CN111057135A - 肿瘤相关基因fbxw7突变相关抗原短肽及其应用 - Google Patents
肿瘤相关基因fbxw7突变相关抗原短肽及其应用 Download PDFInfo
- Publication number
- CN111057135A CN111057135A CN201911337629.4A CN201911337629A CN111057135A CN 111057135 A CN111057135 A CN 111057135A CN 201911337629 A CN201911337629 A CN 201911337629A CN 111057135 A CN111057135 A CN 111057135A
- Authority
- CN
- China
- Prior art keywords
- fbxw7
- short peptide
- mutation
- cells
- vaccine
- 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.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 102
- 101710105178 F-box/WD repeat-containing protein 7 Proteins 0.000 title claims abstract description 84
- 239000000427 antigen Substances 0.000 title claims abstract description 57
- 108091007433 antigens Proteins 0.000 title claims abstract description 57
- 102000036639 antigens Human genes 0.000 title claims abstract description 57
- 230000035772 mutation Effects 0.000 title claims abstract description 41
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 23
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims abstract description 34
- 101150095705 FBXW7 gene Proteins 0.000 claims abstract description 31
- 206010064571 Gene mutation Diseases 0.000 claims abstract description 24
- 229940029030 dendritic cell vaccine Drugs 0.000 claims abstract description 17
- 229960005486 vaccine Drugs 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 210000004443 dendritic cell Anatomy 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000001939 inductive effect Effects 0.000 claims description 7
- 241000282414 Homo sapiens Species 0.000 claims description 6
- 210000001616 monocyte Anatomy 0.000 claims description 6
- 230000000890 antigenic effect Effects 0.000 claims description 2
- 230000005965 immune activity Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 102100028138 F-box/WD repeat-containing protein 7 Human genes 0.000 abstract description 76
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 26
- 210000004027 cell Anatomy 0.000 abstract description 20
- 229920001184 polypeptide Polymers 0.000 abstract description 15
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 8
- 230000006806 disease prevention Effects 0.000 abstract description 7
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 abstract description 5
- 230000008030 elimination Effects 0.000 abstract description 5
- 238000003379 elimination reaction Methods 0.000 abstract description 5
- 230000009466 transformation Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 239000000758 substrate Substances 0.000 description 8
- IOLWXFWVYYCVTJ-NRPADANISA-N Cys-Val-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N IOLWXFWVYYCVTJ-NRPADANISA-N 0.000 description 7
- JWHOIHCOHMZSAR-QWRGUYRKSA-N Tyr-Asp-Gly Chemical compound OC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 JWHOIHCOHMZSAR-QWRGUYRKSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- TZHFJXDKXGZHEN-IHRRRGAJSA-N Met-His-Leu Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(O)=O TZHFJXDKXGZHEN-IHRRRGAJSA-N 0.000 description 6
- 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 6
- ICFRWCLVYFKHJV-FXQIFTODSA-N Val-Cys-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)O)N ICFRWCLVYFKHJV-FXQIFTODSA-N 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- BOKLLPVAQDSLHC-FXQIFTODSA-N Ala-Val-Cys Chemical compound C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)O)N BOKLLPVAQDSLHC-FXQIFTODSA-N 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- IJUTXXAXQODRMW-KBPBESRZSA-N Tyr-Gly-His Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O IJUTXXAXQODRMW-KBPBESRZSA-N 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 108010004073 cysteinylcysteine Proteins 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- VHAQSYHSDKERBS-XPUUQOCRSA-N Ala-Val-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O VHAQSYHSDKERBS-XPUUQOCRSA-N 0.000 description 3
- YNCHFVRXEQFPBY-BQBZGAKWSA-N Asp-Gly-Arg Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N YNCHFVRXEQFPBY-BQBZGAKWSA-N 0.000 description 3
- 108010066805 F-Box Proteins Proteins 0.000 description 3
- 102000018700 F-Box Proteins Human genes 0.000 description 3
- 108091007023 FBXWs Proteins 0.000 description 3
- 102000036353 FBXWs Human genes 0.000 description 3
- QSVMIMFAAZPCAQ-PMVVWTBXSA-N Gly-His-Thr Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QSVMIMFAAZPCAQ-PMVVWTBXSA-N 0.000 description 3
