MD3601533T2 - Procese de producţie a limfocitelor infiltrante în tumori și utilizările acestora în imunoterapie - Google Patents
Procese de producţie a limfocitelor infiltrante în tumori și utilizările acestora în imunoterapie Download PDFInfo
- Publication number
- MD3601533T2 MD3601533T2 MDE20200116T MDE20200116T MD3601533T2 MD 3601533 T2 MD3601533 T2 MD 3601533T2 MD E20200116 T MDE20200116 T MD E20200116T MD E20200116 T MDE20200116 T MD E20200116T MD 3601533 T2 MD3601533 T2 MD 3601533T2
- Authority
- MD
- Moldova
- Prior art keywords
- tils
- til
- expansion
- population
- days
- Prior art date
Links
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 title claims abstract description 1435
- 238000000034 method Methods 0.000 title claims abstract description 550
- 230000008569 process Effects 0.000 title claims description 129
- 238000004519 manufacturing process Methods 0.000 title abstract description 36
- 238000009169 immunotherapy Methods 0.000 title description 8
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 65
- 206010028980 Neoplasm Diseases 0.000 claims description 262
- 108010002350 Interleukin-2 Proteins 0.000 claims description 179
- 239000006143 cell culture medium Substances 0.000 claims description 94
- 239000012634 fragment Substances 0.000 claims description 92
- 230000007704 transition Effects 0.000 claims description 72
- 238000001802 infusion Methods 0.000 claims description 70
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 66
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 62
- 238000005138 cryopreservation Methods 0.000 claims description 49
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 46
- 238000004113 cell culture Methods 0.000 claims description 28
- 238000003306 harvesting Methods 0.000 claims description 27
- 238000012546 transfer Methods 0.000 claims description 27
- 238000012258 culturing Methods 0.000 claims description 16
- 239000012595 freezing medium Substances 0.000 claims description 15
- 230000001502 supplementing effect Effects 0.000 claims description 14
- 238000011282 treatment Methods 0.000 abstract description 65
- 238000011109 contamination Methods 0.000 abstract description 14
- 230000000813 microbial effect Effects 0.000 abstract description 12
- 230000002829 reductive effect Effects 0.000 abstract description 8
- 230000001976 improved effect Effects 0.000 abstract description 7
- 230000010034 metabolic health Effects 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 276
- 102000000588 Interleukin-2 Human genes 0.000 description 177
- 239000000047 product Substances 0.000 description 92
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 88
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 86
- 239000002609 medium Substances 0.000 description 85
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 82
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 80
- 108010074108 interleukin-21 Proteins 0.000 description 79
- 102100030704 Interleukin-21 Human genes 0.000 description 77
- 108010074328 Interferon-gamma Proteins 0.000 description 72
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 71
- 201000011510 cancer Diseases 0.000 description 70
- 108091008874 T cell receptors Proteins 0.000 description 69
- 102000003812 Interleukin-15 Human genes 0.000 description 67
- 108090000172 Interleukin-15 Proteins 0.000 description 67
- 102100037850 Interferon gamma Human genes 0.000 description 63
- 239000007789 gas Substances 0.000 description 61
- 210000001744 T-lymphocyte Anatomy 0.000 description 57
- 230000035899 viability Effects 0.000 description 48
- 210000004369 blood Anatomy 0.000 description 44
- 238000013467 fragmentation Methods 0.000 description 44
- 238000006062 fragmentation reaction Methods 0.000 description 44
- 230000029058 respiratory gaseous exchange Effects 0.000 description 44
- 239000008280 blood Substances 0.000 description 43
- 239000001963 growth medium Substances 0.000 description 41
- 201000001441 melanoma Diseases 0.000 description 41
- 239000000523 sample Substances 0.000 description 38
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 37
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 37
- 210000003071 memory t lymphocyte Anatomy 0.000 description 36
- 230000007423 decrease Effects 0.000 description 35
- 239000003550 marker Substances 0.000 description 35
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 33
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 33
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 31
- 210000003162 effector t lymphocyte Anatomy 0.000 description 31
- 238000000684 flow cytometry Methods 0.000 description 31
- 230000001105 regulatory effect Effects 0.000 description 31
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 30
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 29
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 29
- 101710098275 C-X-C motif chemokine 10 Proteins 0.000 description 29
- 238000012360 testing method Methods 0.000 description 29
- 210000001519 tissue Anatomy 0.000 description 29
- 102000004127 Cytokines Human genes 0.000 description 28
- 108090000695 Cytokines Proteins 0.000 description 28
- 125000003275 alpha amino acid group Chemical group 0.000 description 28
- 241000282414 Homo sapiens Species 0.000 description 27
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 230000002414 glycolytic effect Effects 0.000 description 26
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 25
- 201000010099 disease Diseases 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- 210000002966 serum Anatomy 0.000 description 24
- 238000003556 assay Methods 0.000 description 23
- 239000012636 effector Substances 0.000 description 23
- 238000012545 processing Methods 0.000 description 23
- 230000028327 secretion Effects 0.000 description 23
- 102000055501 telomere Human genes 0.000 description 23
- 108091035539 telomere Proteins 0.000 description 23
- 210000003411 telomere Anatomy 0.000 description 23
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 22
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 22
- 102100027207 CD27 antigen Human genes 0.000 description 21
- 102100032937 CD40 ligand Human genes 0.000 description 21
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 21
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 21
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 21
- 230000000241 respiratory effect Effects 0.000 description 21
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 20
- 229960004397 cyclophosphamide Drugs 0.000 description 20
- 239000008194 pharmaceutical composition Substances 0.000 description 20
- 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 19
- 229960000390 fludarabine Drugs 0.000 description 19
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 19
- 210000004698 lymphocyte Anatomy 0.000 description 19
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 18
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 18
- 108060003951 Immunoglobulin Proteins 0.000 description 18
- 102000017578 LAG3 Human genes 0.000 description 18
- 239000000427 antigen Substances 0.000 description 18
- 108091007433 antigens Proteins 0.000 description 18
- 102000036639 antigens Human genes 0.000 description 18
- 102000018358 immunoglobulin Human genes 0.000 description 18
- -1 CD45Ra Proteins 0.000 description 17
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 17
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 17
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 17
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 17
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 17
- 102100021260 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Human genes 0.000 description 16
- 101000894906 Homo sapiens Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 1 Proteins 0.000 description 16
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 16
- 230000010261 cell growth Effects 0.000 description 16
- 230000034659 glycolysis Effects 0.000 description 16
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 210000004881 tumor cell Anatomy 0.000 description 16
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 15
- 229910002092 carbon dioxide Inorganic materials 0.000 description 15
- 230000003247 decreasing effect Effects 0.000 description 15
- 210000004072 lung Anatomy 0.000 description 15
- 230000001400 myeloablative effect Effects 0.000 description 15
- 238000007792 addition Methods 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 238000002560 therapeutic procedure Methods 0.000 description 14
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 13
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 13
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 13
