CN109414483A - 对补体灭活作用具有抗性的用于治疗癌症的包膜病毒 - Google Patents
对补体灭活作用具有抗性的用于治疗癌症的包膜病毒 Download PDFInfo
- Publication number
- CN109414483A CN109414483A CN201880002553.7A CN201880002553A CN109414483A CN 109414483 A CN109414483 A CN 109414483A CN 201880002553 A CN201880002553 A CN 201880002553A CN 109414483 A CN109414483 A CN 109414483A
- Authority
- CN
- China
- Prior art keywords
- sequence
- albumen
- virus
- peptide
- fusion protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 241000700605 Viruses Species 0.000 title claims abstract description 40
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 20
- 230000000295 complement effect Effects 0.000 title abstract description 20
- 230000002779 inactivation Effects 0.000 title abstract description 11
- 201000011510 cancer Diseases 0.000 title abstract description 10
- 210000004027 cell Anatomy 0.000 claims abstract description 67
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 41
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 41
- 102100025680 Complement decay-accelerating factor Human genes 0.000 claims abstract description 33
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 claims abstract description 33
- 108010076504 Protein Sorting Signals Proteins 0.000 claims abstract description 28
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 26
- 244000309459 oncolytic virus Species 0.000 claims abstract description 15
- 230000003834 intracellular effect Effects 0.000 claims abstract description 14
- 230000003248 secreting effect Effects 0.000 claims abstract description 10
- 210000004899 c-terminal region Anatomy 0.000 claims abstract description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 14
- 150000007523 nucleic acids Chemical class 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 14
- 125000006850 spacer group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 8
- 210000003837 chick embryo Anatomy 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 210000002950 fibroblast Anatomy 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 241000711404 Avian avulavirus 1 Species 0.000 claims description 3
- 239000013604 expression vector Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000028327 secretion Effects 0.000 claims description 2
- 230000006798 recombination Effects 0.000 abstract description 14
- 238000005215 recombination Methods 0.000 abstract description 14
- 108090000623 proteins and genes Proteins 0.000 abstract description 5
- 102000004169 proteins and genes Human genes 0.000 abstract description 4
- 230000035800 maturation Effects 0.000 abstract 1
- 230000014509 gene expression Effects 0.000 description 21
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 14
- 238000011084 recovery Methods 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 235000013601 eggs Nutrition 0.000 description 10
- 239000002245 particle Substances 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 6
- 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 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 210000001161 mammalian embryo Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229940124073 Complement inhibitor Drugs 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 239000004074 complement inhibitor Substances 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 238000013459 approach Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012830 cancer therapeutic Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000024203 complement activation Effects 0.000 description 3
- 230000004154 complement system Effects 0.000 description 3
- -1 egg White nucleic acid Chemical class 0.000 description 3
- 102000034356 gene-regulatory proteins Human genes 0.000 description 3
- 108091006104 gene-regulatory proteins Proteins 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 230000000174 oncolytic effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 210000002845 virion Anatomy 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- UWSONZCNXUSTKW-UHFFFAOYSA-N 4,5-Dimethylthiazole Chemical compound CC=1N=CSC=1C UWSONZCNXUSTKW-UHFFFAOYSA-N 0.000 description 2
- PDQBXRSOSCTGKY-ACZMJKKPSA-N Asn-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N PDQBXRSOSCTGKY-ACZMJKKPSA-N 0.000 description 2
- QPDUWAUSSWGJSB-NGZCFLSTSA-N Asp-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N QPDUWAUSSWGJSB-NGZCFLSTSA-N 0.000 description 2
- 102000016574 Complement C3-C5 Convertases Human genes 0.000 description 2
- 108010067641 Complement C3-C5 Convertases Proteins 0.000 description 2
- 102100030886 Complement receptor type 1 Human genes 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 102000002322 Egg Proteins Human genes 0.000 description 2
- JXBZEDIQFFCHPZ-PEFMBERDSA-N Gln-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N JXBZEDIQFFCHPZ-PEFMBERDSA-N 0.000 description 2
- CVRUVYDNRPSKBM-QEJZJMRPSA-N Gln-Trp-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N CVRUVYDNRPSKBM-QEJZJMRPSA-N 0.000 description 2
- WVWZIPOJECFDAG-AVGNSLFASA-N Glu-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N WVWZIPOJECFDAG-AVGNSLFASA-N 0.000 description 2
- GWNIGUKSRJBIHX-STQMWFEESA-N Gly-Tyr-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)CN)O GWNIGUKSRJBIHX-STQMWFEESA-N 0.000 description 2
- 101000727061 Homo sapiens Complement receptor type 1 Proteins 0.000 description 2
- PMAOIIWHZHAPBT-HJPIBITLSA-N Ile-Tyr-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CS)C(=O)O)N PMAOIIWHZHAPBT-HJPIBITLSA-N 0.000 description 2
- 241000880493 Leptailurus serval Species 0.000 description 2
- SBANPBVRHYIMRR-UHFFFAOYSA-N Leu-Ser-Pro Natural products CC(C)CC(N)C(=O)NC(CO)C(=O)N1CCCC1C(O)=O SBANPBVRHYIMRR-UHFFFAOYSA-N 0.000 description 2
- 102100039373 Membrane cofactor protein Human genes 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- QCARZLHECSFOGG-CIUDSAMLSA-N Pro-Glu-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O QCARZLHECSFOGG-CIUDSAMLSA-N 0.000 description 2
- VYWNORHENYEQDW-YUMQZZPRSA-N Pro-Gly-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H]1CCCN1 VYWNORHENYEQDW-YUMQZZPRSA-N 0.000 description 2
- GZNYIXWOIUFLGO-ZJDVBMNYSA-N Pro-Thr-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZNYIXWOIUFLGO-ZJDVBMNYSA-N 0.000 description 2
- 241000710960 Sindbis virus Species 0.000 description 2
- 102100025292 Stress-induced-phosphoprotein 1 Human genes 0.000 description 2
- ZESGVALRVJIVLZ-VFCFLDTKSA-N Thr-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O ZESGVALRVJIVLZ-VFCFLDTKSA-N 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000004873 anchoring Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 108010060199 cysteinylproline Proteins 0.000 description 2
- 235000014103 egg white Nutrition 0.000 description 2
- 210000000969 egg white Anatomy 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 2
- 108010073472 leucyl-prolyl-proline Proteins 0.000 description 2
- 108010064235 lysylglycine Proteins 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000002574 poison Substances 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 108010077112 prolyl-proline Proteins 0.000 description 2
- 108010029020 prolylglycine Proteins 0.000 description 2
- 108010053725 prolylvaline Proteins 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 108010079202 tyrosyl-alanyl-cysteine Proteins 0.000 description 2
- 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
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- UCIYCBSJBQGDGM-LPEHRKFASA-N Ala-Arg-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N UCIYCBSJBQGDGM-LPEHRKFASA-N 0.000 description 1
- HFBFSOAKPUZCCO-ZLUOBGJFSA-N Ala-Cys-Asn Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N HFBFSOAKPUZCCO-ZLUOBGJFSA-N 0.000 description 1
- CZPAHAKGPDUIPJ-CIUDSAMLSA-N Ala-Gln-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CZPAHAKGPDUIPJ-CIUDSAMLSA-N 0.000 description 1
- OBVSBEYOMDWLRJ-BFHQHQDPSA-N Ala-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@H](C)N OBVSBEYOMDWLRJ-BFHQHQDPSA-N 0.000 description 1
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 1
- ADSGHMXEAZJJNF-DCAQKATOSA-N Ala-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N ADSGHMXEAZJJNF-DCAQKATOSA-N 0.000 description 1
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 1
- VRTOMXFZHGWHIJ-KZVJFYERSA-N Ala-Thr-Arg Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VRTOMXFZHGWHIJ-KZVJFYERSA-N 0.000 description 1
- YJHKTAMKPGFJCT-NRPADANISA-N Ala-Val-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O YJHKTAMKPGFJCT-NRPADANISA-N 0.000 description 1
- UXJCMQFPDWCHKX-DCAQKATOSA-N Arg-Arg-Glu Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(O)=O)C(O)=O UXJCMQFPDWCHKX-DCAQKATOSA-N 0.000 description 1
- NONSEUUPKITYQT-BQBZGAKWSA-N Arg-Asn-Gly Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)O)N)CN=C(N)N NONSEUUPKITYQT-BQBZGAKWSA-N 0.000 description 1
- BEXGZLUHRXTZCC-CIUDSAMLSA-N Arg-Gln-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CO)C(=O)O)N)CN=C(N)N BEXGZLUHRXTZCC-CIUDSAMLSA-N 0.000 description 1
- OHYQKYUTLIPFOX-ZPFDUUQYSA-N Arg-Glu-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OHYQKYUTLIPFOX-ZPFDUUQYSA-N 0.000 description 1
- HPSVTWMFWCHKFN-GARJFASQSA-N Arg-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O HPSVTWMFWCHKFN-GARJFASQSA-N 0.000 description 1
- PHHRSPBBQUFULD-UWVGGRQHSA-N Arg-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N PHHRSPBBQUFULD-UWVGGRQHSA-N 0.000 description 1
- UHFUZWSZQKMDSX-DCAQKATOSA-N Arg-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N UHFUZWSZQKMDSX-DCAQKATOSA-N 0.000 description 1
- LRPZJPMQGKGHSG-XGEHTFHBSA-N Arg-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)O LRPZJPMQGKGHSG-XGEHTFHBSA-N 0.000 description 1
- INOIAEUXVVNJKA-XGEHTFHBSA-N Arg-Thr-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O INOIAEUXVVNJKA-XGEHTFHBSA-N 0.000 description 1
- ZPWMEWYQBWSGAO-ZJDVBMNYSA-N Arg-Thr-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZPWMEWYQBWSGAO-ZJDVBMNYSA-N 0.000 description 1
- POOCJCRBHHMAOS-FXQIFTODSA-N Asn-Arg-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O POOCJCRBHHMAOS-FXQIFTODSA-N 0.000 description 1
- BHQQRVARKXWXPP-ACZMJKKPSA-N Asn-Asp-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)N)N BHQQRVARKXWXPP-ACZMJKKPSA-N 0.000 description 1
- PBSQFBAJKPLRJY-BYULHYEWSA-N Asn-Gly-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)N)N PBSQFBAJKPLRJY-BYULHYEWSA-N 0.000 description 1
- YVXRYLVELQYAEQ-SRVKXCTJSA-N Asn-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N YVXRYLVELQYAEQ-SRVKXCTJSA-N 0.000 description 1
- NYGILGUOUOXGMJ-YUMQZZPRSA-N Asn-Lys-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O NYGILGUOUOXGMJ-YUMQZZPRSA-N 0.000 description 1
- XTMZYFMTYJNABC-ZLUOBGJFSA-N Asn-Ser-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N XTMZYFMTYJNABC-ZLUOBGJFSA-N 0.000 description 1
- FMNBYVSGRCXWEK-FOHZUACHSA-N Asn-Thr-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O FMNBYVSGRCXWEK-FOHZUACHSA-N 0.000 description 1
- GHWWTICYPDKPTE-NGZCFLSTSA-N Asn-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N GHWWTICYPDKPTE-NGZCFLSTSA-N 0.000 description 1
- QQXOYLWJQUPXJU-WHFBIAKZSA-N Asp-Cys-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O QQXOYLWJQUPXJU-WHFBIAKZSA-N 0.000 description 1
- SWTQDYFZVOJVLL-KKUMJFAQSA-N Asp-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)O)N)O SWTQDYFZVOJVLL-KKUMJFAQSA-N 0.000 description 1
- KQBVNNAPIURMPD-PEFMBERDSA-N Asp-Ile-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O KQBVNNAPIURMPD-PEFMBERDSA-N 0.000 description 1
- YFGUZQQCSDZRBN-DCAQKATOSA-N Asp-Pro-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YFGUZQQCSDZRBN-DCAQKATOSA-N 0.000 description 1
- JSHWXQIZOCVWIA-ZKWXMUAHSA-N Asp-Ser-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JSHWXQIZOCVWIA-ZKWXMUAHSA-N 0.000 description 1
- ITGFVUYOLWBPQW-KKHAAJSZSA-N Asp-Thr-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O ITGFVUYOLWBPQW-KKHAAJSZSA-N 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010009575 CD55 Antigens Proteins 0.000 description 1
- 102100022002 CD59 glycoprotein Human genes 0.000 description 1
- 108010034753 Complement Membrane Attack Complex Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- CLDCTNHPILWQCW-CIUDSAMLSA-N Cys-Arg-Glu Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N)CN=C(N)N CLDCTNHPILWQCW-CIUDSAMLSA-N 0.000 description 1
- QLCPDGRAEJSYQM-LPEHRKFASA-N Cys-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N)C(=O)O QLCPDGRAEJSYQM-LPEHRKFASA-N 0.000 description 1
- WVJHEDOLHPZLRV-CIUDSAMLSA-N Cys-Asn-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CS)N WVJHEDOLHPZLRV-CIUDSAMLSA-N 0.000 description 1
- UDPSLLFHOLGXBY-FXQIFTODSA-N Cys-Glu-Glu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UDPSLLFHOLGXBY-FXQIFTODSA-N 0.000 description 1
- LBOLGUYQEPZSKM-YUMQZZPRSA-N Cys-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CS)N LBOLGUYQEPZSKM-YUMQZZPRSA-N 0.000 description 1
- UXIYYUMGFNSGBK-XPUUQOCRSA-N Cys-Gly-Val Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O UXIYYUMGFNSGBK-XPUUQOCRSA-N 0.000 description 1
- HKALUUKHYNEDRS-GUBZILKMSA-N Cys-Leu-Gln Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O HKALUUKHYNEDRS-GUBZILKMSA-N 0.000 description 1
- VPQZSNQICFCCSO-BJDJZHNGSA-N Cys-Leu-Ile Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VPQZSNQICFCCSO-BJDJZHNGSA-N 0.000 description 1
- UCSXXFRXHGUXCQ-SRVKXCTJSA-N Cys-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CS)N UCSXXFRXHGUXCQ-SRVKXCTJSA-N 0.000 description 1
- SMEYEQDCCBHTEF-FXQIFTODSA-N Cys-Pro-Ala Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O SMEYEQDCCBHTEF-FXQIFTODSA-N 0.000 description 1
- CAXGCBSRJLADPD-FXQIFTODSA-N Cys-Pro-Asn Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(O)=O CAXGCBSRJLADPD-FXQIFTODSA-N 0.000 description 1
- 206010050685 Cytokine storm Diseases 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- XXLBHPPXDUWYAG-XQXXSGGOSA-N Gln-Ala-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XXLBHPPXDUWYAG-XQXXSGGOSA-N 0.000 description 1
- AAOBFSKXAVIORT-GUBZILKMSA-N Gln-Asn-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O AAOBFSKXAVIORT-GUBZILKMSA-N 0.000 description 1
- MGJMFSBEMSNYJL-AVGNSLFASA-N Gln-Asn-Tyr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MGJMFSBEMSNYJL-AVGNSLFASA-N 0.000 description 1
- MFJAPSYJQJCQDN-BQBZGAKWSA-N Gln-Gly-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O MFJAPSYJQJCQDN-BQBZGAKWSA-N 0.000 description 1
- XZLLTYBONVKGLO-SDDRHHMPSA-N Gln-Lys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)N)N)C(=O)O XZLLTYBONVKGLO-SDDRHHMPSA-N 0.000 description 1
- CELXWPDNIGWCJN-WDCWCFNPSA-N Gln-Lys-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CELXWPDNIGWCJN-WDCWCFNPSA-N 0.000 description 1
- DCWNCMRZIZSZBL-KKUMJFAQSA-N Gln-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CCC(=O)N)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O DCWNCMRZIZSZBL-KKUMJFAQSA-N 0.000 description 1
- OTQSTOXRUBVWAP-NRPADANISA-N Gln-Ser-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O OTQSTOXRUBVWAP-NRPADANISA-N 0.000 description 1
- DIXKFOPPGWKZLY-CIUDSAMLSA-N Glu-Arg-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O DIXKFOPPGWKZLY-CIUDSAMLSA-N 0.000 description 1
- SBCYJMOOHUDWDA-NUMRIWBASA-N Glu-Asp-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SBCYJMOOHUDWDA-NUMRIWBASA-N 0.000 description 1
- FLQAKQOBSPFGKG-CIUDSAMLSA-N Glu-Cys-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FLQAKQOBSPFGKG-CIUDSAMLSA-N 0.000 description 1
- OGNJZUXUTPQVBR-BQBZGAKWSA-N Glu-Gly-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O OGNJZUXUTPQVBR-BQBZGAKWSA-N 0.000 description 1
- WVTIBGWZUMJBFY-GUBZILKMSA-N Glu-His-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O WVTIBGWZUMJBFY-GUBZILKMSA-N 0.000 description 1
- BXSZPACYCMNKLS-AVGNSLFASA-N Glu-Ser-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O BXSZPACYCMNKLS-AVGNSLFASA-N 0.000 description 1
- CAQXJMUDOLSBPF-SUSMZKCASA-N Glu-Thr-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAQXJMUDOLSBPF-SUSMZKCASA-N 0.000 description 1
- DXMOIVCNJIJQSC-QEJZJMRPSA-N Glu-Trp-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)O)N DXMOIVCNJIJQSC-QEJZJMRPSA-N 0.000 description 1
- RMWAOBGCZZSJHE-UMNHJUIQSA-N Glu-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N RMWAOBGCZZSJHE-UMNHJUIQSA-N 0.000 description 1
- QXUPRMQJDWJDFR-NRPADANISA-N Glu-Val-Ser Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O QXUPRMQJDWJDFR-NRPADANISA-N 0.000 description 1
- QSDKBRMVXSWAQE-BFHQHQDPSA-N Gly-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN QSDKBRMVXSWAQE-BFHQHQDPSA-N 0.000 description 1
- DTPOVRRYXPJJAZ-FJXKBIBVSA-N Gly-Arg-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N DTPOVRRYXPJJAZ-FJXKBIBVSA-N 0.000 description 1
- BPQYBFAXRGMGGY-LAEOZQHASA-N Gly-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)CN BPQYBFAXRGMGGY-LAEOZQHASA-N 0.000 description 1
- STVHDEHTKFXBJQ-LAEOZQHASA-N Gly-Glu-Ile Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O STVHDEHTKFXBJQ-LAEOZQHASA-N 0.000 description 1
- ZQIMMEYPEXIYBB-IUCAKERBSA-N Gly-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN ZQIMMEYPEXIYBB-IUCAKERBSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- AAHSHTLISQUZJL-QSFUFRPTSA-N Gly-Ile-Ile Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O AAHSHTLISQUZJL-QSFUFRPTSA-N 0.000 description 1
- UESJMAMHDLEHGM-NHCYSSNCSA-N Gly-Ile-Leu Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O UESJMAMHDLEHGM-NHCYSSNCSA-N 0.000 description 1
- NTBOEZICHOSJEE-YUMQZZPRSA-N Gly-Lys-Ser Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O NTBOEZICHOSJEE-YUMQZZPRSA-N 0.000 description 1
- OOCFXNOVSLSHAB-IUCAKERBSA-N Gly-Pro-Pro Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OOCFXNOVSLSHAB-IUCAKERBSA-N 0.000 description 1
- CSMYMGFCEJWALV-WDSKDSINSA-N Gly-Ser-Gln Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O CSMYMGFCEJWALV-WDSKDSINSA-N 0.000 description 1
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 1
- LCRDMSSAKLTKBU-ZDLURKLDSA-N Gly-Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN LCRDMSSAKLTKBU-ZDLURKLDSA-N 0.000 description 1
- CUVBTVWFVIIDOC-YEPSODPASA-N Gly-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)CN CUVBTVWFVIIDOC-YEPSODPASA-N 0.000 description 1
- PNUFMLXHOLFRLD-KBPBESRZSA-N Gly-Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=C(O)C=C1 PNUFMLXHOLFRLD-KBPBESRZSA-N 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- 241000175212 Herpesvirales Species 0.000 description 1
- VUUFXXGKMPLKNH-BZSNNMDCSA-N His-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N VUUFXXGKMPLKNH-BZSNNMDCSA-N 0.000 description 1
- CUEQQFOGARVNHU-VGDYDELISA-N His-Ser-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O CUEQQFOGARVNHU-VGDYDELISA-N 0.000 description 1
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 1
- 101000746373 Homo sapiens Granulocyte-macrophage colony-stimulating factor Proteins 0.000 description 1
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 1
- BOTVMTSMOUSDRW-GMOBBJLQSA-N Ile-Arg-Asn Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(O)=O BOTVMTSMOUSDRW-GMOBBJLQSA-N 0.000 description 1
- NBJAAWYRLGCJOF-UGYAYLCHSA-N Ile-Asp-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N NBJAAWYRLGCJOF-UGYAYLCHSA-N 0.000 description 1
- CYHJCEKUMCNDFG-LAEOZQHASA-N Ile-Gln-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)O)N CYHJCEKUMCNDFG-LAEOZQHASA-N 0.000 description 1
- PHIXPNQDGGILMP-YVNDNENWSA-N Ile-Glu-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N PHIXPNQDGGILMP-YVNDNENWSA-N 0.000 description 1
- LPFBXFILACZHIB-LAEOZQHASA-N Ile-Gly-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)O)N LPFBXFILACZHIB-LAEOZQHASA-N 0.000 description 1
- IOVUXUSIGXCREV-DKIMLUQUSA-N Ile-Leu-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 IOVUXUSIGXCREV-DKIMLUQUSA-N 0.000 description 1
- ZDNNDIJTUHQCAM-MXAVVETBSA-N Ile-Ser-Phe Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N ZDNNDIJTUHQCAM-MXAVVETBSA-N 0.000 description 1
- DGTOKVBDZXJHNZ-WZLNRYEVSA-N Ile-Thr-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N DGTOKVBDZXJHNZ-WZLNRYEVSA-N 0.000 description 1
- REXAUQBGSGDEJY-IGISWZIWSA-N Ile-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N REXAUQBGSGDEJY-IGISWZIWSA-N 0.000 description 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- NEEOBPIXKWSBRF-IUCAKERBSA-N Leu-Glu-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O NEEOBPIXKWSBRF-IUCAKERBSA-N 0.000 description 1
- HRTRLSRYZZKPCO-BJDJZHNGSA-N Leu-Ile-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O HRTRLSRYZZKPCO-BJDJZHNGSA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 1
- ZGUMORRUBUCXEH-AVGNSLFASA-N Leu-Lys-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZGUMORRUBUCXEH-AVGNSLFASA-N 0.000 description 1
- INCJJHQRZGQLFC-KBPBESRZSA-N Leu-Phe-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O INCJJHQRZGQLFC-KBPBESRZSA-N 0.000 description 1
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 1
- DPURXCQCHSQPAN-AVGNSLFASA-N Leu-Pro-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DPURXCQCHSQPAN-AVGNSLFASA-N 0.000 description 1
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 1
- NRQRKMYZONPCTM-CIUDSAMLSA-N Lys-Asp-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O NRQRKMYZONPCTM-CIUDSAMLSA-N 0.000 description 1
- PBLLTSKBTAHDNA-KBPBESRZSA-N Lys-Gly-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PBLLTSKBTAHDNA-KBPBESRZSA-N 0.000 description 1
- FHIAJWBDZVHLAH-YUMQZZPRSA-N Lys-Gly-Ser Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FHIAJWBDZVHLAH-YUMQZZPRSA-N 0.000 description 1
- IZJGPPIGYTVXLB-FQUUOJAGSA-N Lys-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N IZJGPPIGYTVXLB-FQUUOJAGSA-N 0.000 description 1
- XIZQPFCRXLUNMK-BZSNNMDCSA-N Lys-Leu-Phe Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCCCN)N XIZQPFCRXLUNMK-BZSNNMDCSA-N 0.000 description 1
- WBSCNDJQPKSPII-KKUMJFAQSA-N Lys-Lys-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(O)=O WBSCNDJQPKSPII-KKUMJFAQSA-N 0.000 description 1
- CTJUSALVKAWFFU-CIUDSAMLSA-N Lys-Ser-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N CTJUSALVKAWFFU-CIUDSAMLSA-N 0.000 description 1
- CAVRAQIDHUPECU-UVOCVTCTSA-N Lys-Thr-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O CAVRAQIDHUPECU-UVOCVTCTSA-N 0.000 description 1
- GVKINWYYLOLEFQ-XIRDDKMYSA-N Lys-Trp-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O GVKINWYYLOLEFQ-XIRDDKMYSA-N 0.000 description 1
- OZVXDDFYCQOPFD-XQQFMLRXSA-N Lys-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCCN)N OZVXDDFYCQOPFD-XQQFMLRXSA-N 0.000 description 1
- GETCJHFFECHWHI-QXEWZRGKSA-N Met-Ile-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)NCC(=O)O)NC(=O)[C@H](CCSC)N GETCJHFFECHWHI-QXEWZRGKSA-N 0.000 description 1
- ZBLSZPYQQRIHQU-RCWTZXSCSA-N Met-Thr-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O ZBLSZPYQQRIHQU-RCWTZXSCSA-N 0.000 description 1
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 1
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 1
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 1
- 208000010359 Newcastle Disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- OMHMIXFFRPMYHB-SRVKXCTJSA-N Phe-Cys-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)O)N OMHMIXFFRPMYHB-SRVKXCTJSA-N 0.000 description 1
- FGXIJNMDRCZVDE-KKUMJFAQSA-N Phe-Cys-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)O)N FGXIJNMDRCZVDE-KKUMJFAQSA-N 0.000 description 1
- JJHVFCUWLSKADD-ONGXEEELSA-N Phe-Gly-Ala Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](C)C(O)=O JJHVFCUWLSKADD-ONGXEEELSA-N 0.000 description 1
- ISYSEOWLRQKQEQ-JYJNAYRXSA-N Phe-His-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O ISYSEOWLRQKQEQ-JYJNAYRXSA-N 0.000 description 1
- QARPMYDMYVLFMW-KKUMJFAQSA-N Phe-Pro-Glu Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(O)=O)C1=CC=CC=C1 QARPMYDMYVLFMW-KKUMJFAQSA-N 0.000 description 1
- ZLAKUZDMKVKFAI-JYJNAYRXSA-N Phe-Pro-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O ZLAKUZDMKVKFAI-JYJNAYRXSA-N 0.000 description 1
- IIEOLPMQYRBZCN-SRVKXCTJSA-N Phe-Ser-Cys Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O IIEOLPMQYRBZCN-SRVKXCTJSA-N 0.000 description 1
- OLZVAVSJEUAOHI-UNQGMJICSA-N Phe-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N)O OLZVAVSJEUAOHI-UNQGMJICSA-N 0.000 description 1
- 102000011420 Phospholipase D Human genes 0.000 description 1
- 108090000553 Phospholipase D Proteins 0.000 description 1
- IFMDQWDAJUMMJC-DCAQKATOSA-N Pro-Ala-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O IFMDQWDAJUMMJC-DCAQKATOSA-N 0.000 description 1
- UVKNEILZSJMKSR-FXQIFTODSA-N Pro-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1 UVKNEILZSJMKSR-FXQIFTODSA-N 0.000 description 1
- MTHRMUXESFIAMS-DCAQKATOSA-N Pro-Asn-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O MTHRMUXESFIAMS-DCAQKATOSA-N 0.000 description 1
- TXPUNZXZDVJUJQ-LPEHRKFASA-N Pro-Asn-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N2CCC[C@@H]2C(=O)O TXPUNZXZDVJUJQ-LPEHRKFASA-N 0.000 description 1
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 1
- QEWBZBLXDKIQPS-STQMWFEESA-N Pro-Gly-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QEWBZBLXDKIQPS-STQMWFEESA-N 0.000 description 1
- RMODQFBNDDENCP-IHRRRGAJSA-N Pro-Lys-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O RMODQFBNDDENCP-IHRRRGAJSA-N 0.000 description 1
- FHZJRBVMLGOHBX-GUBZILKMSA-N Pro-Pro-Asp Chemical compound OC(=O)C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1)C(O)=O FHZJRBVMLGOHBX-GUBZILKMSA-N 0.000 description 1
- FYKUEXMZYFIZKA-DCAQKATOSA-N Pro-Pro-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O FYKUEXMZYFIZKA-DCAQKATOSA-N 0.000 description 1
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 1
- RCYUBVHMVUHEBM-RCWTZXSCSA-N Pro-Pro-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O RCYUBVHMVUHEBM-RCWTZXSCSA-N 0.000 description 1
- LNICFEXCAHIJOR-DCAQKATOSA-N Pro-Ser-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O LNICFEXCAHIJOR-DCAQKATOSA-N 0.000 description 1
- RMJZWERKFFNNNS-XGEHTFHBSA-N Pro-Thr-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMJZWERKFFNNNS-XGEHTFHBSA-N 0.000 description 1
- CXGLFEOYCJFKPR-RCWTZXSCSA-N Pro-Thr-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O CXGLFEOYCJFKPR-RCWTZXSCSA-N 0.000 description 1
- FIODMZKLZFLYQP-GUBZILKMSA-N Pro-Val-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O FIODMZKLZFLYQP-GUBZILKMSA-N 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 1
- GHPQVUYZQQGEDA-BIIVOSGPSA-N Ser-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)N)C(=O)O GHPQVUYZQQGEDA-BIIVOSGPSA-N 0.000 description 1
- ZHYMUFQVKGJNRM-ZLUOBGJFSA-N Ser-Cys-Asn Chemical compound OC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC(N)=O ZHYMUFQVKGJNRM-ZLUOBGJFSA-N 0.000 description 1
- WTPKKLMBNBCCNL-ACZMJKKPSA-N Ser-Cys-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CO)N WTPKKLMBNBCCNL-ACZMJKKPSA-N 0.000 description 1
- VMVNCJDKFOQOHM-GUBZILKMSA-N Ser-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N VMVNCJDKFOQOHM-GUBZILKMSA-N 0.000 description 1
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 1
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 1
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 1
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 1
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 1
- HJAXVYLCKDPPDF-SRVKXCTJSA-N Ser-Phe-Cys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N HJAXVYLCKDPPDF-SRVKXCTJSA-N 0.000 description 1
- RWDVVSKYZBNDCO-MELADBBJSA-N Ser-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CO)N)C(=O)O RWDVVSKYZBNDCO-MELADBBJSA-N 0.000 description 1
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
- NMZXJDSKEGFDLJ-DCAQKATOSA-N Ser-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CCCCN)C(=O)O NMZXJDSKEGFDLJ-DCAQKATOSA-N 0.000 description 1
- FLONGDPORFIVQW-XGEHTFHBSA-N Ser-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FLONGDPORFIVQW-XGEHTFHBSA-N 0.000 description 1
- ILZAUMFXKSIUEF-SRVKXCTJSA-N Ser-Ser-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ILZAUMFXKSIUEF-SRVKXCTJSA-N 0.000 description 1
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 1
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 1
- SNXUIBACCONSOH-BWBBJGPYSA-N Ser-Thr-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CO)C(O)=O SNXUIBACCONSOH-BWBBJGPYSA-N 0.000 description 1
- ANOQEBQWIAYIMV-AEJSXWLSSA-N Ser-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N ANOQEBQWIAYIMV-AEJSXWLSSA-N 0.000 description 1
- XSLXHSYIVPGEER-KZVJFYERSA-N Thr-Ala-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(O)=O XSLXHSYIVPGEER-KZVJFYERSA-N 0.000 description 1
- VFEHSAJCWWHDBH-RHYQMDGZSA-N Thr-Arg-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O VFEHSAJCWWHDBH-RHYQMDGZSA-N 0.000 description 1
- GCXFWAZRHBRYEM-NUMRIWBASA-N Thr-Gln-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N)O GCXFWAZRHBRYEM-NUMRIWBASA-N 0.000 description 1
- BNGDYRRHRGOPHX-IFFSRLJSSA-N Thr-Glu-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)[C@@H](C)O)C(O)=O BNGDYRRHRGOPHX-IFFSRLJSSA-N 0.000 description 1
- FQPDRTDDEZXCEC-SVSWQMSJSA-N Thr-Ile-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O FQPDRTDDEZXCEC-SVSWQMSJSA-N 0.000 description 1
- ZXIHABSKUITPTN-IXOXFDKPSA-N Thr-Lys-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O ZXIHABSKUITPTN-IXOXFDKPSA-N 0.000 description 1
- IQPWNQRRAJHOKV-KATARQTJSA-N Thr-Ser-Lys Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN IQPWNQRRAJHOKV-KATARQTJSA-N 0.000 description 1
- UQCNIMDPYICBTR-KYNKHSRBSA-N Thr-Thr-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O UQCNIMDPYICBTR-KYNKHSRBSA-N 0.000 description 1
- CSNBWOJOEOPYIJ-UVOCVTCTSA-N Thr-Thr-Lys Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(O)=O CSNBWOJOEOPYIJ-UVOCVTCTSA-N 0.000 description 1
- COYHRQWNJDJCNA-NUJDXYNKSA-N Thr-Thr-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O COYHRQWNJDJCNA-NUJDXYNKSA-N 0.000 description 1
- LECUEEHKUFYOOV-ZJDVBMNYSA-N Thr-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](N)[C@@H](C)O LECUEEHKUFYOOV-ZJDVBMNYSA-N 0.000 description 1
- LXXCHJKHJYRMIY-FQPOAREZSA-N Thr-Tyr-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O LXXCHJKHJYRMIY-FQPOAREZSA-N 0.000 description 1
- BKIOKSLLAAZYTC-KKHAAJSZSA-N Thr-Val-Asn Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O BKIOKSLLAAZYTC-KKHAAJSZSA-N 0.000 description 1
- BEWOXKJJMBKRQL-AAEUAGOBSA-N Trp-Gly-Asp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N BEWOXKJJMBKRQL-AAEUAGOBSA-N 0.000 description 1
- RNDWCRUOGGQDKN-UBHSHLNASA-N Trp-Ser-Asp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RNDWCRUOGGQDKN-UBHSHLNASA-N 0.000 description 1
- UJGDFQRPYGJBEH-AAEUAGOBSA-N Trp-Ser-Gly Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)O)N UJGDFQRPYGJBEH-AAEUAGOBSA-N 0.000 description 1
- GSCPHMSPGQSZJT-JYBASQMISA-N Trp-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O GSCPHMSPGQSZJT-JYBASQMISA-N 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- UMXSDHPSMROQRB-YJRXYDGGSA-N Tyr-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O UMXSDHPSMROQRB-YJRXYDGGSA-N 0.000 description 1
- IWRMTNJCCMEBEX-AVGNSLFASA-N Tyr-Glu-Cys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)O IWRMTNJCCMEBEX-AVGNSLFASA-N 0.000 description 1
- NMKJPMCEKQHRPD-IRXDYDNUSA-N Tyr-Gly-Tyr Chemical compound C([C@H](N)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 NMKJPMCEKQHRPD-IRXDYDNUSA-N 0.000 description 1
- BXPOOVDVGWEXDU-WZLNRYEVSA-N Tyr-Ile-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BXPOOVDVGWEXDU-WZLNRYEVSA-N 0.000 description 1
- LQGDFDYGDQEMGA-PXDAIIFMSA-N Tyr-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N LQGDFDYGDQEMGA-PXDAIIFMSA-N 0.000 description 1
- GZUIDWDVMWZSMI-KKUMJFAQSA-N Tyr-Lys-Cys Chemical compound NCCCC[C@@H](C(=O)N[C@@H](CS)C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GZUIDWDVMWZSMI-KKUMJFAQSA-N 0.000 description 1
- WURLIFOWSMBUAR-SLFFLAALSA-N Tyr-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O WURLIFOWSMBUAR-SLFFLAALSA-N 0.000 description 1
- BYOHPUZJVXWHAE-BYULHYEWSA-N Val-Asn-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N BYOHPUZJVXWHAE-BYULHYEWSA-N 0.000 description 1
- DBOXBUDEAJVKRE-LSJOCFKGSA-N Val-Asn-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N DBOXBUDEAJVKRE-LSJOCFKGSA-N 0.000 description 1
- ZEVNVXYRZRIRCH-GVXVVHGQSA-N Val-Gln-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N ZEVNVXYRZRIRCH-GVXVVHGQSA-N 0.000 description 1
- OXVPMZVGCAPFIG-BQFCYCMXSA-N Val-Gln-Trp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N OXVPMZVGCAPFIG-BQFCYCMXSA-N 0.000 description 1
- PMXBARDFIAPBGK-DZKIICNBSA-N Val-Glu-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 PMXBARDFIAPBGK-DZKIICNBSA-N 0.000 description 1
- KZKMBGXCNLPYKD-YEPSODPASA-N Val-Gly-Thr Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O KZKMBGXCNLPYKD-YEPSODPASA-N 0.000 description 1
- PYPZMFDMCCWNST-NAKRPEOUSA-N Val-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N PYPZMFDMCCWNST-NAKRPEOUSA-N 0.000 description 1
- APQIVBCUIUDSMB-OSUNSFLBSA-N Val-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C(C)C)N APQIVBCUIUDSMB-OSUNSFLBSA-N 0.000 description 1
- QRVPEKJBBRYISE-XUXIUFHCSA-N Val-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N QRVPEKJBBRYISE-XUXIUFHCSA-N 0.000 description 1
- LGXUZJIQCGXKGZ-QXEWZRGKSA-N Val-Pro-Asn Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)N)C(=O)O)N LGXUZJIQCGXKGZ-QXEWZRGKSA-N 0.000 description 1
- MIKHIIQMRFYVOR-RCWTZXSCSA-N Val-Pro-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C(C)C)N)O MIKHIIQMRFYVOR-RCWTZXSCSA-N 0.000 description 1
- AJNUKMZFHXUBMK-GUBZILKMSA-N Val-Ser-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N AJNUKMZFHXUBMK-GUBZILKMSA-N 0.000 description 1
- YLBNZCJFSVJDRJ-KJEVXHAQSA-N Val-Thr-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O YLBNZCJFSVJDRJ-KJEVXHAQSA-N 0.000 description 1
- NLNCNKIVJPEFBC-DLOVCJGASA-N Val-Val-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCC(O)=O NLNCNKIVJPEFBC-DLOVCJGASA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 108010008355 arginyl-glutamine Proteins 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 206010052015 cytokine release syndrome Diseases 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010059898 glycyl-tyrosyl-lysine Proteins 0.000 description 1
- 108010010147 glycylglutamine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 229940088013 hycamtin Drugs 0.000 description 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229940079322 interferon 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
- 229960004768 irinotecan Drugs 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 108010034529 leucyl-lysine Proteins 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010031719 prolyl-serine Proteins 0.000 description 1
- 108010070643 prolylglutamic acid Proteins 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 108010050014 systemin Proteins 0.000 description 1
- HOWHQWFXSLOJEF-MGZLOUMQSA-N systemin Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]2N(CCC2)C(=O)[C@H]2N(CCC2)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)C(C)C)CCC1 HOWHQWFXSLOJEF-MGZLOUMQSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108010072986 threonyl-seryl-lysine Proteins 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
- 230000032258 transport Effects 0.000 description 1
- 108010087967 type I signal peptidase Proteins 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 108010015385 valyl-prolyl-proline Proteins 0.000 description 1
- 108010073969 valyllysine Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/768—Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70517—CD8
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
- C12N15/625—DNA sequences coding for fusion proteins containing a sequence coding for a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/10—Cells modified by introduction of foreign genetic material
- C12N5/12—Fused cells, e.g. hybridomas
- C12N5/16—Animal cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/036—Fusion polypeptide containing a localisation/targetting motif targeting to the medium outside of the cell, e.g. type III secretion
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18111—Avulavirus, e.g. Newcastle disease virus
- C12N2760/18132—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
-
- 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
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/18011—Paramyxoviridae
- C12N2760/18111—Avulavirus, e.g. Newcastle disease virus
- C12N2760/18151—Methods of production or purification of viral material
- C12N2760/18152—Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Cell Biology (AREA)
- General Engineering & Computer Science (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
公开了一种重组融合蛋白。所述融合蛋白包含:(a)CD55肽序列,(b)位于所述CD55序列的C末端的连接物序列,(c)位于所述连接物序列的C末端的跨膜结构域,和(d)位于所述跨膜结构域的C末端的细胞内结构域。所述融合蛋白不含GPI锚。所述融合蛋白可以与N末端分泌信号肽一起表达,所述信号肽被切割以在细胞系或包膜病毒的表面上产生成熟蛋白。表达所述融合蛋白的溶瘤病毒对补体灭活作用具有抗性,并且可用于治疗癌症。
Description
序列表索引
以附件C/ST.25文本文件形式电子提交的文件编号为21003-PCT的序列表是本公开的一部分。
背景技术
已经通过感染和破坏肿瘤细胞而测试了作为癌症治疗剂的溶瘤病毒。这些溶瘤病毒包括新城疫病毒、腺病毒、辛德比斯病毒(Sindbis virus)、痘苗病毒(Vaccinia virus)和疱疹病毒等。新城疫病毒(NDV)由于其在肿瘤细胞中优先复制和裂解肿瘤细胞的独特性质而在癌症患者中显示出缩小肿瘤的巨大潜力,推测是由于大多数肿瘤细胞都具有缺陷型干扰素途径的因素(Pecora等,2002;Laurie等,2006;Lorence等,2007)。尽管初步临床结果很有希望,但NDV作为癌症治疗剂的缺点在于:一旦该病毒进入患者体内,大多数NDV颗粒将不可避免地被患者的先天免疫系统——旁路补体途径——破坏。
补体系统是先天和适应性免疫系统的一部分(综述见Volanakis,J.E.,1998.Chapter 2.In The Human Complement Systemin Health and Disease.编者:J.E.Volanakis和M.M.Frank.Marcel Dekker,Inc.,New York pp 9-32)。补体在微生物杀灭以及免疫复合体的运送和清除中起重要作用。补体系统的许多活化产物还与促炎或免疫调节功能有关。补体系统由血浆蛋白和膜相关蛋白组成,这些蛋白以三种酶促激活级联反应组织化:经典途径、凝集素途径和旁路途径。所有这三种途径都可以导致形成终末补体复合物/膜攻击复合物(TCC/MAC)和大量的生物活性产物。
人体细胞和器官具有膜结合的补体调控蛋白家族,以保护它们免受同源补体介导的裂解。这些补体调控蛋白包括CD55(衰变加速因子DAF)、CD46(膜辅因子蛋白MCP)、CD35(补体受体1,CR1)和CD59(反应性裂解的膜抑制剂)(Carroll等,1988;Rey-Campos等,1988;Lublin等,1989;Morgan等,1994;Kim和Song,2006)。
CD55是糖基磷脂酰肌醇(GPI)锚定型蛋白,并且通过在其C末端的糖脂部分(GPI锚)附着于细胞质膜。GPI锚定型蛋白(例如CD55)可被胞吞和降解,或从细胞质膜上切割和释放(Censullo和Davitz,1994a,1994b;Turner,1994)。例如,包括CD55在内的GPI锚定型蛋白可以通过GPI特异性磷脂酶C和D的作用从细胞表面释放(Turner 1994)。这些酶促活性可能控制GPI锚定型蛋白的分解代谢并调控这些蛋白的细胞表面表达(Censullo和Davitz,1994b)。
发明内容
本发明提供了一种重组融合蛋白,其包含:(a)CD55肽序列,(b)位于CD55序列的C末端的连接物序列,(c)位于所述连接物序列的C末端的跨膜结构域,和(d)位于所述跨膜结构域的C末端的细胞内结构域,其中,所述融合蛋白不含GPI锚。本发明还提供了编码所述蛋白的核酸和表达载体,表达所述蛋白的细胞,在病毒膜上并入了所述蛋白的包膜病毒,包含本发明的并入了所述蛋白的病毒的药物组合物,以及治疗方法和所述病毒的用途。
本发明部分地基于以下发现:表达本发明的融合蛋白的病毒对正常人血清的灭活作用具有抗性,这由与不表达该融合蛋白的病毒相比更高的回收率所证明。本发明的工程化细胞所产生的溶瘤包膜病毒在病毒膜上并入了重组融合蛋白形式的补体抑制剂,与在病毒膜上缺乏补体的相应病毒相比,它是更好的癌症治疗剂,并且为癌症患者提供更好的临床结果,这是因为它在进入肿瘤之前在人血清循环中具有存活能力。益处有三方面:1)溶瘤病毒可以在生物反应器中的细胞培养系统中产生;2)与在鸡蛋中产生的亲代溶瘤病毒相比,达到相同的治疗效果所需要的病毒颗粒更少;3)向癌症患者输注更少的病毒颗粒可以减少与大量病毒颗粒相关的副作用,例如细胞因子风暴或杂质相关效应。
其他人(Biswas等,2012;Rangaswamy等,2016)在研究补体调控蛋白CD55对新城疫病毒(NDV)保护作用的效果时使用了天然未修饰的CD55,其包括糖基磷脂酰肌醇(GPI)锚。相反,本发明的融合蛋白省略了GPI锚。不希望受理论束缚,据信省略GPI锚改变了细胞表面上CD55的分解代谢动力学。本发明的融合蛋白能够承受比Biswas和Rangaswamy所用的灭活条件更严格的灭活条件。在他们的灭活测定中,Biswas使用了5至10%的正常人血清,Rangaswamy使用了0.3至5%的正常人血清。以下实施例使用了40%正常人血清对已并入重组融合蛋白的NDV进行灭活测定。
附图说明
图1.编码补体抑制性重组融合蛋白的哺乳动物细胞表达构建体图谱序列,其由分泌信号肽、CD55的四个短共有重复序列(SCR)、柔性连接物、CD8跨膜结构域和截短的CD8细胞内结构域、以及之后的IRES-neo选择性标志物和合成的多聚腺苷酸化信号(polyA)组成。
图2.示出了成熟的补体抑制性融合蛋白在工程化DF1细胞膜上或在经修饰的NDV膜上的取向的图。
图3.补体抑制性重组融合蛋白的细胞表面表达。利用CD55特异性抗体针对融合蛋白表达进行的流式细胞术分析。左侧的柱状图表示作为阴性对照的初始DF1细胞。右边的柱状图表示稳定表达SEQ ID NO:2的DF1细胞(细胞克隆8号)。
图4.在肿瘤细胞系中对工程化DF1细胞(克隆8号)所产生的并入了补体抑制性融合蛋白的NDV进行的细胞毒性测定。
图5.补体抑制性重组融合蛋白的氨基酸序列,其由分泌信号肽、CD55的四个短共有重复序列(SCR)、柔性连接物、CD8跨膜结构域和截短的CD8细胞内结构域组成。(SEQ IDNO:2)
的表示分泌信号肽
常规格式表示CD55的SCR
带单下划线的表示(G4S1)3连接物
粗体表示CD8跨膜结构域
斜体表示截短的CD8细胞内结构域
具体实施方式
根据本发明的融合蛋白,任何CD55肽序列都可用于序列(a)。在一个实施方式中,CD55肽序列是人CD55肽序列。CD55肽序列优选包含CD55的四个短共有重复序列(SCR)。任何柔性连接物都可用于序列(b),例如本领域已知的常规柔性连接物。在一个实施方式中,使用G4S1连接物,优选(G4S1)3连接物。任何跨膜结构域都可用于序列(c),例如本领域已知的常规跨膜结构域。在一个实施方式中,跨膜结构域是CD8跨膜结构域。任何细胞内结构域都可用于序列(d),例如常规细胞内结构域。在一个实施方式中,跨膜结构域是CD8跨膜结构域,优选截短的CD8跨膜结构域。
本发明的融合蛋白可以进一步包含位于序列(a)的N末端的分泌信号肽。根据本发明的优选方法,融合蛋白最初与信号肽一起表达。信号肽将新合成的融合蛋白引导至内质网(ER),在此信号肽被信号肽酶切下。SEQ ID NO:2是具有N末端信号肽的本发明的示例性融合蛋白。SEQ ID NO:3是不具有N末端信号肽的本发明的示例性融合蛋白。
根据本发明的融合蛋白,在N末端信号肽和序列(a)之间,在序列(a)和序列(b)之间,在序列(b)和序列(c)之间,在序列(c)和序列(d)之间,在它们中的任何两个之间,在它们中的任何三个之间,或在所有四个之间,可以可选地存在一个或多个氨基酸的间隔物。在本发明的一个实施方式中,在N末端信号肽和序列(a)之间没有间隔物,换言之,N末端信号肽通过单个肽键与序列(a)共价键合。在另一实施方式中,在N末端信号肽和序列(a)之间存在间隔物。
在本发明的一个实施方式中,在序列(a)和序列(b)之间没有间隔物,换言之,序列(a)通过单个肽键与序列(b)共价键合。在另一实施方式中,在序列(a)和序列(b)之间存在间隔物。在本发明的一个实施方式中,在序列(b)和序列(c)之间没有间隔物,换言之,序列(b)通过单个肽键与序列(c)共价键合。在另一实施方式中,在序列(b)和序列(c)之间存在间隔物。在本发明的一个实施方式中,序列(c)和序列(d)之间没有间隔物,换言之,序列(c)通过单个肽键与序列(d)共价键合。在另一实施方式中,在序列(c)和序列(d)之间存在间隔物。原则上对间隔物的大小没有限制。
CD55含有四个细胞外短共有重复序列(SCR)、富含Ser/Thr/Pro(STP)的区域和GPI锚定结构域。根据本发明的融合蛋白,省略了GPI锚定结构域。富含STP的区域可以存在或不存在。本发明的融合蛋白的编码序列的一个实施方式还包含位于第三肽序列编码序列的C末端的多腺苷酸化信号。多腺苷酸化信号(Poly A)可以是任何Poly A。
本发明提供了编码上述蛋白质的核酸。在一个实施方式中,所述核酸是DNA。它可以在信号肽和序列(a)的编码序列之间、在序列(a)和序列(b)之间、在序列(b)和序列(c)之间、在序列(c)和序列(d)之间或在其他位置可选地包含一个或多个内含子。在本发明的一个实施方式中,所述核酸编码具有序列SEQ ID NO:2或SEQ ID NO:3的蛋白。SEQ ID NO:1是编码具有序列SEQ ID NO:2的蛋白的核酸的一个实例。因为不同的核酸三联密码子编码相同的氨基酸,即称为遗传密码简并性的关系,所以在本发明中可以容易地预见并涵盖编码具有序列SEQ ID NO:2的蛋白的许多其他核酸序列。
本发明的一个实施方式是表达载体,其包含与控制序列(例如启动子)可操作地连接的上述核酸。驱动融合蛋白的启动子可以是任何启动子,并不限于CMV启动子。当在启动子和融合蛋白编码序列之间存在内含子时,可以使用任何合适的常规内含子。例如,β-珠蛋白内含子是合适的。
本发明提供了一种细胞系,其在其细胞表面上稳定表达本发明的融合蛋白。根据本发明,用于蛋白表达的任何常规细胞系都可以使用。在一个实施方式中,细胞系是哺乳动物细胞系。在另一个实施方式中,细胞系是非哺乳动物细胞系,例如DF-1鸡胚胎成纤维细胞细胞系。
本发明提供了一种包膜病毒,其在病毒膜上并入了上述融合蛋白。根据本发明,可以使用任何包膜病毒。在一个实施方式中,所述病毒是溶瘤病毒,例如副粘病毒,例如新城疫病毒(NDV)。在实例中,将重组融合蛋白形式的补体抑制剂并入NDV颗粒的包膜上。本发明的重组融合蛋白可用于除NDV之外的溶瘤病毒,导致产生对宿主补体灭活作用更具抗性的溶瘤病毒颗粒。该融合蛋白形式的新型重组补体抑制剂可用于修饰任何其他哺乳动物细胞(例如HeLa细胞)以产生溶瘤病毒。溶瘤病毒描述于国际专利申请公开WO 2000/062735中,将其内容通过援引并入本文。在下文呈现出结果的实验中,所用的NDV是WO 2000/062735中描述的PPMK107。
可以将该病毒加入包含该病毒和药学上可接受的载体的药物组合物中。本发明提供一种治疗哺乳动物受试者中的肿瘤病况的方法,包括向所述受试者施用有效治疗所述肿瘤病况的量的上述病毒。对于癌症治疗,可以通过任何常规途径将病毒施用给患者,例如通过一次或多次肿瘤内或静脉内注射。对于肿瘤内施用,剂量范围可以是1×107至5×1012pfu/肿瘤。对于静脉内施用,剂量范围可以是1×107至1×10 13pfu/m2。(Pfu是“噬斑形成单位”的缩写。)
本发明的溶瘤病毒也可以经工程化而并入其他分子(例如GMCSF)以增强溶瘤病毒的功效。此外,所述溶瘤病毒可以是带有检查点抑制剂(例如抗PD1或抗PDL1分子)的联合癌症疗法的一部分。此外,所述溶瘤病毒可以是带有其他化学治疗剂的联合癌症疗法的一部分。化学治疗剂可以是但不限于喜树碱化合物,例如伊立替康或托泊替康。
本说明书中提及的所有出版物、专利和专利申请均通过援引整体并入本说明书中,其程度如同具体和单独地指明将每个单独的出版物、专利或专利申请通过援引并入本文一样。与任何上述出版物、专利和专利申请一起公开的任何补充信息也通过援引并入。例如,一些期刊文章在发表时带有通常可以在线获得的补充信息。
通过参考以下实施例,将更好地理解本发明,这些实施例说明但不限制本文所述的发明。
实施例
实施例1
产生了经修饰版本的重组CD55,其具有位于分泌信号肽下游的CD55的四个短共有重复序列(SCR)、随后的柔性连接物(3×G4S1)和CD8跨膜结构域以及截短的CD8细胞内结构域(图1)。将编码序列克隆至具有CMV启动子(驱动重组蛋白表达的合成内含子)的哺乳动物表达构建体中。表达盒还含有药物选择性标志物:位于IRES下游的新霉素磷酸转移酶。基因表达盒的末尾是合成的多腺苷酸化信号。SEQ ID NO:1是该哺乳动物细胞表达构建体的核苷酸序列。SEQ ID NO:2是所表达的蛋白的氨基酸序列。当在鸡胚胎成纤维细胞DF1细胞表面上表达或并入病毒膜上时,信号肽被切下,产生成熟的重组融合蛋白(SEQ ID NO:3),其构造/取向使得CD55SCR位于细胞或病毒膜外部,与细胞或病毒膜相邻的柔性连接物应当为CD55的SCR提供最大的灵活性以发挥其生物学功能,即,使C3转化酶失活,C3转化酶是补体途径的中心调控剂。柔性连接物之后是CD8跨膜结构域和截短的CD8细胞内结构域。
实施例2
通过PEI 25K(聚乙烯亚胺,线性25kDa,Polysciences,目录号23966)介导的转染,将哺乳动物表达构建体转染到鸡胚胎成纤维细胞DF1细胞中。转染后72小时,在300μg/mLG418(氨基糖苷抗生素)中选择转染的细胞,以产生组成型表达SEQ ID NO:2的稳定细胞系。如利用对成熟人CD55具有特异性的单克隆抗体(R&D Systems,目录号MAB20091)所检测的,该稳定细胞系在其细胞表面上组成型表达SEQ ID NO:3。如图3所示,如流式细胞术所分析的,重组融合蛋白在稳定转染有编码重组融合蛋白的构建体的DF1细胞上表达(图3,右侧的柱状图)。初始DF1细胞充当阴性对照(图3,左侧的柱状图)。
实施例3
用从鸡胚蛋产生的野生型NDV来感染在细胞表面上表达SEQ ID NO:3的稳定细胞系。然后在人肿瘤细胞系HT1080上滴定病毒。将等量的病毒(通过PFU来测量)分别与40%正常人血清(NHS)和40%热灭活的正常人血清(iNHS)一起温育。然后通过噬斑测定在HT1080细胞上对与人血清温育后仍存活的病毒进行评分。计算与NHS和与iNHS温育后回收的病毒之比。如表1所示,在鸡胚蛋中产生的病毒的回收率为0.5%,表明由鸡蛋产生的绝大多数NDV颗粒被灭活,最可能是被人类旁路补体途径灭活。同样地,由亲代鸡胚胎成纤维细胞DF1细胞产生的病毒的回收率为0.5%。令人惊讶的是,由在细胞表面上稳定表达SEQ ID NO:3的整体非克隆DF1细胞(bulk non-clonal DF1cells)产生的病毒的回收率为5.8%,超过野生型病毒的10倍。当检查表达SEQ ID NO:3的DF1细胞的共11个克隆群体时,回收率为0.8%至20%,其中5个克隆的回收率评分低于整体非克隆细胞系,而6个克隆的回收率评分高于整体非克隆细胞系(表1)。由8号克隆产生的病毒的回收率为10%,是由鸡胚蛋或亲代DF1细胞产生的病毒的回收率的20倍。由40号克隆产生的病毒的回收率为20%,是由鸡胚蛋或亲代DF1细胞产生的病毒的回收率的40倍。这些数据强烈表明,正常人血清中存在的补体活性快速破坏了由鸡胚蛋或亲代鸡胚胎成纤维细胞DF1细胞产生的NDV颗粒。然而,在相同的实验条件下与40%正常人血清温育后,与鸡蛋或亲代DF1细胞产生的病毒相比,在细胞表面上稳定表达重组补体抑制剂的DF-1细胞所产生的新NDV颗粒显示出了显著的最高40倍的回收率。
表1.由与40%正常人血清(NHS)温育后和与40%热灭活人血清(iNHS)温育后回收的病毒之比测量的病毒回收率
实施例4
使用 AQueous单一溶液评估在其细胞表面上稳定表达补体抑制性融合蛋白的DF1细胞(8号克隆)所产生的NDV的广谱溶瘤活性。该溶液的功能类似于MTT(即3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑鎓)测定,其中代谢活性细胞能够将试剂中的MTS四唑鎓(即3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑鎓)生物还原为可溶性生色甲(chromogenic formazan)。简言之,使三种不同的肿瘤细胞系HT1080(纤维肉瘤)、PANC-1(胰腺上皮癌)和OV-CAR3(卵巢腺癌)在单独的96孔板中生长。第二天,将NDV病毒的连续稀释液加入各孔中,并将板在5%CO2的37℃培养箱中温育6天。第6天,使用分光光度计在490nm处测量每个板上所有孔的吸光度。针对每个细胞系,使用4参数逻辑非线性回归分析计算IC50。这得到HT1080、OV-CAR-3和PANC-1细胞系的最终IC50值分别为255、120和47pfu/孔(图4)。这些结果表明,由在其细胞表面上稳定表达重组补体抑制剂的DF-1细胞所产生的NDV颗粒保留了以剂量依赖性方式裂解各种肿瘤细胞系的能力。
参考文献
Carroll,M.C.,E.M.Alicot,P.J.Katzman,L.B.Klickstein,J.A.Smith,和D.T.Fearon.1988.Organization of the genes encoding complement receptors type1 and 2,decay-accelerating factor,and C4-binding protein in the RCA locus onhuman chromosome 1.J.Exp.Med.167:1271.
Rey-Campos,J.,P.Rubinstein,和S.Rodriguez de Cordoba.1988.A physicalmap of the human regulator of complement activation gene cluster linking thecomplement genes CR1,CR2,DAF,and C4BP.J.Exp.Med.167:664.
Lublin,D.M.,和J.P.Atkinson.1989.Decay-accelerating factor:biochemistry,molecular biology,and function.Annu.Rev.Immunol.7:35.5.
Nakano,Y.,K.Sumida,N.Kikuta,N.H.Miura,T.Tobe,和M.Tomita.1992.Completedetermination of disulfide bonds localized within the short consensus repeatunits of decay accelerating factor(CD55antigen).Biochim.Biophys.Acta 1116:235.
Censullo,P.,和M.A.Davitz.1994a.How GPI-anchored proteins turnover:orwhere do they go after arrival at the plasma membrane.Semin Immunol.6:81.
Censullo,P.,和M.A.Davitz.1994b.The fate of GPI-anchoredmolecules.Braz J.Med.Biol.Res.27:289
Morgan,B.P.,和S.Meri.1994.Membrane proteins that protect againstcomplement lysis.Springer Semin.Immunopathol.15:369.
Turner A.J.1994.PIG-tailed membrane proteins.Essays Biochem.28:113.
Kim D.D.,和W.C.Song.2006.Membrane complement regulatoryproteins.Clin.Immunol.118:127.
Pecora,A.L.,Rizvi,N.,Cohen,G.I.,Meropol,N.J.,Sterman,D.,Marshall,J.L.,Goldberg,S.,Gross,P.,O’Neil,J.D.,Groene,W.S.,Roberts,M.S.,Rabin,H.,Bamat,M.K.,和R.M.Lorence.2002.Phase I trial of intravenous administration ofPV701,an oncolytic virus,in patients with advanced solidcancers.J.Clin.Oncol.20:2251.
Laurie,S.A.,Bell,J.C.,Atkins,H.L.,Roach,J.,Bamat,M.K.,O’Neil,J.D.,Roberts,M.S.,Groene,W.S.,和R.M.Lorence.2006.A phase 1clinical study ofintravenous administration of PV701,an oncolytic virus,using two-stepdesensitization.Clin.Cancer Res.12:2555.Lorence,R.M.,Roberts,M.S.,O’Neil,J.D.,Groene,W.S.,Miller,J.A.,Mueller,S.N.,和M.K.Bamat.2007.Phase 1clinicalexperience using intravenous administration of PV701,an oncolytic Newcastledisease virus.7:157.
Biswas,M.,Johnson,J.B.,Kumar,S.R.P.Parks,G.D.,和E.Subbiah.2012.Incorporation of host complement regulatory proteins intoNewcastle disease virus enhances complement evasion.J.Virol.86:12708.
Rangaswamy,U.S.,Cotter,C.R.,Chang,X.,Jin,H.,和Z.Chen.2016.CD55is akey complement regulatory protein that counteracts complement-mediatedinactivation of Newcastle disease virus.J.Gen.Virol.97:1765.
序列表
<110> 沃尔斯塔特免疫疗法公司
<120> 对补体灭活作用具有抗性的用于治疗癌症的包膜病毒
<130> 21003-PCT
<150> US 62/504,120
<151> 2017-05-10
<160> 3
<170> PatentIn version 3.5
<210> 1
<211> 6606
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<223> 哺乳动物细胞表达构建体
<220>
<221> misc_feature
<222> (1064)..(1165)
<223> 编码分泌信号肽
<220>
<221> misc_feature
<222> (1166)..(2119)
<223> Code for SCR of CD55
<220>
<221> misc_feature
<222> (2120)..(2164)
<223> Code for (G4S1)3 linker
<220>
<221> misc_feature
<222> (2165)..(2227)
<223> 编码CD8跨膜结构域
<220>
<221> misc_feature
<222> (2228)..(2260)
<223> 编码截短的CD8细胞内结构域
<400> 1
tcaatattgg ccattagcca tattattcat tggttatata gcataaatca atattggcta 60
ttggccattg catacgttgt atctatatca taatatgtac atttatattg gctcatgtcc 120
aatatgaccg ccatgttggc attgattatt gactagttat taatagtaat caattacggg 180
gtcattagtt catagcccat atatggagtt ccgcgttaca taacttacgg taaatggccc 240
gcctggctga ccgcccaacg acccccgccc attgacgtca ataatgacgt atgttcccat 300
agtaacgcca atagggactt tccattgacg tcaatgggtg gagtatttac ggtaaactgc 360
ccacttggca gtacatcaag tgtatcatat gccaagtccg ccccctattg acgtcaatga 420
cggtaaatgg cccgcctggc attatgccca gtacatgacc ttacgggact ttcctacttg 480
gcagtacatc tacgtattag tcatcgctat taccatggtg atgcggtttt ggcagtacac 540
caatgggcgt ggatagcggt ttgactcacg gggatttcca agtctccacc ccattgacgt 600
caatgggagt ttgttttggc accaaaatca acgggacttt ccaaaatgtc gtaataaccc 660
cgccccgttg acgcaaatgg gcggtaggcg tgtacggtgg gaggtctata taagcagagc 720
tcgtttagtg aaccgtcaga tcactagaag ctttattgcg gtagtttatc acagttaaat 780
tgctaacgca gtcagtgctt ctgacacaac agtctcgaac ttaagctgca gaagttggtc 840
gtgaggcact gggcaggtaa gtatcaaggt tacaagacag gtttaaggag accaatagaa 900
actgggcttg tcgagacaga gaagactctt gcgtttctga taggcaccta ttggtcttac 960
tgacatccac tttgcctttc tctccacagg tgtccactcc cagttcaatt acagctctta 1020
aggctagagt acttaatacg actcactata ggctagcgcc accatgacag tggccagacc 1080
ttctgtgcct gccgccctgc ctctgctggg agaactgcct agactgctgc tgctggtgct 1140
gctgtgtctg cctgccgtgt ggggcgattg tggcctgcct cccgatgtgc ctaatgccca 1200
gcctgccctg gaaggcagaa ccagcttccc cgaggacacc gtgatcacct acaagtgcga 1260
ggaatccttc gtgaagatcc ccggcgagaa ggatagcgtg atctgcctga agggcagcca 1320
gtggagcgac atcgaagagt tctgcaacag atcctgcgag gtgcccaccc ggctgaatag 1380
cgcctctctg aagcagccct acatcaccca gaactacttc cctgtgggca ccgtggtgga 1440
atacgagtgc agacccggct acagaagaga gccctccctg agccctaagc tgacctgcct 1500
gcagaacctg aagtggtcca ccgccgtgga gttctgtaaa aagaagtcct gccccaaccc 1560
tggcgagatc cggaacggcc agattgatgt gcctggcggc atcctgttcg gcgccacaat 1620
cagcttcagc tgcaacaccg gctacaagct gttcggcagc acctccagct tttgcctgat 1680
cagcggcagc agcgtgcagt ggagtgaccc tctgcctgag tgcagagaga tctactgccc 1740
tgccccccct cagatcgaca acggcatcat tcagggcgag cgggaccact acggctacag 1800
gcagagcgtg acctacgcct gcaacaaggg cttcaccatg atcggcgagc acagcatcta 1860
ctgcaccgtg aacaacgacg agggcgagtg gagcggccca ccccctgagt gtagaggcaa 1920
gagcctgacc agcaaggtgc cccccaccgt gcagaaaccc accaccgtga atgtgcctac 1980
caccgaggtg tccccaacca gccagaaaac aaccaccaag accaccaccc ccaacgccca 2040
ggccaccaga tctacccctg tgtccaggac caccaagcac ttccacgaga caacccctaa 2100
caagggcagc ggcacaaccg gtggcggagg atctggcggc ggaggaagcg gagggggagg 2160
atccatctat atctgggccc ctctggccgg cacctgtggc gtgctgctgc tgtctctcgt 2220
gatcaccctg tactgcaacc accggaaccg gcggagagtg tgatgagaat tcacgcgtgg 2280
tacctctaga gtcgaccctc tagggcggcc aattccgccc ctctccctcc ccccccccta 2340
acgttactgg ccgaagccgc ttggaataag gccggtgtgc gtttgtctat atgttatttt 2400
ccaccatatt gccgtctttt ggcaatgtga gggcccggaa acctggccct gtcttcttga 2460
cgagcattcc taggggtctt tcccctctcg ccaaaggaat gcaaggtctg ttgaatgtcg 2520
tgaaggaagc agttcctctg gaagcttctt gaagacaaac aacgtctgta gcgacccttt 2580
gcaggcagcg gaacccccca cctggcgaca ggtgcctctg cggccaaaag ccacgtgtat 2640
aagatacacc tgcaaaggcg gcacaacccc agtgccacgt tgtgagttgg atagttgtgg 2700
aaagagtcaa atggctctcc tcaagcgtat tcaacaaggg gctgaaggat gcccagaagg 2760
taccccattg tatgggatct gatctggggc ctcggtgcac atgctttaca tgtgtttagt 2820
cgaggttaaa aaaacgtcta ggccccccga accacgggga cgtggttttc ctttgaaaaa 2880
cacgatgata agcttgccac aacccgggat aattcctgca gccaatatgg gatcggccat 2940
tgaacaagat ggattgcacg caggttctcc ggccgcttgg gtggagaggc tattcggcta 3000
tgactgggca caacagacaa tcggctgctc tgatgccgcc gtgttccggc tgtcagcgca 3060
ggggcgcccg gttctttttg tcaagaccga cctgtccggt gccctgaatg aactgcagga 3120
cgaggcagcg cggctatcgt ggctggccac gacgggcgtt ccttgcgcag ctgtgctcga 3180
cgttgtcact gaagcgggaa gggactggct gctattgggc gaagtgccgg ggcaggatct 3240
cctgtcatct caccttgctc ctgccgagaa agtatccatc atggctgatg caatgcggcg 3300
gctgcatacg cttgatccgg ctacctgccc attcgaccac caagcgaaac atcgcatcga 3360
gcgagcacgt actcggatgg aagccggtct tgtcgatcag gatgatctgg acgaagagca 3420
tcaggggctc gcgccagccg aactgttcgc caggctcaag gcgcgcatgc ccgacggcga 3480
tgatctcgtc gtgacccatg gcgatgcctg cttgccgaat atcatggtgg aaaatggccg 3540
cttttctgga ttcatcgact gtggccggct gggtgtggcg gaccgctatc aggacatagc 3600
gttggctacc cgtgatattg ctgaagagct tggcggcgaa tgggctgacc gcttcctcgt 3660
gctttacggt atcgccgctc ccgattcgca gcgcatcgcc ttctatcgcc ttcttgacga 3720
gttcttctga ggggatcaat tctgggcggc ctcgagaata aacaatcatt attttcattg 3780
gatctgtgtg ttggtttttt gtgtgggctt gggggagggg gaggccagaa tgactccaag 3840
agctacagga aggcaggtca gagaccccac tggacaaaca gtggctggac tctgcaccat 3900
aacacacaat caacagggga gtgagctgga tcgagctgct cgagatccgg gctggcgtaa 3960
tagcgaagag gcccgcaccg atcgcccttc ccaacagttg cgcagcctga atggcgaatg 4020
gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg cagcgtgacc 4080
gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc ctttctcgcc 4140
acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg gttccgattt 4200
agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc acgtagtggg 4260
ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt ctttaatagt 4320
ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc ttttgattta 4380
taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta acaaaaattt 4440
aacgcgaatt ttaacaaaat attaacgctt acaatttcct gatgcggtat tttctcctta 4500
cgcatctgtg cggtatttca caccgcatat ggtgcactct cagtacaatc tgctctgatg 4560
ccgcatagtt aagccagccc cgacacccgc caacacccgc tgacgcgccc tgacgggctt 4620
gtctgctccc ggcatccgct tacagacaag ctgtgaccgt ctccgggagc tgcatgtgtc 4680
agaggttttc accgtcatca ccgaaacgcg cgagacgaaa gggcctcgtg atacgcctat 4740
ttttataggt taatgtcatg ataataatgg tttcttagac gtcaggtggc acttttcggg 4800
gaaatgtgcg cggaacccct atttgtttat ttttctaaat acattcaaat atgtatccgc 4860
tcatgagaca ataaccctga taaatgcttc aataatattg aaaaaggaag agtatgagta 4920
ttcaacattt ccgtgtcgcc cttattccct tttttgcggc attttgcctt cctgtttttg 4980
ctcacccaga aacgctggtg aaagtaaaag atgctgaaga tcagttgggt gcacgagtgg 5040
gttacatcga actggatctc aacagcggta agatccttga gagttttcgc cccgaagaac 5100
gttttccaat gatgagcact tttaaagttc tgctatgtgg cgcggtatta tcccgtattg 5160
acgccgggca agagcaactc ggtcgccgca tacactattc tcagaatgac ttggttgagt 5220
actcaccagt cacagaaaag catcttacgg atggcatgac agtaagagaa ttatgcagtg 5280
ctgccataac catgagtgat aacactgcgg ccaacttact tctgacaacg atcggaggac 5340
cgaaggagct aaccgctttt ttgcacaaca tgggggatca tgtaactcgc cttgatcgtt 5400
gggaaccgga gctgaatgaa gccataccaa acgacgagcg tgacaccacg atgcctgtag 5460
caatggcaac aacgttgcgc aaactattaa ctggcgaact acttactcta gcttcccggc 5520
aacaattaat agactggatg gaggcggata aagttgcagg accacttctg cgctcggccc 5580
ttccggctgg ctggtttatt gctgataaat ctggagccgg tgagcgtggg tctcgcggta 5640
tcattgcagc actggggcca gatggtaagc cctcccgtat cgtagttatc tacacgacgg 5700
ggagtcaggc aactatggat gaacgaaata gacagatcgc tgagataggt gcctcactga 5760
ttaagcattg gtaactgtca gaccaagttt actcatatat actttagatt gatttaaaac 5820
ttcattttta atttaaaagg atctaggtga agatcctttt tgataatctc atgaccaaaa 5880
tcccttaacg tgagttttcg ttccactgag cgtcagaccc cgtagaaaag atcaaaggat 5940
cttcttgaga tccttttttt ctgcgcgtaa tctgctgctt gcaaacaaaa aaaccaccgc 6000
taccagcggt ggtttgtttg ccggatcaag agctaccaac tctttttccg aaggtaactg 6060
gcttcagcag agcgcagata ccaaatactg ttcttctagt gtagccgtag ttaggccacc 6120
acttcaagaa ctctgtagca ccgcctacat acctcgctct gctaatcctg ttaccagtgg 6180
ctgctgccag tggcgataag tcgtgtctta ccgggttgga ctcaagacga tagttaccgg 6240
ataaggcgca gcggtcgggc tgaacggggg gttcgtgcac acagcccagc ttggagcgaa 6300
cgacctacac cgaactgaga tacctacagc gtgagctatg agaaagcgcc acgcttcccg 6360
aagggagaaa ggcggacagg tatccggtaa gcggcagggt cggaacagga gagcgcacga 6420
gggagcttcc agggggaaac gcctggtatc tttatagtcc tgtcgggttt cgccacctct 6480
gacttgagcg tcgatttttg tgatgctcgt caggggggcg gagcctatgg aaaaacgcca 6540
gcaacgcggc ctttttacgg ttcctggcct tttgctggcc ttttgctcac atggctcgac 6600
agatct 6606
<210> 2
<211> 399
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 融合蛋白
<220>
<221> 信号
<222> (1)..(34)
<223> 分泌信号肽
<220>
<221> 肽
<222> (35)..(352)
<223> SCR of CD55
<220>
<221> MISC_FEATURE
<222> (353)..(367)
<223> (G4S1)3 linker
<220>
<221> 跨膜
<222> (368)..(388)
<223> CD8跨膜结构域
<220>
<221> 结构域
<222> (389)..(399)
<223> 截短的CD8细胞内结构域
<400> 2
Met Thr Val Ala Arg Pro Ser Val Pro Ala Ala Leu Pro Leu Leu Gly
1 5 10 15
Glu Leu Pro Arg Leu Leu Leu Leu Val Leu Leu Cys Leu Pro Ala Val
20 25 30
Trp Gly Asp Cys Gly Leu Pro Pro Asp Val Pro Asn Ala Gln Pro Ala
35 40 45
Leu Glu Gly Arg Thr Ser Phe Pro Glu Asp Thr Val Ile Thr Tyr Lys
50 55 60
Cys Glu Glu Ser Phe Val Lys Ile Pro Gly Glu Lys Asp Ser Val Ile
65 70 75 80
Cys Leu Lys Gly Ser Gln Trp Ser Asp Ile Glu Glu Phe Cys Asn Arg
85 90 95
Ser Cys Glu Val Pro Thr Arg Leu Asn Ser Ala Ser Leu Lys Gln Pro
100 105 110
Tyr Ile Thr Gln Asn Tyr Phe Pro Val Gly Thr Val Val Glu Tyr Glu
115 120 125
Cys Arg Pro Gly Tyr Arg Arg Glu Pro Ser Leu Ser Pro Lys Leu Thr
130 135 140
Cys Leu Gln Asn Leu Lys Trp Ser Thr Ala Val Glu Phe Cys Lys Lys
145 150 155 160
Lys Ser Cys Pro Asn Pro Gly Glu Ile Arg Asn Gly Gln Ile Asp Val
165 170 175
Pro Gly Gly Ile Leu Phe Gly Ala Thr Ile Ser Phe Ser Cys Asn Thr
180 185 190
Gly Tyr Lys Leu Phe Gly Ser Thr Ser Ser Phe Cys Leu Ile Ser Gly
195 200 205
Ser Ser Val Gln Trp Ser Asp Pro Leu Pro Glu Cys Arg Glu Ile Tyr
210 215 220
Cys Pro Ala Pro Pro Gln Ile Asp Asn Gly Ile Ile Gln Gly Glu Arg
225 230 235 240
Asp His Tyr Gly Tyr Arg Gln Ser Val Thr Tyr Ala Cys Asn Lys Gly
245 250 255
Phe Thr Met Ile Gly Glu His Ser Ile Tyr Cys Thr Val Asn Asn Asp
260 265 270
Glu Gly Glu Trp Ser Gly Pro Pro Pro Glu Cys Arg Gly Lys Ser Leu
275 280 285
Thr Ser Lys Val Pro Pro Thr Val Gln Lys Pro Thr Thr Val Asn Val
290 295 300
Pro Thr Thr Glu Val Ser Pro Thr Ser Gln Lys Thr Thr Thr Lys Thr
305 310 315 320
Thr Thr Pro Asn Ala Gln Ala Thr Arg Ser Thr Pro Val Ser Arg Thr
325 330 335
Thr Lys His Phe His Glu Thr Thr Pro Asn Lys Gly Ser Gly Thr Thr
340 345 350
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile
355 360 365
Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser
370 375 380
Leu Val Ile Thr Leu Tyr Cys Asn His Arg Asn Arg Arg Arg Val
385 390 395
<210> 3
<211> 365
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 成熟的融合蛋白(切除信号肽后)
<220>
<221> 肽
<222> (1)..(318)
<223> SCR of CD55
<220>
<221> MISC_FEATURE
<222> (319)..(333)
<223> (G4S1)3 linker
<220>
<221> 跨膜
<222> (334)..(354)
<223> CD8跨膜结构域
<220>
<221> DOMAIN
<222> (355)..(365)
<223> 截短的CD8细胞内结构域
<400> 3
Asp Cys Gly Leu Pro Pro Asp Val Pro Asn Ala Gln Pro Ala Leu Glu
1 5 10 15
Gly Arg Thr Ser Phe Pro Glu Asp Thr Val Ile Thr Tyr Lys Cys Glu
20 25 30
Glu Ser Phe Val Lys Ile Pro Gly Glu Lys Asp Ser Val Ile Cys Leu
35 40 45
Lys Gly Ser Gln Trp Ser Asp Ile Glu Glu Phe Cys Asn Arg Ser Cys
50 55 60
Glu Val Pro Thr Arg Leu Asn Ser Ala Ser Leu Lys Gln Pro Tyr Ile
65 70 75 80
Thr Gln Asn Tyr Phe Pro Val Gly Thr Val Val Glu Tyr Glu Cys Arg
85 90 95
Pro Gly Tyr Arg Arg Glu Pro Ser Leu Ser Pro Lys Leu Thr Cys Leu
100 105 110
Gln Asn Leu Lys Trp Ser Thr Ala Val Glu Phe Cys Lys Lys Lys Ser
115 120 125
Cys Pro Asn Pro Gly Glu Ile Arg Asn Gly Gln Ile Asp Val Pro Gly
130 135 140
Gly Ile Leu Phe Gly Ala Thr Ile Ser Phe Ser Cys Asn Thr Gly Tyr
145 150 155 160
Lys Leu Phe Gly Ser Thr Ser Ser Phe Cys Leu Ile Ser Gly Ser Ser
165 170 175
Val Gln Trp Ser Asp Pro Leu Pro Glu Cys Arg Glu Ile Tyr Cys Pro
180 185 190
Ala Pro Pro Gln Ile Asp Asn Gly Ile Ile Gln Gly Glu Arg Asp His
195 200 205
Tyr Gly Tyr Arg Gln Ser Val Thr Tyr Ala Cys Asn Lys Gly Phe Thr
210 215 220
Met Ile Gly Glu His Ser Ile Tyr Cys Thr Val Asn Asn Asp Glu Gly
225 230 235 240
Glu Trp Ser Gly Pro Pro Pro Glu Cys Arg Gly Lys Ser Leu Thr Ser
245 250 255
Lys Val Pro Pro Thr Val Gln Lys Pro Thr Thr Val Asn Val Pro Thr
260 265 270
Thr Glu Val Ser Pro Thr Ser Gln Lys Thr Thr Thr Lys Thr Thr Thr
275 280 285
Pro Asn Ala Gln Ala Thr Arg Ser Thr Pro Val Ser Arg Thr Thr Lys
290 295 300
His Phe His Glu Thr Thr Pro Asn Lys Gly Ser Gly Thr Thr Gly Gly
305 310 315 320
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Tyr Ile
325 330 335
Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu Ser Leu Val
340 345 350
Ile Thr Leu Tyr Cys Asn His Arg Asn Arg Arg Arg Val
355 360 365
Claims (34)
1.一种融合蛋白,其包含:(a)CD55肽序列,(b)位于所述CD55序列的C末端的连接物序列,(c)位于所述连接物序列的C末端的跨膜结构域,和(d)位于所述跨膜结构域的C末端的细胞内结构域,其中,所述融合蛋白不含GPI锚。
2.如权利要求1所述的蛋白,其中,所述CD55肽序列是人CD55肽序列。
3.如权利要求1所述的蛋白,其中,序列(a)包含CD55的四个短共有重复序列(SCR)。
4.如权利要求1所述的蛋白,其中,所述连接物是(G4S1)3连接物。
5.如权利要求1所述的蛋白,其中,跨膜结构域是CD8跨膜结构域。
6.如权利要求1所述的蛋白,其中,所述细胞内结构域是截短的CD8细胞内结构域。
7.如权利要求1所述的蛋白,其中,肽序列(a)通过单个肽键与肽序列(b)共价键合。
8.如权利要求1所述的蛋白,其中,肽序列(a)通过间隔物与肽序列(b)共价键合。
9.如权利要求1所述的蛋白,其中,肽序列(b)通过单个肽键与肽序列(c)共价键合。
10.如权利要求1所述的蛋白,其中,肽序列(b)通过间隔物与肽序列(c)共价键合。
11.如权利要求1所述的蛋白,其中,肽序列(c)通过单个肽键与肽序列(d)共价键合。
12.如权利要求1所述的蛋白,其中,肽序列(c)通过间隔物与肽序列(d)共价键合。
13.如权利要求1所述的蛋白,其中,所述融合蛋白还包含位于序列(a)的N末端的分泌信号肽。
14.如权利要求13所述的蛋白,其中,所述分泌信号肽是CD55的分泌信号肽。
15.如权利要求13所述的蛋白,其中,N末端的分泌信号肽通过单个肽与序列(a)共价键合。
16.如权利要求13所述的蛋白,其中,N末端的分泌信号肽通过间隔物与序列(a)共价键合。
17.如权利要求1所述的蛋白,其具有序列SEQ ID NO:2。
18.如权利要求1所述的蛋白,其具有序列SEQ ID NO:3。
19.编码权利要求1至18中任一项所述的蛋白的核酸。
20.如权利要求19所述的核酸,其中所述核酸是DNA。
21.如权利要求20所述的核酸,其还包含一个或多个内含子。
22.如权利要求19所述的核酸,其编码具有序列SEQ ID NO:2的蛋白。
23.如权利要求22所述的核酸,其具有序列SEQ ID NO:1。
24.一种表达载体,其包含与控制序列可操作地连接的权利要求19至23中任一项所述的核酸。
25.一种细胞系,其在细胞表面上稳定地表达权利要求1至18中任一项所述的蛋白。
26.如权利要求25所述的细胞系,其中,所述细胞系是哺乳动物细胞系。
27.如权利要求25所述的细胞系,其中,所述细胞系是DF-1鸡胚胎成纤维细胞细胞系。
28.一种包膜病毒,其在病毒膜上并入了权利要求1至18中任一项所述的蛋白。
29.如权利要求28所述的病毒,其中,所述病毒是溶瘤病毒。
30.如权利要求29所述的病毒,其中,所述溶瘤病毒是新城疫病毒。
31.一种药物组合物,其包含权利要求29或30所述的病毒和药学上可接受的载体。
32.一种治疗哺乳动物受试者的肿瘤病况的方法,所述方法包括向所述受试者施用有效治疗所述病况的量的权利要求28所述的病毒。
33.如权利要求32所述的方法,其中,肿瘤内施用所述病毒。
34.如权利要求32所述的方法,其中,静脉内施用所述病毒。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762504120P | 2017-05-10 | 2017-05-10 | |
US62/504,120 | 2017-05-10 | ||
PCT/US2018/032018 WO2018209052A1 (en) | 2017-05-10 | 2018-05-10 | Enveloped virus resistant to complement inactivation for the treatment of cancer |
Publications (1)
Publication Number | Publication Date |
---|---|
CN109414483A true CN109414483A (zh) | 2019-03-01 |
Family
ID=64105722
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201880002553.7A Pending CN109414483A (zh) | 2017-05-10 | 2018-05-10 | 对补体灭活作用具有抗性的用于治疗癌症的包膜病毒 |
Country Status (12)
Country | Link |
---|---|
US (2) | US11274141B2 (zh) |
EP (1) | EP3621635A4 (zh) |
JP (1) | JP7161940B2 (zh) |
KR (2) | KR102662049B1 (zh) |
CN (1) | CN109414483A (zh) |
AU (1) | AU2018265258B2 (zh) |
BR (1) | BR112018075281A2 (zh) |
CA (1) | CA3026892A1 (zh) |
IL (1) | IL263979B2 (zh) |
MX (1) | MX2018015599A (zh) |
WO (1) | WO2018209052A1 (zh) |
ZA (1) | ZA201808040B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113736810A (zh) * | 2021-09-08 | 2021-12-03 | 阿思科力(苏州)生物科技有限公司 | 构建体、载体、蛋白、细胞、制备方法、产品及应用 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20190129077A (ko) | 2017-03-15 | 2019-11-19 | 팬디온 테라퓨틱스, 인코포레이티드 | 표적화된 면역관용 |
CN111010866A (zh) | 2017-05-24 | 2020-04-14 | 潘迪恩治疗公司 | 靶向免疫耐受性 |
US10946068B2 (en) | 2017-12-06 | 2021-03-16 | Pandion Operations, Inc. | IL-2 muteins and uses thereof |
US10174091B1 (en) | 2017-12-06 | 2019-01-08 | Pandion Therapeutics, Inc. | IL-2 muteins |
WO2021168079A1 (en) | 2020-02-21 | 2021-08-26 | Pandion Operations, Inc. | Tissue targeted immunotolerance with a cd39 effector |
WO2022182206A1 (ko) * | 2021-02-26 | 2022-09-01 | 신라젠(주) | 항암 바이러스 및 이의 용도 |
KR20240003051A (ko) * | 2022-06-29 | 2024-01-08 | 신라젠(주) | Cd55 및 cd59를 동시 발현하는 항암 바이러스 |
WO2024054040A1 (ko) * | 2022-09-07 | 2024-03-14 | 신라젠(주) | 항암 바이러스의 신규 용도 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1302305A (zh) * | 1998-04-02 | 2001-07-04 | 里格尔制药公司 | 引起紧密结构形成的肽 |
CN104159926A (zh) * | 2011-12-01 | 2014-11-19 | 普腾生技有限公司 | 补体和vegf途径的蛋白质抑制剂及其使用方法 |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5374548A (en) * | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
DE69432409T2 (de) | 1993-04-30 | 2003-12-24 | Wellstat Biologics Corp | Verwendung der NDV zur Herstellung eines Medikaments zur Krebsbehandlung |
JPH10313865A (ja) * | 1997-05-15 | 1998-12-02 | Deinabetsuku Kenkyusho:Kk | ヒト補体制御因子が呈示されたベクター |
US6475756B1 (en) * | 1997-11-21 | 2002-11-05 | Gesellschaft Fuer Biotechnologische Forschung Mbh(Gbf) | Development of viruses resistant to inactivation by the human complement system |
WO1999032648A1 (en) | 1997-12-22 | 1999-07-01 | The University Of Tennessee Research Corporation | Recombinant rhabdovirus containing a heterologous fusion protein |
JP2003530301A (ja) | 1999-04-15 | 2003-10-14 | ウェルスタット バイオロジクス コーポレイション | ウイルスを用いた新生物の処置 |
AU2003298650B2 (en) | 2002-11-15 | 2010-03-11 | Musc Foundation For Research Development | Complement receptor 2 targeted complement modulators |
EP1784506B1 (en) * | 2004-07-21 | 2010-08-25 | Dana-Farber Cancer Institute, Inc. | Lentiviral vectors and uses thereof |
JP5050198B2 (ja) * | 2006-09-05 | 2012-10-17 | 国立大学法人大阪大学 | ヒト補体制御因子発現遺伝子およびその利用 |
EP2118320A4 (en) | 2007-02-06 | 2010-05-19 | Genizon Biosciences Inc | GENE CARD OF HUMAN GENES ASSOCIATED WITH HYPERACTIVITY ATTENTION DEFICIT DISORDER (ADHD) |
US20100120665A1 (en) * | 2007-03-01 | 2010-05-13 | Advanced Vision Therapies, Inc. | Treatment of diseases characterized by inflammation |
US8877896B2 (en) | 2008-02-15 | 2014-11-04 | Tufts University | Compositions, methods and kits for modeling, diagnosing, and treating complement disorders |
JP2014516517A (ja) | 2011-04-29 | 2014-07-17 | キージーン・エン・フェー | グリホサート耐性強化 |
JP6162102B2 (ja) | 2011-05-05 | 2017-07-12 | ウェルスタット イムノセラピューティクス, エルエルシー | 補体b因子アナログおよびその用途 |
EP3129470B1 (en) * | 2014-04-07 | 2021-04-07 | Novartis Ag | Treatment of cancer using anti-cd19 chimeric antigen receptor |
JP6694875B2 (ja) | 2014-05-15 | 2020-05-20 | ナショナル ユニヴァーシティ オブ シンガポール | 改変ナチュラルキラー細胞及びその使用 |
WO2016164308A1 (en) * | 2015-04-06 | 2016-10-13 | Subdomain, Llc | De novo binding domain containing polypeptides and uses thereof |
GB201507119D0 (en) * | 2015-04-27 | 2015-06-10 | Ucl Business Plc | Nucleic Acid Construct |
US20160361360A1 (en) | 2015-06-12 | 2016-12-15 | Immunomedics, Inc. | Disease therapy with chimeric antigen receptor (car) constructs and t cells (car-t) or nk cells (car-nk) expressing car constructs |
US20190282640A1 (en) | 2016-05-19 | 2019-09-19 | Turnstone Limited Partnership | Pseudotyped oncolytic rhabdoviruses and their use in combination therapy |
-
2018
- 2018-05-10 BR BR112018075281-9A patent/BR112018075281A2/pt unknown
- 2018-05-10 JP JP2018564966A patent/JP7161940B2/ja active Active
- 2018-05-10 WO PCT/US2018/032018 patent/WO2018209052A1/en unknown
- 2018-05-10 IL IL263979A patent/IL263979B2/en unknown
- 2018-05-10 KR KR1020187037869A patent/KR102662049B1/ko active IP Right Grant
- 2018-05-10 CN CN201880002553.7A patent/CN109414483A/zh active Pending
- 2018-05-10 AU AU2018265258A patent/AU2018265258B2/en active Active
- 2018-05-10 KR KR1020247013722A patent/KR20240073085A/ko active Application Filing
- 2018-05-10 MX MX2018015599A patent/MX2018015599A/es unknown
- 2018-05-10 CA CA3026892A patent/CA3026892A1/en active Pending
- 2018-05-10 EP EP18798575.9A patent/EP3621635A4/en active Pending
- 2018-05-10 US US16/303,729 patent/US11274141B2/en active Active
- 2018-11-28 ZA ZA2018/08040A patent/ZA201808040B/en unknown
-
2022
- 2022-02-18 US US17/674,990 patent/US20220169701A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1302305A (zh) * | 1998-04-02 | 2001-07-04 | 里格尔制药公司 | 引起紧密结构形成的肽 |
CN104159926A (zh) * | 2011-12-01 | 2014-11-19 | 普腾生技有限公司 | 补体和vegf途径的蛋白质抑制剂及其使用方法 |
Non-Patent Citations (1)
Title |
---|
杜瑞琴等: "嵌合跨膜型人 CD55基因的重组逆病毒表达质粒的构建" * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113736810A (zh) * | 2021-09-08 | 2021-12-03 | 阿思科力(苏州)生物科技有限公司 | 构建体、载体、蛋白、细胞、制备方法、产品及应用 |
CN113736810B (zh) * | 2021-09-08 | 2024-05-24 | 苏州因特药物研发有限公司 | 构建体、载体、蛋白、细胞、制备方法、产品及应用 |
Also Published As
Publication number | Publication date |
---|---|
JP7161940B2 (ja) | 2022-10-27 |
AU2018265258B2 (en) | 2023-01-05 |
IL263979A (en) | 2019-02-28 |
BR112018075281A2 (pt) | 2020-02-11 |
IL263979B2 (en) | 2023-09-01 |
AU2018265258A1 (en) | 2019-01-17 |
CA3026892A1 (en) | 2018-11-15 |
RU2018146446A (ru) | 2021-06-10 |
RU2018146446A3 (zh) | 2021-09-10 |
IL263979B1 (en) | 2023-05-01 |
US11274141B2 (en) | 2022-03-15 |
JP2020519230A (ja) | 2020-07-02 |
EP3621635A1 (en) | 2020-03-18 |
KR20240073085A (ko) | 2024-05-24 |
KR20200005721A (ko) | 2020-01-16 |
US20220169701A1 (en) | 2022-06-02 |
EP3621635A4 (en) | 2021-02-24 |
US20190194292A1 (en) | 2019-06-27 |
WO2018209052A1 (en) | 2018-11-15 |
ZA201808040B (en) | 2019-09-25 |
KR102662049B1 (ko) | 2024-05-23 |
MX2018015599A (es) | 2019-05-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102662049B1 (ko) | 암 치료용 보체 불활성화 내성의 외피 바이러스 | |
CN112680466B (zh) | 一种表达人源ace2的动物模型及其用途 | |
KR20220066914A (ko) | 부정맥 유발성 우심실 심근병증의 유전자 요법 조성물 및 치료 | |
KR101258949B1 (ko) | 활성형 재조합 혈액응고 9인자의 대량생산 방법 | |
CN112522271B (zh) | 一种sgRNA及其应用 | |
CN111269888B (zh) | 一种adipsin基因修饰的脂肪干细胞、制备方法及其应用 | |
CN114107390B (zh) | 一种用于表达抗体IgG1的rAAV载体及其应用 | |
CN117715660A (zh) | 右心室致心律失常性心肌病的基因治疗组合物和治疗 | |
CN109055428A (zh) | 一种重组腺相关病毒载体及其制备方法与应用 | |
CN112877351A (zh) | 一种用于防治新冠病毒感染的重组质粒、重组乳酸杆菌表达系统及其应用 | |
CN110438053B (zh) | 一种适用于聚球藻的生物封存系统、构建方法及应用 | |
KR102673828B1 (ko) | off-the-shelf 줄기세포 및 면역세포, 이를 포함하는 약학적 조성물 | |
KR101885438B1 (ko) | 유전자치료 벡터시스템 및 전구약물 유전자 | |
CN112301058B (zh) | 一种重组腺相关病毒载体及其制备方法与应用 | |
CN111793632A (zh) | 变异的Gsdmd-C核酸片段,包含所述核酸片段的载体及应用 | |
RU2791051C2 (ru) | Оболочечный вирус, резистентный к инактивации комплементом, для лечения злокачественных новообразований | |
CN110225977B (zh) | 基因治疗载体系统和药物前体基因 | |
CN112342228B (zh) | 表达抗vegf融合蛋白的aav病毒载体及其应用 | |
CN109735558B (zh) | 一种重组car19-il24基因、慢病毒载体、car19-il24-t细胞及应用 | |
US20020103144A1 (en) | Retroviral gene transfer vectors | |
CN111088204A (zh) | 表达Caspase-3重组scFv78的重组大肠杆菌及其功能验证方法 | |
CN110938648A (zh) | 一种真菌分泌表达载体、构建方法及其应用 | |
RU2805173C1 (ru) | Способ получения генно-модифицированных лабораторных животных с нуль-аллелем гена P2rx3 | |
CN112180087B (zh) | 检测鸭疫里默氏杆菌抗体的elisa方法及其试剂盒和应用 | |
CN112301057B (zh) | 一种重组腺相关病毒载体及其制备方法与应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20240619 Address after: American Maryland Applicant after: Pharmaceutical Co.,Ltd. Country or region after: U.S.A. Address before: American Maryland Applicant before: WELLSTAT IMMUNOTHERAPEUTICS, LLC Country or region before: U.S.A. |