- ALOBJFDJTMQQPW-ONGXEEELSA-N Gly-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)CN ALOBJFDJTMQQPW-ONGXEEELSA-N 0.000 description 3
- JCOSMKPAOYDKRO-AVGNSLFASA-N His-Glu-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N JCOSMKPAOYDKRO-AVGNSLFASA-N 0.000 description 3
- BPOHQCZZSFBSON-KKUMJFAQSA-N His-Leu-His Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O BPOHQCZZSFBSON-KKUMJFAQSA-N 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108091054437 MHC class I family Proteins 0.000 description 3
- XKJUFUPCHARJKX-UWVGGRQHSA-N Met-Gly-His Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CNC=N1 XKJUFUPCHARJKX-UWVGGRQHSA-N 0.000 description 3
- 108010033276 Peptide Fragments Proteins 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- BDMWLJLPPUCLNV-XGEHTFHBSA-N Ser-Thr-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BDMWLJLPPUCLNV-XGEHTFHBSA-N 0.000 description 3
- AAOPYWQQBXHINJ-DZKIICNBSA-N Val-Gln-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N AAOPYWQQBXHINJ-DZKIICNBSA-N 0.000 description 3
- 108010006886 Vitrogen Proteins 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 108010027345 wheylin-1 peptide Proteins 0.000 description 3
- 101100243447 Arabidopsis thaliana PER53 gene Proteins 0.000 description 2
- CMQOGWZUKPHLHL-DCAQKATOSA-N His-Cys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CN=CN1)N CMQOGWZUKPHLHL-DCAQKATOSA-N 0.000 description 2
- KFQDSSNYWKZFOO-LSJOCFKGSA-N His-Val-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O KFQDSSNYWKZFOO-LSJOCFKGSA-N 0.000 description 2
- 102000011961 Maturation-Promoting Factor Human genes 0.000 description 2
- 108010075942 Maturation-Promoting Factor Proteins 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 101150080074 TP53 gene Proteins 0.000 description 2
- MANXHLOVEUHVFD-DCAQKATOSA-N Val-His-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CS)C(=O)O)N MANXHLOVEUHVFD-DCAQKATOSA-N 0.000 description 2
- BMOFUVHDBROBSE-DCAQKATOSA-N Val-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N BMOFUVHDBROBSE-DCAQKATOSA-N 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000005911 anti-cytotoxic effect Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 241001647372 Chlamydia pneumoniae Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 102000003909 Cyclin E Human genes 0.000 description 1
- 108090000257 Cyclin E Proteins 0.000 description 1
- WYZLWZNAWQNLGQ-FXQIFTODSA-N Cys-Cys-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)N WYZLWZNAWQNLGQ-FXQIFTODSA-N 0.000 description 1
- SCOPAVYZWHPDBA-DCAQKATOSA-N Cys-Met-His Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CS)N SCOPAVYZWHPDBA-DCAQKATOSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- UWSMZKRTOZEGDD-CUJWVEQBSA-N His-Thr-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O UWSMZKRTOZEGDD-CUJWVEQBSA-N 0.000 description 1
- 101001060231 Homo sapiens F-box/WD repeat-containing protein 7 Proteins 0.000 description 1
- KXODZBLFVFSLAI-AVGNSLFASA-N Leu-His-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CN=CN1 KXODZBLFVFSLAI-AVGNSLFASA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 101100533604 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) scon-3 gene Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 230000018199 S phase Effects 0.000 description 1
- 101150089938 SKP1 gene Proteins 0.000 description 1
- 101100176789 Schizosaccharomyces pombe (strain 972 / ATCC 24843) gsk3 gene Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- CURFABYITJVKEW-QTKMDUPCSA-N Thr-Val-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O CURFABYITJVKEW-QTKMDUPCSA-N 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- IJBTVYLICXHDRI-FXQIFTODSA-N Val-Ala-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O IJBTVYLICXHDRI-FXQIFTODSA-N 0.000 description 1
- IJBTVYLICXHDRI-UHFFFAOYSA-N Val-Ala-Ala Natural products CC(C)C(N)C(=O)NC(C)C(=O)NC(C)C(O)=O IJBTVYLICXHDRI-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 238000011502 immune monitoring Methods 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 238000010200 validation analysis Methods 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
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- 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
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- 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
- C12N2501/70—Enzymes
- C12N2501/72—Transferases [EC 2.]
- C12N2501/727—Kinases (EC 2.7.)
-
- 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
- C12N2501/998—Proteins not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2502/00—Coculture with; Conditioned medium produced by
- C12N2502/11—Coculture with; Conditioned medium produced by blood or immune system cells
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Engineering & Computer Science (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本发明公开了FBXW7突变相关抗原短肽及其应用。所述FBXW7突变相关抗原短肽的序列如SEQ ID NO:1‑20任一所示。该短肽具有与DC细胞上MHC I分子高度的亲和力，并能有效地刺激、诱导产生特异性细胞毒性T淋巴细胞(CTLs)，可用于FBXW7基因突变细胞的免疫清除，进而预防FBXW7基因突变相关疾病的发生，尤其是FBXW7基因突变相关肿瘤疾病的预防；因此本发明的FBXW7抗原短肽具备良好的多肽疫苗及DC疫苗的潜力，具有良好的临床转化及疾病预防潜力。而且，本发明的FBXW7抗原短肽长度较短，化学合成难度小，可以直接合成得到高纯的产物，应用成本大大降低，同时效果明确，具有很好的应用前景。
Description
技术领域
本发明属于生物医药技术领域。更具体地，涉及肿瘤相关基因FBXW7突变相关抗原短肽及其应用。
背景技术
FBXW7基因在人类染色体中定位于4q31，由1个特异性的外显子和10个共有的外显子组成，经拼接产生FBXW7a、FBXW7β和FBXW7γ三种转录产物，FBXW7基因组成在人类高度保守：①FBXW7包含了若干蛋白质相互作用的保守结构域，可以使SCF与S期相关的蛋白1(skp1)直接结合，募集SCF其他组分；②FBXW的N末端包含8个WD40的重复序列，构成底物结合域，这些重复序列可能是底物直接相互作用的结合点；③FBXW7的另外一个结构域称为D结构域，可促进FBXW7二聚化，虽然对底物识别并不重要，但泛素识别结合底物需要依靠FBXW7二聚化。不同的亚型在细胞的定位不同，FBXW7α主要在核内，FBXW7β主要在胞质，FBXW7γ－主要在核仁，FBXW7的不同定位可以调节各自的功能，这种调节作用可能与不同信号通路有关。
FBXW7含有3个保守的蛋白质-蛋白质相互作用结构域，即F-box、WD40重复序列和D结构域。F-box的作用是与SKPl结合，进而募集SCF其他组分；WD40重复序列与靶蛋白上的CDC4磷酸-降解决定子(CDPs)的磷酸化氨基酸相互作用，介导FBXW7与靶蛋白结合；D结构域的功能是促进FBXW7二聚化。FBXW7有单体和二聚体两种作用方式，某些底物如cyclin E和c-myc可以被FBXW7单体高效降解。但是某些底物的CDP与FBXW7的亲和力较弱，需要FBXW7二聚体才能降解。FBXW7是研究较多的F-box家族蛋白的成员，目前的研究结果均支持FBXW7是一个抑癌因子。FBXW7参与肿瘤抑制的作用与以下三点有关：1)已经明确的FBXW7的特异性底物中绝大部分是癌蛋白，FBXW7基因突变会导致相应的底物蛋白表达增加；2)FBXW7在6％～8％的肿瘤中有突变，是决定预后的良好标志物；3)FBXW7的突变与P53基因的突变有关，FBXW7和P53协同抑制肿瘤的侵袭和转移。因此，维持FBXW7的正常对维持细胞的正常功能和预防相关癌症等疾病非常重要。
利用肿瘤相关抗原短肽诱导建立肿瘤抗原肽特异性CTL，从而获得具有特异性杀伤肿瘤细胞的CTL克隆，被激活的CTL可以杀死相应的靶细胞，发挥免疫监视作用。而该技术的关键前提是获得免疫原性、特异性好、能够诱导产生特异性细胞毒性T淋巴细胞的相关抗原短肽。
发明内容
本发明旨在针对肿瘤相关基因FBXW7开发FBXW7基因突变相关抗原短肽，所述FBXW7基因突变相关抗原短肽具有与DC细胞上MHC I分子高度的亲和力，并能有效地刺激、诱导产生特异性细胞毒性T淋巴细胞(CTLs)，可用于FBXW7基因突变细胞的免疫清除，具备良好的多肽疫苗及DC疫苗的潜力。
本发明的目的是提供肿瘤相关基因FBXW7突变相关抗原短肽。
本发明另一目的是提供该短肽在制备用于FBXW7突变的DC疫苗中的应用。
本发明再一目的是提供一种用于FBXW7突变的DC疫苗。
本发明上述目的通过以下技术方案实现：
本发明人通过T细胞表位预测综合平台NetCTL数据库(http://www.cbs.dtu.dk/services/NetCTL)在线分析，通过生物信息学预测，发现COSM22932、COSM22965、COSM99604、COSM22975、COSM23000的突变多肽能够与MHC-I类分子结合(FBXW7的这几个突变位点在大肠癌、血液淋巴瘤、胆管癌、胃癌等实体瘤中检出)。说明该位点是免疫清除FBXW7基因突变细胞的重要靶点。而免疫学研究证实，CD8阳性T淋巴细胞CTL发挥细胞免疫的原理为：CTL细胞通过识别与MHC-I分子结合的抗原肽被激活，被激活的CTL可以杀死相应的靶细胞，发挥免疫监视作用。因此，本发明通过生物信息学技术预测FBXW7突变序列与T淋巴细胞受体(TCR)及MHC I类分子的结合能力，同时分析其表达定位于细胞膜外，设计优化了针对肿瘤相关基因FBXW7突变相关抗原短肽，本发明筛选得到的FBXW7抗原短肽，其多肽序列优选为SEQ ID NO:1-20任一所示，所得FBXW7抗原短肽具有与DC细胞上MHC I分子高度的亲和力并能有效地刺激、诱导产生特异性细胞毒性T淋巴细胞(CTLs)，抑制肿瘤细胞生长，说明其具备良好的多肽疫苗及DC疫苗的潜力，具有良好的临床转化及疾病预防前景。
因此，以下产品及应用均应在本发明的保护范围之内：
肿瘤相关基因FBXW7突变相关抗原短肽，序列如SEQ ID NO:1-20任一所示。以所述短肽为活性抗原成分与辅剂可制成FBXW7突变短肽产品。
所述短肽在制备可诱导产生特异性细胞毒性T淋巴细胞的产品中的应用。具体地，特异性细胞毒性T淋巴细胞的诱导方法为：使用SEQ ID NO:1-20的FBXW7突变短肽中的至少一条经抗原提呈细胞与CD8+T细胞共培养，可诱导得到FBXW7突变特异性细胞毒性T细胞。
所述短肽在制备人体免疫活性调节剂中的应用，具体是作为活性抗原成分调节人体免疫活性。短肽抗原在细胞内经过一系列加工处理，形成特定片段即抗原肽与MHC 1类分子完全匹配后提呈到细胞表面被相应T细胞受体(TCR)识别，组成抗原肽-MHC-TCR复合物，从而激活细胞毒性T淋巴细胞(CTL)。
所述短肽在制备预防FBXW7基因突变及相关疾病的产品中的应用，尤其是FBXW7基因突变相关肿瘤。所述产品包括疫苗，如DC疫苗或单核细胞疫苗等。
抗原肽-MHC-TCR复合物，激活细胞毒性T淋巴细胞，激活的特异性T淋巴细胞能够杀伤携带FBXW7突变的异常细胞。特异性细胞毒性T淋巴细胞的诱导方法：使用SEQ ID NO:1-20所示FBXW7突变短肽中的至少一条经抗原提呈细胞与CD8+T细胞共培养，诱导得到FBXW7突变特异性细胞毒性T细胞。
基于此，本发明还提供一种用于预防FBXW7基因突变及相关疾病的DC疫苗或单核细胞疫苗，由本发明SEQ ID NO:1-20任一所示短肽与树突状细胞或单核细胞加载制成。
将SEQ ID NO:1-20任一条所示FBXW7短肽与树突状细胞(dendritic cell，DC)加载回输，可以作为DC疫苗用于疾病预防，刺激机体产生多肽特异性抗细胞毒性T细胞，进而实现FBXW7基因突变相关疾病的预防，尤其是FBXW7基因突变相关肿瘤的预防。
具体地，疫苗为静脉回输型疫苗。
在所述预防FBXW7基因突变及相关疾病的DC疫苗的制备方法中，选用vitrogen因子作为佐剂增加DC细胞活性，特异性的抗原肽体外致敏树突状细胞，获得自体树突状细胞制剂，作为静脉回输型肺炎衣原体相关慢病防治疫苗。具体制备方法为：以成熟促进因子，同时以Vitrogan因子作为佐剂，促进DC细胞成熟；然后向诱导成熟的DC细胞培养体系中加入本发明的短肽，收集负载有短肽片段的DC细胞，用生理盐水洗涤后，用生理盐水重悬即得到DC疫苗。
更具体地，作为一种可选择的方案，所述DC疫苗的制备步骤如下：
S1.DC细胞的提取与诱导：
S11.获取未成熟DC细胞
采集健康捐献者的外周血，通过淋巴细胞分离液分离出单个核细胞，培养基中，37℃、5％CO2条件下常规培养3小时后，贴壁细胞为未成熟DC细胞；
S12.未成熟DC细胞的扩增培养
37℃、5％CO2条件下培养5天，期间隔天换液，完成未成熟DC细胞(imDC细胞)的扩增培养；
S13.DC细胞的诱导
加入成熟促进因子，同时以Vitrogan因子作为佐剂，促进DC细胞成熟；
S2.多肽的负载：
诱导DC细胞成熟5天后，向培养体系中加入本发明的短肽；
S3.制备DC疫苗：
离心收集负载有短肽片段的DC细胞，用生理盐水洗涤细胞3次，最后将负载有短肽片段的DC细胞用生理盐水重悬，即得到DC疫苗。
本发明选用特异性的表位多肽，体外致敏自体DC细胞，制备DC细胞制剂，可以对患者进行静脉回输，重建机体全身免疫平衡，启动免疫系统，对基因突变肿瘤细胞特异性治疗。采用的DC技术，用多种特异性抗原肽联合激活树突细胞，这些抗原肽具有极强的特异性，诱导具有更高活性的树突状细胞携带多种抗原信息，回输进入人体后可刺激机体免疫，可以达到诱导人体产生特异性抗体及特异性CTL细胞，从而可以有效预防FBXW7基因突变及相关疾病的发生发展。
本发明具有以下有益效果：
本发明的FBXW7抗原短肽具有与DC细胞上MHC I分子高度的亲和力，并能有效地刺激、诱导产生特异性细胞毒性T淋巴细胞(CTLs)；而产生的特异性细胞毒性T淋巴细胞可用于FBXW7基因突变细胞的免疫清除，进而预防FBXW7基因突变相关疾病的发生，尤其是肿瘤疾病的预防。
本发明的FBXW7抗原短肽可用于制备多肽疫苗及DC疫苗，具有良好的临床转化及疾病预防前景。
而且，本发明的FBXW7抗原短肽长度较短，有其不可比拟的应用优势，且化学合成难度小，可以直接合成得到高纯的产物，应用成本大大降低，同时效果明确，具有很好的应用潜力。
附图说明
图1是FBXW7突变相关抗原短肽特异性CTL IFN-γ释放实验结果。
图2是FBXW7突变相关抗原短肽对靶细胞的杀伤活性的对比。
具体实施方式
以下结合说明书附图和具体实施例来进一步说明本发明，但实施例并不对本发明做任何形式的限定。除非特别说明，本发明采用的试剂、方法和设备为本技术领域常规试剂、方法和设备。
除非特别说明，本发明所用试剂和材料均为市购。
实施例1FBXW7基因突变肽的T细胞表位预测及FBXW7短肽设计
1、通过T细胞表位预测数据综合平台(http://www.cbs.dtu.dk/services/NetCTL)和生物信息学技术，分析预测与T细胞表位受体(TCR)及MHC I类分子高亲和力的多肽序列。研究获得，获得一系列FBXW7突变相关抗原短肽。
2、从上述多肽中筛选出50条预测评分高且预测毒性较小的多肽片段，进行进一步研究。具体实验如下：
FBXW7突变短肽特异性CTL克隆建立的方法如下：
通过流式分选健康捐献者的105个CD8+T细胞，加入负载FBXW7突变短肽的Mo-DCs104个，间隔1周刺激2次，再使用丝裂霉素C处理过的负载FBXW7短肽的自体外周血单个核细胞(PBMC)105个刺激1次，从而获得CTL细胞。
采用以上体外诱导建立FBXW7基因突变短肽特异性CTL细胞的方法，吸取细胞培养上清液，通过检测上清液中IFN-γ含量。
结果显示，如表1所示的20条多肽具有特异性免疫应答效应，可以激活T淋巴细胞，诱导分泌IFN-γ(如图1所示)。同时结果也显示，20条多肽与上述预测出的50条多肽的预测评分高低的对应关系不显著相关，预测结果参考性较差。
表1
实施例2抑制肿瘤生长试验
实施例1得到20条具有特异性免疫应答效应、可以激活T淋巴细胞的FBXW7突变短肽。从中随机挑选5条短肽，继续进一步验证实验。
分别将5条短肽所诱导的细胞培养上清液对肺癌细胞A549进行培养。对照组分为不加载短肽和加载无义短肽两组。
结果显示，与对照组相比，5条短肽所诱导的上清液均可明显抑制肿瘤细胞生长，明显降低肿瘤活性(如图2所示)。
实验结果表明，本发明建立的CTL表位是极其有效的。通过将SEQ ID NO:1-20任一所示FBXW7突变短肽经树突状细胞提呈与细胞毒性淋巴T细胞共培养，可诱导筛选得到FBXW7突变特异性细胞毒性T淋巴细胞。这种FBXW7突变抗原特异性细胞毒性T淋巴细胞可用于FBXW7基因突变细胞的免疫清除，进而预防FBXW7基因突变相关疾病的发生，尤其是肿瘤疾病的预防。因此，将SEQ ID NO:1-20任一条所示FBXW7短肽与树突状细胞(dendriticcell，DC)加载回输，可以作为DC疫苗用于疾病预防，刺激机体产生多肽特异性抗细胞毒性T细胞，进而实现FBXW7基因突变相关疾病的预防，尤其是肿瘤的预防。
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。
SEQUENCE LISTING
<110> 维塔恩（广州）医药有限公司
<120> 肿瘤相关基因FBXW7突变相关抗原短肽及其应用
<130>
<160> 20
<170> PatentIn version 3.3
<210> 1
<211> 15
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 1
Tyr Gly His Thr Ser Thr Val Cys Cys Met His Leu His Glu Lys
1 5 10 15
<210> 2
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 2
Tyr Gly His Thr Ser Thr Val Cys Cys Met His Leu His Glu
1 5 10
<210> 3
<211> 13
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 3
Tyr Gly His Thr Ser Thr Val Cys Cys Met His Leu His
1 5 10
<210> 4
<211> 13
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 4
Tyr Gly His Thr Ser Thr Val His Cys Met His Leu His
1 5 10
<210> 5
<211> 12
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 5
Gly His Thr Ser Thr Val His Cys Met His Leu His
1 5 10
<210> 6
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 6
Gly His Thr Ser Thr Val Cys Cys Met His Leu His Glu Lys
1 5 10
<210> 7
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 7
Gly His Thr Ser Thr Val His Cys Met His Leu His Glu Lys
1 5 10
<210> 8
<211> 13
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 8
His Thr Ser Thr Val His Cys Met His Leu His Glu Lys
1 5 10
<210> 9
<211> 12
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 9
Thr Ser Thr Val Cys Cys Met His Leu His Glu Lys
1 5 10
<210> 10
<211> 12
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 10
Thr Ser Thr Val His Cys Met His Leu His Glu Lys
1 5 10
<210> 11
<211> 15
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 11
Met Gly His Val Ala Ala Val Gly Cys Val Gln Tyr Asp Gly Arg
1 5 10 15
<210> 12
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 12
Met Gly His Val Ala Ala Val Gly Cys Val Gln Tyr Asp Gly
1 5 10
<210> 13
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 13
Gly His Val Ala Ala Val Cys Cys Val Gln Tyr Asp Gly Arg
1 5 10
<210> 14
<211> 13
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 14
His Val Ala Ala Val Cys Cys Val Gln Tyr Asp Gly Arg
1 5 10
<210> 15
<211> 12
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 15
Val Ala Ala Val Cys Cys Val Gln Tyr Asp Gly Arg
1 5 10
<210> 16
<211> 15
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 16
Met Gly His Val Ala Ala Val Leu Cys Val Gln Tyr Asp Gly Arg
1 5 10 15
<210> 17
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 17
Gly His Val Ala Ala Val Cys Cys Val Gln Tyr Asp Gly Arg
1 5 10
<210> 18
<211> 14
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 18
Gly His Val Ala Ala Val Leu Cys Val Gln Tyr Asp Gly Arg
1 5 10
<210> 19
<211> 13
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 19
His Val Ala Ala Val Gly Cys Val Gln Tyr Asp Gly Arg
1 5 10
<210> 20
<211> 12
<212> PRT
<213> FBXW7突变相关抗原短肽
<400> 20
Val Ala Ala Val Cys Cys Val Gln Tyr Asp Gly Arg
1 5 10
Claims (10)
1.肿瘤相关基因FBXW7突变相关抗原短肽，其特征在于，序列如SEQ ID NO:1-20任一所示。
2.权利要求1所述短肽在制备可诱导产生特异性细胞毒性T淋巴细胞的产品中的应用。
3.权利要求1所述短肽在制备人体免疫活性调节剂中的应用。
4.根据权利要求3所述应用，其特征在于，所述短肽是作为活性抗原成分调节人体免疫活性。
5.权利要求1所述短肽在制备预防FBXW7基因突变的产品中的应用。
6.权利要求1所述短肽在制备可预防FBXW7基因突变相关疾病的产品中的应用。
7.权利要求1所述短肽在制备预防FBXW7基因突变的DC疫苗或单核细胞疫苗方面的应用。
8.权利要求1所述短肽在制备预防FBXW7基因突变相关疾病的DC疫苗或单核细胞疫苗方面的应用。
9.根据权利要求6或8所述应用，其特征在于，所述FBXW7基因突变相关疾病是FBXW7基因突变相关肿瘤。
10.一种用于预防FBXW7基因突变的疫苗，其特征在于，由权利要求1所述短肽与树突状细胞或单核细胞加载制成。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911337629.4A CN111057135A (zh) | 2019-12-23 | 2019-12-23 | 肿瘤相关基因fbxw7突变相关抗原短肽及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911337629.4A CN111057135A (zh) | 2019-12-23 | 2019-12-23 | 肿瘤相关基因fbxw7突变相关抗原短肽及其应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111057135A true CN111057135A (zh) | 2020-04-24 |
Family
ID=70302544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911337629.4A Withdrawn CN111057135A (zh) | 2019-12-23 | 2019-12-23 | 肿瘤相关基因fbxw7突变相关抗原短肽及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111057135A (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281508A (zh) * | 1997-12-19 | 2001-01-24 | 法玛西雅厄普约翰美国公司 | 人sel－10多肽及编码其的多核苷酸 |
| CN106243213A (zh) * | 2016-08-15 | 2016-12-21 | 安军 | 一种肿瘤相关抗原XAGE‑1b短肽及应用 |
| WO2018102585A1 (en) * | 2016-11-30 | 2018-06-07 | Advaxis, Inc. | Personalized immunotherapy in combination with immunotherapy targeting recurrent cancer mutations |
| CN109517053A (zh) * | 2018-11-28 | 2019-03-26 | 生命谷（海南）生物科技股份有限公司 | 肿瘤相关基因ret突变短肽及其应用 |
| CN109575118A (zh) * | 2018-12-17 | 2019-04-05 | 英普乐孚生物技术(上海)有限公司 | 用于制备dc疫苗的多肽片段及dc疫苗 |
| CN109970846A (zh) * | 2018-12-19 | 2019-07-05 | 广州美萨生物科技有限公司 | 一种肿瘤相关抗原XAGE-1b九肽及其应用 |
-
2019
- 2019-12-23 CN CN201911337629.4A patent/CN111057135A/zh not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1281508A (zh) * | 1997-12-19 | 2001-01-24 | 法玛西雅厄普约翰美国公司 | 人sel－10多肽及编码其的多核苷酸 |
| CN106243213A (zh) * | 2016-08-15 | 2016-12-21 | 安军 | 一种肿瘤相关抗原XAGE‑1b短肽及应用 |
| WO2018102585A1 (en) * | 2016-11-30 | 2018-06-07 | Advaxis, Inc. | Personalized immunotherapy in combination with immunotherapy targeting recurrent cancer mutations |
| CN109517053A (zh) * | 2018-11-28 | 2019-03-26 | 生命谷（海南）生物科技股份有限公司 | 肿瘤相关基因ret突变短肽及其应用 |
| CN109575118A (zh) * | 2018-12-17 | 2019-04-05 | 英普乐孚生物技术(上海)有限公司 | 用于制备dc疫苗的多肽片段及dc疫苗 |
| CN109970846A (zh) * | 2018-12-19 | 2019-07-05 | 广州美萨生物科技有限公司 | 一种肿瘤相关抗原XAGE-1b九肽及其应用 |
Non-Patent Citations (2)
| Title |
|---|
| NISHI KOTHARI 等: "Increased incidence of FBXW7 and POLE proofreading domain mutations in young adult colorectal cancers", 《CANCER》 * |
| 龚建 等: "FBXW7在结直肠癌中的研究进展", 《临床与病理杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11555814B2 (en) | Method for activation of helper t cell and composition for use in the method | |
| van Elsas et al. | Host genetics and tumor environment determine the functional impact of neutrophils in mouse tumor models | |
| CN116970058B (zh) | 针对tp53基因r249s突变的肿瘤新抗原多肽及其应用 | |
| CN114250198A (zh) | 一种增强免疫细胞抗肿瘤效果的方法 | |
| CN111777677A (zh) | 一种egfr t790m 新抗原表位肽及其在治疗肿瘤中的应用 | |
| CN102898508B (zh) | 封闭TGF-β受体或IL-10受体的多肽、其药物组合物及其用途 | |
| JP2007126442A (ja) | 癌特異的抗原 | |
| CN111171136A (zh) | 肿瘤相关基因PDGFRα突变相关抗原短肽及其应用 | |
| CN117024522A (zh) | 针对pik3ca基因e545k突变的肿瘤新抗原多肽及其应用 | |
| CN111057135A (zh) | 肿瘤相关基因fbxw7突变相关抗原短肽及其应用 | |
| CN111072763A (zh) | 肿瘤相关基因gnas突变相关抗原短肽及其应用 | |
| CN115850377A (zh) | 基于nras基因q61k突变的肿瘤新抗原多肽及其应用 | |
| CN111116734A (zh) | 肿瘤相关基因c-kit突变相关抗原短肽及其应用 | |
| CN111087448A (zh) | 肿瘤相关基因jak2突变相关抗原短肽及其应用 | |
| CN111057690A (zh) | 肿瘤相关基因braf突变相关抗原短肽及其应用 | |
| CN116948004B (zh) | 针对ctnnb1基因h36p突变的肿瘤新抗原多肽及其应用 | |
| CN115785204B (zh) | 肺癌特异性分子靶标08及其用途 | |
| CN115785203B (zh) | 肺癌特异性分子靶标10及其用途 | |
| CN115785205B (zh) | 肺癌特异性分子靶标09及其用途 | |
| CN115785207B (zh) | 肺癌特异性分子靶标02及其用途 | |
| CN115785206B (zh) | 肺癌特异性分子靶标07及其用途 | |
| CN117552115B (zh) | 用于诱导肿瘤特异性免疫响应的通用型抗原肽库及其应用 | |
| CN115785212B (zh) | 肺癌特异性分子靶标03及其用途 | |
| CN115785211B (zh) | 肺癌特异性分子靶标04及其用途 | |
| CN115785208B (zh) | 肺癌特异性分子靶标01及其用途 |
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 | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20200424 |
|
| WW01 | Invention patent application withdrawn after publication |