- 230000002503 metabolic effect Effects 0.000 description 13
- 230000000638 stimulation Effects 0.000 description 13
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 description 12
- 230000004913 activation Effects 0.000 description 12
- 230000003321 amplification Effects 0.000 description 12
- 235000011089 carbon dioxide Nutrition 0.000 description 12
- 230000012010 growth Effects 0.000 description 12
- 238000003199 nucleic acid amplification method Methods 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 239000006228 supernatant Substances 0.000 description 12
- 206010008342 Cervix carcinoma Diseases 0.000 description 11
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 11
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 11
- 108700025316 aldesleukin Proteins 0.000 description 11
- 230000000735 allogeneic effect Effects 0.000 description 11
- 210000003719 b-lymphocyte Anatomy 0.000 description 11
- 230000001413 cellular effect Effects 0.000 description 11
- 201000010881 cervical cancer Diseases 0.000 description 11
- 238000002512 chemotherapy Methods 0.000 description 11
- 238000011534 incubation Methods 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 10
- 239000000306 component Substances 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 150000007523 nucleic acids Chemical class 0.000 description 10
- 206010006187 Breast cancer Diseases 0.000 description 9
- 208000026310 Breast neoplasm Diseases 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 102000000704 Interleukin-7 Human genes 0.000 description 9
- 108010002586 Interleukin-7 Proteins 0.000 description 9
- 229960005310 aldesleukin Drugs 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 238000001990 intravenous administration Methods 0.000 description 9
- 208000020816 lung neoplasm Diseases 0.000 description 9
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 9
- 102000039446 nucleic acids Human genes 0.000 description 9
- 108020004707 nucleic acids Proteins 0.000 description 9
- 230000036961 partial effect Effects 0.000 description 9
- 238000002108 rapid electrokinetic patterning Methods 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 102100028757 Chondroitin sulfate proteoglycan 4 Human genes 0.000 description 8
- 101000916489 Homo sapiens Chondroitin sulfate proteoglycan 4 Proteins 0.000 description 8
- 101001055157 Homo sapiens Interleukin-15 Proteins 0.000 description 8
- 102000004388 Interleukin-4 Human genes 0.000 description 8
- 108090000978 Interleukin-4 Proteins 0.000 description 8
- 206010033128 Ovarian cancer Diseases 0.000 description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 description 8
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 8
- 229960000106 biosimilars Drugs 0.000 description 8
- 230000001472 cytotoxic effect Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 102000056003 human IL15 Human genes 0.000 description 8
- 201000005202 lung cancer Diseases 0.000 description 8
- 239000011550 stock solution Substances 0.000 description 8
- 238000003860 storage Methods 0.000 description 8
- 108010074708 B7-H1 Antigen Proteins 0.000 description 7
- 206010005003 Bladder cancer Diseases 0.000 description 7
- 101000971533 Homo sapiens Killer cell lectin-like receptor subfamily G member 1 Proteins 0.000 description 7
- 102100021457 Killer cell lectin-like receptor subfamily G member 1 Human genes 0.000 description 7
- 101150030213 Lag3 gene Proteins 0.000 description 7
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 7
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 7
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000002617 apheresis Methods 0.000 description 7
- 239000006285 cell suspension Substances 0.000 description 7
- 238000012512 characterization method Methods 0.000 description 7
- 231100000433 cytotoxic Toxicity 0.000 description 7
- 229940126534 drug product Drugs 0.000 description 7
- 230000003463 hyperproliferative effect Effects 0.000 description 7
- 230000000977 initiatory effect Effects 0.000 description 7
- 210000000265 leukocyte Anatomy 0.000 description 7
- 239000000825 pharmaceutical preparation Substances 0.000 description 7
- 230000035755 proliferation Effects 0.000 description 7
- 230000010076 replication Effects 0.000 description 7
- 201000005112 urinary bladder cancer Diseases 0.000 description 7
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 6
- BMZRVOVNUMQTIN-UHFFFAOYSA-N Carbonyl Cyanide para-Trifluoromethoxyphenylhydrazone Chemical compound FC(F)(F)OC1=CC=C(NN=C(C#N)C#N)C=C1 BMZRVOVNUMQTIN-UHFFFAOYSA-N 0.000 description 6
- 238000008157 ELISA kit Methods 0.000 description 6
- 102000006354 HLA-DR Antigens Human genes 0.000 description 6
- 108010058597 HLA-DR Antigens Proteins 0.000 description 6
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 6
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 6
- 102000008070 Interferon-gamma Human genes 0.000 description 6
- 102100033467 L-selectin Human genes 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 108010004469 allophycocyanin Proteins 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 231100000050 cytotoxic potential Toxicity 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 238000002509 fluorescent in situ hybridization Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 229960003130 interferon gamma Drugs 0.000 description 6
- 230000006540 mitochondrial respiration Effects 0.000 description 6
- 210000000822 natural killer cell Anatomy 0.000 description 6
- 230000009257 reactivity Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
- MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 description 5
- MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 description 5
- MNULEGDCPYONBU-YNZHUHFTSA-N (4Z,18Z,20Z)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC1C(C2C)OC(=O)\C=C/C(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)C\C=C/C=C\C(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-YNZHUHFTSA-N 0.000 description 5
- MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 description 5
- MNULEGDCPYONBU-UHFFFAOYSA-N 4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 description 5
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 5
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 description 5
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 5
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 5
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 5
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 5
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 5
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 239000010836 blood and blood product Substances 0.000 description 5
- 229940125691 blood product Drugs 0.000 description 5
- 238000003570 cell viability assay Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000011260 co-administration Methods 0.000 description 5
- 230000000139 costimulatory effect Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000029087 digestion Effects 0.000 description 5
- 238000002224 dissection Methods 0.000 description 5
- 238000010494 dissociation reaction Methods 0.000 description 5
- 230000005593 dissociations Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 239000012737 fresh medium Substances 0.000 description 5
- 208000014829 head and neck neoplasm Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000001506 immunosuppresive effect Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 201000009546 lung large cell carcinoma Diseases 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 229930191479 oligomycin Natural products 0.000 description 5
- MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000010257 thawing Methods 0.000 description 5
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 4
- 230000002407 ATP formation Effects 0.000 description 4
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 4
- UIFFUZWRFRDZJC-UHFFFAOYSA-N Antimycin A1 Natural products CC1OC(=O)C(CCCCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-UHFFFAOYSA-N 0.000 description 4
- NQWZLRAORXLWDN-UHFFFAOYSA-N Antimycin-A Natural products CCCCCCC(=O)OC1C(C)OC(=O)C(NC(=O)c2ccc(NC=O)cc2O)C(C)OC(=O)C1CCCC NQWZLRAORXLWDN-UHFFFAOYSA-N 0.000 description 4
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 229930182566 Gentamicin Natural products 0.000 description 4
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 4
- 102000001398 Granzyme Human genes 0.000 description 4
- 108060005986 Granzyme Proteins 0.000 description 4
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 4
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 4
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- 101001010621 Homo sapiens Interleukin-21 Proteins 0.000 description 4
- 101000852998 Homo sapiens Interleukin-27 subunit alpha Proteins 0.000 description 4
- 101001002709 Homo sapiens Interleukin-4 Proteins 0.000 description 4
- 101001043807 Homo sapiens Interleukin-7 Proteins 0.000 description 4
- 101001043809 Homo sapiens Interleukin-7 receptor subunit alpha Proteins 0.000 description 4
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 4
- 241000701806 Human papillomavirus Species 0.000 description 4
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 4
- 102100036678 Interleukin-27 subunit alpha Human genes 0.000 description 4
- 102100021593 Interleukin-7 receptor subunit alpha Human genes 0.000 description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 description 4
- 206010023774 Large cell lung cancer Diseases 0.000 description 4
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 4
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 4
- 241001529936 Murinae Species 0.000 description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
- 206010038389 Renal cancer Diseases 0.000 description 4
- 208000006265 Renal cell carcinoma Diseases 0.000 description 4
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 4
- 238000011467 adoptive cell therapy Methods 0.000 description 4
- PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 description 4
- UIFFUZWRFRDZJC-SBOOETFBSA-N antimycin A Chemical compound C[C@H]1OC(=O)[C@H](CCCCCC)[C@@H](OC(=O)CC(C)C)[C@H](C)OC(=O)[C@H]1NC(=O)C1=CC=CC(NC=O)=C1O UIFFUZWRFRDZJC-SBOOETFBSA-N 0.000 description 4
- PVEVXUMVNWSNIG-UHFFFAOYSA-N antimycin A3 Natural products CC1OC(=O)C(CCCC)C(OC(=O)CC(C)C)C(C)OC(=O)C1NC(=O)C1=CC=CC(NC=O)=C1O PVEVXUMVNWSNIG-UHFFFAOYSA-N 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 229960002518 gentamicin Drugs 0.000 description 4
- 201000010536 head and neck cancer Diseases 0.000 description 4
- 102000055229 human IL4 Human genes 0.000 description 4
- 102000052622 human IL7 Human genes 0.000 description 4
- 229940072221 immunoglobulins Drugs 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 201000010982 kidney cancer Diseases 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 208000021039 metastatic melanoma Diseases 0.000 description 4
- 210000005087 mononuclear cell Anatomy 0.000 description 4
- 229960003301 nivolumab Drugs 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000036387 respiratory rate Effects 0.000 description 4
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 4
- 229940080817 rotenone Drugs 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 230000002463 transducing effect Effects 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 3
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 3
- PBUUPFTVAPUWDE-UGZDLDLSSA-N 2-[[(2S,4S)-2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2lambda5-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid Chemical compound OS(=O)(=O)CCS[C@H]1CCO[P@](=O)(N(CCCl)CCCl)N1 PBUUPFTVAPUWDE-UGZDLDLSSA-N 0.000 description 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
- 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 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 206010066476 Haematological malignancy Diseases 0.000 description 3
- 208000017604 Hodgkin disease Diseases 0.000 description 3
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 3
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 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
- 229930182816 L-glutamine Natural products 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 102000003735 Mesothelin Human genes 0.000 description 3
- 108090000015 Mesothelin Proteins 0.000 description 3
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 3
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 210000004241 Th2 cell Anatomy 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 238000011198 co-culture assay Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 108700023159 delta Opioid Receptors Proteins 0.000 description 3
- 102000048124 delta Opioid Receptors Human genes 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000027721 electron transport chain Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000012239 gene modification Methods 0.000 description 3
- 230000005017 genetic modification Effects 0.000 description 3
- 235000013617 genetically modified food Nutrition 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 238000001361 intraarterial administration Methods 0.000 description 3
- 210000001165 lymph node Anatomy 0.000 description 3
- 229950000547 mafosfamide Drugs 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000010627 oxidative phosphorylation Effects 0.000 description 3
- 229960002621 pembrolizumab Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 208000037821 progressive disease Diseases 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 230000000392 somatic effect Effects 0.000 description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 description 3
- 238000012289 standard assay Methods 0.000 description 3
- 229960002385 streptomycin sulfate Drugs 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 238000012762 unpaired Student’s t-test Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 108010041397 CD4 Antigens Proteins 0.000 description 2
- 108010029697 CD40 Ligand Proteins 0.000 description 2
- 108010032795 CD8 receptor Proteins 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 102000029816 Collagenase Human genes 0.000 description 2
- 108060005980 Collagenase Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 241001559542 Hippocampus hippocampus Species 0.000 description 2
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 2
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 2
- 101001055145 Homo sapiens Interleukin-2 receptor subunit beta Proteins 0.000 description 2
- 101001023379 Homo sapiens Lysosome-associated membrane glycoprotein 1 Proteins 0.000 description 2
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 2
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 2
- 230000005353 IP-10 production Effects 0.000 description 2
- 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 2
- 108010038498 Interleukin-7 Receptors Proteins 0.000 description 2
- 102000010782 Interleukin-7 Receptors Human genes 0.000 description 2
- 206010052178 Lymphocytic lymphoma Diseases 0.000 description 2
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 108700031757 NKTR-214 Proteins 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 2
- 108010087408 alpha-beta T-Cell Antigen Receptors Proteins 0.000 description 2
- 102000006707 alpha-beta T-Cell Antigen Receptors Human genes 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 230000005975 antitumor immune response Effects 0.000 description 2
- 238000013475 authorization Methods 0.000 description 2
- 229940121413 bempegaldesleukin Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 239000012503 blood component Substances 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 210000003690 classically activated macrophage Anatomy 0.000 description 2
- 229960002424 collagenase Drugs 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 230000003750 conditioning effect Effects 0.000 description 2
- 238000011262 co‐therapy Methods 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 208000031513 cyst Diseases 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 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 2
- 229940088598 enzyme Drugs 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000012997 ficoll-paque Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000004023 fresh frozen plasma Substances 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000011194 good manufacturing practice Methods 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 210000004408 hybridoma Anatomy 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000014828 interferon-gamma production Effects 0.000 description 2
- 102000008616 interleukin-15 receptor activity proteins Human genes 0.000 description 2
- 108040002039 interleukin-15 receptor activity proteins Proteins 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000007913 intrathecal administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 210000004324 lymphatic system Anatomy 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 230000006677 mitochondrial metabolism Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012806 monitoring device Methods 0.000 description 2
- 230000023185 monocyte chemotactic protein-1 production Effects 0.000 description 2
- 210000000581 natural killer T-cell Anatomy 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229940087463 proleukin Drugs 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 210000003289 regulatory T cell Anatomy 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000003319 supportive effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 2
- SSOORFWOBGFTHL-OTEJMHTDSA-N (4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2,6-diaminohexanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-oxopentanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SSOORFWOBGFTHL-OTEJMHTDSA-N 0.000 description 1
- LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 1
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241001227713 Chiron Species 0.000 description 1
- 102000036364 Cullin Ring E3 Ligases Human genes 0.000 description 1
- 108091007045 Cullin Ring E3 Ligases Proteins 0.000 description 1
- 206010013457 Dissociation Diseases 0.000 description 1
- 102000015782 Electron Transport Complex III Human genes 0.000 description 1
- 108010024882 Electron Transport Complex III Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 102000000849 HMGB Proteins Human genes 0.000 description 1
- 108010001860 HMGB Proteins Proteins 0.000 description 1
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 101001009603 Homo sapiens Granzyme B Proteins 0.000 description 1
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 1
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
- 101000872170 Homo sapiens Polycomb complex protein BMI-1 Proteins 0.000 description 1
- 101000946860 Homo sapiens T-cell surface glycoprotein CD3 epsilon chain Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000000743 Interleukin-5 Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102100031413 L-dopachrome tautomerase Human genes 0.000 description 1
- 101710093778 L-dopachrome tautomerase Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 102100024894 PR domain zinc finger protein 1 Human genes 0.000 description 1
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100033566 Polycomb complex protein BMI-1 Human genes 0.000 description 1
- 108010009975 Positive Regulatory Domain I-Binding Factor 1 Proteins 0.000 description 1
- 229940122117 Potassium channel agonist Drugs 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- 101710173693 Short transient receptor potential channel 1 Proteins 0.000 description 1
- 101710173694 Short transient receptor potential channel 2 Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108091008035 T cell costimulatory receptors Proteins 0.000 description 1
- 102100035794 T-cell surface glycoprotein CD3 epsilon chain Human genes 0.000 description 1
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000006536 aerobic glycolysis Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000002715 bioenergetic effect Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 201000002758 colorectal adenoma Diseases 0.000 description 1
- 238000010960 commercial process Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 208000018459 dissociative disease Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 230000006867 granzyme B production Effects 0.000 description 1
- 230000007773 growth pattern Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 102000055277 human IL2 Human genes 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 229940100994 interleukin-7 Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 208000019420 lymphoid neoplasm Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 238000013188 needle biopsy Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 108010007425 oligomycin sensitivity conferring protein Proteins 0.000 description 1
- 229950002610 otelixizumab Drugs 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 238000010827 pathological analysis Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229930192851 perforin Natural products 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229950010773 pidilizumab Drugs 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- 238000002616 plasmapheresis Methods 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 108091005475 signaling receptors Proteins 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229950007213 spartalizumab Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229950010127 teplizumab Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000004061 uncoupling agent Substances 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 229950004393 visilizumab Drugs 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/10—Preservation of living parts
- A01N1/16—Physical preservation processes
- A01N1/162—Temperature processes, e.g. following predefined temperature changes over time
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
-
- 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
- A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
- A61K40/41—Vertebrate antigens
- A61K40/42—Cancer antigens
- A61K40/428—Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55522—Cytokines; Lymphokines; Interferons
- A61K2039/55527—Interleukins
- A61K2039/55533—IL-2
-
- 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
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K40/00—Cellular immunotherapy
- A61K40/50—Cellular immunotherapy characterised by the use of allogeneic 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
- C12N2500/00—Specific components of cell culture medium
- C12N2500/90—Serum-free medium, which may still contain naturally-sourced components
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/04—Immunosuppressors, e.g. cyclosporin, tacrolimus
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2302—Interleukin-2 (IL-2)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2315—Interleukin-15 (IL-15)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2321—Interleukin-21 (IL-21)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/24—Interferons [IFN]
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
- C12N2501/603—Oct-3/4
-
- 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
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system 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
- C12N2506/00—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells
- C12N2506/30—Differentiation of animal cells from one lineage to another; Differentiation of pluripotent cells from cancer cells, e.g. reversion of tumour cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Environmental Sciences (AREA)
- Dentistry (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762478506P | 2017-03-29 | 2017-03-29 | |
| US201762539410P | 2017-07-31 | 2017-07-31 | |
| US201762548306P | 2017-08-21 | 2017-08-21 | |
| US201762554538P | 2017-09-05 | 2017-09-05 | |
| US201762559374P | 2017-09-15 | 2017-09-15 | |
| US201762567121P | 2017-10-02 | 2017-10-02 | |
| US201762577655P | 2017-10-26 | 2017-10-26 | |
| US201762582874P | 2017-11-07 | 2017-11-07 | |
| US201762596374P | 2017-12-08 | 2017-12-08 | |
| PCT/US2018/012633 WO2018182817A1 (en) | 2017-03-29 | 2018-01-05 | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MD3601533T2 true MD3601533T2 (ro) | 2021-07-31 |
Family
ID=61569356
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MDE20200116T MD3601533T2 (ro) | 2017-03-29 | 2018-01-05 | Procese de producţie a limfocitelor infiltrante în tumori și utilizările acestora în imunoterapie |
| MDE20201130T MD3730608T2 (ro) | 2017-03-29 | 2018-01-05 | Procese de producere de limfocite infiltrante tumorale și utilizarea acestora în imunoterapie |
| MDE20201056T MD3722415T2 (ro) | 2017-03-29 | 2018-01-05 | Procese de producție a limfocitelor infiltrante în tumori și utilizările acestora în imunoterapie |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MDE20201130T MD3730608T2 (ro) | 2017-03-29 | 2018-01-05 | Procese de producere de limfocite infiltrante tumorale și utilizarea acestora în imunoterapie |
| MDE20201056T MD3722415T2 (ro) | 2017-03-29 | 2018-01-05 | Procese de producție a limfocitelor infiltrante în tumori și utilizările acestora în imunoterapie |
Country Status (37)
Families Citing this family (123)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3628322A1 (en) | 2013-03-01 | 2020-04-01 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Cd8+ t cells that also express pd-1 and/or tim-3 for the treatment of cancer |
| GB201522097D0 (en) | 2015-12-15 | 2016-01-27 | Cellular Therapeutics Ltd | Cells |
| MX2019004707A (es) | 2016-10-26 | 2019-08-12 | Iovance Biotherapeutics Inc | Reestimulacion de linfocitos infiltrantes de tumor crioconservados. |
| US11261428B2 (en) | 2018-03-15 | 2022-03-01 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| US11332713B2 (en) | 2016-11-16 | 2022-05-17 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| CA3049165A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof |
| GB201700621D0 (en) | 2017-01-13 | 2017-03-01 | Guest Ryan Dominic | Method,device and kit for the aseptic isolation,enrichment and stabilsation of cells from mammalian solid tissue |
| BR112019018915A2 (pt) | 2017-03-15 | 2020-04-14 | Pandion Therapeutics Inc | imunotolerância direcionada |
| JOP20190224A1 (ar) | 2017-03-29 | 2019-09-26 | Iovance Biotherapeutics Inc | عمليات من أجل إنتاج الخلايا اللمفاوية المرتشحة للأورام واستخداماتها في العلاج المناعي |
| US11254913B1 (en) | 2017-03-29 | 2022-02-22 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
| JP2020521452A (ja) | 2017-05-24 | 2020-07-27 | パンディオン・セラピューティクス・インコーポレイテッド | 標的化免疫寛容 |
| EP3635097A1 (en) * | 2017-06-05 | 2020-04-15 | Iovance Biotherapeutics, Inc. | Methods of using tumor infiltrating lymphocytes in double-refractory melanoma |
| EP4501408A3 (en) * | 2017-11-17 | 2025-04-09 | Iovance Biotherapeutics, Inc. | Til expansion from fine needle aspirates and small biopsies |
| US20200299349A1 (en) | 2017-11-21 | 2020-09-24 | The Board Of Trustees Of The Leland Stanford Junior University | Partial agonists of interleukin-2 |
| EP3714041A1 (en) | 2017-11-22 | 2020-09-30 | Iovance Biotherapeutics, Inc. | Expansion of peripheral blood lymphocytes (pbls) from peripheral blood |
| USRE50550E1 (en) | 2017-12-06 | 2025-08-26 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| US10946068B2 (en) | 2017-12-06 | 2021-03-16 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
| US10174091B1 (en) | 2017-12-06 | 2019-01-08 | Pandion Therapeutics, Inc. | IL-2 muteins |
| SG11202006541UA (en) | 2018-01-08 | 2020-08-28 | Iovance Biotherapeutics Inc | Processes for generating til products enriched for tumor antigen-specific t-cells |
| US11713446B2 (en) | 2018-01-08 | 2023-08-01 | Iovance Biotherapeutics, Inc. | Processes for generating TIL products enriched for tumor antigen-specific T-cells |
| US20190284553A1 (en) | 2018-03-15 | 2019-09-19 | KSQ Therapeutics, Inc. | Gene-regulating compositions and methods for improved immunotherapy |
| MA52667B1 (fr) * | 2018-03-29 | 2024-07-31 | Iovance Biotherapeutics, Inc. | Procédés de production de lymphocytes infiltrant les tumeurs et leurs utilisations en immunothérapie |
| US20210130779A1 (en) | 2018-04-27 | 2021-05-06 | Iovance Biotherapeutics, Inc. | Closed process for expansion and gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy |
| WO2019217753A1 (en) * | 2018-05-10 | 2019-11-14 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
| JP7600123B2 (ja) | 2018-10-15 | 2024-12-16 | ニューリックス セラピューティクス,インコーポレイテッド | ユビキチンプロテオソーム経路を介してbtkを分解するための二官能性化合物 |
| CA3118493A1 (en) * | 2018-11-05 | 2020-05-14 | Iovance Biotherapeutics, Inc. | Expansion of tils utilizing akt pathway inhibitors |
| TW202039831A (zh) | 2018-11-05 | 2020-11-01 | 美商艾歐凡斯生物治療公司 | 對抗pd-1抗體呈現難治性之非小細胞肺癌(nsclc)病患之治療 |
| TW202039830A (zh) | 2018-11-05 | 2020-11-01 | 美商艾歐凡斯生物治療公司 | 用於製造腫瘤浸潤性淋巴細胞之方法及其在免疫療法中之用途 |
| US20230039976A1 (en) * | 2018-11-05 | 2023-02-09 | Iovance Biotherapeutics, Inc. | Selection of improved tumor reactive t-cells |
| KR20210111746A (ko) * | 2018-11-08 | 2021-09-13 | 감마델타 테라퓨틱스 리미티드 | 세포를 단리 및 증식하는 방법 |
| JP7710372B2 (ja) * | 2018-12-19 | 2025-07-18 | アイオバンス バイオセラピューティクス,インコーポレイテッド | 操作されたサイトカイン受容体対を使用して腫瘍浸潤リンパ球を拡大培養する方法及びその使用 |
| US20220112557A1 (en) | 2019-01-10 | 2022-04-14 | Iovance Biotherapeutics, Inc. | System and methods for monitoring adoptive cell therapy clonality and persistence |
| WO2020167518A1 (en) | 2019-02-13 | 2020-08-20 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading btk via ubiquitin proteosome pathway |
| US20220249559A1 (en) | 2019-05-13 | 2022-08-11 | Iovance Biotherapeutics, Inc. | Methods and compositions for selecting tumor infiltrating lymphocytes and uses of the same in immunotherapy |
| WO2020236875A1 (en) | 2019-05-20 | 2020-11-26 | Pandion Therapeutics, Inc. | Madcam targeted immunotolerance |
| US20220257656A1 (en) * | 2019-07-10 | 2022-08-18 | National Cancer Center | Specific marker for identifying t cells specifically attacking cancer cells |
| GB201911066D0 (en) | 2019-08-02 | 2019-09-18 | Achilles Therapeutics Ltd | T cell therapy |
| WO2021030482A1 (en) * | 2019-08-12 | 2021-02-18 | Bellicum Pharmaceuticals, Inc. | Improved formulations for immune cells |
| WO2021032779A1 (en) | 2019-08-19 | 2021-02-25 | Universität Basel | Cell therapy methods |
| EP4034141A1 (en) | 2019-09-24 | 2022-08-03 | Nurix Therapeutics, Inc. | Cbl inhibitors and compositions for expansion of immune cells |
| JP2022553389A (ja) * | 2019-10-25 | 2022-12-22 | アイオバンス バイオセラピューティクス,インコーポレイテッド | 腫瘍浸潤リンパ球の遺伝子編集及び免疫療法におけるその使用 |
| US11820781B2 (en) | 2019-12-04 | 2023-11-21 | Nurix Therapeutics, Inc. | Bifunctional compounds for degrading BTK via ubiquitin proteosome pathway |
| US12516291B2 (en) | 2019-12-11 | 2026-01-06 | Iovance Biotherapeutics, Inc. | Processes for the production of tumor infiltrating lymphocytes (TILs) and methods of using the same |
| WO2021123832A1 (en) | 2019-12-20 | 2021-06-24 | Instil Bio (Uk) Limited | Devices and methods for isolating tumor infiltrating lymphocytes and uses thereof |
| EP4090674A4 (en) | 2020-01-14 | 2024-01-24 | Synthekine, Inc. | Biased il2 muteins methods and compositions |
| US11981715B2 (en) | 2020-02-21 | 2024-05-14 | Pandion Operations, Inc. | Tissue targeted immunotolerance with a CD39 effector |
| US12159700B2 (en) * | 2020-04-22 | 2024-12-03 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
| WO2021219990A1 (en) | 2020-04-28 | 2021-11-04 | Achilles Therapeutics Uk Limited | T cell therapy |
| US12365871B2 (en) | 2020-04-28 | 2025-07-22 | Lyell Immunopharma, Inc. | Methods for culturing cells |
| CN116018158A (zh) * | 2020-04-30 | 2023-04-25 | 转化基因组学研究所 | 新抗原知情的肿瘤浸润性淋巴细胞癌免疫疗法 |
| EP4146794A1 (en) | 2020-05-04 | 2023-03-15 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy |
| TW202208616A (zh) | 2020-05-04 | 2022-03-01 | 美商艾歐凡斯生物治療公司 | 改良之腫瘤反應性t細胞的選擇 |
| GB202006989D0 (en) * | 2020-05-12 | 2020-06-24 | Gammadelta Therapeutics Ltd | Methods for isolating gamma delta t cells |
| JP7785699B2 (ja) * | 2020-05-29 | 2025-12-15 | シャンハイ ジュンセル セラピューティクス カンパニー リミテッド | 腫瘍浸潤リンパ球の種細胞培地及びその使用 |
| CN111876381A (zh) * | 2020-07-22 | 2020-11-03 | 中美冠科生物技术(太仓)有限公司 | 一种t细胞模型及其在体外人源pd-1抗体药效评价中的应用 |
| WO2022076606A1 (en) | 2020-10-06 | 2022-04-14 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
| US20230372397A1 (en) * | 2020-10-06 | 2023-11-23 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
| TW202237824A (zh) | 2020-11-23 | 2022-10-01 | 美商萊爾免疫藥物股份有限公司 | 培養免疫細胞之方法 |
| JP2024501127A (ja) | 2020-11-25 | 2024-01-11 | 上海君賽生物科技有限公司 | 腫瘍浸潤リンパ球培地及びその使用 |
| WO2022111573A1 (zh) | 2020-11-25 | 2022-06-02 | 上海君赛生物科技有限公司 | 增强细胞杀伤的药物组合物及其用途 |
| TW202241468A (zh) * | 2020-12-11 | 2022-11-01 | 美商艾歐凡斯生物治療公司 | 用腫瘤浸潤性淋巴球療法與braf抑制劑及/或mek抑制劑組合治療癌症患者 |
| CA3202483A1 (en) * | 2020-12-17 | 2022-06-23 | Maria Fardis | Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors |
| US20240123067A1 (en) * | 2020-12-17 | 2024-04-18 | Iovance Biotherapeutics, Inc. | Treatment of cancers with tumor infiltrating lymphocyte therapies |
| EP4263808A2 (en) * | 2020-12-18 | 2023-10-25 | Instil Bio (Uk) Limited | Processing of tumor infiltrating lymphocytes |
| WO2022130016A1 (en) | 2020-12-18 | 2022-06-23 | Instil Bio (Uk) Limited | Tumor infiltrating lymphocytes and anti-cd47 therapeutics |
| JP2024500748A (ja) * | 2020-12-18 | 2024-01-10 | インスティル バイオ (ユーケイ) リミテッド | 腫瘍浸潤リンパ球の処理 |
| CN114686430A (zh) * | 2020-12-31 | 2022-07-01 | 上海赛比曼生物科技有限公司 | 一种制备til的方法 |
| TW202242085A (zh) | 2020-12-31 | 2022-11-01 | 美商艾歐凡斯生物治療公司 | 供自動生產腫瘤浸潤淋巴球的裝置和方法 |
| JPWO2022145490A1 (https=) * | 2021-01-04 | 2022-07-07 | ||
| TW202241508A (zh) * | 2021-01-29 | 2022-11-01 | 美商艾歐凡斯生物治療公司 | 細胞介素相關之腫瘤浸潤性淋巴球組合物及方法 |
| CA3207359A1 (en) | 2021-02-05 | 2022-08-11 | Cecile Chartier-Courtaud | Adjuvant therapy for cancer |
| KR20230150833A (ko) | 2021-02-25 | 2023-10-31 | 라이엘 이뮤노파마, 인크. | 세포 배양 방법 |
| WO2022187741A2 (en) | 2021-03-05 | 2022-09-09 | Iovance Biotherapeutics, Inc. | Tumor storage and cell culture compositions |
| WO2022198141A1 (en) * | 2021-03-19 | 2022-09-22 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd69 selection and gene knockout in tils |
| AU2022246174A1 (en) | 2021-03-25 | 2023-09-14 | Iovance Biotherapeutics, Inc. | Methods and compositions for t-cell coculture potency assays and use with cell therapy products |
| JP2024512978A (ja) * | 2021-03-30 | 2024-03-21 | ネオジェント コーポレーション | 免疫細胞組成物を生成するための方法 |
| EP4320435A1 (en) | 2021-04-09 | 2024-02-14 | Achilles Therapeutics UK Limited | Batch release assay for pharmaceutical products relating to t cell therapies |
| GB202109886D0 (en) | 2021-07-08 | 2021-08-25 | Achilles Therapeutics Uk Ltd | Assay |
| EP4326287A2 (en) | 2021-04-19 | 2024-02-28 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
