/EP2020/052867 WO2020161186A1 (en) | 2019-02-08 | 2020-02-05 | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3129140A1 true CA3129140A1 (en) | 2020-08-13 |
Family
ID=69374312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3129140A Pending CA3129140A1 (en) | 2019-02-08 | 2020-02-05 | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US20220184119A1 (enExample) |
| EP (2) | EP3920939B1 (enExample) |
| JP (2) | JP7663500B2 (enExample) |
| KR (1) | KR20210124237A (enExample) |
| CN (1) | CN113727720A (enExample) |
| AU (1) | AU2020217868A1 (enExample) |
| BR (1) | BR112021015429A2 (enExample) |
| CA (1) | CA3129140A1 (enExample) |
| CL (1) | CL2021002067A1 (enExample) |
| CO (1) | CO2021010347A2 (enExample) |
| CU (1) | CU20210067A7 (enExample) |
| DK (1) | DK3920939T3 (enExample) |
| ES (1) | ES3002958T3 (enExample) |
| FI (1) | FI3920939T3 (enExample) |
| HR (1) | HRP20250016T1 (enExample) |
| HU (1) | HUE070174T2 (enExample) |
| IL (1) | IL285122A (enExample) |
| LT (1) | LT3920939T (enExample) |
| MX (1) | MX2021009507A (enExample) |
| PL (1) | PL3920939T3 (enExample) |
| PT (1) | PT3920939T (enExample) |
| RS (1) | RS66364B1 (enExample) |
| SG (1) | SG11202108339TA (enExample) |
| SI (1) | SI3920939T1 (enExample) |
| SM (1) | SMT202500012T1 (enExample) |
| WO (1) | WO2020161186A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021129927A1 (en) * | 2019-12-23 | 2021-07-01 | Biontech Cell & Gene Therapies Gmbh | Treatment with immune effector cells engineered to express an antigen receptor |
| KR20240133791A (ko) * | 2021-12-09 | 2024-09-04 | 비온테크 에스이 | Cldn6를 발현하는 암을 치료하기 위한 키메라 항원 수용체 변형 세포 |
| WO2024046572A1 (en) * | 2022-09-01 | 2024-03-07 | BioNTech SE | Chimeric antigen receptor-modified cells for the treatment of cldn6 expressing cancer |
| CN114478802B (zh) * | 2022-01-28 | 2023-05-26 | 郑州大学 | 一种嵌合抗原受体及其应用 |
| CN114410588B (zh) * | 2022-01-29 | 2022-11-04 | 西安电子科技大学 | 一种α1β1整合素依赖增强型CAR巨噬细胞及其制备方法和应用 |
| CN119654342B (zh) * | 2022-07-28 | 2025-07-18 | 乐普创一生物科技（上海）有限公司 | 抗MerTK抗体及其用途 |
| KR20250046264A (ko) * | 2022-07-29 | 2025-04-02 | 레전드 바이오테크 아일랜드 리미티드 | 클라우딘6 겹합 모이어티 및 이의 용도 |
| WO2024088325A1 (zh) * | 2022-10-25 | 2024-05-02 | 科济生物医药（上海）有限公司 | 抗体及其应用 |
| WO2025184170A1 (en) | 2024-02-27 | 2025-09-04 | Overt Bio, Inc. | Methods and compositions for improving t cell function in an immunosuppressive environment |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HK1047109A1 (zh) | 1999-10-15 | 2003-02-07 | University Of Massachusetts | 作为指定基因干预工具的rna干预轨迹基因 |
| US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
| WO2001096584A2 (en) | 2000-06-12 | 2001-12-20 | Akkadix Corporation | Materials and methods for the control of nematodes |
| WO2013143555A1 (en) | 2012-03-26 | 2013-10-03 | Biontech Ag | Rna formulation for immunotherapy |
| EP4026909A1 (en) * | 2013-12-19 | 2022-07-13 | Novartis AG | Human mesothelin chimeric antigen receptors and uses thereof |
| DK3126381T4 (da) * | 2014-04-01 | 2022-04-04 | Biontech Cell&Gene Therapies Gmbh | Claudin-6-specifikke immunoreceptorer og t-celleepitoper |
| MA40921A (fr) * | 2014-11-05 | 2017-09-12 | Abbvie Stemcentrx Llc | Récepteurs antigéniques chimériques anti-cldn et procédés d'utilisation |
| CN106146666B (zh) * | 2015-03-26 | 2019-09-06 | 科济生物医药（上海）有限公司 | 靶向cldn6的免疫效应细胞及其制备方法和应用 |
| WO2016180467A1 (en) | 2015-05-11 | 2016-11-17 | Biontech Cell & Gene Therapies Gmbh | Enhancing the effect of car-engineered t cells by means of nucleic acid vaccination |
| JP7654240B2 (ja) * | 2017-09-19 | 2025-04-01 | マサチューセッツ インスティテュート オブ テクノロジー | キメラ抗原受容体ｔ細胞治療のための組成物およびその使用 |
| CN109206524B (zh) * | 2018-09-25 | 2022-04-05 | 山东兴瑞生物科技有限公司 | 抗Claudin18A2嵌合抗原受体、其修饰的T细胞及T细胞制备方法和用途 |
-
2020
- 2020-02-05 RS RS20250008A patent/RS66364B1/sr unknown
- 2020-02-05 PL PL20702482.9T patent/PL3920939T3/pl unknown
- 2020-02-05 SG SG11202108339TA patent/SG11202108339TA/en unknown
- 2020-02-05 WO PCT/EP2020/052867 patent/WO2020161186A1/en not_active Ceased
- 2020-02-05 US US17/310,463 patent/US20220184119A1/en active Pending
- 2020-02-05 LT LTEPPCT/EP2020/052867T patent/LT3920939T/lt unknown
- 2020-02-05 MX MX2021009507A patent/MX2021009507A/es unknown
- 2020-02-05 DK DK20702482.9T patent/DK3920939T3/da active
- 2020-02-05 EP EP20702482.9A patent/EP3920939B1/en active Active
- 2020-02-05 JP JP2021546261A patent/JP7663500B2/ja active Active
- 2020-02-05 KR KR1020217024706A patent/KR20210124237A/ko active Pending
- 2020-02-05 SI SI202030558T patent/SI3920939T1/sl unknown
- 2020-02-05 PT PT207024829T patent/PT3920939T/pt unknown
- 2020-02-05 FI FIEP20702482.9T patent/FI3920939T3/fi active
- 2020-02-05 CN CN202080026088.8A patent/CN113727720A/zh active Pending
- 2020-02-05 SM SM20250012T patent/SMT202500012T1/it unknown
- 2020-02-05 CA CA3129140A patent/CA3129140A1/en active Pending
- 2020-02-05 EP EP24208680.9A patent/EP4501351A3/en active Pending
- 2020-02-05 CU CU2021000067A patent/CU20210067A7/es unknown
- 2020-02-05 HR HRP20250016TT patent/HRP20250016T1/hr unknown
- 2020-02-05 ES ES20702482T patent/ES3002958T3/es active Active
- 2020-02-05 BR BR112021015429-9A patent/BR112021015429A2/pt unknown
- 2020-02-05 AU AU2020217868A patent/AU2020217868A1/en active Pending
- 2020-02-05 HU HUE20702482A patent/HUE070174T2/hu unknown
-
2021
- 2021-07-25 IL IL285122A patent/IL285122A/en unknown
- 2021-08-05 CL CL2021002067A patent/CL2021002067A1/es unknown
- 2021-08-05 CO CONC2021/0010347A patent/CO2021010347A2/es unknown
-
2024
- 2024-12-26 JP JP2024230070A patent/JP2025060882A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2020217868A1 (en) | 2021-08-12 |
| JP2025060882A (ja) | 2025-04-10 |
| ES3002958T3 (en) | 2025-03-10 |
| PT3920939T (pt) | 2025-01-08 |
| RS66364B1 (sr) | 2025-01-31 |
| LT3920939T (lt) | 2025-01-10 |
| EP3920939B1 (en) | 2024-11-13 |
| CU20210067A7 (es) | 2022-03-07 |
| EP4501351A3 (en) | 2025-05-07 |
| CO2021010347A2 (es) | 2022-01-17 |
| MX2021009507A (es) | 2021-09-08 |
| FI3920939T3 (fi) | 2025-01-03 |
| PL3920939T3 (pl) | 2025-02-17 |
| CL2021002067A1 (es) | 2022-03-11 |
| DK3920939T3 (da) | 2025-01-13 |
| HUE070174T2 (hu) | 2025-05-28 |
| SI3920939T1 (sl) | 2025-03-31 |
| CN113727720A (zh) | 2021-11-30 |
| SG11202108339TA (en) | 2021-08-30 |
| WO2020161186A1 (en) | 2020-08-13 |
| SMT202500012T1 (it) | 2025-03-12 |
| BR112021015429A2 (pt) | 2021-10-05 |
| KR20210124237A (ko) | 2021-10-14 |
| EP3920939A1 (en) | 2021-12-15 |
| US20220184119A1 (en) | 2022-06-16 |
| JP7663500B2 (ja) | 2025-04-16 |
| IL285122A (en) | 2021-09-30 |
| EP4501351A2 (en) | 2025-02-05 |
| JP2022520059A (ja) | 2022-03-28 |
| HRP20250016T1 (hr) | 2025-03-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3920939B1 (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers | |
| JP7648530B2 (ja) | Ｃａｒ操作されたｔ細胞およびサイトカインを含む治療 | |
| JP7775078B2 (ja) | 免疫エフェクタ細胞の特異的活性化のためのインターロイキン２受容体（ｉｌ２ｒ）およびインターロイキン２（ｉｌ２）バリアント | |
| US20230000962A1 (en) | Treatment involving immune effector cells genetically modified to express antigen receptors | |
| RU2826058C2 (ru) | Модифицированные клетки с химерным антигеновым рецептором для лечения рака, экспрессирующего CLDN6 | |
| HK40122808A (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers | |
| US20250025505A1 (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6 expressing cancer | |
| HK40068564A (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers | |
| HK40068564B (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers | |
| WO2024046572A1 (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6 expressing cancer | |
| RU2832154C2 (ru) | Варианты рецептора интерлейкина-2 (il2r) и интерлейкина-2 (il2) для специфической активации иммунных эффекторных клеток | |
| HK40065151A (en) | Chimeric antigen receptor-modified cells for the treatment of cldn6-expressing cancers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20240202 |