CN113461797B - 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 - Google Patents
一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 Download PDFInfo
- Publication number
- CN113461797B CN113461797B CN202110906408.5A CN202110906408A CN113461797B CN 113461797 B CN113461797 B CN 113461797B CN 202110906408 A CN202110906408 A CN 202110906408A CN 113461797 B CN113461797 B CN 113461797B
- Authority
- CN
- China
- Prior art keywords
- artificial sequence
- target antigen
- cancer target
- cells
- ctl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000427 antigen Substances 0.000 title claims abstract description 90
- 108091007433 antigens Proteins 0.000 title claims abstract description 90
- 102000036639 antigens Human genes 0.000 title claims abstract description 90
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 75
- 201000011510 cancer Diseases 0.000 title claims abstract description 54
- 210000003101 oviduct Anatomy 0.000 title claims abstract description 52
- 201000001342 Fallopian tube cancer Diseases 0.000 claims abstract description 22
- 208000013452 Fallopian tube neoplasm Diseases 0.000 claims abstract description 22
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000002147 killing effect Effects 0.000 abstract description 14
- 238000012216 screening Methods 0.000 abstract description 13
- 238000004458 analytical method Methods 0.000 abstract description 8
- 238000001514 detection method Methods 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 97
- 108010002350 Interleukin-2 Proteins 0.000 description 17
- 238000012258 culturing Methods 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000012163 sequencing technique Methods 0.000 description 9
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 6
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 239000008055 phosphate buffer solution Substances 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010088729 HLA-A*02:01 antigen Proteins 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 102210024051 HLA-B*15:01 Human genes 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 3
- HRKOLWXWQSDMSK-XIRDDKMYSA-N Trp-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N HRKOLWXWQSDMSK-XIRDDKMYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 108010037850 glycylvaline Proteins 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 108010026333 seryl-proline Proteins 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- CCDFBRZVTDDJNM-GUBZILKMSA-N Ala-Leu-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O CCDFBRZVTDDJNM-GUBZILKMSA-N 0.000 description 2
- IOXWDLNHXZOXQP-FXQIFTODSA-N Asp-Met-Ser Chemical compound CSCC[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N IOXWDLNHXZOXQP-FXQIFTODSA-N 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- SYTFJIQPBRJSOK-NKIYYHGXSA-N Gln-Thr-His Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 SYTFJIQPBRJSOK-NKIYYHGXSA-N 0.000 description 2
- UTKUTMJSWKKHEM-WDSKDSINSA-N Glu-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O UTKUTMJSWKKHEM-WDSKDSINSA-N 0.000 description 2
- VSVZIEVNUYDAFR-YUMQZZPRSA-N Gly-Ala-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN VSVZIEVNUYDAFR-YUMQZZPRSA-N 0.000 description 2
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 2
- 102100028972 HLA class I histocompatibility antigen, A alpha chain Human genes 0.000 description 2
- 108010075704 HLA-A Antigens Proteins 0.000 description 2
- 102210042925 HLA-A*02:01 Human genes 0.000 description 2
- 101001134706 Homo sapiens Protein LIAT1 Proteins 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- WNGVUZWBXZKQES-YUMQZZPRSA-N Leu-Ala-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O WNGVUZWBXZKQES-YUMQZZPRSA-N 0.000 description 2
- 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 2
- PESQCPHRXOFIPX-UHFFFAOYSA-N N-L-methionyl-L-tyrosine Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 PESQCPHRXOFIPX-UHFFFAOYSA-N 0.000 description 2
- MPGJIHFJCXTVEX-KKUMJFAQSA-N Phe-Arg-Glu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O MPGJIHFJCXTVEX-KKUMJFAQSA-N 0.000 description 2
- 102100033315 Protein LIAT1 Human genes 0.000 description 2
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 2
- 108010047495 alanylglycine Proteins 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 238000003501 co-culture Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
- 108010050848 glycylleucine Proteins 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- RCQRKPUXJAGEEC-ZLUOBGJFSA-N Ala-Cys-Cys Chemical compound C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O RCQRKPUXJAGEEC-ZLUOBGJFSA-N 0.000 description 1
- NHLAEBFGWPXFGI-WHFBIAKZSA-N Ala-Gly-Asn Chemical compound C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N NHLAEBFGWPXFGI-WHFBIAKZSA-N 0.000 description 1
- AWZKCUCQJNTBAD-SRVKXCTJSA-N Ala-Leu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCCN AWZKCUCQJNTBAD-SRVKXCTJSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- NKBQZKVMKJJDLX-SRVKXCTJSA-N Arg-Glu-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O NKBQZKVMKJJDLX-SRVKXCTJSA-N 0.000 description 1
- COXMUHNBYCVVRG-DCAQKATOSA-N Arg-Leu-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O COXMUHNBYCVVRG-DCAQKATOSA-N 0.000 description 1
- YLVGUOGAFAJMKP-JYJNAYRXSA-N Arg-Met-Tyr Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N YLVGUOGAFAJMKP-JYJNAYRXSA-N 0.000 description 1
- ICRHGPYYXMWHIE-LPEHRKFASA-N Arg-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ICRHGPYYXMWHIE-LPEHRKFASA-N 0.000 description 1
- OGZBJJLRKQZRHL-KJEVXHAQSA-N Arg-Thr-Tyr Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OGZBJJLRKQZRHL-KJEVXHAQSA-N 0.000 description 1
- LFWOQHSQNCKXRU-UFYCRDLUSA-N Arg-Tyr-Phe Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 LFWOQHSQNCKXRU-UFYCRDLUSA-N 0.000 description 1
- IARGXWMWRFOQPG-GCJQMDKQSA-N Asn-Ala-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IARGXWMWRFOQPG-GCJQMDKQSA-N 0.000 description 1
- DAPLJWATMAXPPZ-CIUDSAMLSA-N Asn-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(N)=O DAPLJWATMAXPPZ-CIUDSAMLSA-N 0.000 description 1
- WQSCVMQDZYTFQU-FXQIFTODSA-N Asn-Cys-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O WQSCVMQDZYTFQU-FXQIFTODSA-N 0.000 description 1
- GNKVBRYFXYWXAB-WDSKDSINSA-N Asn-Glu-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O GNKVBRYFXYWXAB-WDSKDSINSA-N 0.000 description 1
- MYCSPQIARXTUTP-SRVKXCTJSA-N Asn-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(=O)N)N MYCSPQIARXTUTP-SRVKXCTJSA-N 0.000 description 1
- CRNKLABLTICXDV-GUBZILKMSA-N Asp-His-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N CRNKLABLTICXDV-GUBZILKMSA-N 0.000 description 1
- HKEZZWQWXWGASX-KKUMJFAQSA-N Asp-Leu-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 HKEZZWQWXWGASX-KKUMJFAQSA-N 0.000 description 1
- AWPWHMVCSISSQK-QWRGUYRKSA-N Asp-Tyr-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(O)=O AWPWHMVCSISSQK-QWRGUYRKSA-N 0.000 description 1
- SURTWIXUHQNUGN-GUBZILKMSA-N Cys-Arg-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)N SURTWIXUHQNUGN-GUBZILKMSA-N 0.000 description 1
- PORWNQWEEIOIRH-XHNCKOQMSA-N Cys-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CS)N)C(=O)O PORWNQWEEIOIRH-XHNCKOQMSA-N 0.000 description 1
- WVLZTXGTNGHPBO-SRVKXCTJSA-N Cys-Leu-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O WVLZTXGTNGHPBO-SRVKXCTJSA-N 0.000 description 1
- MKVKKORBPTUSNX-LPEHRKFASA-N Cys-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CS)N MKVKKORBPTUSNX-LPEHRKFASA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- SHERTACNJPYHAR-ACZMJKKPSA-N Gln-Ala-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O SHERTACNJPYHAR-ACZMJKKPSA-N 0.000 description 1
- SXIJQMBEVYWAQT-GUBZILKMSA-N Gln-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N SXIJQMBEVYWAQT-GUBZILKMSA-N 0.000 description 1
- UVAOVENCIONMJP-GUBZILKMSA-N Gln-Cys-Leu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O UVAOVENCIONMJP-GUBZILKMSA-N 0.000 description 1
- SRZLHYPAOXBBSB-HJGDQZAQSA-N Glu-Arg-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SRZLHYPAOXBBSB-HJGDQZAQSA-N 0.000 description 1
- PCBBLFVHTYNQGG-LAEOZQHASA-N Glu-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N PCBBLFVHTYNQGG-LAEOZQHASA-N 0.000 description 1
- QQLBPVKLJBAXBS-FXQIFTODSA-N Glu-Glu-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O QQLBPVKLJBAXBS-FXQIFTODSA-N 0.000 description 1
- KASDBWKLWJKTLJ-GUBZILKMSA-N Glu-Glu-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O KASDBWKLWJKTLJ-GUBZILKMSA-N 0.000 description 1
- RAUDKMVXNOWDLS-WDSKDSINSA-N Glu-Gly-Ser Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O RAUDKMVXNOWDLS-WDSKDSINSA-N 0.000 description 1
- VGUYMZGLJUJRBV-YVNDNENWSA-N Glu-Ile-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O VGUYMZGLJUJRBV-YVNDNENWSA-N 0.000 description 1
- RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
- DJTXYXZNNDDEOU-WHFBIAKZSA-N Gly-Asn-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)CN)C(=O)N DJTXYXZNNDDEOU-WHFBIAKZSA-N 0.000 description 1
- FMVLWTYYODVFRG-BQBZGAKWSA-N Gly-Asn-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)CN FMVLWTYYODVFRG-BQBZGAKWSA-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
- PAWIVEIWWYGBAM-YUMQZZPRSA-N Gly-Leu-Ala Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O PAWIVEIWWYGBAM-YUMQZZPRSA-N 0.000 description 1
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 1
- JBJNKUOMNZGQIM-PYJNHQTQSA-N His-Arg-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JBJNKUOMNZGQIM-PYJNHQTQSA-N 0.000 description 1
- LBHOVGUGOBINDL-KKUMJFAQSA-N His-Asp-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O LBHOVGUGOBINDL-KKUMJFAQSA-N 0.000 description 1
- 101000973439 Homo sapiens NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101000613614 Homo sapiens Protein mono-ADP-ribosyltransferase PARP10 Proteins 0.000 description 1
- 101001130433 Homo sapiens Ras-related protein Rap-2c Proteins 0.000 description 1
- 101000679307 Homo sapiens T cell receptor gamma constant 2 Proteins 0.000 description 1
- 101000904724 Homo sapiens Transmembrane glycoprotein NMB Proteins 0.000 description 1
- QLRMMMQNCWBNPQ-QXEWZRGKSA-N Ile-Arg-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)O)N QLRMMMQNCWBNPQ-QXEWZRGKSA-N 0.000 description 1
- QTUSJASXLGLJSR-OSUNSFLBSA-N Ile-Arg-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N QTUSJASXLGLJSR-OSUNSFLBSA-N 0.000 description 1
- HPCFRQWLTRDGHT-AJNGGQMLSA-N Ile-Leu-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O HPCFRQWLTRDGHT-AJNGGQMLSA-N 0.000 description 1
- HGCNKOLVKRAVHD-UHFFFAOYSA-N L-Met-L-Phe Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 HGCNKOLVKRAVHD-UHFFFAOYSA-N 0.000 description 1
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- LZDNBBYBDGBADK-UHFFFAOYSA-N L-valyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C(C)C)C(O)=O)=CNC2=C1 LZDNBBYBDGBADK-UHFFFAOYSA-N 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- ZURHXHNAEJJRNU-CIUDSAMLSA-N Leu-Asp-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZURHXHNAEJJRNU-CIUDSAMLSA-N 0.000 description 1
- YWYQSLOTVIRCFE-SRVKXCTJSA-N Leu-His-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O YWYQSLOTVIRCFE-SRVKXCTJSA-N 0.000 description 1
- AUBMZAMQCOYSIC-MNXVOIDGSA-N Leu-Ile-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O AUBMZAMQCOYSIC-MNXVOIDGSA-N 0.000 description 1
- JKSIBWITFMQTOA-XUXIUFHCSA-N Leu-Ile-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O JKSIBWITFMQTOA-XUXIUFHCSA-N 0.000 description 1
- PTRKPHUGYULXPU-KKUMJFAQSA-N Leu-Phe-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O PTRKPHUGYULXPU-KKUMJFAQSA-N 0.000 description 1
- SVBJIZVVYJYGLA-DCAQKATOSA-N Leu-Ser-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O SVBJIZVVYJYGLA-DCAQKATOSA-N 0.000 description 1
- BGGTYDNTOYRTTR-MEYUZBJRSA-N Leu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(C)C)N)O BGGTYDNTOYRTTR-MEYUZBJRSA-N 0.000 description 1
- FACUGMGEFUEBTI-SRVKXCTJSA-N Lys-Asn-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CCCCN FACUGMGEFUEBTI-SRVKXCTJSA-N 0.000 description 1