| CN117203328A (zh) | 2021-04-27 | 2023-12-08 | 武田药品工业株式会社 | 重组抗原呈递细胞 |
| WO2022245754A1 (en) | 2021-05-17 | 2022-11-24 | Iovance Biotherapeutics, Inc. | Pd-1 gene-edited tumor infiltrating lymphocytes and uses of same in immunotherapy |
| DE102021002748A1 (de) | 2021-05-27 | 2022-12-01 | Zellwerk Gmbh | Verfahren zur Herstellung von Tumor-infiltrierten T-Lymphozyten (TIL) und deren Verwendung als Zell-Therapeutika für die Behandlung humaner Tumoren |
| AU2022292928A1 (en) * | 2021-06-17 | 2024-01-25 | CBio A/S | Multistep process for culturing tumor-infiltrating lymphocytes for therapeutic use |
| WO2022269250A1 (en) | 2021-06-22 | 2022-12-29 | Achilles Therapeutics Uk Limited | A method for producing antigen-specific t cells |
| US20240365776A1 (en) * | 2021-07-22 | 2024-11-07 | Iovance Biotherapeutics, Inc | Method for cryopreservation of solid tumor fragments |
| US20240342285A1 (en) | 2021-07-28 | 2024-10-17 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors |
| IL311333A (en) | 2021-09-09 | 2024-05-01 | Iovance Biotherapeutics Inc | Processes for generating til products using pd-1 talen knockdown |
| EP4404969A1 (en) | 2021-09-24 | 2024-07-31 | Iovance Biotherapeutics, Inc. | Expansion processes and agents for tumor infiltrating lymphocytes |
| AU2022379494A1 (en) | 2021-10-26 | 2024-05-30 | Nurix Therapeutics, Inc. | Piperidinylpyrazine-carboxamide compounds for treating and preventing cancer and for degrading btk |
| WO2023077015A2 (en) | 2021-10-27 | 2023-05-04 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
| WO2023077034A1 (en) | 2021-10-28 | 2023-05-04 | Lyell Immunopharma, Inc. | Methods for culturing immune cells |
| EP4430167A1 (en) | 2021-11-10 | 2024-09-18 | Iovance Biotherapeutics, Inc. | Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes |
| WO2023137472A2 (en) | 2022-01-14 | 2023-07-20 | Tune Therapeutics, Inc. | Compositions, systems, and methods for programming t cell phenotypes through targeted gene repression |
| US20250134999A1 (en) | 2022-01-14 | 2025-05-01 | Tune Therapeutics, Inc. | Compositions, systems, and methods for programming t cell phenotypes through targeted gene activation |
| US20250101380A1 (en) * | 2022-01-28 | 2025-03-27 | Iovance Biotherapeutics, Inc. | Tumor infiltrating lymphocytes engineered to express payloads |
| WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
| EP4504220A1 (en) | 2022-04-06 | 2025-02-12 | Iovance Biotherapeutics, Inc. | Treatment of nsclc patients with tumor infiltrating lymphocyte therapies |
| CA3248034A1 (en) | 2022-04-15 | 2023-10-19 | Iovance Biotherapeutics, Inc. | METHODS FOR EXPANSION OF TIL CELLS BY MEANS OF SPECIFIC CYTOKINE COMBINATIONS AND/OR AKT INHIBITOR TREATMENT |
| EP4522202A1 (en) | 2022-05-10 | 2025-03-19 | Iovance Biotherapeutics, Inc. | Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with an il-15r agonist |
| US20260008990A1 (en) | 2022-07-06 | 2026-01-08 | Iovance Biotherapeutics, Inc. | Devices and processes for automated production of tumor infiltrating lymphocytes |
| GB202210006D0 (en) | 2022-07-07 | 2022-08-24 | Achilles Therapeutics Uk Ltd | Analysis of T cell samples |
| EP4565683A1 (en) | 2022-08-01 | 2025-06-11 | Iovance Biotherapeutics, Inc. | Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies |
| EP4583890A1 (en) | 2022-09-09 | 2025-07-16 | Iovance Biotherapeutics, Inc. | Processes for generating til products using pd-1/tigit talen double knockdown |
| EP4583889A1 (en) | 2022-09-09 | 2025-07-16 | Iovance Biotherapeutics, Inc. | Processes for generating til products using pd-1/tigit talen double knockdown |
| US12181192B2 (en) * | 2022-09-16 | 2024-12-31 | Black & Decker, Inc. | Methods and devices for controlling the temperature of a surface |
| CN120239746A (zh) | 2022-09-19 | 2025-07-01 | 图恩疗法股份有限公司 | 用于调节t细胞功能的组合物、系统和方法 |
| WO2024098027A1 (en) | 2022-11-04 | 2024-05-10 | Iovance Biotherapeutics, Inc. | Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd103 selection |
| EP4623072A2 (en) | 2022-11-21 | 2025-10-01 | Iovance Biotherapeutics, Inc. | Two-dimensional processes for the expansion of tumor infiltrating lymphocytes and therapies therefrom |
| WO2024112711A2 (en) | 2022-11-21 | 2024-05-30 | Iovance Biotherapeutics, Inc. | Methods for assessing proliferation potency of gene-edited t cells |
| WO2024118836A1 (en) | 2022-11-30 | 2024-06-06 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes with shortened rep step |
| WO2024178397A2 (en) | 2023-02-24 | 2024-08-29 | Elevatebio Technologies, Inc. | Modified immune effector cells and methods of use |
| DE102023002417B3 (de) | 2023-06-15 | 2024-12-05 | Zellwerk Gmbh | Verfahren zur Expansion von Zellen |
| WO2025006811A1 (en) | 2023-06-27 | 2025-01-02 | Lyell Immunopharma, Inc. | Methods for culturing immune cells |
| AU2024296516A1 (en) | 2023-07-13 | 2026-01-22 | Iovance Biotherapeutics, Inc. | Cytokine encoding lentiviral vectors and uses thereof for making tumor infiltrating lymphocytes |
| WO2025029840A1 (en) | 2023-07-31 | 2025-02-06 | Tune Therapeutics, Inc. | Compositions and methods for multiplexed activation and repression of t cell gene expression |
| CN121909284A (zh) | 2023-07-31 | 2026-04-21 | 图恩疗法股份有限公司 | 用于调节il-2基因表达的组合物和方法 |
| WO2025038289A1 (en) * | 2023-08-17 | 2025-02-20 | H. Lee Moffitt Cancer Center And Research Institute Inc. | Using 12 chemokine signature to select sting agonist and til treatments for solid tumors |
| WO2025047660A1 (ja) * | 2023-08-31 | 2025-03-06 | 国立大学法人筑波大学 | 腫瘍性濾胞制御性t細胞及び腫瘍性濾胞殺細胞性t細胞を定量する方法、腫瘍性濾胞制御性t細胞及び腫瘍性濾胞殺細胞性t細胞をスクリーニングする方法、治療用組成物、及びキット |
| WO2025054540A1 (en) | 2023-09-08 | 2025-03-13 | Iovance Biotherapeutics, Inc. | Methods of gene-editing using programmable nucleases |
| WO2025101484A1 (en) | 2023-11-06 | 2025-05-15 | Iovance Biotherapeutics, Inc. | Treatment of endometrial cancers with tumor infiltrating lymphocyte therapies |
| WO2025256538A1 (zh) * | 2024-06-12 | 2025-12-18 | 北京沙砾生物医药股份有限公司 | 一种细胞产品中检测肿瘤残留的方法 |
| WO2026006604A1 (en) | 2024-06-26 | 2026-01-02 | Lyell Immunopharma, Inc. | Feeder cell replacement |
| CN118710478B (zh) * | 2024-08-27 | 2025-01-03 | 福州大学 | 基于改进麻雀搜索算法的地铁突发运营中断客流疏运方法 |
Family Cites Families (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US5206344A (en) | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| AU7873187A (en) | 1986-08-08 | 1988-02-24 | University Of Minnesota | Method of culturing leukocytes |
| US7479269B2 (en) | 1988-11-23 | 2009-01-20 | Genetics Institute, Llc | Methods for selectively enriching TH1 and TH2 cells |
| US6905680B2 (en) | 1988-11-23 | 2005-06-14 | Genetics Institute, Inc. | Methods of treating HIV infected subjects |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| US6352694B1 (en) | 1994-06-03 | 2002-03-05 | Genetics Institute, Inc. | Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells |
| US5089261A (en) | 1989-01-23 | 1992-02-18 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US4902502A (en) | 1989-01-23 | 1990-02-20 | Cetus Corporation | Preparation of a polymer/interleukin-2 conjugate |
| US5126132A (en) | 1989-08-21 | 1992-06-30 | The United States Of America As Represented By The Department Of Health And Human Services | Tumor infiltrating lymphocytes as a treatment modality for human cancer |
| US7175843B2 (en) | 1994-06-03 | 2007-02-13 | Genetics Institute, Llc | Methods for selectively stimulating proliferation of T cells |
| US7572631B2 (en) | 2000-02-24 | 2009-08-11 | Invitrogen Corporation | Activation and expansion of T cells |
| US6867041B2 (en) | 2000-02-24 | 2005-03-15 | Xcyte Therapies, Inc. | Simultaneous stimulation and concentration of cells |
| ES2382636T3 (es) | 2000-10-31 | 2012-06-12 | Surmodics Pharmaceuticals, Inc. | Método para producir composiciones para la administración mejorada de moléculas bioactivas |
| US20050084967A1 (en) | 2002-06-28 | 2005-04-21 | Xcyte Therapies, Inc. | Compositions and methods for eliminating undesired subpopulations of T cells in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation |
| WO2004003142A2 (en) | 2002-06-28 | 2004-01-08 | Xcyte Therapies, Inc. | Compositions and methods for restoring immune repertoire in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation |
| AU2003265948B8 (en) | 2002-09-06 | 2009-09-03 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Immunotherapy with in vitro-selected antigen-specific lymphocytes after nonmyeloablative lymphodepleting chemotherapy |
| ITMI20022118A1 (it) | 2002-10-04 | 2004-04-05 | Abiogen Pharma Spa | Procedimento per la coltura su larga scala di t-linfociti in un sistema omogeneo. |
| CN101120083B (zh) | 2003-10-08 | 2013-03-27 | 威尔森沃尔夫制造公司 | 利用透气性材料进行细胞培养的方法及装置 |
| RU2494107C2 (ru) | 2005-05-09 | 2013-09-27 | Оно Фармасьютикал Ко., Лтд. | Моноклональные антитела человека к белку программируемой смерти 1 (pd-1) и способы лечения рака с использованием анти-pd-1-антител самостоятельно или в комбинации с другими иммунотерапевтическими средствами |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
| US8211424B2 (en) | 2005-12-21 | 2012-07-03 | Sentoclone International Ab | Method for treating malignant melanoma |
| EP1966370B1 (en) | 2005-12-21 | 2013-02-20 | SentoClone International AB | Method for obtaining T-lymphocytes |
| US8206702B2 (en) | 2005-12-21 | 2012-06-26 | Sentoclone International Ab | Method for expansion of tumour-reactive T-lymphocytes for immunotherapy of patients with cancer |
| US8007785B2 (en) | 2005-12-21 | 2011-08-30 | Sentoclone International Ab | Method for treating colon cancer with tumour-reactive T-lymphocytes |
| FR2911346B1 (fr) * | 2007-01-12 | 2012-12-07 | Ct Hospitalier Universitaire De Nantes | Procede de culture in vitro de lymphocytes t,en particulier de lymphocytes t infiltrant les tumeurs dits til |
| US7951365B2 (en) | 2007-06-27 | 2011-05-31 | Deifiera Falun Ab | Method for expansion of tumour-reactive T-lymphocytes for immunotherapy of patients with specific cancer types |
| EP2203746B1 (en) * | 2007-09-24 | 2013-03-06 | Technion Research & Development Foundation Ltd. | T cell subpopulations capable of treating cancer |
| US20150320798A1 (en) | 2012-11-27 | 2015-11-12 | The Johns Hopkins University | Use of Post-Transplant Cyclophosphamide Treated Allogeneic Marrow Infiltrating Lymphocytes to Augment Anti-Tumor Immunity |
| WO2014085437A2 (en) | 2012-11-27 | 2014-06-05 | The Johns Hopkins University | Use of post-transplant cyclophosphamide treated allogeneic marrow infiltrating lymphocytes to augment anti-tumor immunity |
| US8383099B2 (en) | 2009-08-28 | 2013-02-26 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adoptive cell therapy with young T cells |
| US8809050B2 (en) | 2009-12-08 | 2014-08-19 | Wilson Wolf Manufacturing | Methods of cell culture for adoptive cell therapy |
| US8956860B2 (en) | 2009-12-08 | 2015-02-17 | Juan F. Vera | Methods of cell culture for adoptive cell therapy |
| US20130115617A1 (en) | 2009-12-08 | 2013-05-09 | John R. Wilson | Methods of cell culture for adoptive cell therapy |
| ES2866674T3 (es) | 2010-11-12 | 2021-10-19 | Nektar Therapeutics | Conjugados de una fracción de IL-2 y un polímero |
| WO2012129201A1 (en) | 2011-03-22 | 2012-09-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of growing tumor infiltrating lymphocytes in gas-permeable containers |
| EP2697367B1 (en) | 2011-04-13 | 2018-12-19 | Immunicum AB | Method for proliferation of antigen-specific t cells |
| AU2012324644B2 (en) * | 2011-10-21 | 2014-08-28 | Cell Medica Limited | Device for the aseptic expansion of cells |
| GB201121308D0 (en) * | 2011-12-12 | 2012-01-25 | Cell Medica Ltd | Process |
| CN102816734A (zh) | 2012-05-09 | 2012-12-12 | 阮润生 | 一种肿瘤抗原特异性t细胞的获取方法 |
| SG11201407226WA (en) | 2012-05-18 | 2014-12-30 | Wolf Wilson Mfg Corp | Improved methods of cell culture for adoptive cell therapy |
| CN104411819B (zh) | 2012-06-11 | 2019-05-10 | 威尔逊沃夫制造公司 | 用于过继细胞疗法的改进的细胞培养方法 |
| RU2671897C2 (ru) | 2013-03-01 | 2018-11-07 | Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретари, Департмент Оф Хелс Энд Хьюман Сёрвисез | Способы получения из опухоли обогащенных популяций реактивных в отношении опухоли т-клеток |
| EP3628322A1 (en) | 2013-03-01 | 2020-04-01 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Cd8+ t cells that also express pd-1 and/or tim-3 for the treatment of cancer |
| CN118562610A (zh) | 2013-06-24 | 2024-08-30 | 威尔逊沃夫制造公司 | 用于透气性细胞培养过程的封闭系统装置和方法 |
| JP6616295B2 (ja) * | 2013-07-15 | 2019-12-04 | アメリカ合衆国 | 抗ヒトパピローマウイルス抗原t細胞の調製方法 |
| WO2015039100A1 (en) | 2013-09-16 | 2015-03-19 | The Trustees Of The University Of Pennsylvania | Cd137 enrichment for efficient tumor infiltrating lymphocyte selection |
| JP2017511375A (ja) | 2014-03-20 | 2017-04-20 | エイチ リー モフィット キャンサー センター アンド リサーチ インスティテュート インコーポレイテッド | 養子細胞療法のための腫瘍浸潤リンパ球 |
| WO2015157636A1 (en) | 2014-04-10 | 2015-10-15 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy |
| RU2763795C2 (ru) | 2014-04-23 | 2022-01-11 | Джуно Терапьютикс, Инк. | Способы выделения, культивирования и генетической инженерии популяций клеток иммунной системы для адоптивной терапии |
| AU2015273501B2 (en) | 2014-06-11 | 2021-01-21 | Polybiocept Gmbh | Expansion of lymphocytes with a cytokine composition for active cellular immunotherapy |
| EP3155426B1 (en) | 2014-06-13 | 2023-07-19 | Immudex ApS | General detection and isolation of specific cells by binding of labeled molecules |
| US9687510B2 (en) | 2014-09-04 | 2017-06-27 | The Johns Hopkins University | Activation of marrow infiltrating lymphocytes in hypoxic alternating with normoxic conditions |
| AU2014407539B2 (en) * | 2014-10-02 | 2020-10-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of isolating T cell receptors having antigenic specificity for a cancer-specific mutation |
| EP3034092A1 (en) | 2014-12-17 | 2016-06-22 | Université de Lausanne | Adoptive immunotherapy for treating cancer |
| US10544392B2 (en) | 2015-05-01 | 2020-01-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of isolating T cells and T cell receptors having antigenic specificity for a cancer-specific mutation from peripheral blood |
| FR3040396A1 (fr) | 2015-06-30 | 2017-03-03 | Chu Nantes | Procede de cryoconservation de lymphocytes infiltrant la tumeur |
| FR3038324B1 (fr) | 2015-06-30 | 2020-10-30 | Lab Francais Du Fractionnement | Procede de cryoconservation de cellules a visee therapeutique |
| WO2017048614A1 (en) | 2015-09-15 | 2017-03-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of isolating tumor-reactive t cell receptors from tumor or peripheral blood |
| SG11201803330WA (en) | 2015-10-22 | 2018-05-30 | Juno Therapeutics Gmbh | Methods for culturing cells and kits and apparatus for same |
| CN108463547A (zh) | 2015-10-28 | 2018-08-28 | 生命技术股份公司 | 通过改变细胞表面信号和信号比选择性扩增不同的t细胞亚群 |
| KR20190037243A (ko) | 2016-06-28 | 2019-04-05 | 지니우스 바이오테크놀로지 인코포레이티드 | 면역치료를 위한 티 세포 조성물 |
| CN106244538A (zh) | 2016-08-04 | 2016-12-21 | 英普乐孚生物技术(上海)有限公司 | 一种恶性腹水来源的til细胞的分离培养方法 |
| KR102561356B1 (ko) | 2016-09-14 | 2023-08-03 | 애브비 바이오테라퓨틱스 인크. | 항-pd-1 항체 및 이의 용도 |
| MX2019004707A (es) | 2016-10-26 | 2019-08-12 | Iovance Biotherapeutics Inc | Reestimulacion de linfocitos infiltrantes de tumor crioconservados. |
| TWI788307B (zh) | 2016-10-31 | 2023-01-01 | 美商艾歐凡斯生物治療公司 | 用於擴增腫瘤浸潤性淋巴細胞之工程化人造抗原呈現細胞 |
| US11401507B2 (en) | 2016-11-17 | 2022-08-02 | Iovance Biotherapeutics, Inc. | Remnant tumor infiltrating lymphocytes and methods of preparing and using the same |
| WO2018102761A1 (en) | 2016-12-02 | 2018-06-07 | City Of Hope | Methods for manufacturing and expanding t cells expressing chimeric antigen receptors and other receptors |
| CN106591232A (zh) | 2017-01-04 | 2017-04-26 | 安徽安龙基因医学检验所有限公司 | 一种高效的pd‑1‑cd8+t细胞的培养方法 |
| BR112019013940A2 (pt) | 2017-01-06 | 2020-02-11 | Iovance Biotherapeutics, Inc. | Método de tratar um câncer com uma população de linfócitos infiltrantes de tumor, processo para preparação de uma população de linfócitos infiltrantes de tumor, população de linfócitos infiltrantes de tumor, e, composição farmacêutica. |
| CA3049165A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof |
| SG11201908271WA (en) | 2017-03-14 | 2019-10-30 | Juno Therapeutics Inc | Methods for cryogenic storage |
| US11254913B1 (en) | 2017-03-29 | 2022-02-22 | Iovance Biotherapeutics, Inc. | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |
| JOP20190224A1 (ar) | 2017-03-29 | 2019-09-26 | Iovance Biotherapeutics Inc | عمليات من أجل إنتاج الخلايا اللمفاوية المرتشحة للأورام واستخداماتها في العلاج المناعي |
| US20200224161A1 (en) | 2017-05-10 | 2020-07-16 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof |
| EP3635097A1 (en) | 2017-06-05 | 2020-04-15 | Iovance Biotherapeutics, Inc. | Methods of using tumor infiltrating lymphocytes in double-refractory melanoma |
| CN107384867B (zh) | 2017-08-04 | 2020-09-11 | 北京世纪劲得生物技术有限公司 | 一种肿瘤组织til细胞制备方法及专用培养基 |
| US11713446B2 (en) | 2018-01-08 | 2023-08-01 | Iovance Biotherapeutics, Inc. | Processes for generating TIL products enriched for tumor antigen-specific T-cells |
| US12159700B2 (en) | 2020-04-22 | 2024-12-03 | Iovance Biotherapeutics, Inc. | Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy |
-
2017
- 2017-06-16 JO JOP/2019/0224A patent/JOP20190224A1/ar unknown
-
2018
- 2018-01-05 MD MDE20200116T patent/MD3601533T2/ro unknown
- 2018-01-05 PE PE2019001976A patent/PE20191841A1/es unknown
- 2018-01-05 JP JP2019553050A patent/JP7169291B2/ja active Active
- 2018-01-05 RS RS20210622A patent/RS61863B1/sr unknown
- 2018-01-05 NZ NZ796152A patent/NZ796152A/en unknown
- 2018-01-05 HR HRP20210677TT patent/HRP20210677T1/hr unknown
- 2018-01-05 RS RS20250109A patent/RS66452B1/sr unknown
- 2018-01-05 EP EP23195819.0A patent/EP4279574A3/en active Pending
- 2018-01-05 CA CA3057975A patent/CA3057975A1/en active Pending
- 2018-01-05 PL PL18709132T patent/PL3601533T3/pl unknown
- 2018-01-05 EP EP20161179.5A patent/EP3730608B1/en active Active
- 2018-01-05 IL IL305198A patent/IL305198A/en unknown
- 2018-01-05 MA MA68856A patent/MA68856B1/fr unknown
- 2018-01-05 FI FIEP20161179.5T patent/FI3730608T3/fi active
- 2018-01-05 SM SM20250027T patent/SMT202500027T1/it unknown
- 2018-01-05 HU HUE18709132A patent/HUE054829T2/hu unknown
- 2018-01-05 DK DK20161179.5T patent/DK3730608T3/da active
- 2018-01-05 AU AU2018243355A patent/AU2018243355B2/en active Active
- 2018-01-05 HU HUE20161276A patent/HUE070256T2/hu unknown
- 2018-01-05 LT LTEP20161179.5T patent/LT3730608T/lt unknown
- 2018-01-05 ES ES20161179T patent/ES3009885T3/es active Active
- 2018-01-05 SM SM20210298T patent/SMT202100298T1/it unknown
- 2018-01-05 PT PT201611795T patent/PT3730608T/pt unknown
- 2018-01-05 SI SI201830278T patent/SI3601533T1/sl unknown
- 2018-01-05 MA MA68598A patent/MA68598B1/fr unknown
- 2018-01-05 HR HRP20250068TT patent/HRP20250068T1/hr unknown
- 2018-01-05 HR HRP20241688TT patent/HRP20241688T1/hr unknown
- 2018-01-05 US US15/863,634 patent/US10894063B2/en active Active
- 2018-01-05 LT LTEP20161276.9T patent/LT3722415T/lt unknown
- 2018-01-05 PL PL20161276.9T patent/PL3722415T3/pl unknown
- 2018-01-05 EP EP18709132.7A patent/EP3601533B1/en active Active
- 2018-01-05 ES ES18709132T patent/ES2874335T3/es active Active
- 2018-01-05 HU HUE20161179A patent/HUE070176T2/hu unknown
- 2018-01-05 KR KR1020247023861A patent/KR20240114787A/ko active Pending
- 2018-01-05 MD MDE20201130T patent/MD3730608T2/ro unknown
- 2018-01-05 SG SG11201908994R patent/SG11201908994RA/en unknown
- 2018-01-05 SI SI201831186T patent/SI3730608T1/sl unknown
- 2018-01-05 EP EP21175134.2A patent/EP3910055A1/en active Pending
- 2018-01-05 MD MDE20201056T patent/MD3722415T2/ro unknown
- 2018-01-05 PT PT201612769T patent/PT3722415T/pt unknown
- 2018-01-05 DK DK20161276.9T patent/DK3722415T3/da active
- 2018-01-05 KR KR1020197031407A patent/KR102686794B1/ko active Active
- 2018-01-05 NZ NZ796142A patent/NZ796142A/en unknown
- 2018-01-05 TW TW107100568A patent/TWI799402B/zh active
- 2018-01-05 PT PT187091327T patent/PT3601533T/pt unknown
- 2018-01-05 RS RS20250044A patent/RS66400B1/sr unknown
- 2018-01-05 CN CN201880035181.8A patent/CN110785486A/zh active Pending
- 2018-01-05 BR BR112019020326A patent/BR112019020326A2/pt unknown
- 2018-01-05 CR CR20190487A patent/CR20190487A/es unknown
- 2018-01-05 ES ES20161276T patent/ES3008832T3/es active Active
- 2018-01-05 EP EP20161276.9A patent/EP3722415B1/en active Active
- 2018-01-05 EP EP20183493.4A patent/EP3766964A1/en active Pending
- 2018-01-05 SM SM20250040T patent/SMT202500040T1/it unknown
- 2018-01-05 MX MX2019011768A patent/MX2019011768A/es unknown
- 2018-01-05 PL PL20161179.5T patent/PL3730608T3/pl unknown
- 2018-01-05 DK DK18709132.7T patent/DK3601533T3/da active
- 2018-01-05 TN TNP/2019/000273A patent/TN2019000273A1/en unknown
- 2018-01-05 SI SI201831203T patent/SI3722415T1/sl unknown
- 2018-01-05 LT LTEP18709132.7T patent/LT3601533T/lt unknown
- 2018-01-05 WO PCT/US2018/012633 patent/WO2018182817A1/en not_active Ceased
- 2018-01-05 UA UAA201910623A patent/UA130566C2/uk unknown
- 2018-01-05 FI FIEP20161276.9T patent/FI3722415T3/fi active
- 2018-01-18 US US15/874,718 patent/US10166257B2/en active Active
- 2018-02-08 US US15/892,311 patent/US10130659B2/en active Active
- 2018-03-29 US US15/940,901 patent/US10918666B2/en active Active
- 2018-06-29 JP JP2020552291A patent/JP7522037B2/ja active Active
- 2018-06-29 US US17/041,305 patent/US12121541B2/en active Active
- 2018-09-19 US US16/136,157 patent/US10420799B2/en active Active
- 2018-09-19 US US16/136,147 patent/US10272113B2/en active Active
- 2018-11-15 US US16/192,707 patent/US10537595B2/en active Active
- 2018-11-27 US US16/201,957 patent/US10398734B2/en active Active
- 2018-11-28 US US16/203,478 patent/US10363273B2/en active Active
- 2018-11-28 US US16/203,467 patent/US10463697B2/en active Active
-
2019
- 2019-05-29 US US16/425,767 patent/US10695372B2/en active Active
- 2019-05-29 US US16/425,778 patent/US10646517B2/en active Active
- 2019-05-29 US US16/425,746 patent/US10639330B2/en active Active
- 2019-09-23 IL IL26954319A patent/IL269543A/en unknown
- 2019-09-27 PH PH12019502247A patent/PH12019502247A1/en unknown
- 2019-09-27 CL CL2019002769A patent/CL2019002769A1/es unknown
- 2019-09-30 MX MX2024002827A patent/MX2024002827A/es unknown
- 2019-10-28 CO CONC2019/0011995A patent/CO2019011995A2/es unknown
- 2019-10-29 EC ECSENADI201977884A patent/ECSP19077884A/es unknown
-
2020
- 2020-01-17 US US16/746,416 patent/US10653723B1/en active Active
- 2020-04-14 US US16/848,442 patent/US10933094B2/en active Active
- 2020-04-14 US US16/848,454 patent/US10946044B2/en active Active
- 2020-04-14 US US16/848,361 patent/US10905718B2/en active Active
- 2020-04-14 US US16/848,426 patent/US10953047B2/en active Active
- 2020-04-14 US US16/848,386 patent/US10953046B2/en active Active
- 2020-04-14 US US16/848,474 patent/US10946045B2/en active Active
- 2020-05-20 US US16/879,711 patent/US10925900B2/en active Active
- 2020-10-22 CL CL2020002737A patent/CL2020002737A1/es unknown
- 2020-12-02 US US17/110,207 patent/US11083752B2/en active Active
- 2020-12-18 US US17/127,795 patent/US11052115B2/en active Active
- 2020-12-18 US US17/127,840 patent/US11052116B2/en active Active
- 2020-12-18 US US17/127,768 patent/US11007225B1/en active Active
- 2020-12-18 US US17/127,790 patent/US11007226B2/en active Active
-
2021
- 2021-01-12 US US17/147,080 patent/US20210128623A1/en active Pending
- 2021-01-12 US US17/147,096 patent/US12226434B2/en active Active
- 2021-01-12 US US17/147,073 patent/US11013770B1/en active Active
- 2021-01-12 US US17/147,412 patent/US20210214685A1/en active Pending
- 2021-01-12 US US17/147,090 patent/US11040070B2/en active Active
- 2021-01-13 US US17/148,475 patent/US11168303B2/en active Active
- 2021-01-13 US US17/148,508 patent/US11168304B2/en active Active
- 2021-05-14 CY CY20211100416T patent/CY1124136T1/el unknown
- 2021-05-20 US US17/326,088 patent/US11202803B1/en active Active
- 2021-07-22 US US17/383,280 patent/US11304979B2/en active Active
- 2021-07-22 US US17/383,276 patent/US11273180B2/en active Active
- 2021-07-22 US US17/383,272 patent/US11202804B2/en active Active
- 2021-07-22 US US17/382,831 patent/US11241456B2/en active Active
- 2021-09-21 US US17/480,596 patent/US11337998B2/en active Active
- 2021-09-21 US US17/480,534 patent/US11291687B2/en active Active
- 2021-09-21 US US17/480,587 patent/US11344579B2/en active Active
- 2021-09-21 US US17/480,525 patent/US11273181B2/en active Active
-
2022
- 2022-07-01 US US17/856,800 patent/US11517592B1/en active Active
- 2022-07-01 US US17/856,793 patent/US20230015649A1/en active Pending
- 2022-07-01 US US17/856,806 patent/US20230133298A1/en active Pending
- 2022-08-03 US US17/817,279 patent/US11541077B2/en active Active
- 2022-08-03 US US17/817,226 patent/US12558375B2/en active Active
- 2022-08-03 US US17/817,217 patent/US20220395533A1/en active Pending
- 2022-08-03 US US17/817,281 patent/US11529372B1/en active Active
- 2022-08-03 US US17/817,273 patent/US20230045899A1/en active Pending
- 2022-08-03 US US17/817,207 patent/US12194061B2/en active Active
- 2022-08-03 US US17/817,276 patent/US20220387498A1/en active Pending
- 2022-08-03 US US17/817,239 patent/US20230012086A1/en active Pending
- 2022-08-03 US US17/817,232 patent/US11998568B2/en active Active
- 2022-10-28 JP JP2022173683A patent/JP7814287B2/ja active Active
- 2022-10-28 JP JP2022173682A patent/JP7772680B2/ja active Active
- 2022-10-28 JP JP2022173684A patent/JP7817138B2/ja active Active
-
2024
- 2024-10-24 JP JP2024187597A patent/JP2025023951A/ja active Pending
- 2024-11-22 US US18/957,327 patent/US12485145B2/en active Active
- 2024-12-17 US US18/984,525 patent/US20250121008A1/en active Pending
- 2024-12-17 US US18/984,595 patent/US20250121009A1/en active Pending
-
2025
- 2025-01-22 AU AU2025200434A patent/AU2025200434A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7772680B2 (ja) | 腫瘍浸潤リンパ球の製造方法及び免疫療法におけるその使用方法 | |
| MD3775165T2 (ro) | Procese de producție a limfocitelor infiltrante în tumori și utilizările acestora în imunoterapie | |
| HK40057107A (en) | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy | |
| HK40039383B (en) | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy | |
| HK40022738A (en) | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy | |
| HK40022738B (en) | Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy |