JP7462560B2 - 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 - Google Patents
組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 Download PDFInfo
- Publication number
- JP7462560B2 JP7462560B2 JP2020537509A JP2020537509A JP7462560B2 JP 7462560 B2 JP7462560 B2 JP 7462560B2 JP 2020537509 A JP2020537509 A JP 2020537509A JP 2020537509 A JP2020537509 A JP 2020537509A JP 7462560 B2 JP7462560 B2 JP 7462560B2
- Authority
- JP
- Japan
- Prior art keywords
- sialidase
- seq
- human
- immunoglobulin
- neu2
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102000005348 Neuraminidase Human genes 0.000 title claims description 464
- 108010006232 Neuraminidase Proteins 0.000 title claims description 464
- 108020001507 fusion proteins Proteins 0.000 title claims description 103
- 102000037865 fusion proteins Human genes 0.000 title claims description 101
- 238000000034 method Methods 0.000 title description 65
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 316
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 290
- 229920001184 polypeptide Polymers 0.000 claims description 289
- 238000006467 substitution reaction Methods 0.000 claims description 165
- 101150084651 Neu2 gene Proteins 0.000 claims description 143
- 108060003951 Immunoglobulin Proteins 0.000 claims description 126
- 102000018358 immunoglobulin Human genes 0.000 claims description 126
- 229940127121 immunoconjugate Drugs 0.000 claims description 124
- 239000000427 antigen Substances 0.000 claims description 122
- 108091007433 antigens Proteins 0.000 claims description 122
- 102000036639 antigens Human genes 0.000 claims description 122
- 206010028980 Neoplasm Diseases 0.000 claims description 117
- 230000027455 binding Effects 0.000 claims description 117
- 230000014509 gene expression Effects 0.000 claims description 110
- 239000002773 nucleotide Substances 0.000 claims description 84
- 125000003729 nucleotide group Chemical group 0.000 claims description 84
- 235000001014 amino acid Nutrition 0.000 claims description 78
- 229940024606 amino acid Drugs 0.000 claims description 61
- 201000011510 cancer Diseases 0.000 claims description 49
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 41
- -1 CD86 Proteins 0.000 claims description 38
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 35
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 35
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 30
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 30
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 28
- 239000013604 expression vector Substances 0.000 claims description 27
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 17
- 230000001965 increasing effect Effects 0.000 claims description 16
- 239000004472 Lysine Substances 0.000 claims description 13
- 108010002350 Interleukin-2 Proteins 0.000 claims description 12
- 102000000588 Interleukin-2 Human genes 0.000 claims description 12
- 108090001005 Interleukin-6 Proteins 0.000 claims description 12
- 102000004889 Interleukin-6 Human genes 0.000 claims description 12
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 11
- 235000004279 alanine Nutrition 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 150000007523 nucleic acids Chemical class 0.000 claims description 9
- 102100035793 CD83 antigen Human genes 0.000 claims description 8
- 102000006354 HLA-DR Antigens Human genes 0.000 claims description 8
- 108010058597 HLA-DR Antigens Proteins 0.000 claims description 8
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 claims description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 8
- 108050003558 Interleukin-17 Proteins 0.000 claims description 6
- 102000013691 Interleukin-17 Human genes 0.000 claims description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 235000003704 aspartic acid Nutrition 0.000 claims description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 5
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 4
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 123
- 210000004027 cell Anatomy 0.000 description 108
- 230000000694 effects Effects 0.000 description 86
- 229960000575 trastuzumab Drugs 0.000 description 76
- 102000008986 Janus Human genes 0.000 description 66
- 108050000950 Janus Proteins 0.000 description 66
- 201000009030 Carcinoma Diseases 0.000 description 60
- 108090000623 proteins and genes Proteins 0.000 description 58
- 241000699666 Mus <mouse, genus> Species 0.000 description 48
- 241000699670 Mus sp. Species 0.000 description 48
- 102000004169 proteins and genes Human genes 0.000 description 47
- 238000011282 treatment Methods 0.000 description 47
- 239000012634 fragment Substances 0.000 description 45
- 235000018102 proteins Nutrition 0.000 description 45
- 150000001413 amino acids Chemical class 0.000 description 44
- 125000000539 amino acid group Chemical group 0.000 description 41
- 230000035772 mutation Effects 0.000 description 37
- 101150029707 ERBB2 gene Proteins 0.000 description 36
- 108090000790 Enzymes Proteins 0.000 description 31
- 102000004190 Enzymes Human genes 0.000 description 31
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 31
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 31
- 239000000562 conjugate Substances 0.000 description 31
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical group SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 30
- 241000238565 lobster Species 0.000 description 28
- 239000000203 mixture Substances 0.000 description 28
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 27
- 210000004899 c-terminal region Anatomy 0.000 description 26
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 23
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 22
- 238000012360 testing method Methods 0.000 description 21
- 239000003981 vehicle Substances 0.000 description 21
- 108010029485 Protein Isoforms Proteins 0.000 description 19
- 102000001708 Protein Isoforms Human genes 0.000 description 19
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 19
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 18
- 102100022166 E3 ubiquitin-protein ligase NEURL1 Human genes 0.000 description 18
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 18
- 101150024252 Neu1 gene Proteins 0.000 description 18
- 230000002209 hydrophobic effect Effects 0.000 description 18
- 101150029672 Neu3 gene Proteins 0.000 description 17
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 16
- 206010006187 Breast cancer Diseases 0.000 description 15
- 208000026310 Breast neoplasm Diseases 0.000 description 15
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 15
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 15
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 15
- 238000007792 addition Methods 0.000 description 15
- 238000012217 deletion Methods 0.000 description 15
- 230000037430 deletion Effects 0.000 description 15
- 230000003993 interaction Effects 0.000 description 15
- 229920001223 polyethylene glycol Polymers 0.000 description 15
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
- 108010029031 Regulatory-Associated Protein of mTOR Proteins 0.000 description 14
- 102100040969 Regulatory-associated protein of mTOR Human genes 0.000 description 14
- 210000004443 dendritic cell Anatomy 0.000 description 14
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 13
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 13
- 210000001744 T-lymphocyte Anatomy 0.000 description 13
- 238000013459 approach Methods 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000003607 modifier Substances 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 101900324552 Salmonella typhimurium Sialidase Proteins 0.000 description 12
- 230000007423 decrease Effects 0.000 description 12
- 239000007928 intraperitoneal injection Substances 0.000 description 12
- 229920000642 polymer Polymers 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 210000004881 tumor cell Anatomy 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 229930182817 methionine Natural products 0.000 description 11
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 11
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 10
- 230000004913 activation Effects 0.000 description 10
- 235000018417 cysteine Nutrition 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 9
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 230000002255 enzymatic effect Effects 0.000 description 9
- 239000011159 matrix material Substances 0.000 description 9
- 230000004614 tumor growth Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 208000009956 adenocarcinoma Diseases 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 238000003776 cleavage reaction Methods 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 229960002621 pembrolizumab Drugs 0.000 description 8
- 230000007017 scission Effects 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 7
- 108010076504 Protein Sorting Signals Proteins 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 238000009472 formulation Methods 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 101710117290 Aldo-keto reductase family 1 member C4 Proteins 0.000 description 6
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 101001123851 Homo sapiens Sialidase-2 Proteins 0.000 description 6
- 101001123847 Homo sapiens Sialidase-3 Proteins 0.000 description 6
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 6
- 125000002059 L-arginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 6
- 125000002068 L-phenylalanino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 6
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 6
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 6
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 6
- 238000002869 basic local alignment search tool Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 102000054572 human NEU2 Human genes 0.000 description 6
- 102000047740 human Neu3 Human genes 0.000 description 6
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 238000002559 palpation Methods 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 238000001890 transfection Methods 0.000 description 6
- 229940045513 CTLA4 antagonist Drugs 0.000 description 5
- 102100031940 Epithelial cell adhesion molecule Human genes 0.000 description 5
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 5
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 5
- 230000023445 activated T cell autonomous cell death Effects 0.000 description 5
- 238000011374 additional therapy Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000003501 co-culture Methods 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 239000007850 fluorescent dye Substances 0.000 description 5
- 229960002989 glutamic acid Drugs 0.000 description 5
- 238000005734 heterodimerization reaction Methods 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Chemical group OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 230000004777 loss-of-function mutation Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 5
- 210000000822 natural killer cell Anatomy 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 235000004400 serine Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 4
- VHSHLMUCYSAUQU-UHFFFAOYSA-N 2-hydroxypropyl methacrylate Chemical compound CC(O)COC(=O)C(C)=C VHSHLMUCYSAUQU-UHFFFAOYSA-N 0.000 description 4
- 108020005544 Antisense RNA Proteins 0.000 description 4
- 239000004475 Arginine Chemical group 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 238000011725 BALB/c mouse Methods 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 102000005720 Glutathione transferase Human genes 0.000 description 4
- 108010070675 Glutathione transferase Proteins 0.000 description 4
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 4
- 101000935587 Homo sapiens Flavin reductase (NADPH) Proteins 0.000 description 4
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 4
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 4
- 108090001090 Lectins Proteins 0.000 description 4
- 102000004856 Lectins Human genes 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical group OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 229960005395 cetuximab Drugs 0.000 description 4
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 4
- 229960002286 clodronic acid Drugs 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229960002204 daratumumab Drugs 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 229950002026 girentuximab Drugs 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000002523 lectin Substances 0.000 description 4
- 230000002132 lysosomal effect Effects 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- 238000011330 nucleic acid test Methods 0.000 description 4
- 229960002450 ofatumumab Drugs 0.000 description 4
- 229960001972 panitumumab Drugs 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 229920003213 poly(N-isopropyl acrylamide) Polymers 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 229960004641 rituximab Drugs 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 description 4
- 230000005748 tumor development Effects 0.000 description 4
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 3
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 3
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 3
- 239000012275 CTLA-4 inhibitor Substances 0.000 description 3
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 3
- 208000009458 Carcinoma in Situ Diseases 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010014733 Endometrial cancer Diseases 0.000 description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 208000001382 Experimental Melanoma Diseases 0.000 description 3
- 201000001342 Fallopian tube cancer Diseases 0.000 description 3
- 208000013452 Fallopian tube neoplasm Diseases 0.000 description 3
- 108010087819 Fc receptors Proteins 0.000 description 3
- 102000009109 Fc receptors Human genes 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 3
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 3
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 3
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 3
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 3
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 3
- 102000002698 KIR Receptors Human genes 0.000 description 3
- 108010043610 KIR Receptors Proteins 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical group NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 102100028389 Melanoma antigen recognized by T-cells 1 Human genes 0.000 description 3
- 208000003445 Mouth Neoplasms Diseases 0.000 description 3
- 102100023123 Mucin-16 Human genes 0.000 description 3
- 206010061534 Oesophageal squamous cell carcinoma Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 239000012270 PD-1 inhibitor Substances 0.000 description 3
- 239000012668 PD-1-inhibitor Substances 0.000 description 3
- 239000012271 PD-L1 inhibitor Substances 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- 241000725643 Respiratory syncytial virus Species 0.000 description 3
- 108010047827 Sialic Acid Binding Immunoglobulin-like Lectins Proteins 0.000 description 3
- 102000007073 Sialic Acid Binding Immunoglobulin-like Lectins Human genes 0.000 description 3
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 241000607626 Vibrio cholerae Species 0.000 description 3
- 206010047741 Vulval cancer Diseases 0.000 description 3
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000000611 antibody drug conjugate Substances 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229950009791 durvalumab Drugs 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 201000010536 head and neck cancer Diseases 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 208000014018 liver neoplasm Diseases 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 229960003301 nivolumab Drugs 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 229940121655 pd-1 inhibitor Drugs 0.000 description 3
- 229940121656 pd-l1 inhibitor Drugs 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004845 protein aggregation Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 102200049817 rs74626221 Human genes 0.000 description 3
- 125000005629 sialic acid group Chemical group 0.000 description 3
- 238000002741 site-directed mutagenesis Methods 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000002992 thymic effect Effects 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 201000005112 urinary bladder cancer Diseases 0.000 description 3
- 206010046766 uterine cancer Diseases 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 229940118696 vibrio cholerae Drugs 0.000 description 3
- 201000005102 vulva cancer Diseases 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- ZADWXFSZEAPBJS-SNVBAGLBSA-N (2r)-2-amino-3-(1-methylindol-3-yl)propanoic acid Chemical compound C1=CC=C2N(C)C=C(C[C@@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-SNVBAGLBSA-N 0.000 description 2
- YPBKTZBXSBLTDK-PKNBQFBNSA-N (3e)-3-[(3-bromo-4-fluoroanilino)-nitrosomethylidene]-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole Chemical compound NS(=O)(=O)NCCNC1=NON\C1=C(N=O)/NC1=CC=C(F)C(Br)=C1 YPBKTZBXSBLTDK-PKNBQFBNSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 102100026402 Adhesion G protein-coupled receptor E2 Human genes 0.000 description 2
- 101710096292 Adhesion G protein-coupled receptor E2 Proteins 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- 102100035526 B melanoma antigen 1 Human genes 0.000 description 2
- 101710131520 B melanoma antigen 1 Proteins 0.000 description 2
- 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 2
- 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 102100027052 Bone morphogenetic protein receptor type-1B Human genes 0.000 description 2
- 101710120271 Bone morphogenetic protein receptor type-1B Proteins 0.000 description 2
- 102100026008 Breakpoint cluster region protein Human genes 0.000 description 2
- 206010058354 Bronchioloalveolar carcinoma Diseases 0.000 description 2
- 102100025905 C-Jun-amino-terminal kinase-interacting protein 4 Human genes 0.000 description 2
- 101710105201 C-Jun-amino-terminal kinase-interacting protein 4 Proteins 0.000 description 2
- 108010008629 CA-125 Antigen Proteins 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
- 102000005572 Cathepsin A Human genes 0.000 description 2
- 108010059081 Cathepsin A Proteins 0.000 description 2
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 102100036466 Delta-like protein 3 Human genes 0.000 description 2
- 101710112748 Delta-like protein 3 Proteins 0.000 description 2
- 102100026245 E3 ubiquitin-protein ligase RNF43 Human genes 0.000 description 2
- 101710109241 E3 ubiquitin-protein ligase RNF43 Proteins 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102100037241 Endoglin Human genes 0.000 description 2
- 102000010451 Folate receptor alpha Human genes 0.000 description 2
- 108050001931 Folate receptor alpha Proteins 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
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 2
- 102000010956 Glypican Human genes 0.000 description 2
- 108050001154 Glypican Proteins 0.000 description 2
- 108050007237 Glypican-3 Proteins 0.000 description 2
- 102100039622 Granulocyte colony-stimulating factor receptor Human genes 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 101000890604 Homo sapiens A-kinase anchor protein 4 Proteins 0.000 description 2
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 description 2
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 2
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 2
- 101000746364 Homo sapiens Granulocyte colony-stimulating factor receptor Proteins 0.000 description 2
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 description 2
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 2
- 101001062222 Homo sapiens Receptor-binding cancer antigen expressed on SiSo cells Proteins 0.000 description 2