- OSZTUONKUMCWEP-XUXIUFHCSA-N Met-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC OSZTUONKUMCWEP-XUXIUFHCSA-N 0.000 description 1
- BJPQKNHZHUCQNQ-SRVKXCTJSA-N Met-Pro-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCSC)N BJPQKNHZHUCQNQ-SRVKXCTJSA-N 0.000 description 1
- FAKYXUOUQCRGMO-FDARSICLSA-N Met-Trp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCSC)N FAKYXUOUQCRGMO-FDARSICLSA-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
- 108010066427 N-valyltryptophan Proteins 0.000 description 1
- 102100022195 NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial Human genes 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- SXJGROGVINAYSH-AVGNSLFASA-N Phe-Gln-Asp Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N SXJGROGVINAYSH-AVGNSLFASA-N 0.000 description 1
- UNBFGVQVQGXXCK-KKUMJFAQSA-N Phe-Ser-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O UNBFGVQVQGXXCK-KKUMJFAQSA-N 0.000 description 1
- GOUWCZRDTWTODO-YDHLFZDLSA-N Phe-Val-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O GOUWCZRDTWTODO-YDHLFZDLSA-N 0.000 description 1
- ALJGSKMBIUEJOB-FXQIFTODSA-N Pro-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@@H]1CCCN1 ALJGSKMBIUEJOB-FXQIFTODSA-N 0.000 description 1
- WPQKSRHDTMRSJM-CIUDSAMLSA-N Pro-Asp-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 WPQKSRHDTMRSJM-CIUDSAMLSA-N 0.000 description 1
- AIZVVCMAFRREQS-GUBZILKMSA-N Pro-Cys-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AIZVVCMAFRREQS-GUBZILKMSA-N 0.000 description 1
- FRKBNXCFJBPJOL-GUBZILKMSA-N Pro-Glu-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O FRKBNXCFJBPJOL-GUBZILKMSA-N 0.000 description 1
- LEIKGVHQTKHOLM-IUCAKERBSA-N Pro-Pro-Gly Chemical compound OC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 LEIKGVHQTKHOLM-IUCAKERBSA-N 0.000 description 1
- FDMCIBSQRKFSTJ-RHYQMDGZSA-N Pro-Thr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O FDMCIBSQRKFSTJ-RHYQMDGZSA-N 0.000 description 1
- 102100040847 Protein mono-ADP-ribosyltransferase PARP10 Human genes 0.000 description 1
- 102100031422 Ras-related protein Rap-2c Human genes 0.000 description 1
- SMIDBHKWSYUBRZ-ACZMJKKPSA-N Ser-Glu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O SMIDBHKWSYUBRZ-ACZMJKKPSA-N 0.000 description 1
- UQFYNFTYDHUIMI-WHFBIAKZSA-N Ser-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CO UQFYNFTYDHUIMI-WHFBIAKZSA-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
- 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
- PMTWIUBUQRGCSB-FXQIFTODSA-N Ser-Val-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O PMTWIUBUQRGCSB-FXQIFTODSA-N 0.000 description 1
- 102100022571 T cell receptor gamma constant 2 Human genes 0.000 description 1
- KCRQEJSKXAIULJ-FJXKBIBVSA-N Thr-Gly-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O KCRQEJSKXAIULJ-FJXKBIBVSA-N 0.000 description 1
- JKGGPMOUIAAJAA-YEPSODPASA-N Thr-Gly-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O JKGGPMOUIAAJAA-YEPSODPASA-N 0.000 description 1
- NQQMWWVVGIXUOX-SVSWQMSJSA-N Thr-Ser-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NQQMWWVVGIXUOX-SVSWQMSJSA-N 0.000 description 1
- RVMNUBQWPVOUKH-HEIBUPTGSA-N Thr-Ser-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RVMNUBQWPVOUKH-HEIBUPTGSA-N 0.000 description 1
- BTAJAOWZCWOHBU-HSHDSVGOSA-N Thr-Val-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)[C@@H](C)O)C(C)C)C(O)=O)=CNC2=C1 BTAJAOWZCWOHBU-HSHDSVGOSA-N 0.000 description 1
- BPGDJSUFQKWUBK-KJEVXHAQSA-N Thr-Val-Tyr Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BPGDJSUFQKWUBK-KJEVXHAQSA-N 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- FNOQJVHFVLVMOS-AAEUAGOBSA-N Trp-Gly-Asn Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N FNOQJVHFVLVMOS-AAEUAGOBSA-N 0.000 description 1
- FFWCYWZIVFIUDM-OYDLWJJNSA-N Trp-Val-Trp Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O FFWCYWZIVFIUDM-OYDLWJJNSA-N 0.000 description 1
- CTDPLKMBVALCGN-JSGCOSHPSA-N Tyr-Gly-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O CTDPLKMBVALCGN-JSGCOSHPSA-N 0.000 description 1
- WVGKPKDWYQXWLU-BZSNNMDCSA-N Tyr-His-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CCCCN)C(=O)O)N)O WVGKPKDWYQXWLU-BZSNNMDCSA-N 0.000 description 1
- WDGDKHLSDIOXQC-ACRUOGEOSA-N Tyr-Leu-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 WDGDKHLSDIOXQC-ACRUOGEOSA-N 0.000 description 1
- SCZJKZLFSSPJDP-ACRUOGEOSA-N Tyr-Phe-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O SCZJKZLFSSPJDP-ACRUOGEOSA-N 0.000 description 1
- TYFLVOUZHQUBGM-IHRRRGAJSA-N Tyr-Ser-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 TYFLVOUZHQUBGM-IHRRRGAJSA-N 0.000 description 1
- ASQFIHTXXMFENG-XPUUQOCRSA-N Val-Ala-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O ASQFIHTXXMFENG-XPUUQOCRSA-N 0.000 description 1
- KKHRWGYHBZORMQ-NHCYSSNCSA-N Val-Arg-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKHRWGYHBZORMQ-NHCYSSNCSA-N 0.000 description 1
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 1
- VXCAZHCVDBQMTP-NRPADANISA-N Val-Cys-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N VXCAZHCVDBQMTP-NRPADANISA-N 0.000 description 1
- PIFJAFRUVWZRKR-QMMMGPOBSA-N Val-Gly-Gly Chemical compound CC(C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O PIFJAFRUVWZRKR-QMMMGPOBSA-N 0.000 description 1
- OFTXTCGQJXTNQS-XGEHTFHBSA-N Val-Thr-Ser Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](C(C)C)N)O OFTXTCGQJXTNQS-XGEHTFHBSA-N 0.000 description 1
- HTONZBWRYUKUKC-RCWTZXSCSA-N Val-Thr-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O HTONZBWRYUKUKC-RCWTZXSCSA-N 0.000 description 1
- GUIYPEKUEMQBIK-JSGCOSHPSA-N Val-Tyr-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCC(O)=O GUIYPEKUEMQBIK-JSGCOSHPSA-N 0.000 description 1
- PGBMPFKFKXYROZ-UFYCRDLUSA-N Val-Tyr-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)O)N PGBMPFKFKXYROZ-UFYCRDLUSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000006978 adaptation Effects 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
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 108010009111 arginyl-glycyl-glutamic acid Proteins 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- 108010068265 aspartyltyrosine Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 108010004073 cysteinylcysteine Proteins 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000005002 female reproductive tract Anatomy 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010049041 glutamylalanine Proteins 0.000 description 1
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 1
- 108010089804 glycyl-threonine Proteins 0.000 description 1
- 108010081551 glycylphenylalanine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 1
- 238000002843 lactate dehydrogenase assay Methods 0.000 description 1
- 108010057821 leucylproline Proteins 0.000 description 1
- 108010012058 leucyltyrosine Proteins 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 108700004896 tripeptide FEG Proteins 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2302—Interleukin-2 (IL-2)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明提供了一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的CTL细胞及其应用，属于肿瘤治疗技术领域。本发明中所述输卵管癌靶标抗原的氨基酸序列如SEQ ID No.16所示；本发明所述的输卵管癌靶标抗原是基于患者肿瘤组织的全外显子检测结果，通过预测分析、筛选获得的有效的肿瘤抗原，利用所述输卵管癌靶标抗原培养获得的CTL细胞，对肿瘤具有特异性的杀伤作用；本发明提供的输卵管癌靶标抗原可以应用于输卵管癌的治疗。
Description
本申请是申请日为2020年03月18日、申请号为202010190785.9、发明名称为《一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的CTL细胞及其应用》的分案申请。
技术领域
本发明属于肿瘤治疗技术领域，尤其涉及一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的CTL细胞及其应用。
背景技术
原发性输卵管癌是一种少见的女性生殖道恶性肿瘤。其发病率占妇科恶性肿瘤的0.5％。以40～65岁居多，多发生于绝经后妇女。目前对于输卵管癌的治疗原则是以手术为主，辅助放疗、化疗的综合治疗。
随着精准治疗的推广，常规的化疗、放疗和靶向已无法满足肿瘤的个性化和多变性，因此，寻找个性化的肿瘤新抗原，培养识别个性化肿瘤新抗原的CTL，将是彻底清除肿瘤的有效方法。
发明内容
有鉴于此，本发明的目的在于提供一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的CTL细胞及其应用；本发明提供的输卵管癌靶标抗原组合是基于患者肿瘤组织的全外显子检测结果，通过预测分析、筛选获得的有效的肿瘤抗原，利用所述输卵管癌靶标抗原组合培养获得的CTL细胞，对肿瘤具有特异性的杀伤作用；本发明提供的输卵管癌靶标抗原特异性针对同一种HLA类型的输卵管癌，实现个性化治疗。
本发明提供了一种输卵管癌靶标抗原组合，包括氨基酸序列如SEQ ID No.7、SEQID No.8、SEQ ID No.9、SEQ ID No.16、SEQ ID No.23、SEQ ID No.31和SEQ ID No.45所示的抗原中的一种或几种。
本发明提供了所述的输卵管癌靶标抗原组合在制备治疗输卵管癌的药物中的应用。
本发明提供了所述的输卵管癌靶标抗原组合在制备治疗输卵管癌的CTL细胞中的应用。
本发明提供了一种CTL细胞，所述CTL细胞为所述的输卵管癌靶标抗原组合刺激培养的CTL细胞。
本发明提供了所述的CTL细胞的制备方法，包括以下步骤：
1)将CTL细胞浓度调整至2～3×105cells/mL；
2)将调整细胞浓度后的CTL细胞、IL-2和所述的输卵管癌靶标抗原组合混合获得培养体系；
3)将所述培养体系进行培养获得输卵管癌靶标抗原组合刺激培养的CTL细胞。
优选的，IL-2在培养体系中的终浓度为150～250U/mL。
优选的，所述的输卵管癌靶标抗原组合中每一种输卵管癌靶标抗原在培养体系中的终浓度为40～60ng/mL。
优选的，步骤3)中所述培养的温度为36～38℃，所述培养的时间为22～26h。
优选的，步骤1)中所述的CTL细胞是通过PBMC细胞与APC细胞共培养获得。
本发明提供了所述的CTL细胞在制备治疗输卵管癌药物中的应用。
本发明的有益效果：本发明提供的输卵管癌靶标抗原组合是基于患者肿瘤组织的全外显子测序结果，通过预测分析、筛选获得的有效的肿瘤抗原，利用所述输卵管癌靶标抗原组合刺激培养获得的CTL细胞，对肿瘤具有特异性的杀伤作用；对所述CTL细胞培养后，流式分析细胞表型，结果显示NKT(CD56+CD3+)比例为29.31％，CD8+T细胞的比例为50.93％。
附图说明
图1为输卵管癌靶标抗原1～26号筛选结果；
图2为输卵管癌靶标抗原27～50号筛选结果
图3为输卵管癌靶标抗原组合9号和16号刺激培养的CTL对负载抗原多肽的靶细胞和只负载HLA的靶细胞的杀伤效率对比；
图4为输卵管癌靶标抗原组合31号和45号刺激培养的CTL对负载抗原多肽的靶细胞和只负载HLA的靶细胞的杀伤效率对比；
图5为输卵管癌靶标抗原组合7号、8号和23号刺激培养的CTL对负载抗原多肽的靶细胞和只负载HLA的靶细胞的杀伤效率对比；
图6为输卵管癌靶标抗原组合刺激培养的CTL流式分析细胞表型结果。
具体实施方式
本发明提供了一种输卵管癌靶标抗原组合，包括氨基酸序列如SEQ ID No.7、SEQID No.8、SEQ ID No.9、SEQ ID No.16、SEQ ID No.23、SEQ ID No.31和SEQ ID No.45所示的抗原中的一种或几种；具体如下所示：
| 多肽编号 | HLA Allele | MT Epitope Seq | |
| 7 | NDUFS1 | HLA-B*15:01 | RLSVAGNCRMY(SEQ ID No.7) |
| 8 | C17orf97 | HLA-B*15:01 | RYQCLALKGF(SEQ ID No.8) |
| 9 | RAP2C | HLA-A*26:01 | YHKEIEVD(SEQ ID No.9) |
| 16 | PARP10 | HLA-A*26:01 | TVYGTGVYF(SEQ ID No.16) |
| 23 | C17orf97 | HLA-B*15:01 | QCLALKGF(SEQ ID No.23) |
| 31 | GPNMB | HLA-A*02:01 | VDVEEMCLLTV(SEQ ID No.31) |
| 45 | TRGC2 | HLA-A*02:01 | LLGRTAFC(SEQ ID No.45) |
在本发明中，所述输卵管癌靶标抗原组合优选的通过对患者肿瘤组织进行全外显子测序，通过分析测序结果、筛选获得的有效的肿瘤抗原。本发明对所述外显子测序的方法没有特殊限定，采用本领域常规的外显子测序方法即可。本发明在获得所述外显子测序的结果后，优选的采用肿瘤新抗原分析技术对外显子测序结果进行分析，在本发明中，所述分析优选的采用ImmunoMining肿瘤个体化新抗原分析预测软件进行，所述软件著作权的登记号:2019SR0130720。
本发明提供了所述的输卵管癌靶标抗原组合在制备治疗输卵管癌的药物中的应用。在本发明中，所述输卵管癌靶标抗原组合通过刺激培养CTL细胞实现对输卵管癌的治疗。
本发明还提供了所述的输卵管癌靶标抗原组合在制备治疗输卵管癌的CTL细胞中的应用。在本发明中，利用所述输卵管癌靶标抗原组合刺激培养CTL细胞，使获得的CTL细胞对于负载所述输卵管癌靶标抗原组合的细胞具有特异性的杀伤作用。
本发明提供了一种CTL细胞，所述CTL细胞为所述的输卵管癌靶标抗原组合刺激培养的CTL细胞。
本发明还提供了所述的CTL细胞的制备方法，包括以下步骤：1)将CTL细胞浓度调整至2～3×105cells/mL；2)将调整细胞浓度后的CTL细胞、IL-2和所述的输卵管癌靶标抗原组合混合获得培养体系；3)将所述培养体系进行培养获得输卵管癌靶标抗原组合刺激培养的CTL细胞。
在本发明中，所述CTL细胞优选的是通过PBMC细胞与APC细胞共培养获得。在本发明中，所述APC细胞的培养步骤优选的如下：将PBMC细胞复苏培养后，以输卵管癌靶标抗原溶液重悬培养获得。在本发明中，所述复苏培养的培养基优选为1640+10％(v/v)FBS；所述复苏培养的时间优选为22～26h，更优选为24h；所述复苏培养的温度优选为37℃，所述复苏培养的环境二氧化碳浓度优选为5％；所述复苏培养前PBMC细胞的浓度优选为1×106cells/mL；所述复苏培养前PBMC细胞的浓度优选的通过以复苏培养基稀释调整。本发明在所述复苏培养后，优选的进行离心收集细胞，所述离心的转速优选为1400～1600rpm，更优选为1500rpm，所述离心的时间优选为4～6min，更优选为5min。
在本发明中，所述输卵管癌靶标抗原溶液优选的包括以下组分：1640+10％FBS+150～250U/mL IL-2+1500～1700U/mL GM-CSF+40～60ng/mL输卵管癌靶标抗原(每一种输卵管癌靶标抗原的浓度)，更优选为1640+10％FBS+200U/mL IL-2+1600U/mL GM-CSF+50ng/mL输卵管癌靶标抗原。在本发明中，所述IL-2为细胞生长因子，能使T细胞长期存活，刺激T细胞进人细胞分裂周期；所述GM-CSF在体外可刺激中性粒细胞和巨噬细胞的集落形成；本发明对所述IL-2和GM-CSF的来源没有特殊限定，采用本领域常规的IL-2和GM-CSF即可。
在本发明中，以所述输卵管癌靶标抗原溶液重悬上述离心收集的细胞进行重悬培养。在本发明中，重悬后的细胞密度优选为1×106cells/mL，所述重悬培养的时间优选为22～26h，更优选为24h；所述重悬培养的温度优选为37℃，所述复苏培养的环境二氧化碳浓度优选为5％。本发明在所述重悬培养后获得APC细胞。
在本发明中，将上述培养获得的APC细胞和PBMC细胞共培养获得CTL细胞。在本发明中，所述APC细胞和PBMC细胞的数量比例优选为1:(90～110)，更优选为1:100。在本发明中，所述共培养的时间优选为20～22d，更优选为21d。在本发明中，当共培养48h后，每天向所述共培养体系中添加IL-2，使所述IL-2的终浓度为400～600U/mL，更优选为500U/mL。
本发明在获得所述CTL细胞后，将所述CTL细胞浓度调整至2～3×105cells/mL，更优选为2.5×105cells/mL。
在本发明中，将调整细胞浓度后的CTL细胞、IL-2和所述的输卵管癌靶标抗原组合混合获得培养体系。在本发明中，IL-2在培养体系中的终浓度优选为150～250U/mL，更优选为200U/mL；所述的输卵管癌靶标抗原组合中每一种输卵管癌靶标抗原在培养体系中的终浓度优选为40～60ng/mL，更优选为50ng/mL。
在本发明中，将所述培养体系进行培养获得输卵管癌靶标抗原组合刺激培养的CTL细胞。在本发明中，所述培养的温度优选为36～38℃，更优选为37℃，所述培养的时间优选为22～26h，更优选为24h。本发明在所述培养后，优选的收集所述输卵管癌靶标抗原组合刺激培养的CTL细胞；所述收集优选的采用离心的方法，所述离心的转速优选为1000～1500rpm，所述离心的时间优选为5～10min。
本发明提供了所述的CTL细胞在制备治疗输卵管癌药物中的应用。在本发明中，所述CTL细胞能够特异性杀伤肿瘤细胞，对负载所述输卵管癌靶标抗原组合的肿瘤细胞的杀伤力远远大于未负载所述输卵管癌靶标抗原的肿瘤细胞。本发明对所述药物的剂型没有特殊限定，采用本领域常规的细胞药物剂型即可。
下面结合实施例对本发明提供的技术方案进行详细的说明，但是不能把它们理解为对本发明保护范围的限定。
实施例1
肿瘤组织的全外显子测序结果，采用ImmunoMining肿瘤个体化新抗原分析预测软件进行肿瘤新抗原分析，所述软件著作权的登记号:2019SR0130720。鼎成肽源生物信息技术有限公司，获得50条预测抗原；对预测的50条抗原进行合成(由南京金斯瑞多肽合成部合成)。
表1多肽序列及对应编号
1.共培养制备APC：
1)复苏冻存PBMC(2.5×107cells)，以1640+10％FBS稀释冻存液，1500rpm离心5min，以10mL 1640+10％FBS重悬，1×106cells/mL，37℃、5％CO2复苏培养24h；
2)分别配制抗原多肽溶液，1640+10％FBS+200U/mL IL-2+1600U/mL GM-CSF，每一种抗原多肽的终浓度为50ng/mL，混匀后备用；
3)1500rpm离心5min，离心收集细胞，以多肽溶液重悬细胞，密度调整至1×106cells/mL；
4)37℃、5％CO2培养24h后，细胞为APC，轻轻吹打细胞混匀备用。
2.共培养
1)离心收集PBMC，1640+10％FBS重悬，计数调整至1×106cells/mL；
2)按照PBMC：APC数量比为100:1的比例加入APC，混匀，记为Day 0；
3)37℃、5％CO2培养48h后，每天按照总体积补加IL-2，确保IL-2的终浓度为200U/mL；
4)培养至Day 21时，收集细胞即为CTL；
3.肿瘤新抗原的筛选：
1)收集上述培养获得的CTL细胞，以1640+10％FBS重悬，计数调整至2×106cells/mL；
2)10mL CTL细胞+10mL 1640+10％FBS将细胞调整至1×106cells/mL，再加入8μL500U/μL IL-2，IL-2终浓度为200U/mL，再分至96孔板中(平底)，200μL/孔；
3)每孔加入不同的抗原，即上述1～50号抗原，体积为5μL，浓度为2μg/mL多肽；设置阳性对照OKT3 167 ng/mL、medium对照和CTL；
4)37℃5％CO2培养24h后，1500rpm离心10min，转移170μL上清至新的96孔板中；
5)为避免吸到细胞，再将步骤6)中新的96孔板进行1500rpm离心10min，转移110μL上清至新的96孔板；
6)以R&D ELISA试剂盒检测细胞上清中IFN-γ的释放量，以此来进行抗原的筛选。
筛选结果如图1和图2所示，IFN-γ的释放水平超过对照的，认为是有效的新抗原，其中7号、8号、9号、16号、23号、31号和45号多肽为筛选获得的有效的新的输卵管癌特异性抗原。
4.靶细胞的构建
1)通过人工合成的方法，进行HLA-A2601基因、HLA-A0201基因和HLA-B1501基因的合成(委托金维智生物科技有限公司)，分别将合成的HLA-A2601基因、HLA-A0201基因和HLA-B1501基因构建到pCDH表达载体上NheⅠ和Bam HⅠ酶切位点之间。
HLA-A2601(SEQ ID No.51)：
atggccgtcatggcgccccgaaccctcgtcctgctactctcgggggccctggccctgacccagacctgggcgggctcccactccatgaggtatttctacacctccgtgtcccggcccggccgcggggagccccgcttcatcgccgtgggctacgtggacgacacgcagttcgtgcggttcgacagcgacgccgcgagccagaggatggagccgcgggcgccgtggatagagcaggaggggccggagtattgggaccggaacacacggaatgtgaaggcccactcacagactgaccgagcgaacctggggaccctgcgcggctactacaaccagagcgaggacggttctcacaccatccagaggatgtatggctgcgacgtggggccggacgggcgcttcctccgcgggtaccagcaggacgcttacgacggcaaggattacatcgccctgaacgaggacctgcgctcttggaccgcggcggacatggcggctcagatcacccagcgcaagtgggagacggcccatgaggcggagcagtggagagcctacctggagggccggtgcgtggagtggctccgcagatacctggagaacgggaaggagacgctgcagcgcacggacgcccccaagacgcatatgactcaccacgctgtctctgaccatgaggccaccctgaggtgctgggccctgagcttctaccctgcggagatcacactgacctggcagcgggatggggaggaccagacccaggacacggagctcgtggagaccaggcctgcaggggatgggaccttccagaagtgggcgtctgtggtggtgccttctggacaggagcagagatacacctgccatgtgcagcatgagggtctgcccaagcccctcaccctgagatgggagccgtcttcccagcccaccatccccatcgtgggcatcattgctggcctggttctctttggagctgtgatcgctggagctgtggtcgctgctgtgatgtggaggaggaagagctcagatagaaaaggagggagctactctcaggctgcaagcagtgacagtgcccagggctctgatatgtctctcacagcttgtaaagtgtga
HLA-A0201(SEQ ID No.52)：
atggccgtcatggcgccccgaaccctcgtcctgctactctcgggggctctggccctgacccagacctgggcgggctctcactccatgaggtatttcttcacatccgtgtcccggcccggccgcggggagccccgcttcatcgcagtgggctacgtggacgacacgcagttcgtgcggttcgacagcgacgccgcgagccagaggatggagccgcgggcgccgtggatagagcaggagggtccggagtattgggacggggagacacggaaagtgaaggcccactcacagactcaccgagtggacctggggaccctgcgcggctactacaaccagagcgaggccggttctcacaccgtccagaggatgtatggctgcgacgtggggtcggactggcgcttcctccgcgggtaccaccagtacgcctacgacggcaaggattacatcgccctgaaagaggacctgcgctcttggaccgcggcggacatggcagctcagaccaccaagcacaagtgggaggcggcccatgtggcggagcagttgagagcctacctggagggcacgtgcgtggagtggctccgcagatacctggagaacgggaaggagacgctgcagcgcacggacgcccccaaaacgcatatgactcaccacgctgtctctgaccatgaagccaccctgaggtgctgggccctgagcttctaccctgcggagatcacactgacctggcagcgggatggggaggaccagacccaggacacggagctcgtggagaccaggcctgcaggggatggaaccttccagaagtgggcggctgtggtggtgccttctggacaggagcagagatacacctgccatgtgcagcatgagggtttgcccaagcccctcaccctgagatgggagccgtcttcccagcccaccatccccatcgtgggcatcattgctggcctggttctctttggagctgtgatcactggagctgtggtcgctgctgtgatgtggaggaggaagagctcagatagaaaaggagggagctactctcaggctgcaagcagtgacagtgcccagggctctgatgtgtctctcacagcttgtaaagtgtga
HLA-B1501(SEQ ID No.53)：
atgcgggtcacggcgccccgaaccgtcctcctgctgctctcgggagccctggccctgaccgagacctgggccggctcccactccatgaggtatttctacaccgccatgtcccggcccggccgcggggagccccgcttcatcgcagtgggctacgtggacgacacccagttcgtgaggttcgacagcgacgccgcgagtccgaggatggcgccccgggcgccatggatagagcaggaggggccggagtattgggaccgggagacacagatctccaagaccaacacacagacttaccgagagagcctgcggaacctgcgcggctactacaaccagagcgaggccgggtctcacaccctccagaggatgtacggctgcgacgtggggccggacgggcgcctcctccgcgggcatgaccagtccgcctacgacggcaaggattacatcgccctgaacgaggacctgagctcctggaccgcggcggacacggcggctcagatcacccagcgcaagtgggaggcggcccgtgaggcggagcagtggagagcctacctggagggcctgtgcgtggagtggctccgcagatacctggagaacgggaaggagacgctgcagcgcgcggaccccccaaagacacatgtgacccaccaccccatctctgaccatgaggccaccctgaggtgctgggccctgggcttctaccctgcggagatcacactgacctggcagcgggatggcgaggaccaaactcaggacaccgagcttgtggagaccagaccagcaggagatagaaccttccagaagtgggcagctgtggtggtgccttctggagaagagcagagatacacatgccatgtacagcatgaggggctgccgaagcccctcaccctgagatgggagccatcttcccagtccaccatccccatcgtgggcattgttgctggcctggctgtcctagcagttgtggtcatcggagctgtggtcgctactgtgatgtgtaggaggaagagctcaggtggaaaaggagggagctactctcaggctgcgtccagcgacagtgcccagggctctgatgtgtctctcacagcttga
将上述得到的重组质粒转化感受态细胞，挑取单克隆，进行测序，选择测序结果正确的克隆，进行后续实验；
2)以天根质粒大提试剂盒(购自于天根生化科技(北京)有限公司)进行质粒的提取，方法按照厂家说明书操作。
3)慢病毒包装：复苏293T细胞，传两代后用于慢病毒包装；细胞转染：(T175培养瓶)细胞密度为2×107个/瓶；取一支15mL离心管(标记为A)，将包装质粒4K(17μg)、6K(34μg)和目的质粒(51μg)加入1mLjetPRIME配套的Buffer中，轻轻地混匀。将jetPRIME(标记为B)缓慢滴加入A离心管中，加入同时匀速晃动A管，得到C溶液，之后静置10min；将T175中旧的培养基倒出，将18mL DMEM(不含抗生素和血清)加入C中，加入T175培养瓶中，置于37℃，5％CO2培养箱中培养。转染4～6h后，吸去含有转染复合物的培养基，更换为37℃预热的新鲜培养基。培养48h和72h并收集。
4)慢病毒转染3T3细胞：使用DMEM配制含有7％FBS的全细胞培养基，记为DMEM。使用DMEM把3T3细胞浓度调整到5×105/mL，加入6孔板，每孔1mL，37℃培养箱孵育过夜。弃去6孔板中DMEM培养基，使用1mLAIM-V-P混匀病毒液加入对应各孔中。培养3天后转入T75培养瓶中，加入嘌呤霉素进行筛选；筛选6天后，得到稳定表达HLA-A2601、HLA-A0201和HLA-B1501的3T3细胞，标记为3T3-HLA；
5.杀伤实验——LDH法
1)收集靶细胞3T3和3T3-HLA，1000rpm离心5min；
2)以PBS洗一遍，1000rpm离心5min；
3)加入抗原溶液，9号和16号抗原为一组；31号和45号为一组，7号、8号和23号为一组，每组中每种抗原浓度为50ng/mL，体积为3mL，进行有效新抗原组合的负载，37℃负载4h；
4)1000rpm离心5min，除去多余溶液，并以PBS洗2次；
5)以1640+2％FBS重悬后，计数调整至8×104cells/mL，分至96孔板中(U型底)，50μL/孔，备用；
6)收集CTL细胞，1000rpm离心5min；
7)以PBS洗一遍，1000rpm离心5min；
8)以1640+2％FBS重悬细胞计数后，分至96孔板中(U型底)，50μL/孔，设置效靶比(CTL：3T3-HLA或CTL：3T3-HLA负载抗原组合)为40:1、20:1、10:1、5:1、2.5:1和1.25:1；37℃5％CO2共孵育20h后，进行LDH检测，LDH检测的试剂盒为Cytotoxicity LDH Assay
厂家：Dojindo货号为CK12。
结果如图3、图4和图5所示，经过抗原刺激培养的CTL，对负载抗原多肽的靶细胞比只负载HLA的靶细胞具有更高的杀伤效率，说明，培养的CTL，可以识别此抗原，且具有特异的杀伤作用，可以作为输卵管癌治疗的首选抗原。
6.流式分型
1)收集CTL，1000rpm离心5min；
2)1×106cells/管，加入CD3、CD4、CD8和CD56的抗体，室温避光30min；
3)PBS洗两次，1000rpm离心5min；
4)PBS重悬，上机检测。
以筛选到有效新抗原，进行CTL的培养，流式分析细胞表型，结果如图6所示，NKT(CD56+CD3+)比例为29.31％，50.93％为CD8+T细胞；NK会产生非特异性的杀伤，NK比例低说明非特异性的杀伤小，特异性杀伤作用显著。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
序列表
<110> 北京鼎成肽源生物技术有限公司
<120> 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的CTL细胞及其应用
<160> 53
<170> SIPOSequenceListing 1.0
<210> 1
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
Ala Leu Ala Arg Ala Val Ser Ala Val
1 5
<210> 2
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 2
Glu Lys Ser Glu Ala Gly Leu Ala Gly Ala Leu
1 5 10
<210> 3
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 3
Gly Leu Ala Gly Ala Leu Ala Arg Ala Val
1 5 10
<210> 4
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 4
Gly Ala Leu Ala Arg Ala Val Ser Ala Val
1 5 10
<210> 5
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 5
Leu Ala Arg Ala Val Ser Ala Val Lys Asn Met
1 5 10
<210> 6
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 6
Ser Val Ala Gly Asn Cys Arg Met Tyr
1 5
<210> 7
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 7
Arg Leu Ser Val Ala Gly Asn Cys Arg Met Tyr
1 5 10
<210> 8
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 8
Arg Tyr Gln Cys Leu Ala Leu Lys Gly Phe
1 5 10
<210> 9
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 9
Tyr His Lys Glu Ile Glu Val Asp
1 5
<210> 10
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 10
Asn Leu His Asp Tyr Gly Val Arg Glu Leu
1 5 10
<210> 11
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 11
Leu Asp Asn Asn Asn Leu His Asp Tyr Gly Val
1 5 10
<210> 12
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 12
Lys Asn Leu Tyr Phe Leu Leu Ile Gln Ile
1 5 10
<210> 13
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 13
Thr Val Trp Gly Asn Met Leu Ile Val Val
1 5 10
<210> 14
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 14
Val Thr Val Trp Gly Asn Met Leu Ile Val
1 5 10
<210> 15
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 15
Asn Ala Thr Val Tyr Gly Thr Gly Val Tyr
1 5 10
<210> 16
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 16
Thr Val Tyr Gly Thr Gly Val Tyr Phe
1 5
<210> 17
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 17
Ile Arg Ser Pro Gln Thr His Ile Leu Leu Val
1 5 10
<210> 18
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 18
Thr Ser Ile Arg Ser Pro Gln Thr His Ile Leu
1 5 10
<210> 19
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 19
Gln Thr His Ile Leu Leu Val Gly Gly
1 5
<210> 20
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 20
Asp Leu Phe Glu Gly Ser Asn Glu Gly Ser Leu
1 5 10
<210> 21
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 21
Trp Glu Met Ser Ser Leu Phe Arg Glu Leu
1 5 10
<210> 22
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 22
Tyr Ser Val Ile Arg Gly Glu Val
1 5
<210> 23
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 23
Gln Cys Leu Ala Leu Lys Gly Phe
1 5
<210> 24
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 24
Phe Ser Leu Pro Glu Glu Tyr Val
1 5
<210> 25
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 25
His Arg Ile Pro Cys Arg Asp Met Ser Pro
1 5 10
<210> 26
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 26
Asp Met Ser Pro Thr Leu Ile Arg Thr
1 5
<210> 27
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 27
Trp Val Trp Val Thr Ser Thr Gly Arg
1 5
<210> 28
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 28
Glu Ala Gly Leu Ala Gly Ala Leu
1 5
<210> 29
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 29
Leu Ala Arg Ala Val Ser Ala Val Lys Asn Met
1 5 10
<210> 30
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 30
Ser Glu Ala Gly Leu Ala Gly Ala Leu
1 5
<210> 31
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 31
Val Asp Val Glu Glu Met Cys Leu Leu Thr Val
1 5 10
<210> 32
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 32
Phe Val Asn Met Trp Ile Glu Arg Thr Ile Tyr
1 5 10
<210> 33
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 33
Gly Thr Gly Pro Pro Gly Gly Ala Leu Tyr
1 5 10
<210> 34
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 34
Ile Arg Ser Pro Gln Thr His Ile Leu
1 5
<210> 35
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 35
Cys Gln Pro Ala Cys Cys Met Pro Val Ser
1 5 10
<210> 36
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 36
Val Cys Gln Pro Ala Cys Cys Met Pro
1 5
<210> 37
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 37
Leu Ser Val Ala Gly Asn Cys Arg Met Tyr
1 5 10
<210> 38
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 38
Leu His Asp Tyr Gly Val Arg Glu Leu
1 5
<210> 39
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 39
Thr Val Trp Gly Asn Met Leu Ile Val
1 5
<210> 40
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 40
Ser Leu Ser Ser Gly Ser Ser Gly Ala
1 5
<210> 41
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 41
Ala Arg Ala Pro Val Ala Ala Ile Ile
1 5
<210> 42
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 42
Gly Gly Ser Ala Leu Phe Ser Glu Tyr
1 5
<210> 43
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 43
Asp His Glu Glu Asn Val Ala Leu Glu
1 5
<210> 44
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 44
Gln Asp His Glu Glu Asn Val Ala Leu Glu Ala
1 5 10
<210> 45
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 45
Leu Leu Gly Arg Thr Ala Phe Cys
1 5
<210> 46
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 46
Leu Val Trp Glu Met Ser Ser Leu Phe
1 5
<210> 47
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 47
Trp Glu Met Ser Ser Leu Phe Arg Glu Leu
1 5 10
<210> 48
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 48
Arg Thr Tyr Arg Tyr Phe Tyr Leu Phe Ile
1 5 10
<210> 49
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 49
Thr Ser Thr Gln Ala Ser Pro Asp Gln Leu Leu
1 5 10
<210> 50
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 50
Leu Tyr Thr Trp Glu Met Phe Gln Asp Pro Val
1 5 10
<210> 51
<211> 1098
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 51
atggccgtca tggcgccccg aaccctcgtc ctgctactct cgggggccct ggccctgacc 60
cagacctggg cgggctccca ctccatgagg tatttctaca cctccgtgtc ccggcccggc 120
cgcggggagc cccgcttcat cgccgtgggc tacgtggacg acacgcagtt cgtgcggttc 180
gacagcgacg ccgcgagcca gaggatggag ccgcgggcgc cgtggataga gcaggagggg 240
ccggagtatt gggaccggaa cacacggaat gtgaaggccc actcacagac tgaccgagcg 300
aacctgggga ccctgcgcgg ctactacaac cagagcgagg acggttctca caccatccag 360
aggatgtatg gctgcgacgt ggggccggac gggcgcttcc tccgcgggta ccagcaggac 420
gcttacgacg gcaaggatta catcgccctg aacgaggacc tgcgctcttg gaccgcggcg 480
gacatggcgg ctcagatcac ccagcgcaag tgggagacgg cccatgaggc ggagcagtgg 540
agagcctacc tggagggccg gtgcgtggag tggctccgca gatacctgga gaacgggaag 600
gagacgctgc agcgcacgga cgcccccaag acgcatatga ctcaccacgc tgtctctgac 660
catgaggcca ccctgaggtg ctgggccctg agcttctacc ctgcggagat cacactgacc 720
tggcagcggg atggggagga ccagacccag gacacggagc tcgtggagac caggcctgca 780
ggggatggga ccttccagaa gtgggcgtct gtggtggtgc cttctggaca ggagcagaga 840
tacacctgcc atgtgcagca tgagggtctg cccaagcccc tcaccctgag atgggagccg 900
tcttcccagc ccaccatccc catcgtgggc atcattgctg gcctggttct ctttggagct 960
gtgatcgctg gagctgtggt cgctgctgtg atgtggagga ggaagagctc agatagaaaa 1020
ggagggagct actctcaggc tgcaagcagt gacagtgccc agggctctga tatgtctctc 1080
acagcttgta aagtgtga 1098
<210> 52
<211> 1098
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 52
atggccgtca tggcgccccg aaccctcgtc ctgctactct cgggggctct ggccctgacc 60
cagacctggg cgggctctca ctccatgagg tatttcttca catccgtgtc ccggcccggc 120
cgcggggagc cccgcttcat cgcagtgggc tacgtggacg acacgcagtt cgtgcggttc 180
gacagcgacg ccgcgagcca gaggatggag ccgcgggcgc cgtggataga gcaggagggt 240
ccggagtatt gggacgggga gacacggaaa gtgaaggccc actcacagac tcaccgagtg 300
gacctgggga ccctgcgcgg ctactacaac cagagcgagg ccggttctca caccgtccag 360
aggatgtatg gctgcgacgt ggggtcggac tggcgcttcc tccgcgggta ccaccagtac 420
gcctacgacg gcaaggatta catcgccctg aaagaggacc tgcgctcttg gaccgcggcg 480
gacatggcag ctcagaccac caagcacaag tgggaggcgg cccatgtggc ggagcagttg 540
agagcctacc tggagggcac gtgcgtggag tggctccgca gatacctgga gaacgggaag 600
gagacgctgc agcgcacgga cgcccccaaa acgcatatga ctcaccacgc tgtctctgac 660
catgaagcca ccctgaggtg ctgggccctg agcttctacc ctgcggagat cacactgacc 720
tggcagcggg atggggagga ccagacccag gacacggagc tcgtggagac caggcctgca 780
ggggatggaa ccttccagaa gtgggcggct gtggtggtgc cttctggaca ggagcagaga 840
tacacctgcc atgtgcagca tgagggtttg cccaagcccc tcaccctgag atgggagccg 900
tcttcccagc ccaccatccc catcgtgggc atcattgctg gcctggttct ctttggagct 960
gtgatcactg gagctgtggt cgctgctgtg atgtggagga ggaagagctc agatagaaaa 1020
ggagggagct actctcaggc tgcaagcagt gacagtgccc agggctctga tgtgtctctc 1080
acagcttgta aagtgtga 1098
<210> 53
<211> 1089
<212> DNA
<213> 人工序列(Artificial Sequence)
<400> 53
atgcgggtca cggcgccccg aaccgtcctc ctgctgctct cgggagccct ggccctgacc 60
gagacctggg ccggctccca ctccatgagg tatttctaca ccgccatgtc ccggcccggc 120
cgcggggagc cccgcttcat cgcagtgggc tacgtggacg acacccagtt cgtgaggttc 180
gacagcgacg ccgcgagtcc gaggatggcg ccccgggcgc catggataga gcaggagggg 240
ccggagtatt gggaccggga gacacagatc tccaagacca acacacagac ttaccgagag 300
agcctgcgga acctgcgcgg ctactacaac cagagcgagg ccgggtctca caccctccag 360
aggatgtacg gctgcgacgt ggggccggac gggcgcctcc tccgcgggca tgaccagtcc 420
gcctacgacg gcaaggatta catcgccctg aacgaggacc tgagctcctg gaccgcggcg 480
gacacggcgg ctcagatcac ccagcgcaag tgggaggcgg cccgtgaggc ggagcagtgg 540
agagcctacc tggagggcct gtgcgtggag tggctccgca gatacctgga gaacgggaag 600
gagacgctgc agcgcgcgga ccccccaaag acacatgtga cccaccaccc catctctgac 660
catgaggcca ccctgaggtg ctgggccctg ggcttctacc ctgcggagat cacactgacc 720
tggcagcggg atggcgagga ccaaactcag gacaccgagc ttgtggagac cagaccagca 780
ggagatagaa ccttccagaa gtgggcagct gtggtggtgc cttctggaga agagcagaga 840
tacacatgcc atgtacagca tgaggggctg ccgaagcccc tcaccctgag atgggagcca 900
tcttcccagt ccaccatccc catcgtgggc attgttgctg gcctggctgt cctagcagtt 960
gtggtcatcg gagctgtggt cgctactgtg atgtgtagga ggaagagctc aggtggaaaa 1020
ggagggagct actctcaggc tgcgtccagc gacagtgccc agggctctga tgtgtctctc 1080
acagcttga 1089
Claims (2)
1.一种输卵管癌靶标抗原，其特征在于，所述输卵管癌靶标抗原的氨基酸序列如SEQID No.16和SEQ ID No.9所示。
2.权利要求1所述的输卵管癌靶标抗原在制备治疗输卵管癌的药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110906408.5A CN113461797B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110906408.5A CN113461797B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202010190785.9A CN111363008B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的ctl细胞及其应用 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010190785.9A Division CN111363008B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的ctl细胞及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113461797A CN113461797A (zh) | 2021-10-01 |
| CN113461797B true CN113461797B (zh) | 2023-05-09 |
Family
ID=71204667
Family Applications (10)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111572060.7A Active CN114315964B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110909053.5A Pending CN113388024A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202010190785.9A Active CN111363008B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的ctl细胞及其应用 |
| CN202110906411.7A Active CN113429473B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110906408.5A Active CN113461797B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110906413.6A Pending CN113461798A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110906479.5A Pending CN113388022A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202111572058.XA Active CN114249806B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110907920.1A Pending CN113461799A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110909042.7A Pending CN113388023A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
Family Applications Before (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111572060.7A Active CN114315964B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110909053.5A Pending CN113388024A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202010190785.9A Active CN111363008B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原组合刺激培养的ctl细胞及其应用 |
| CN202110906411.7A Active CN113429473B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110906413.6A Pending CN113461798A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110906479.5A Pending CN113388022A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202111572058.XA Active CN114249806B (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原组合、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110907920.1A Pending CN113461799A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
| CN202110909042.7A Pending CN113388023A (zh) | 2020-03-18 | 2020-03-18 | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (10) | CN114315964B (zh) |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070166366A1 (en) * | 2003-05-01 | 2007-07-19 | Jian-Yun Dong | Autologous upregulation mechanism allowing optimized cell type-specific and regulated gene expression cells |
| US9593340B2 (en) * | 2007-10-15 | 2017-03-14 | Admedus Vaccines Pty Ltd. | Expression system for modulating an immune response |
| EP2347769A1 (en) * | 2010-01-20 | 2011-07-27 | Glycotope GmbH | Cancer stem cell markers and uses thereof |
| US20140228423A1 (en) * | 2011-06-01 | 2014-08-14 | Baylor College Of Medicine | Biomarkers and therapy for cancer |
| GB201501017D0 (en) * | 2014-12-23 | 2015-03-04 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against hepatocellular carcinoma (HCC) and other cancers |
| CN104830797A (zh) * | 2015-05-05 | 2015-08-12 | 杨光华 | 基于sp17抗原的dc细胞、靶向性免疫细胞群及其制备方法和用途 |
| HRP20231392T1 (hr) * | 2015-05-15 | 2024-04-26 | The General Hospital Corporation | Antagonistička protutijela na superobitelj receptora za faktor tumorske nekroze |
| EP3297660A2 (en) * | 2015-05-20 | 2018-03-28 | The Broad Institute Inc. | Shared neoantigens |
| CN104926944B (zh) * | 2015-05-22 | 2018-04-13 | 北京康爱瑞浩生物科技股份有限公司空港分公司 | 多靶点复合抗原负载cd8+细胞毒性t淋巴细胞的制备方法及其用途 |
| CN105349488A (zh) * | 2015-12-04 | 2016-02-24 | 深圳源正细胞医疗技术有限公司 | 一种诱导肿瘤特异性t细胞的组合因子及其获得肿瘤特异性t细胞的方法 |
| CN106047817A (zh) * | 2016-07-28 | 2016-10-26 | 深圳爱生再生医学科技有限公司 | Car‑t细胞及其制备方法与应用 |
| CN106589133A (zh) * | 2016-10-21 | 2017-04-26 | 闾军 | 一种新的增强型抗原联合多肽诱导肝癌特异性ctl细胞的制备及应用 |
| CN106432463A (zh) * | 2016-10-28 | 2017-02-22 | 南京麦科林生物医药科技有限公司 | 一种肿瘤特异性抗原tsp70及其应用 |
| CN108567977B (zh) * | 2017-03-13 | 2022-04-12 | 复旦大学 | 一种免疫增强剂、免疫治疗药物组合物及其制备与用途 |
| WO2019114762A1 (zh) * | 2017-12-12 | 2019-06-20 | 科济生物医药（上海）有限公司 | 免疫效应细胞和辐射联用治疗肿瘤 |
| CN110144326A (zh) * | 2018-02-12 | 2019-08-20 | 深圳宾德生物技术有限公司 | 一种靶向性抗肿瘤t细胞及其制备方法和应用 |
| US20190346457A1 (en) * | 2018-03-13 | 2019-11-14 | Government Of The Unted States, As Represented By The Secretary Of The Army | Assays and methods for detection and targeted treatment of hydrosalpinx |
| CN110305220B (zh) * | 2018-03-27 | 2022-10-11 | 孙嘉琳 | 一种癌靶向增强型抗肿瘤融合蛋白及制备方法及用途 |
| CN109294982B (zh) * | 2018-09-30 | 2020-11-06 | 北京鼎成肽源生物技术有限公司 | 一种rff2细胞 |
| CN109824781B (zh) * | 2019-01-21 | 2022-07-19 | 卢英 | 抗人her 2抗原的特异性嵌合抗原受体、编码基因和表达载体以及应用 |
| CN109796535B (zh) * | 2019-01-30 | 2022-11-15 | 重庆福美干细胞生物科技发展有限公司 | 靶向叶酸受体α的嵌合抗原受体及其在制备预防或治疗恶性肿瘤药物中的用途 |
| CN110205298B (zh) * | 2019-06-11 | 2020-05-15 | 焦顺昌 | 一种靶向kras突变的异体抗原递呈细胞、构建方法及肠癌特异性ctl细胞的制备方法 |
| CN110172089B (zh) * | 2019-06-11 | 2020-01-07 | 北京鼎成肽源生物技术有限公司 | 一种kras突变多抗原组合、靶向kras突变肿瘤ctl及其应用 |
| CN110184238A (zh) * | 2019-06-11 | 2019-08-30 | 北京鼎成肽源生物技术有限公司 | 一种靶向kras多发突变肿瘤的特异性ctl细胞的制备方法及应用 |
| CN110551198B (zh) * | 2019-09-27 | 2020-04-21 | 北京鼎成肽源生物技术有限公司 | 一种肺癌抗原组合及其应用、细胞毒性t淋巴细胞 |
-
2020
- 2020-03-18 CN CN202111572060.7A patent/CN114315964B/zh active Active
- 2020-03-18 CN CN202110909053.5A patent/CN113388024A/zh active Pending
- 2020-03-18 CN CN202010190785.9A patent/CN111363008B/zh active Active
- 2020-03-18 CN CN202110906411.7A patent/CN113429473B/zh active Active
- 2020-03-18 CN CN202110906408.5A patent/CN113461797B/zh active Active
- 2020-03-18 CN CN202110906413.6A patent/CN113461798A/zh active Pending
- 2020-03-18 CN CN202110906479.5A patent/CN113388022A/zh active Pending
- 2020-03-18 CN CN202111572058.XA patent/CN114249806B/zh active Active
- 2020-03-18 CN CN202110907920.1A patent/CN113461799A/zh active Pending
- 2020-03-18 CN CN202110909042.7A patent/CN113388023A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN113388024A (zh) | 2021-09-14 |
| CN113388023A (zh) | 2021-09-14 |
| CN114315964A (zh) | 2022-04-12 |
| CN111363008A (zh) | 2020-07-03 |
| CN113429473B (zh) | 2022-11-04 |
| CN113461797A (zh) | 2021-10-01 |
| CN113388022A (zh) | 2021-09-14 |
| CN113429473A (zh) | 2021-09-24 |
| CN113461798A (zh) | 2021-10-01 |
| CN111363008B (zh) | 2021-11-16 |
| CN114315964B (zh) | 2023-06-13 |
| CN114249806A (zh) | 2022-03-29 |
| CN113461799A (zh) | 2021-10-01 |
| CN114249806B (zh) | 2023-06-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110551198B (zh) | 一种肺癌抗原组合及其应用、细胞毒性t淋巴细胞 | |
| CN106581668B (zh) | 一种抗原表位肽组合物及其应用 | |
| CN108546679B (zh) | 在体外大量扩增人类成熟高活性树突状细胞的方法及其应用 | |
| WO2024109339A1 (zh) | 一种Caerin1.1/1.9联合抗CD47抗体在制备治疗黑色素瘤药物中的应用 | |
| CN110195042B (zh) | 一种树突状细胞的制备方法及应用 | |
| Horvat et al. | Production of interleukin 2 and interleukin 4 by immune CD4− CD8+ and their role in the generation of antigen‐specific cytotoxic T cells | |
| CN113461797B (zh) | 一种输卵管癌靶标抗原、输卵管癌靶标抗原刺激培养的ctl细胞及其应用 | |
| CN111393504B (zh) | 一种肝癌抗原组合及其应用、细胞毒性t淋巴细胞 | |
| CN114225008B (zh) | 转录因子btb-cnc同源体1在非霍奇金淋巴瘤治疗中的应用 | |
| CN111333698B (zh) | 一种乳腺癌靶标抗原组合、乳腺癌靶标抗原组合刺激培养的ctl细胞及其应用 | |
| CN111363009B (zh) | 一种直肠癌靶标抗原及其刺激培养的ctl细胞及其应用 | |
| CN111777677A (zh) | 一种egfr t790m 新抗原表位肽及其在治疗肿瘤中的应用 | |
| Dai et al. | Induction of Functional Hepatocyte-Like Cells by Overexpression of FOXA3 and HNF4α in Rat Bone Marrow Mesenchymal Stem Cells | |
| CN111333711B (zh) | 一种肺癌抗原组合及其应用、细胞毒性t淋巴细胞 | |
| CN112023048A (zh) | 一种对阿糖胞苷耐药的稳转重组b淋巴细胞白血病细胞系的构建方法及其应用 | |
| WO2018032619A1 (zh) | 可溶性蛋白baff在b细胞体外培养及扩增的应用 | |
| WO2024179465A1 (zh) | 表达膜结合细胞因子的肿瘤浸润淋巴细胞 | |
| WO2024140113A1 (zh) | 药物组合物 | |
| WO2005026326A2 (en) | Generation of chicken cell lines from embryonic stem cells and germ cells | |
| JP2002517409A (ja) | 抗原提示細胞組成物の調製およびインビボ投与のための方法 | |
| CN115212231A (zh) | 调节间充质干细胞免疫调节功能方法和试剂 | |
| CN118028235A (zh) | 人工抗原提呈细胞及其制备方法和应用 | |
| CN118772260A (zh) | 一种分离的tcr及其用途 | |
| CN117838728A (zh) | Til及其在制备杀伤肿瘤干细胞的药物中的应用 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Rong Inventor after: Wang Haiyan Inventor before: Jiao Shunchang Inventor before: Zhang Rong Inventor before: Wang Haiyan |
|
| CB03 | Change of inventor or designer information |