- 101000835745 Homo sapiens Teratocarcinoma-derived growth factor 1 Proteins 0.000 description 2
- 101000638251 Homo sapiens Tumor necrosis factor ligand superfamily member 9 Proteins 0.000 description 2
- 241000341655 Human papillomavirus type 16 Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 description 2
- 102100039813 Inactive tyrosine-protein kinase 7 Human genes 0.000 description 2
- 101710120843 Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 2
- 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102100038224 Kremen protein 2 Human genes 0.000 description 2
- 101710113599 Kremen protein 2 Proteins 0.000 description 2
- 125000000415 L-cysteinyl group Chemical group O=C([*])[C@@](N([H])[H])([H])C([H])([H])S[H] 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical group OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 2
- 102100020862 Lymphocyte activation gene 3 protein Human genes 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 108010010995 MART-1 Antigen Proteins 0.000 description 2
- 102100037020 Melanoma antigen preferentially expressed in tumors Human genes 0.000 description 2
- 101710178381 Melanoma antigen preferentially expressed in tumors Proteins 0.000 description 2
- 102000051089 Melanotransferrin Human genes 0.000 description 2
- 108700038051 Melanotransferrin Proteins 0.000 description 2
- 102000007298 Mucin-1 Human genes 0.000 description 2
- 108010008707 Mucin-1 Proteins 0.000 description 2
- 108010008699 Mucin-4 Proteins 0.000 description 2
- 102000007270 Mucin-4 Human genes 0.000 description 2
- 101100079847 Mus musculus Neu1 gene Proteins 0.000 description 2
- 101100079853 Mus musculus Neu2 gene Proteins 0.000 description 2
- 101100079857 Mus musculus Neu3 gene Proteins 0.000 description 2
- 101100516398 Mus musculus Neu4 gene Proteins 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
- 102000003729 Neprilysin Human genes 0.000 description 2
- 108090000028 Neprilysin Proteins 0.000 description 2
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 108091007744 Programmed cell death receptors Proteins 0.000 description 2
- 102100029000 Prolactin receptor Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 102100038358 Prostate-specific antigen Human genes 0.000 description 2
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 2
- 102100029165 Receptor-binding cancer antigen expressed on SiSo cells Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 101800001271 Surface protein Proteins 0.000 description 2
- 229940123237 Taxane Drugs 0.000 description 2
- 102100026404 Teratocarcinoma-derived growth factor 1 Human genes 0.000 description 2
- 102100021393 Transcriptional repressor CTCFL Human genes 0.000 description 2
- 101710128101 Transcriptional repressor CTCFL Proteins 0.000 description 2
- RTKIYFITIVXBLE-UHFFFAOYSA-N Trichostatin A Natural products ONC(=O)C=CC(C)=CC(C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-UHFFFAOYSA-N 0.000 description 2
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 2
- 102100022205 Tumor necrosis factor receptor superfamily member 21 Human genes 0.000 description 2
- 101710187751 Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 description 2
- 208000006593 Urologic Neoplasms Diseases 0.000 description 2
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- 108700020467 WT1 Proteins 0.000 description 2
- 102000040856 WT1 Human genes 0.000 description 2
- 210000001766 X chromosome Anatomy 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 208000002517 adenoid cystic carcinoma Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 229960003852 atezolizumab Drugs 0.000 description 2
- 229950002916 avelumab Drugs 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 108700041286 delta Proteins 0.000 description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000006862 enzymatic digestion Effects 0.000 description 2
- 229950006370 epacadostat Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
- 102000051957 human ERBB2 Human genes 0.000 description 2
- 102000054751 human RUNX1T1 Human genes 0.000 description 2
- 230000005746 immune checkpoint blockade Effects 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 201000004933 in situ carcinoma Diseases 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229950001014 intetumumab Drugs 0.000 description 2
- 229960005386 ipilimumab Drugs 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229950011263 lirilumab Drugs 0.000 description 2
- 230000007787 long-term memory Effects 0.000 description 2
- 229920001427 mPEG Polymers 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 238000008995 multiplex Luminex assay kit Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 210000004897 n-terminal region Anatomy 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229950010773 pidilizumab Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001562 poly(N-(2-hydroxypropyl)methacrylamide) Polymers 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229940068965 polysorbates Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 208000004259 scirrhous adenocarcinoma Diseases 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 208000000649 small cell carcinoma Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 229950007217 tremelimumab Drugs 0.000 description 2
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 2
- 229950005972 urelumab Drugs 0.000 description 2
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- OHRURASPPZQGQM-QSVHVVLASA-N (1r,4s,7z,10s,16e,21r)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-QSVHVVLASA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- FFILOTSTFMXQJC-QCFYAKGBSA-N (2r,4r,5s,6s)-2-[3-[(2s,3s,4r,6s)-6-[(2s,3r,4r,5s,6r)-5-[(2s,3r,4r,5r,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-[(2r,3s,4r,5r,6r)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(e)-3-hydroxy-2-(octadecanoylamino)octadec-4-enoxy]oxan-3-yl]oxy-3-hy Chemical compound O[C@@H]1[C@@H](O)[C@H](OCC(NC(=O)CCCCCCCCCCCCCCCCC)C(O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO[C@]2(O[C@@H]([C@@H](N)[C@H](O)C2)C(O)C(O)CO)C(O)=O)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 FFILOTSTFMXQJC-QCFYAKGBSA-N 0.000 description 1
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
- 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
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- WHBMMWSBFZVSSR-GSVOUGTGSA-N (R)-3-hydroxybutyric acid Chemical compound C[C@@H](O)CC(O)=O WHBMMWSBFZVSSR-GSVOUGTGSA-N 0.000 description 1
- PJOHVEQSYPOERL-SHEAVXILSA-N (e)-n-[(4r,4as,7ar,12br)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a-yl]-3-(4-methylphenyl)prop-2-enamide Chemical compound C1=CC(C)=CC=C1\C=C\C(=O)N[C@]1(CCC(=O)[C@@H]2O3)[C@H]4CC5=CC=C(O)C3=C5[C@]12CCN4CC1CC1 PJOHVEQSYPOERL-SHEAVXILSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- FPKVOQKZMBDBKP-UHFFFAOYSA-N 1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 FPKVOQKZMBDBKP-UHFFFAOYSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- DMSDCBKFWUBTKX-UHFFFAOYSA-N 2-methyl-1-nitrosoguanidine Chemical compound CN=C(N)NN=O DMSDCBKFWUBTKX-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- QXZGLTYKKZKGLN-UHFFFAOYSA-N 4-(2,5-dioxopyrrolidin-1-yl)oxy-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)ON1C(=O)CCC1=O QXZGLTYKKZKGLN-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
- 102100022464 5'-nucleotidase Human genes 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 102000007471 Adenosine A2A receptor Human genes 0.000 description 1
- 108010085277 Adenosine A2A receptor Proteins 0.000 description 1
- 229940123702 Adenosine A2a receptor antagonist Drugs 0.000 description 1
- 101150051188 Adora2a gene Proteins 0.000 description 1
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
- 102100022749 Aminopeptidase N Human genes 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 102100038080 B-cell receptor CD22 Human genes 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- 229940123944 B7-H3 antagonist Drugs 0.000 description 1
- 229940116375 B7-H4 antagonist Drugs 0.000 description 1
- 229940125565 BMS-986016 Drugs 0.000 description 1
- 229940111018 BTLA antagonist Drugs 0.000 description 1
- 102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000013165 Bowen disease Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 108700012439 CA9 Proteins 0.000 description 1
- 102100024217 CAMPATH-1 antigen Human genes 0.000 description 1
- 108010049990 CD13 Antigens Proteins 0.000 description 1
- 108010065524 CD52 Antigen Proteins 0.000 description 1
- 102100025570 Cancer/testis antigen 1 Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 102100024423 Carbonic anhydrase 9 Human genes 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000035970 Chromosome Breakpoints Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102100038449 Claudin-6 Human genes 0.000 description 1
- 102100026097 Claudin-9 Human genes 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 208000006402 Ductal Carcinoma Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- MBYXEBXZARTUSS-QLWBXOBMSA-N Emetamine Natural products O(C)c1c(OC)cc2c(c(C[C@@H]3[C@H](CC)CN4[C@H](c5c(cc(OC)c(OC)c5)CC4)C3)ncc2)c1 MBYXEBXZARTUSS-QLWBXOBMSA-N 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 102100035139 Folate receptor alpha Human genes 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000008999 Giant Cell Carcinoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- BUEFQXUHTUZXHR-LURJTMIESA-N Gly-Gly-Pro zwitterion Chemical compound NCC(=O)NCC(=O)N1CCC[C@H]1C(O)=O BUEFQXUHTUZXHR-LURJTMIESA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 108010007707 Hepatitis A Virus Cellular Receptor 2 Proteins 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 description 1
- 101000884305 Homo sapiens B-cell receptor CD22 Proteins 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- 101000856237 Homo sapiens Cancer/testis antigen 1 Proteins 0.000 description 1
- 101000914324 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 5 Proteins 0.000 description 1
- 101000882898 Homo sapiens Claudin-6 Proteins 0.000 description 1
- 101000912661 Homo sapiens Claudin-9 Proteins 0.000 description 1
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000606465 Homo sapiens Inactive tyrosine-protein kinase 7 Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 1
- 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 1
- 101001063456 Homo sapiens Leucine-rich repeat-containing G-protein coupled receptor 5 Proteins 0.000 description 1
- 101001039113 Homo sapiens Leucine-rich repeat-containing protein 15 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000578784 Homo sapiens Melanoma antigen recognized by T-cells 1 Proteins 0.000 description 1
- 101000623901 Homo sapiens Mucin-16 Proteins 0.000 description 1
- 101000934338 Homo sapiens Myeloid cell surface antigen CD33 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101001024605 Homo sapiens Next to BRCA1 gene 1 protein Proteins 0.000 description 1
- 101001123448 Homo sapiens Prolactin receptor Proteins 0.000 description 1
- 101000880769 Homo sapiens Protein SSX1 Proteins 0.000 description 1
- 101000863882 Homo sapiens Sialic acid-binding Ig-like lectin 7 Proteins 0.000 description 1
- 101000863883 Homo sapiens Sialic acid-binding Ig-like lectin 9 Proteins 0.000 description 1
- 101000884271 Homo sapiens Signal transducer CD24 Proteins 0.000 description 1
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 1
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 1
- 101000801433 Homo sapiens Trophoblast glycoprotein Proteins 0.000 description 1
- 101000801254 Homo sapiens Tumor necrosis factor receptor superfamily member 16 Proteins 0.000 description 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 1
- 101000808114 Homo sapiens Uroplakin-1b Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 210000005131 Hürthle cell Anatomy 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 101710099452 Inactive tyrosine-protein kinase 7 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
- 102100032816 Integrin alpha-6 Human genes 0.000 description 1
- 108010041100 Integrin alpha6 Proteins 0.000 description 1
- 102000000426 Integrin alpha6 Human genes 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 102000012011 Isocitrate Dehydrogenase Human genes 0.000 description 1
- 108010075869 Isocitrate Dehydrogenase Proteins 0.000 description 1
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- WQZGKKKJIJFFOK-DHVFOXMCSA-N L-galactose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-DHVFOXMCSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 102100031036 Leucine-rich repeat-containing G-protein coupled receptor 5 Human genes 0.000 description 1
- 102100040645 Leucine-rich repeat-containing protein 15 Human genes 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000000265 Lobular Carcinoma Diseases 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 102100028524 Lysosomal protective protein Human genes 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100027754 Mast/stem cell growth factor receptor Kit Human genes 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 102000013013 Member 2 Subfamily G ATP Binding Cassette Transporter Human genes 0.000 description 1
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108090000015 Mesothelin Proteins 0.000 description 1
- 102000003735 Mesothelin Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 102000015728 Mucins Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 102100025243 Myeloid cell surface antigen CD33 Human genes 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- HRNLUBSXIHFDHP-UHFFFAOYSA-N N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC1=NC=CC(C=2C=NC=CC=2)=N1 HRNLUBSXIHFDHP-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 101800000597 N-terminal peptide Proteins 0.000 description 1
- 102400000108 N-terminal peptide Human genes 0.000 description 1
- 108091008877 NK cell receptors Proteins 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 102000010648 Natural Killer Cell Receptors Human genes 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- RMINQIRDFIBNLE-NNRWGFCXSA-N O-[N-acetyl-alpha-neuraminyl-(2->6)-N-acetyl-alpha-D-galactosaminyl]-L-serine Chemical compound O1[C@H](OC[C@H](N)C(O)=O)[C@H](NC(=O)C)[C@@H](O)[C@@H](O)[C@H]1CO[C@@]1(C(O)=O)O[C@@H]([C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C1 RMINQIRDFIBNLE-NNRWGFCXSA-N 0.000 description 1
- YGACXVRLDHEXKY-WXRXAMBDSA-N O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 Chemical compound O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 YGACXVRLDHEXKY-WXRXAMBDSA-N 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000016978 Orphan receptors Human genes 0.000 description 1
- 108070000031 Orphan receptors Proteins 0.000 description 1
- 229940124060 PD-1 antagonist Drugs 0.000 description 1
- 229940123751 PD-L1 antagonist Drugs 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102100036031 Podocalyxin Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 239000004285 Potassium sulphite Substances 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 241001415846 Procellariidae Species 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010002519 Prolactin Receptors Proteins 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102100037687 Protein SSX1 Human genes 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108010024221 Proto-Oncogene Proteins c-bcr Proteins 0.000 description 1
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 206010070308 Refractory cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 229940127395 Ribonucleotide Reductase Inhibitors Drugs 0.000 description 1
- 208000025316 Richter syndrome Diseases 0.000 description 1
- AUVVAXYIELKVAI-UHFFFAOYSA-N SJ000285215 Natural products N1CCC2=CC(OC)=C(OC)C=C2C1CC1CC2C3=CC(OC)=C(OC)C=C3CCN2CC1CC AUVVAXYIELKVAI-UHFFFAOYSA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 201000001542 Schneiderian carcinoma Diseases 0.000 description 1
- 102100029946 Sialic acid-binding Ig-like lectin 7 Human genes 0.000 description 1
- 102100029965 Sialic acid-binding Ig-like lectin 9 Human genes 0.000 description 1
- 108050000175 Sialidase-2 Proteins 0.000 description 1
- 102100028755 Sialidase-2 Human genes 0.000 description 1
- 108050000176 Sialidase-3 Proteins 0.000 description 1
- 102100028756 Sialidase-3 Human genes 0.000 description 1
- 102100038081 Signal transducer CD24 Human genes 0.000 description 1
- 208000003252 Signet Ring Cell Carcinoma Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 206010068771 Soft tissue neoplasm Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108010002687 Survivin Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 1
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 101150052863 THY1 gene Proteins 0.000 description 1
- 229940123803 TIM3 antagonist Drugs 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 102100033579 Trophoblast glycoprotein Human genes 0.000 description 1
- 102000018690 Trypsinogen Human genes 0.000 description 1
- 108010027252 Trypsinogen Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- 102100038853 Uroplakin-1b Human genes 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000012018 Yolk sac tumor Diseases 0.000 description 1
- 229950005186 abagovomab Drugs 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 229950009084 adecatumumab Drugs 0.000 description 1
- 210000002534 adenoid Anatomy 0.000 description 1
- 239000002467 adenosine A2a receptor antagonist Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229910001508 alkali metal halide Inorganic materials 0.000 description 1
- 150000008045 alkali metal halides Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- 229950009106 altumomab Drugs 0.000 description 1
- 229950001537 amatuximab Drugs 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 210000002255 anal canal Anatomy 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940044684 anti-microtubule agent Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229950005725 arcitumomab Drugs 0.000 description 1
- 229950000847 ascrinvacumab Drugs 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 208000016894 basaloid carcinoma Diseases 0.000 description 1
- 201000000450 basaloid squamous cell carcinoma Diseases 0.000 description 1
- 208000003373 basosquamous carcinoma Diseases 0.000 description 1
- 229950007843 bavituximab Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 229950003269 bectumomab Drugs 0.000 description 1
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 238000005460 biophysical method Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229950002903 bivatuzumab Drugs 0.000 description 1
- 229960003008 blinatumomab Drugs 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- RSIHSRDYCUFFLA-DYKIIFRCSA-N boldenone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 RSIHSRDYCUFFLA-DYKIIFRCSA-N 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000003714 breast lobular carcinoma Diseases 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 229950001178 capromab Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229960000419 catumaxomab Drugs 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229950006647 cixutumumab Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 210000002777 columnar cell Anatomy 0.000 description 1
- 238000002742 combinatorial mutagenesis Methods 0.000 description 1
- 201000011050 comedo carcinoma Diseases 0.000 description 1
- 230000001609 comparable effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 229950007276 conatumumab Drugs 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 201000011063 cribriform carcinoma Diseases 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229950007409 dacetuzumab Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- RSIHSRDYCUFFLA-UHFFFAOYSA-N dehydrotestosterone Natural products O=C1C=CC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 RSIHSRDYCUFFLA-UHFFFAOYSA-N 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 229950007998 demcizumab Drugs 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 229950002756 depatuxizumab Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229950008962 detumomab Drugs 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 229960004497 dinutuximab Drugs 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003968 dna methyltransferase inhibitor Substances 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229950009964 drozitumab Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229950011453 dusigitumab Drugs 0.000 description 1
- 229950000006 ecromeximab Drugs 0.000 description 1
- 229960001776 edrecolomab Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229960004137 elotuzumab Drugs 0.000 description 1
- 229950004647 emactuzumab Drugs 0.000 description 1
- AUVVAXYIELKVAI-CKBKHPSWSA-N emetine Chemical compound N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@@H]1CC AUVVAXYIELKVAI-CKBKHPSWSA-N 0.000 description 1
- 229960002694 emetine Drugs 0.000 description 1
- AUVVAXYIELKVAI-UWBTVBNJSA-N emetine Natural products N1CCC2=CC(OC)=C(OC)C=C2[C@H]1C[C@H]1C[C@H]2C3=CC(OC)=C(OC)C=C3CCN2C[C@H]1CC AUVVAXYIELKVAI-UWBTVBNJSA-N 0.000 description 1
- 229950004255 emibetuzumab Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 208000001991 endodermal sinus tumor Diseases 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229950001752 enoticumab Drugs 0.000 description 1
- 229950010640 ensituximab Drugs 0.000 description 1
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 1
- 229950009760 epratuzumab Drugs 0.000 description 1
- 229950008579 ertumaxomab Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 229950009569 etaracizumab Drugs 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229950009929 farletuzumab Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229950002846 ficlatuzumab Drugs 0.000 description 1
- 229950008085 figitumumab Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229950010320 flanvotumab Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 102000006815 folate receptor Human genes 0.000 description 1
- 108020005243 folate receptor Proteins 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229950002140 futuximab Drugs 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 229950004896 ganitumab Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229950000918 glembatumumab Drugs 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 108010051307 glycyl-glycyl-proline Proteins 0.000 description 1
- 210000002503 granulosa cell Anatomy 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000013210 hematogenous Diseases 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 210000004276 hyalin Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229950006359 icrucumab Drugs 0.000 description 1
- 229950002200 igovomab Drugs 0.000 description 1
- 229950005646 imgatuzumab Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229950009034 indoximod Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
- 229950010939 iratumumab Drugs 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229950007752 isatuximab Drugs 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229960002014 ixabepilone Drugs 0.000 description 1
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000003367 kinetic assay Methods 0.000 description 1
- 229950000518 labetuzumab Drugs 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229950002884 lexatumumab Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- KRTIYQIPSAGSBP-KLAILNCOSA-N linrodostat Chemical compound C1(CCC(CC1)C1=C2C=C(F)C=CC2=NC=C1)[C@@H](C)C(=O)NC1=CC=C(Cl)C=C1 KRTIYQIPSAGSBP-KLAILNCOSA-N 0.000 description 1
- 229950002950 lintuzumab Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229950004563 lucatumumab Drugs 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 201000000014 lung giant cell carcinoma Diseases 0.000 description 1
- 201000000966 lung oat cell carcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 201000010953 lymphoepithelioma-like carcinoma Diseases 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 229950001869 mapatumumab Drugs 0.000 description 1
- 229950003135 margetuximab Drugs 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 230000000684 melanotic effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 229950003734 milatuzumab Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229950002142 minretumomab Drugs 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229950003063 mitumomab Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229950008353 narnatumab Drugs 0.000 description 1
- 208000014761 nasopharyngeal type undifferentiated carcinoma Diseases 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 229960000513 necitumumab Drugs 0.000 description 1
- 229950002697 nesvacumab Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229950010203 nimotuzumab Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000002777 nucleoside Chemical class 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 229960003347 obinutuzumab Drugs 0.000 description 1
- 229950008516 olaratumab Drugs 0.000 description 1
- 229950000846 onartuzumab Drugs 0.000 description 1
- 229950002104 ontuxizumab Drugs 0.000 description 1
- 229950007283 oregovomab Drugs 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229950000121 otlertuzumab Drugs 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- FPOHNWQLNRZRFC-ZHACJKMWSA-N panobinostat Chemical compound CC=1NC2=CC=CC=C2C=1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FPOHNWQLNRZRFC-ZHACJKMWSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 229950004260 parsatuzumab Drugs 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 229950010966 patritumab Drugs 0.000 description 1
- 229960005570 pemtumomab Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 108091005706 peripheral membrane proteins Proteins 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229960002087 pertuzumab Drugs 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229940126620 pintumomab Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 108090000917 podocalyxin Proteins 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229950009904 pritumumab Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 208000029817 pulmonary adenocarcinoma in situ Diseases 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 229950011613 racotumomab Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229950011639 radretumab Drugs 0.000 description 1
- 229960002633 ramucirumab Drugs 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 229950003238 rilotumumab Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000007416 salivary gland adenoid cystic carcinoma Diseases 0.000 description 1
- 208000014212 sarcomatoid carcinoma Diseases 0.000 description 1
- 229950007308 satumomab Drugs 0.000 description 1
- 229950008834 seribantumab Drugs 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 229950008684 sibrotuzumab Drugs 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000008123 signet ring cell adenocarcinoma Diseases 0.000 description 1
- 229960003323 siltuximab Drugs 0.000 description 1
- 229950009513 simtuzumab Drugs 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 229950011267 solitomab Drugs 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 229950007213 spartalizumab Drugs 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229950009696 tamtuvetmab Drugs 0.000 description 1
- 229950007435 tarextumab Drugs 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940066453 tecentriq Drugs 0.000 description 1
- 229950001289 tenatumomab Drugs 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229950010259 teprotumumab Drugs 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 235000008521 threonine Nutrition 0.000 description 1
- 125000000341 threoninyl group Chemical class [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229950004742 tigatuzumab Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 229950005808 tovetumab Drugs 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 150000004654 triazenes Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 229950004593 ublituximab Drugs 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000003741 urothelium Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229950003520 utomilumab Drugs 0.000 description 1
- 229950008718 vantictumab Drugs 0.000 description 1
- 229950000449 vanucizumab Drugs 0.000 description 1
- 229950000815 veltuzumab Drugs 0.000 description 1
- 208000008662 verrucous carcinoma Diseases 0.000 description 1
- 229950010789 vesencumab Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229960000237 vorinostat Drugs 0.000 description 1
- 229950003511 votumumab Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229950008250 zalutumumab Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01018—Exo-alpha-sialidase (3.2.1.18), i.e. trans-sialidase
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
- A61K47/6815—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6855—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from breast cancer cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/812—Breast
-
- 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
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/61—Fusion polypeptide containing an enzyme fusion for detection (lacZ, luciferase)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oncology (AREA)
- Cell Biology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
本願は、2018年1月3日に出願された米国仮特許出願第62/613,363号および2018年11月2日に出願された米国仮特許出願第62/755,279号の利益および優先権を主張し、上記出願のそれぞれの全開示は、それらの全体において参照により本明細書に援用される。
本発明は一般的に、組換えヒトシアリダーゼおよび組換えシアリダーゼ融合タンパク質、ならびに癌の治療におけるそれらの使用に関する。
増加する一連の証拠は、腫瘍進行の種々の病理生理学的段階でのグリカンおよび特にシアログリカンについての役割を支持する。グリカンは、腫瘍増殖、侵入、血行性の転移および新脈管形成を制御する(Fuster et al. (2005) NAT. REV. CANCER 5(7): 526-42)。細胞表面糖コンジュゲートのシアリル化(sialylation)は、癌において頻繁に変化し、シアリル化腫瘍関連炭水化物抗原の発現を生じる。腫瘍細胞によるシアリル化グリカンの発現は時々、腫瘍の攻撃性および転移能力の増加と関連する。
本発明は、部分的に、癌細胞の表面からシアル酸および/またはシアル酸含有分子を除去し、および/または腫瘍微小環境からシアル酸および/またはシアル酸含有分子を除去し、および/または腫瘍微小環境においてシアル酸および/またはシアル酸含有分子の濃度を低減することに有用であるように、適切な基質特異性および活性を有するヒトシアリダーゼ酵素の組換え変異体形態ならびにかかる酵素を含む融合タンパク質および/または抗体コンジュゲートを作製することが可能であるという発見に基づく。
本発明は、以下の図面を参照してより完全に理解され得る。
本発明の種々の特徴および局面を以下により詳細に記載する。本発明は、野生型ヒトシアリダーゼに対して少なくとも1つの変異、例えば少なくとも1つのアミノ酸の置換、欠失または付加(挿入)を含む組換えヒトシアリダーゼを提供する。該変異、または変異の組合せは、シアリダーゼの発現、活性または発現と活性の両方を向上し得、癌の診断および/または治療におけるその使用を向上し得る。
本明細書で使用する場合、用語「シアリダーゼ」は、基質、例えば糖タンパク質または糖脂質から末端シアル酸残基を切断する任意の酵素またはその機能性断片をいう。用語、シアリダーゼは、野生型シアリダーゼ配列に対して1つ以上のアミノ酸の置換、欠失または挿入を有するバリアント、および/またはシアリダーゼを含む融合タンパク質もしくはコンジュゲートを含む。シアリダーゼはノイラミニダーゼとも称され、そうではないと示されない限り、2つの用語は本明細書において交換可能に使用される。本明細書で使用する場合、シアリダーゼの用語「機能性断片」は、対応する全長の天然に存在するシアリダーゼの酵素活性の例えば少なくとも10%、少なくとも20%、少なくとも30%、少なくとも40%、少なくとも50%、少なくとも60%、少なくとも70%、少なくとも80%、少なくとも90%または100%を保持する全長シアリダーゼの断片をいう。シアリダーゼ酵素活性は、例えば蛍光発生基質4-メチルウンベリフェリル-N-アセチルノイラミン酸(4MU-NeuAc)からのシアル酸の放出を測定することを含む当該技術分野で公知の任意の方法によりアッセイされ得る。ある態様において、機能性断片は、全長の天然に存在するシアリダーゼ中に存在する少なくとも100、150、200、250、300、310、320、330、340、350、360または370の連続したアミノ酸を含む。
ある態様において、組換え変異体ヒトシアリダーゼは、少なくとも1つのシステイン(cys、C)残基の置換を含む。シアリダーゼ中の特定のシステイン残基は、タンパク質凝集の結果として機能性タンパク質の発現を阻害し得ることが発見されている。したがって、ある態様において、組換え変異体ヒトシアリダーゼは、遊離システイン(例えばNeu1(配列番号:7)について、C111、C117、C171、C183、C218、C240、C242およびC252;Neu2(配列番号:1)について、C125、C196、C219、C272、C332およびC352;Neu3(配列番号:8)について、C7、C90、C99、C106、C127、C136、C189、C194、C226、C242、C250、C273、C279、C295、C356、C365、C368、C384、C383、C394およびC415;ならびにNeu4(配列番号:10)について、C88、C125、C126、C186、C191、C211、C223、C239、C276、C437、C453、C480およびC481)の少なくとも1つの変異を含む。遊離システインは任意のアミノ酸により置換され得る。ある態様において、遊離システインは、セリン(ser、S)、イソロイシン(iso、I)、バリン(val、V)、フェニルアラニン(phe、F)、ロイシン(leu、L)またはアラニン(ala、A)で置換される。Neu2における例示的なシステイン置換としては、C125A、C125I、C125S、C125V、C196A、C196L、C196V、C272S、C272V、C332A、C332S、C332V、C352LおよびC352Vが挙げられる。
タンパク質の等電点(pI)は、正味の電荷がゼロであるpHである。pIはまた、タンパク質が最小の可溶性であり、タンパク質を発現および精製する能力に影響するpHを示す。一般的に、タンパク質は、そのpIが溶液のpHよりも2単位高い場合に良好な溶解性を有する。ヒトNeu2は、7.5の予想pIを有する。したがって、ヒトNeu2は、中性pHの周囲で最小の可溶性であり、発現系および生理学系は中性pHにあるのでこれは望ましくない。対照的に、良好な溶解性および組み換え発現を示すネズミチフス菌由来のシアリダーゼ(St-シアリダーゼ)は、9.6のpIを有する。したがって、ヒトNeu2または他のヒトシアリダーゼの発現を増加するために、組換え変異体ヒトシアリダーゼは、1つ以上のアミノ酸置換(1つまたは複数)を含むように設計され得、ここで該置換(1つまたは複数)は、置換を有さないシアリダーゼに対して、シアリダーゼのpIを増加する。さらに、シアリダーゼの表面上の疎水性アミノ酸の数の減少は、例えば凝集を低減することによりシアリダーゼの発現を向上し得る。したがって、ヒトNeu2または他のヒトシアリダーゼの発現を増加するために、組換え変異体ヒトシアリダーゼは、1つ以上のアミノ酸置換(1つまたは複数)を含むように設計され得、ここで該置換(1つまたは複数)は、置換(1つまたは複数)を有さないシアリダーゼに対して、シアリダーゼの表面の疎水性を減少する。
2つ以上のアミノ酸のペプチド配列の、ヒトシアリダーゼのN末端への付加は、シアリダーゼの発現および/または活性を向上し得ることが発見されている。ある態様において、ペプチドは、少なくとも2アミノ酸長、例えば2~20、2~10、2~5または2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19もしくは20アミノ酸長である。ある態様において、ペプチドは、αへリックス形成し得るかまたはαヘリックスを形成するための傾向を有し得る。
本発明はさらに、以下の置換:I187K、A328E、K370NまたはH210Nの少なくとも1つを含む組換え変異体ヒトNeu2シアリダーゼを提供する。ある態様において、組換え変異体ヒトNeu2は、アミノ酸SMDQGSTW(配列番号:16)またはSTDGGKTW(配列番号:17)によるアミノ酸GDYDAPTHQVQW(配列番号:15)の置換を含む。ある態様において、組換え変異体ヒトNeu2は、アミノ酸QTPLEAAC(配列番号:19)によるアミノ酸PRPPAPEA(配列番号:18)の置換を含む。ある態様において、組換え変異体ヒトNeu2は、アミノ酸SQNDGES(配列番号:21)によるアミノ酸NPRPPAPEA(配列番号:20)の置換を含む。
過シアリル化された癌細胞上および/または腫瘍微小環境中のシアル酸の選択的な除去を促進するために、本明細書に記載されるようなシアリダーゼをかかる細胞またはかかる腫瘍微小環境に標的化することが有用であり得る。さらに、被験体におけるシアリダーゼによるシアル酸の除去を促進するために、被験体におけるシアリダーゼの血漿半減期を延長することが有用であり得る。これらは、融合タンパク質および/または抗体コンジュゲート(例えば化学的にコンジュゲートされたコンジュゲート)においてシアリダーゼを含むことにより達成され得る。
本明細書に記載される融合タンパク質のシアリダーゼ部分は、任意のシアリダーゼ、例えば真菌、細菌、非ヒト哺乳動物またはヒトのシアリダーゼであり得る。ある態様において、シアリダーゼ部分は、野生型ヒトシアリダーゼに対して、少なくとも1つの変異、例えば上述のような少なくとも1つのアミノ酸の置換、欠失または付加を含む組換えヒトシアリダーゼである。
本明細書で使用する場合、そうではないと示されない限り、用語「抗体」は、完全(intact)な抗体(例えば完全なモノクローナル抗体)、またはその断片、例えば抗体のFc断片(例えばモノクローナル抗体のFc断片)、または抗体の抗原結合断片(例えばモノクローナル抗体の抗原結合断片)、例えば改変されたか、作り変えられたかまたは化学的にコンジュゲートされた完全な抗体、抗原結合断片またはFc断片を意味すると解される。抗原結合断片の例としては、Fab、Fab'、(Fab')2、Fv、単鎖抗体(例えばscFv)、ミニボディおよびダイアボディが挙げられる。改変されたかまたは作り変えられた抗体の例としては、キメラ抗体、ヒト化抗体および多重特異性的抗体(例えば二重特異的抗体)が挙げられる。化学的にコンジュゲートされた抗体の例は、毒素部分にコンジュゲートされた抗体である。
ある態様において、融合タンパク質のシアリダーゼ部分は、融合タンパク質の抗体部分(例えば免疫グロブリンFcドメインおよび/または免疫グロブリン抗原結合ドメイン)に直接、連結または融合し得る。他の態様において、シアリダーゼ部分は、リンカーにより抗体部分に共有結合され得る。
本発明はさらに、本明細書に開示される融合タンパク質を含む抗体コンジュゲートを提供する。抗体コンジュゲートは、単一のポリペプチド鎖(すなわち本明細書に開示される融合タンパク質)を含み得るか、または抗体コンジュゲートは、さらなるポリペプチド鎖(例えば1、2または3のさらなるポリペプチド鎖)を含み得る。例えば、抗体コンジュゲートは、組換え変異体ヒトシアリダーゼ酵素および免疫グロブリン重鎖を含む第1のポリペプチド(融合タンパク質)、ならびに免疫グロブリン軽鎖を含む第2のポリペプチドを含み得、ここで例えば該免疫グロブリン重鎖および軽鎖は一緒になって、単一の抗原結合部位を画定する。
組換えヒトシアリダーゼ、融合タンパク質、例えば本明細書に開示されるもの、抗体または抗体コンジュゲート、例えば本明細書に開示されるものを作製するための方法は当該技術分野で公知である。例えば、軽鎖可変領域および/または重鎖可変領域をコードするDNA分子は、化学的にまたは組換えDNA方法論により合成し得る。例えば、該抗体の配列は、適切な合成核酸プライマーを使用して、従来のハイブリダイゼーション技術またはポリメラーゼ連鎖反応(PCR)技術によりハイブリドーマからクローニングされ得る。目的の可変領域をコードする得られたDNA分子を、例えば定常領域コーディング配列および発現制御配列などの他の適切なヌクレオチド配列にライゲーションして、所望の抗体をコードする従来の遺伝子発現構築物(すなわち発現ベクター)を作製し得る。所定の」遺伝子構築物の作製は当該技術分野の通常の技術の範囲内である。
治療的用途のために、組換えヒトシアリダーゼまたはその融合タンパク質および/または抗体コンジュゲートは、好ましくは薬学的に許容され得る担体と組み合される。用語「薬学的に許容され得る」は、本明細書で使用する場合、正常な医学的判断の範囲内で、過度な毒性、刺激、アレルギー応答または他の問題もしくは合併症なく、妥当な利益/リスク比に釣り合って、ヒトおよび動物の組織との接触における使用に適した化合物、材料、組成物および/または剤型をいう。
本明細書に開示される組成物および方法は、被験体において種々の形態の癌を治療するためまたは被験体において癌の増殖を阻害するために使用され得る。本発明は、被験体において癌を治療する方法を提供する。該方法は、被験体に、組換えヒトシアリダーゼまたはその融合タンパク質および/または抗体コンジュゲート、例えば本明細書に開示される組換えヒトシアリダーゼ、融合タンパク質または抗体コンジュゲートの有効量を、単独または別の治療剤と組み合わせて投与して、被験体において癌を治療する工程を含む。用語「有効量」は、本明細書で使用する場合、有益または所望の結果をもたらすのに十分な活性剤(例えば本発明の組換えヒトシアリダーゼまたはその融合タンパク質)の量をいう。有効量は1つ以上の投与、適用または用量において投与され得、特定の製剤または投与経路に限定されることを意図しない。
以下の実施例は単なる説明であり、いかなる方法においても本発明の範囲または内容を限定することは意図しない。
この実施例には、発現を高めるおよび/または凝集を低減するためのシステイン残基の置換を有する組換えヒトシアリダーゼ(Neu1、Neu2およびNeu3)の構築が記載される。
この実施例には、ヒトシアリダーゼの表面露出残基を作り変えることにより、シアリダーゼの等電点(pI)を増加し得および/またはシアリダーゼ上の表面の疎水性を低減して可溶性を向上し得および/またはタンパク質凝集を減少し得ることが示される。
この実施例には、ヒトシアリダーゼのN末端への短いペプチドの付加により、シアリダーゼの発現および/または活性を増加し得ることが示される。
この実施例には、N末端とC末端の間の疎水性相互作用および/または水素結合を増加するようにヒトシアリダーゼのNまたはC末端における残基を変異させることにより、シアリダーゼの安定性および/または発現を増加し得ることが示される。
この実施例には、ヒトシアリダーゼのN末端メチオニンを変異させることにより、シアリダーゼの安定性および/または発現を増加し得ることが示される。
この実施例には、変異および変異の組合せは、シアリダーゼの安定性および/または発現を増加し得ることが示される。
この実施例には、抗体-シアリダーゼ遺伝子的融合タンパク質ならびに細菌性および変異体ヒトシアリダーゼを有する融合タンパク質を含む抗体シアリダーゼコンジュゲート(ASC)の構築および発現が記載される。
この実施例には、細菌性シアリダーゼを含む抗体シアリダーゼコンジュゲート(ASC)のインビボ投与が記載される。
この実施例には、細菌性シアリダーゼを有する抗体シアリダーゼコンジュゲート(ASC)のインビボ投与が記載される。
この実施例には、細菌性シアリダーゼを有する抗体シアリダーゼコンジュゲート(ASC)のインビボ投与が記載される。
この実施例には、抗体シアリダーゼコンジュゲート(ASC)による腫瘍細胞からの末端シアル酸の標的化切断が記載される。
この実施例には、抗体シアリダーゼコンジュゲート(ASC)による樹状細胞(DC)活性化の癌細胞媒介阻害の低減が記載される。
この実施例には、ヒトシアリダーゼを有する抗体シアリダーゼコンジュゲート(ASC)による末梢血単核細胞(PBMC)における前炎症性サイトカインの誘導が記載される。
この実施例には、宿主-腫瘍微小環境モデル系への抗体シアリダーゼコンジュゲート(ASC)の添加後の免疫関連活性の増加が記載される。
この実施例には、細菌性シアリダーゼを含む抗体シアリダーゼコンジュゲート(ASC)のインビボ投与が記載される。
この実施例には、ヒトシアリダーゼを含む抗体シアリダーゼコンジュゲート(ASC)のインビボ投与が記載される。
本明細書で言及される特許文献および科学論文のそれぞれの全開示は、全ての目的で参照により援用される。
本発明は、その精神または本質的な特徴から逸脱することなく他の特定の形態で実現され得る。そのため、前述の態様は、全ての局面において本明細書に記載される発明の限定ではなく、例示としてみなされる。したがって、本発明の範囲は、前述の記載ではなく添付の特許請求の範囲により示され、特許請求の範囲の同等物の意味および範囲内にある全ての変更が本発明に包含されることが意図される。
本発明の態様として以下のものが挙げられる。
項1
組換え変異体ヒトシアリダーゼ酵素であって、シアリダーゼが、N末端およびC末端を含み、かつ:
(a) 少なくとも1つの野生型システイン残基の置換;
(b) 少なくとも1つの野生型アミノ酸残基の置換、ここで該置換は、置換を有さないシアリダーゼに対して、シアリダーゼの等電点(pI)を増加し、および/またはシアリダーゼの疎水性を減少する;
(c) シアリダーゼのN末端でN末端アミノ酸と共有結合する少なくとも2アミノ酸残基長のペプチド;
(d) 少なくとも1つの野生型アミノ酸残基の置換、ここで該置換は、置換を有さないシアリダーゼに対して、シアリダーゼのN末端およびC末端の間で疎水性相互作用および/または水素結合を増加する;および/または
(e) シアリダーゼのN末端でのN末端メチオニンの置換もしくは欠失
を含む、酵素。
項2
組換え変異体ヒトシアリダーゼ酵素であって、シアリダーゼが、N末端およびC末端を含み、かつ:
(a) 少なくとも1つの野生型システイン残基の置換;
(b) 少なくとも1つの野生型アミノ酸残基の置換、ここで該置換は、置換を有さないシアリダーゼに対して、シアリダーゼの等電点(pI)を増加しおよび/またはシアリダーゼの疎水性を低減する;
(c) シアリダーゼのN末端でN末端アミノ酸と共有結合する少なくとも2アミノ酸残基長のペプチド;および/または
(d) 少なくとも1つの野生型アミノ酸残基の置換、ここで該置換は、置換を有さないシアリダーゼに対して、シアリダーゼのN末端およびC末端の間で、疎水性相互作用および/または水素結合を増加する、
を含む、酵素。
項3
Neu1、Neu2、Neu3およびNeu4から選択される、項1または2記載のシアリダーゼ。
項4
Neu2である、項3記載のシアリダーゼ。
項5
システイン残基の置換を含む、項1~4いずれか記載のシアリダーゼ
項6
システイン残基が遊離システイン残基である、項5記載のシアリダーゼ。
項7
システイン残基が、セリン、イソロイシン、バリン、フェニルアラニン、ロイシンまたはアラニンにより置換される、項5または6記載のシアリダーゼ。
項8
野生型ヒトNeu2(配列番号:1)の332位に対応する位置でシステイン残基の置換を含む、項5~7いずれか記載のシアリダーゼ。
項9
野生型ヒトNeu2の332位に対応する位置で、システイン残基がアラニンにより置換される(C332A)、項8記載のシアリダーゼ。
項10
野生型ヒトNeu2(配列番号:1)の352位に対応する位置でシステイン残基の置換を含む、項5~9いずれか記載のシアリダーゼ。
項11
野生型ヒトNeu2の352位に対応する位置で、システイン残基がロイシンにより置換される(C352L)、項10記載のシアリダーゼ。
項12
C332AおよびC352L置換を含む、項9または11記載のシアリダーゼ。
項13
シアリダーゼが少なくとも1つの野生型アミノ酸残基の置換を含み、該置換が、置換を有さないシアリダーゼに対して、シアリダーゼの等電点(pI)を増加しおよび/またはシアリダーゼの疎水性を減少する、項1~12いずれか記載のシアリダーゼ。
項14
シアリダーゼが野生型アミノ酸残基の置換を含み、該置換が、置換を有さないシアリダーゼに対して、シアリダーゼの等電点(pI)を増加する、項13記載のシアリダーゼ。
項15
シアリダーゼが野生型アミノ酸残基の置換を含み、該置換が、置換を有さないシアリダーゼに対して、シアリダーゼの疎水性を減少する、項13または14記載のシアリダーゼ。
項16
野生型アミノ酸残基が、溶媒接近可能なアミノ酸残基である、項13~15いずれか記載のシアリダーゼ。
項17
野生型アミノ酸が、リジン、アルギニンまたはヒスチジンにより置換される、項13~16いずれか記載のシアリダーゼ。
項18
野生型アミノ酸がリジンにより置換される、項17記載のシアリダーゼ。
項19
野生型ヒトNeu2(配列番号:1)の2位に対応する位置でアラニン残基の置換を含む、項13~18いずれか記載のシアリダーゼ。
項20
野生型ヒトNeu2の2位に対応する位置でアラニン残基がリジンにより置換される(A2K)、項19記載のシアリダーゼ。
項21
シアリダーゼのN末端に融合される少なくとも2アミノ酸残基長のペプチドを含む、項1~20記載のシアリダーゼ。
項22
ペプチドが、シアリダーゼのN末端アミノ酸残基に融合される、項21記載のシアリダーゼ。
項23
ペプチドが、2アミノ酸残基長~20アミノ酸残基長である、項21または22記載のシアリダーゼ。
項24
ペプチドが、少なくとも5アミノ酸残基長である、項21~23いずれか記載のシアリダーゼ。
項25
ペプチドが、野生型マウス胸腺Neu2由来のアミノ酸配列(配列番号:2)を含む、項21~24いずれか記載のシアリダーゼ。
項26
ペプチドが、EDLRP(配列番号:3)を含む、項21~25いずれか記載のシアリダーゼ。
項27
ペプチドが、MEDLRP(配列番号:4)を含む、項21~26いずれか記載のシアリダーゼ。
項28
シアリダーゼが、少なくとも1つの野生型アミノ酸残基の置換を含み、該置換が、置換を有さないシアリダーゼに対して、シアリダーゼのN末端およびC末端の間の疎水性相互作用および/または水素結合を増加する、項1~27いずれか記載のシアリダーゼ。
項29
野生型ヒトNeu2(配列番号:1)の6位に対応する位置でバリン残基の置換を含む、項28記載のシアリダーゼ。
項30
野生型ヒトNeu2の6位に対応する位置のバリン残基がチロシンにより置換される(V6Y)、項29記載のシアリダーゼ。
項31
シアリダーゼのN末端で、N末端メチオニンの置換または欠失を含む、項1~30いずれか記載のシアリダーゼ。
項32
野生型ヒトNeu2(配列番号:1)の1位に対応する位置でメチオニン残基の置換を含む、項31記載のシアリダーゼ。
項33
野生型ヒトNeu2の1位に対応する位置でのメチオニン残基が、アラニンにより置換される(M1A)、項32記載のシアリダーゼ。
項34
野生型ヒトNeu2の1位に対応する位置でのメチオニン残基が、アスパラギン酸により置換される(M1D)、項32記載のシアリダーゼ。
項35
対応する野生型シアリダーゼとは異なる基質特異性を有する、項1~34いずれか記載のシアリダーゼ。
項36
α2,3、α2,6および/またはα2,8連結を切断し得る、項35記載のシアリダーゼ。
項37
α2,3およびα2,8連結を切断し得る、項36記載のシアリダーゼ。
項38
配列番号:5、配列番号:6、配列番号:36、配列番号:37、配列番号:38、配列番号:39、配列番号:70、配列番号:71、配列番号:72または配列番号:73を含む、項1~37いずれか記載のシアリダーゼ。
項39
配列番号:5、配列番号:6、配列番号:36、配列番号:37、配列番号:38または配列番号:39を含む、項1~37いずれか記載のシアリダーゼ。
項40
配列番号:36、配列番号:37、配列番号:38、配列番号:39、配列番号:70、配列番号:71、配列番号:72または配列番号:73を含む、項1~37いずれか記載のシアリダーゼ。
項41
配列番号:36、配列番号:37、配列番号:38または配列番号:39を含む、項1~37いずれか記載のシアリダーゼ。
項42
配列番号:5または配列番号:6を含む、項1~37いずれか記載のシアリダーゼ。
項43
表2、3、4、5、6または7のいずれか1つに記載されるシアリダーゼを含む、変異体シアリダーゼ酵素。
項44
(a) シアリダーゼ酵素;ならびに
(b) 免疫グロブリンFcドメインおよび/または免疫グロブリン抗原結合ドメインを含む、融合タンパク質であって、
シアリダーゼならびに免疫グロブリンFcドメインおよび/または免疫グロブリン抗原結合ドメインが、ペプチド結合またはアミノ酸リンカーにより連結される、融合タンパク質。
項45
シアリダーゼがヒトシアリダーゼである、項44記載の融合タンパク質。
項46
シアリダーゼが、項1~43いずれか記載の組換え変異体ヒトシアリダーゼである、項44または45記載の融合タンパク質。
項47
免疫グロブリンFcドメインを含む、項44~46いずれか記載の融合タンパク質。
項48
免疫グロブリンFcドメインが、ヒトIgG1、IgG2、IgG3、IgG4、IgA1、IgA2、IgD、IgEまたはIgMのFcドメインに由来する、項47記載の融合タンパク質。
項49
免疫グロブリンFcドメインが、ヒトIgG1、IgG2、IgG3またはIgG4のFcドメインに由来する、項48記載の融合タンパク質。
項50
免疫グロブリンFcドメインが、ヒトIgG1 Fcドメインに由来する、項49記載の融合タンパク質。
項51
免疫グロブリン抗原結合ドメインを含む、項44~50いずれか記載の融合タンパク質。
項52
免疫グロブリン抗原結合ドメインが、第2の免疫グロブリン抗原結合ドメインに結合されて、抗原結合部位を生じる、項51記載の融合タンパク質。
項53
免疫グロブリン抗原結合ドメインが、トラスツズマブ、セツキシマブ、ダラツムマブ、ギレンツキシマブ、パニツムマブ、オファツムマブおよびリツキシマブから選択される抗体に由来する、項51または52記載の融合タンパク質。
項54
免疫グロブリン抗原結合ドメインがトラスツズマブに由来する、項53記載の融合タンパク質。
項55
配列番号:43、配列番号:44、配列番号:45、配列番号:46、配列番号:47、配列番号:48、配列番号:49、配列番号:50、配列番号:51、配列番号:52、配列番号:53、配列番号:54、配列番号:63、配列番号:74、配列番号:75、配列番号:76、配列番号:77、配列番号:78または配列番号:79を含む、項44~54いずれか記載の融合タンパク質。
項56
配列番号:43、配列番号:44、配列番号:45、配列番号:46、配列番号:47、配列番号:48、配列番号:49、配列番号:50、配列番号:51、配列番号:52、配列番号:53または配列番号:54を含む、項44~54いずれか記載の融合タンパク質。
項57
項44~56いずれか記載の融合タンパク質を含む、抗体コンジュゲート。
項58
単一のシアリダーゼを含む、項57記載の抗体コンジュゲート。
項59
2つのシアリダーゼを含む、項58記載の抗体コンジュゲート。
項60
2つのシアリダーゼが同一である、項59記載の抗体コンジュゲート。
項61
単一の抗原結合部位を含む、項57~60いずれか記載の抗体コンジュゲート。
項62
2つの抗原結合部位を含む、項57~61いずれか記載の抗体コンジュゲート。
項63
2つの抗原結合部位が同一である、項62記載の抗体コンジュゲート。
項64
約135kDa~約165kDaの分子量を有する、項57~63いずれか記載の抗体コンジュゲート。
項65
約215kDa~約245kDaの分子量を有する、項57~63いずれか記載の抗体コンジュゲート。
項66
抗体コンジュゲートが、
(a) 免疫グロブリン軽鎖を含む第1のポリペプチド;
(b) 免疫グロブリン重鎖を含む第2のポリペプチド;ならびに
(c) 免疫グロブリンFcドメインおよびシアリダーゼを含む第3のポリペプチド
を含み、
第1および第2のポリペプチドが一緒になって共有結合し、第2および第3のポリペプチドが一緒になって結合し、第1のポリペプチドおよび第2のポリペプチドが一緒になって抗原結合部位を画定する、項57~65いずれか記載の抗体コンジュゲート。
項67
第3のポリペプチドが、N末端からC末端の方向で、シアリダーゼおよび免疫グロブリンFcドメインを含む、項66記載の抗体コンジュゲート。
項68
第1のポリペプチドが配列番号:49を含む、項66または67記載の抗体コンジュゲート。
項69
第2のポリペプチドが配列番号:50を含む、項66~68いずれか記載の抗体コンジュゲート。
項70
第3のポリペプチドが、配列番号:51、配列番号:52、配列番号:53、配列番号:54、配列番号:76、配列番号:77、配列番号:78または配列番号:79を含む、項66~69いずれか記載の抗体コンジュゲート。
項71
第3のポリペプチドが、配列番号:51、配列番号:52、配列番号:53または配列番号:54を含む、項66~69いずれか記載の抗体コンジュゲート。
項72
融合タンパク質が:
(a) 第1の免疫グロブリン軽鎖を含む第1のポリペプチド;
(b) 第1の免疫グロブリン重鎖および第1のシアリダーゼを含む第2のポリペプチド;
(c) 第2の免疫グロブリン重鎖および第2のシアリダーゼを含む第3のポリペプチド;ならびに
(d) 第2の免疫グロブリン軽鎖を含む第4のポリペプチド
を含み、
第1および第2のポリペプチドが一緒になって共有結合し、第3および第4のポリペプチドが一緒になって共有結合し、第2および第3のポリペプチドが一緒になって共有結合し、第1のポリペプチドおよび第2のポリペプチドが一緒になって第1の抗原結合部位を画定し、第3のポリペプチドおよび第4のポリペプチドが一緒になって第2の抗原結合部位を画定する、項57~65いずれか記載の抗体コンジュゲート。
項73
第2および第3のポリペプチドが、N末端からC末端の方向で、第1および第2の免疫グロブリン重鎖ならびに第1および第2のシアリダーゼのそれぞれを含む、項72記載の抗体コンジュゲート。
項74
融合タンパク質が:
(a) 第1のシアリダーゼ、第1の免疫グロブリンFcドメインおよび第1の一本鎖可変断片(scFv)を含む第1のポリペプチド;ならびに
(b) 第2のシアリダーゼ、第2の免疫グロブリンFcドメインおよび第2の一本鎖可変断片(scFv)を含む第2のポリペプチド
を含み、
第1および第2のポリペプチドが一緒になって共有結合し、第1のscFvが第1の抗原結合部位を画定し、第2のscFvが第2の抗原結合部位を画定する、
項57~65いずれか記載の抗体コンジュゲート。
項75
第1のポリペプチドが、N末端からC末端の方向で、第1のシアリダーゼ、第1の免疫グロブリンFcドメインおよび第1のscFvを含み、第2のポリペプチドが、N末端からC末端の方向で、第2のシアリダーゼ、第2の免疫グロブリンFcドメインおよび第2のscFvを含む、項74記載の抗体コンジュゲート。
項76
第1のポリペプチドが、配列番号:43、配列番号:44、配列番号:45、配列番号:46、配列番号:47、配列番号:48、配列番号:74または配列番号:75を含む、項74または75記載の抗体コンジュゲート。
項77
第1のポリペプチドが、配列番号:43、配列番号:44、配列番号:45、配列番号:46、配列番号:47または配列番号:48を含む、項74または75記載の抗体コンジュゲート。
項78
第2のポリペプチドが、配列番号:43、配列番号:44、配列番号:45、配列番号:46、配列番号:47、配列番号:48、配列番号:74または配列番号:75を含む、項74~77いずれか記載の抗体コンジュゲート。
項79
第2のポリペプチドが、配列番号:43、配列番号:44、配列番号:45、配列番号:46、配列番号:47または配列番号:48を含む、項74~77いずれか記載の抗体コンジュゲート。
項80
項1~43いずれか記載の組換え変異体ヒトシアリダーゼ、項44~56いずれか記載の融合タンパク質、または項57~79いずれか記載の抗体コンジュゲートの少なくとも一部をコードするヌクレオチド配列を含む、単離された核酸。
項81
項80記載の核酸を含む発現ベクター。
項82
項81記載の発現ベクターを含む宿主細胞。
項83
項1~43いずれか記載の組換え変異体ヒトシアリダーゼ、項44~56いずれか記載の融合タンパク質、または項57~79いずれか記載の抗体コンジュゲートを含む、医薬組成物。
項84
癌の治療を必要とする被験体において癌を治療する方法であって、該方法が、該被験体に、項1~43いずれか記載の組換え変異体ヒトシアリダーゼ、項44~56いずれか記載の融合タンパク質、項57~79いずれか記載の抗体コンジュゲート、または項83記載の医薬組成物の有効量を投与する工程を含む、方法。
項85
癌の治療を必要とする被験体において癌を治療する方法であって、該方法が、該被験体に、項44~56いずれか記載の融合タンパク質、項57~79いずれか記載の抗体コンジュゲート、または項83記載の医薬組成物の有効量を投与する工程を含む、方法。
項86
癌が上皮癌である、項85記載の方法。
項87
上皮癌が、子宮内膜癌、卵巣癌、子宮頸癌、外陰癌、子宮癌、ファローピウス管癌、乳癌、前立腺癌、肺癌、膵臓癌、泌尿器癌、膀胱癌、頭頸部癌、口腔癌および肝臓癌から選択される、項86記載の方法。
項88
細胞または組織においてHLA-DR、CD86、CD83、IFNγ、IL-1b、IL-6、TNFα、IL-17A、IL-2またはIL-6の発現を増加する方法であって、該方法が、該細胞または組織と、項1~43いずれか記載の組換え変異体ヒトシアリダーゼ、項44~56いずれか記載の融合タンパク質、項57~79いずれか記載の抗体コンジュゲート、または項83記載の医薬組成物の有効量を接触させる工程を含む、方法。
項89
細胞が、樹状細胞および末梢血単核細胞(PBMC)から選択される、項88記載の方法。
Claims (13)
- 組換え変異体ヒトシアリダーゼであって、シアリダーゼが、N末端およびC末端を含み、かつ:
(a) 野生型ヒトNeu2(配列番号:1)の332位に対応する位置でのシステイン残基の置換、ここで該システイン残基が、アラニンにより置換される(C332A);
(b) 野生型ヒトNeu2(配列番号:1)の6位に対応する位置でのバリン残基の置換、ここで該バリン残基がチロシンにより置換される(V6Y);および
(c) 野生型ヒトNeu2(配列番号:1)の1位に対応する位置でのメチオニン残基の置換、ここで該メチオニン残基が、アスパラギン酸により置換される(M1D)、
を含み、該組換え変異体ヒトシアリダーゼがヒトシアリダーゼの活性を有し、配列番号:39のアミノ酸配列と少なくとも95%同一であるアミノ酸配列を有する、組換え変異体ヒトシアリダーゼ。 - Neu2である、請求項1記載の組換え変異体ヒトシアリダーゼ。
- シアリダーゼが、野生型ヒトNeu2(配列番号:1)の187位に対応する位置で、イソロイシン残基のリジンによる置換(I187K)をさらに含む、請求項1または2記載の組換え変異体ヒトシアリダーゼ。
- (a) 請求項1~3いずれか記載の組換え変異体ヒトシアリダーゼ;ならびに
(b) 免疫グロブリンFcドメインおよび/または免疫グロブリン抗原結合ドメインを含む、融合タンパク質であって、
シアリダーゼならびに免疫グロブリンFcドメインおよび/または免疫グロブリン抗原結合ドメインが、ペプチド結合またはアミノ酸リンカーにより連結される、融合タンパク質。 - 請求項4記載の融合タンパク質を含む、抗体コンジュゲート。
- 抗体コンジュゲートが、
(a) 免疫グロブリン軽鎖を含む第1のポリペプチド;
(b) 免疫グロブリン重鎖を含む第2のポリペプチド;ならびに
(c) 免疫グロブリンFcドメインおよび該組換え変異体ヒトシアリダーゼを含む第3のポリペプチド
を含み、
第1および第2のポリペプチドが一緒になって共有結合し、第2および第3のポリペプチドが一緒になって共有結合し、第1のポリペプチドおよび第2のポリペプチドが一緒になって抗原結合部位を画定する、請求項5記載の抗体コンジュゲート。 - 請求項1~3いずれか記載の組換え変異体ヒトシアリダーゼをコードするヌクレオチド配列を含む、単離された核酸。
- 請求項7記載の核酸を含む発現ベクター。
- 請求項8記載の発現ベクターを含む宿主細胞。
- 請求項1~3いずれか記載の組換え変異体ヒトシアリダーゼを含む、医薬組成物。
- 癌の治療を必要とする被験体において癌を治療するための、請求項10記載の医薬組成物。
- 癌の治療を必要とする被験体において癌を治療するための医薬組成物であって、請求項5記載の抗体コンジュゲートを含む、医薬組成物。
- 細胞または組織においてHLA-DR、CD86、CD83、IFNγ、IL-1b、TNFα、IL-17A、IL-2またはIL-6の発現を増加するための、請求項10記載の医薬組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2023206452A JP2024026296A (ja) | 2018-01-03 | 2023-12-06 | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862613363P | 2018-01-03 | 2018-01-03 | |
US62/613,363 | 2018-01-03 | ||
US201862755279P | 2018-11-02 | 2018-11-02 | |
US62/755,279 | 2018-11-02 | ||
PCT/US2019/012207 WO2019136167A1 (en) | 2018-01-03 | 2019-01-03 | Recombinant human sialidases, sialidase fusion proteins, and methods of using the same |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023206452A Division JP2024026296A (ja) | 2018-01-03 | 2023-12-06 | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021509585A JP2021509585A (ja) | 2021-04-01 |
JP7462560B2 true JP7462560B2 (ja) | 2024-04-05 |
Family
ID=67144286
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020537509A Active JP7462560B2 (ja) | 2018-01-03 | 2019-01-03 | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 |
JP2023206452A Pending JP2024026296A (ja) | 2018-01-03 | 2023-12-06 | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023206452A Pending JP2024026296A (ja) | 2018-01-03 | 2023-12-06 | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 |
Country Status (10)
Country | Link |
---|---|
US (1) | US11965188B2 (ja) |
EP (1) | EP3735458A4 (ja) |
JP (2) | JP7462560B2 (ja) |
KR (1) | KR20200128385A (ja) |
CN (1) | CN112135904A (ja) |
AU (1) | AU2019205912A1 (ja) |
CA (1) | CA3087529A1 (ja) |
IL (1) | IL275779A (ja) |
MX (1) | MX2020007024A (ja) |
WO (1) | WO2019136167A1 (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20220105179A1 (en) * | 2019-02-21 | 2022-04-07 | The General Hospital Corporation | Glycoengineering immunoglobulin e |
WO2021003468A2 (en) * | 2019-07-03 | 2021-01-07 | Palleon Pharmaceuticals Inc. | Recombinant sialidases and methods of using the same |
EP3994180A4 (en) * | 2019-07-03 | 2023-08-02 | Palleon Pharmaceuticals Inc. | SIALIDASE-HER2 ANTIBODY FUSION PROTEINS AND THEIR METHODS OF USE |
BR112021026789A2 (pt) * | 2019-07-03 | 2022-05-10 | Palleon Pharmaceuticals Inc | Sialidases humanas recombinantes, proteínas de fusão de sialidase e métodos de uso das mesmas |
BR112022014568A2 (pt) * | 2020-01-23 | 2022-09-27 | Exuma Biotech Corp | Receptores de antígeno quiméricos contra her2 e métodos de uso dos mesmos |
IL299559A (en) * | 2020-07-03 | 2023-02-01 | Palleon Pharmaceuticals Inc | Recombinant sialidases with reduced protease sensitivity, sialidase fusion proteins and methods of using them |
WO2022150516A1 (en) * | 2021-01-06 | 2022-07-14 | Palleon Pharmaceuticals Inc. | Sialidase-her2-antibody fusion proteins and methods of use thereof |
WO2022150507A1 (en) * | 2021-01-06 | 2022-07-14 | Palleon Pharmaceuticals Inc. | Sialidase-pd-1-antibody fusion proteins and methods of use thereof |
KR102579433B1 (ko) * | 2021-03-04 | 2023-09-15 | 한국생명공학연구원 | 지질 대사 기능 장애 동물 모델로서의 neu2 결손마우스 및 이의 용도 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170165334A1 (en) | 2015-12-11 | 2017-06-15 | Tianxin Wang | Methods to Treat Diseases with Protein, Peptide, Antigen Modification and Hemopurification |
Family Cites Families (68)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2620649C3 (de) | 1976-05-11 | 1980-11-06 | Behringwerke Ag, 3550 Marburg | Immunologisches Adjuvans |
US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
US7060676B2 (en) | 1999-12-20 | 2006-06-13 | Trustees Of Tufts College | T. cruzi-derived neurotrophic agents and methods of use therefor |
AU5133601A (en) | 2000-04-07 | 2001-10-23 | Ellis L Kline | Methods and compositions for treating neoplasms |
FR2828386B1 (fr) | 2001-08-10 | 2004-06-11 | Jean Noel Acquaviva | Ecran de vision coupe-vent |
WO2003068821A2 (en) | 2002-02-14 | 2003-08-21 | Immunomedics, Inc. | Anti-cd20 antibodies and fusion proteins thereof and methods of use |
US8084036B2 (en) | 2002-11-22 | 2011-12-27 | Nexbio, Inc. | Broad spectrum anti-viral therapeutics and prophylaxis |
US7807174B2 (en) | 2002-11-22 | 2010-10-05 | Nexbio, Inc. | Class of therapeutic protein based molecules |
US8512710B2 (en) | 2002-11-22 | 2013-08-20 | Ansun Biopharma, Inc. | Class of therapeutic protein based molecules |
KR20110110825A (ko) | 2003-11-10 | 2011-10-07 | 유에이비 리서치 파운데이션 | 세균의 운반 및 cns 침입을 감소시키기 위한 조성물 및 이를 이용한 방법 |
KR102109867B1 (ko) | 2006-01-24 | 2020-05-13 | 안선 바이오파르마, 아이엔씨. | 고분자 미소 구체들의 조제를 위한 기술 |
TWI421257B (zh) | 2006-03-10 | 2014-01-01 | Wyeth Corp | 抗5t4抗體及其用途 |
EP2389951A1 (en) | 2006-03-23 | 2011-11-30 | Novartis AG | Anti-tumor cell antigen antibody therapeutics |
CN100376689C (zh) | 2006-03-28 | 2008-03-26 | 北京大学 | 一种预测达菲类药物用药安全性的方法 |
WO2008033520A2 (en) | 2006-09-15 | 2008-03-20 | The Regents Of The University Of California | Bifidobacterial gene sequences and their use |
EP1938835A1 (en) | 2006-12-29 | 2008-07-02 | Pevion Biotech AG | Non-specific immunostimulating agents |
CN101636489B (zh) | 2007-02-20 | 2014-08-13 | 帝斯曼知识产权资产管理有限公司 | 新颖的唾液酸酶 |
US8329195B2 (en) | 2007-05-23 | 2012-12-11 | The Uab Research Foundation | Detoxified pneumococcal neuraminidase and uses thereof |
US8187591B2 (en) | 2007-10-11 | 2012-05-29 | The Regents Of The University Of California | Methods of treating coagulopathy |
PT4209510T (pt) | 2008-12-09 | 2024-04-02 | Hoffmann La Roche | Anticorpos anti-pm-l1 e a sua utilização para a melhoria do funcionamento das células t |
AU2010315024B2 (en) | 2009-11-06 | 2015-02-12 | Nexbio, Inc. | Methods, compounds and compositions for treatment and prophylaxis in the respiratory tract |
CN104254541A (zh) | 2012-03-16 | 2014-12-31 | 弗·哈夫曼-拉罗切有限公司 | 改造的构象稳定蛋白质 |
CA2871706C (en) | 2012-04-30 | 2019-12-03 | Biocon Limited | Targeted/immunomodulatory fusion proteins and methods for making same |
KR20150023729A (ko) | 2012-06-14 | 2015-03-05 | 암브룩스, 인코포레이티드 | 핵 수용체 리간드 폴리펩티드에 접합된 항-psma 항체 |
UA105278C2 (ru) | 2012-09-06 | 2014-04-25 | Інститут Біології Клітини Нан України | Способ получения каталитически активных антител (абзимов) с сиалидазной активностью |
AR093984A1 (es) | 2012-12-21 | 2015-07-01 | Merck Sharp & Dohme | Anticuerpos que se unen a ligando 1 de muerte programada (pd-l1) humano |
EP2968622B1 (en) | 2013-03-13 | 2021-05-12 | Imaginab, Inc. | Antigen binding constructs to cd8 |
KR102186997B1 (ko) | 2013-03-15 | 2020-12-07 | 안선 바이오파르마, 아이엔씨. | 단백질 정제의 신규한 방법 |
EP2984104B1 (en) | 2013-04-12 | 2017-11-01 | Danmarks Tekniske Universitet | A mutant sialidase having trans-sialidase activity for use in production of sialylated glycans |
WO2014201034A2 (en) | 2013-06-10 | 2014-12-18 | Ansun Biopharma, Inc. | Treatment for polyomavirus infection |
US20160120961A1 (en) | 2013-06-10 | 2016-05-05 | Ansun Biopharma, Inc. | Treatment of merkel cell polyomavirus infection |
US20160229882A1 (en) | 2013-09-17 | 2016-08-11 | The Regents Of The University Of California | Non-enzymatic, salt-mediated synthesis of polynucleic acids |
WO2015184356A1 (en) | 2014-05-30 | 2015-12-03 | Ansun Biopharma, Inc. | Treatment of middle east respiratory syndrome coronavirus |
WO2016038064A1 (en) | 2014-09-10 | 2016-03-17 | Innate Pharma | Cross reactive siglec antibodies |
US10328128B2 (en) | 2014-09-17 | 2019-06-25 | Ansun Biopharma, Inc. | Treatment of infection by human enterovirus D68 |
US10138268B2 (en) | 2014-10-10 | 2018-11-27 | Enzypep B.V. | Peptide fragment condensation and cyclisation using a subtilisin variant with improved synthesis over hydrolysis ratio |
JP2018500934A (ja) * | 2014-12-22 | 2018-01-18 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Cmp依存性シアリダーゼ活性 |
BR112017019559B1 (pt) | 2015-03-13 | 2020-08-04 | Cytomx Therapeutics, Inc | Anticorpos anti-pdl1, anticorpos anti-pdl1 ativáveis, e métodos de uso destes |
US20180177852A1 (en) * | 2015-06-08 | 2018-06-28 | Ansun Biopharma, Inc. | Treatment of human metapneumovirus |
US10428318B2 (en) | 2015-06-09 | 2019-10-01 | Glycom A/S | Mutated sialidases |
EP3120856A1 (en) | 2015-07-23 | 2017-01-25 | imv Technologies | Process and composition for low dose insemination |
EP3402516A4 (en) | 2016-01-12 | 2020-01-08 | Palleon Pharmaceuticals Inc. | USE OF ANTIBODIES DIRECTED AGAINST SIGLEC-7 OR SIGLEC-9 IN THE TREATMENT OF CANCER |
AR107483A1 (es) | 2016-01-29 | 2018-05-02 | Hanmi Pharm Ind Co Ltd | Conjugado de enzimas terapéuticas |
GB201602105D0 (en) | 2016-02-05 | 2016-03-23 | Inst Of Food Res | Intramolecular Trains- Sialidase |
CN107216389B (zh) | 2016-03-18 | 2022-03-29 | 和迈生物科技有限公司 | 抗pd-l1纳米抗体及其编码序列和用途 |
WO2017180587A2 (en) | 2016-04-11 | 2017-10-19 | Obsidian Therapeutics, Inc. | Regulated biocircuit systems |
US20180271997A1 (en) | 2016-05-31 | 2018-09-27 | Tianxin Wang | Methods and Reagents to Treat Tumor and Cancer |
US20190125859A1 (en) | 2016-06-03 | 2019-05-02 | Icahn School Of Medicine At Mount Sinai | Influenza virus vaccination regimens |
SG11201811719RA (en) | 2016-07-01 | 2019-01-30 | Univ Leland Stanford Junior | Conjugates for targeted cell surface editing |
GB201611535D0 (en) | 2016-07-01 | 2016-08-17 | King S College London | Methods and compositions for treating cancer with siglec-9 activity modulators |
EP3478315A4 (en) | 2016-07-01 | 2020-03-25 | The Board of Trustees of the Leland Stanford Junior University | METHODS AND COMPOSITIONS FOR INHIBITING THE INHIBITOR IMMUNE RECEPTOR |
GB201616006D0 (en) | 2016-09-20 | 2016-11-02 | Univ Court Of The Univ Of St Andrews The | Cell modulation |
JP7042220B2 (ja) | 2016-12-28 | 2022-03-25 | Jcrファーマ株式会社 | 凍結乾燥製剤 |
CN106906236B (zh) | 2017-04-10 | 2020-04-10 | 中国科学院深海科学与工程研究所 | 唾液酸酶基因重组表达载体及其构建方法,唾液酸酶及其制备方法 |
WO2018231661A1 (en) | 2017-06-12 | 2018-12-20 | Tianxin Wang | Methods and reagents to treat tumor and cancer |
GB201717945D0 (en) | 2017-10-31 | 2017-12-13 | Nat Univ Ireland Galway | Method for treatment of cancer |
EP3569618A1 (en) | 2018-05-19 | 2019-11-20 | Boehringer Ingelheim International GmbH | Antagonizing cd73 antibody |
US20220370527A1 (en) | 2018-07-20 | 2022-11-24 | Ansun Biopharma, Inc. | Delivery of sialidase to cancer cells, immune cells and the tumor microenvironment |
EP3906096A4 (en) | 2019-01-03 | 2023-03-01 | Palleon Pharmaceuticals Inc. | METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER WITH IMMUNE CELLS |
US20220105179A1 (en) | 2019-02-21 | 2022-04-07 | The General Hospital Corporation | Glycoengineering immunoglobulin e |
KR20220045930A (ko) | 2019-04-30 | 2022-04-13 | 마이얼로이드 테라퓨틱스, 인크. | 조작된 키메라 융합 단백질 조성물 및 이의 사용 방법 |
WO2021003464A1 (en) | 2019-07-03 | 2021-01-07 | Palleon Pharmaceuticals Inc. | Sialidase-pd-l1-antibody fusion proteins and methods of use thereof |
BR112021026789A2 (pt) | 2019-07-03 | 2022-05-10 | Palleon Pharmaceuticals Inc | Sialidases humanas recombinantes, proteínas de fusão de sialidase e métodos de uso das mesmas |
WO2021003468A2 (en) | 2019-07-03 | 2021-01-07 | Palleon Pharmaceuticals Inc. | Recombinant sialidases and methods of using the same |
AU2020298628A1 (en) | 2019-07-03 | 2022-02-03 | Palleon Pharmaceuticals Inc. | Sialidase-CD20-antibody fusion proteins and methods of use thereof |
EP3994180A4 (en) | 2019-07-03 | 2023-08-02 | Palleon Pharmaceuticals Inc. | SIALIDASE-HER2 ANTIBODY FUSION PROTEINS AND THEIR METHODS OF USE |
IL299559A (en) | 2020-07-03 | 2023-02-01 | Palleon Pharmaceuticals Inc | Recombinant sialidases with reduced protease sensitivity, sialidase fusion proteins and methods of using them |
CN111763259B (zh) | 2020-09-03 | 2020-12-15 | 北京百奥赛图基因生物技术有限公司 | 抗cd40抗体及其用途 |
-
2019
- 2019-01-03 EP EP19736174.4A patent/EP3735458A4/en active Pending
- 2019-01-03 JP JP2020537509A patent/JP7462560B2/ja active Active
- 2019-01-03 MX MX2020007024A patent/MX2020007024A/es unknown
- 2019-01-03 CN CN201980017083.6A patent/CN112135904A/zh active Pending
- 2019-01-03 WO PCT/US2019/012207 patent/WO2019136167A1/en unknown
- 2019-01-03 US US16/958,914 patent/US11965188B2/en active Active
- 2019-01-03 CA CA3087529A patent/CA3087529A1/en active Pending
- 2019-01-03 KR KR1020207022113A patent/KR20200128385A/ko not_active Application Discontinuation
- 2019-01-03 AU AU2019205912A patent/AU2019205912A1/en active Pending
-
2020
- 2020-07-01 IL IL275779A patent/IL275779A/en unknown
-
2023
- 2023-12-06 JP JP2023206452A patent/JP2024026296A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170165334A1 (en) | 2015-12-11 | 2017-06-15 | Tianxin Wang | Methods to Treat Diseases with Protein, Peptide, Antigen Modification and Hemopurification |
Non-Patent Citations (4)
Title |
---|
ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY,2010年,VOL.64,p.403-479 |
Glycobiology,2010年,vol. 20 no. 9,p.1127-1138及びSupporting information |
Glycoconjugate Journal,1998年,15,p.769-775 |
J. Mol. Biol.,1982年,157,p.105-132 |
Also Published As
Publication number | Publication date |
---|---|
KR20200128385A (ko) | 2020-11-12 |
CA3087529A1 (en) | 2019-07-11 |
MX2020007024A (es) | 2020-10-28 |
JP2024026296A (ja) | 2024-02-28 |
EP3735458A4 (en) | 2022-04-27 |
WO2019136167A1 (en) | 2019-07-11 |
US20200339968A1 (en) | 2020-10-29 |
AU2019205912A1 (en) | 2020-07-16 |
US11965188B2 (en) | 2024-04-23 |
IL275779A (en) | 2020-08-31 |
EP3735458A1 (en) | 2020-11-11 |
CN112135904A (zh) | 2020-12-25 |
JP2021509585A (ja) | 2021-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7462560B2 (ja) | 組換えヒトシアリダーゼ、シアリダーゼ融合タンパク質およびそれらの使用方法 | |
US20220356457A1 (en) | Recombinant human sialidases, sialidase fusion proteins, and methods of using the same | |
WO2020142727A1 (en) | Methods and compositions for treating cancer with immune cells | |
US20220372458A1 (en) | Sialidase-pd-l1-antibody fusion proteins and methods of use thereof | |
US20230265406A1 (en) | Recombinant sialidases with reduced protease sensitivity, sialidase fusion proteins, and methods of using the same | |
US20220380742A1 (en) | Sialidase-cd20-antibody fusion proteins and methods of use thereof | |
US20240059773A1 (en) | Sialidase-pd-1-antibody fusion proteins and methods of use thereof | |
US20240059792A1 (en) | Sialidase-her2-antibody fusion proteins and methods of use thereof | |
JP2024501771A (ja) | 抗pd-l1抗体及びその融合タンパク質 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211224 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211224 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221209 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230308 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20230508 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230607 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20230807 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231206 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20231207 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20240126 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240305 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240326 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7462560 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |