CN105504015B - A kind of restricted antitumor CTL epitope peptide of MHC-I classes - Google Patents
A kind of restricted antitumor CTL epitope peptide of MHC-I classes Download PDFInfo
- Publication number
- CN105504015B CN105504015B CN201610076778.XA CN201610076778A CN105504015B CN 105504015 B CN105504015 B CN 105504015B CN 201610076778 A CN201610076778 A CN 201610076778A CN 105504015 B CN105504015 B CN 105504015B
- Authority
- CN
- China
- Prior art keywords
- mhc
- epitope peptide
- peptide
- epitope
- classes
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
Abstract
A kind of restricted antitumor CTL epitope peptide of MHC I classes can be combined with the binding site of people's MHC I class molecules, can activate the epitope peptide of the cytotoxic T lymphocyte of specificity, 2 epitope peptides are with following amino acid sequences：E1, Tyr Ile Met Phe Val Asp Pro Ser Leu；E2, Tyr Leu Val Ala Leu Ser Tyr Thr Leu；The epitope peptide combined with people's MHC I class molecules, for sequestered polypeptide, pattern of fusion polypeptide and mosaic type polypeptide with the amino acid sequence；And the various forms of condensates that one of 2 kinds of polypeptides described above are monomer.The method that the invention is combined using computer modeling technique with experiment, improve the accuracy of epitope peptide screening, peptide material is only the small peptide of 9 peptides, it is readily synthesized in vitro, it can induce and generate notable anti tumor immune response, it is worth, is applied in immunotherapy of tumors technical field with very big commercial industriesization.
Description
Technical field
The present invention relates to a kind of restricted antitumor CTL epitope peptides of MHC-I classes in immunotherapy of tumors technical field.
Background technology
In recent years, with going deep into immune response Study on Molecular Mechanism, the immunocyte of body is gradually recognized
It is not the overall molecule corresponding to various pathogen or native antigen, but for the anti-of various antigen molecule
Former epitope, i.e. proteantigen are to embody its immunologic specificity by its epitope.It is current studies have shown that CD8+T cells institute
The target antigen of identification needs first to handle through antigen presenting cell, is presented in the form of " Antigenic Peptide-MHC-I classes molecule " compound later
In antigen presenting cell or target cell surface, the Antigenic Peptide combined accordingly with MHC-I class molecules is CTL epitopes.Epitope peptide
Can activation-inducing generate Specific CTL Cells, can have certain kill to the matched tumour of human leukocyte antigen (HLA) distribution type
Hinder effect.Therefore, the new issue that a kind of restricted antitumor CTL epitope peptide of MHC-I classes is anxious to be resolved at present is researched and developed.
Invention content
The purpose of the present invention is to provide a kind of restricted antitumor CTL epitope peptide of MHC-I classes, which is pair and people master
It wants the peptide molecule that histocompatibility complex (MHC) I class molecules combine to be predicted, screened and identified, energy and people is provided
The binding site of MHC-I class molecules is combined, can activate specificity cytotoxic T lymphocyte (CTL cells) epitope
Peptide, to effective killing tumor cell, achieve the purpose that treat tumour and the epitope peptide preparing for clinical treatment and
Detect the purposes in tumor disease vaccine.
The object of the present invention is achieved like this：A kind of restricted antitumor CTL epitope peptide of MHC-I classes, can be with people MHC-I
The binding site of class molecule is combined, and can activate the epitope peptide of the cytotoxic T lymphocyte of specificity, 2 epitope peptide tools
There are the following amino acid sequences to be：
E1, Tyr Ile Met Phe Val Asp Pro Ser Leu；
E2, Tyr Leu Val Ala Leu Ser Tyr Thr Leu；
The epitope peptide combined with people's MHC-I class molecules, for the sequestered polypeptide with the amino acid sequence, fusion
Type polypeptide and mosaic type polypeptide；And the various forms of condensates that one of 2 kinds of polypeptides described above are monomer；
The restricted targeting anti-tumor CTL epitope peptides of the MHC-I classes can by artificial synthesized, or by prokaryotic cell or
Eukaryotic cell expression purifying obtains；
The restricted antitumor CTL epitope peptide of MHC-I classes is according to the machine of epitope peptide and MHC-I class interactions of molecules
Reason, prediction obtains epitope peptide, and can effectively be combined with MHC-I class molecules according to it and can activate the spy of T lymphocyte specific
Property is accredited as effective epitope peptide, and the epitope peptide length only 9 amino acid sequences are readily synthesized in vitro, facilitate clinical application；
Epitope peptide involved by the restricted antitumor CTL epitope peptide of MHC-I classes and egg known to function or property
White matter is merged or is fitted into, i.e., these protein molecules or chimeric molecule contain polypeptid acid sequence of the present invention, tool
There is the same or similar activity of these polypeptides.
The present invention is characterized by offer and can be combined with the binding site of people's MHC-I class molecules, can activate specificity
Cytotoxic T lymphocyte (CTL cells) epitope peptide.Its basic principle is：Bioinformatics Proof-Of Principle epitope first
The theoretical binding ability of peptide and MHC-I class molecules, and T2 affinity experiment further verification epitope is combined by computer simulation
The binding force of peptide and MHC-I class molecules；Then epitope peptide is purified, and is analyzed by HPLC-MS by the synthesis of Fmoc principles, HPLC
Its purity and molecular weight；Epitope inducing peptide CTL cells finally are loaded using DC, and by swollen from different MHC-I molecular phenotypes
Tumor target cell is mixed, and observation CTL cellular immunities kill the restricted of the MHC-I molecules of target cell.A kind of MHC-I classes limitation
Property antitumor CTL epitope peptide compared with prior art, have using computer modeling technique with the method that is combined is tested, into one
Step improves the accuracy of epitope peptide screening, and peptide material is only the small peptide of 9 peptides, is readily synthesized in vitro, and generation can be induced notable
Anti tumor immune response has many advantages, such as very big commercial industriesization value, will be widely used in immunotherapy of tumors skill
In art field.
Description of the drawings
The following describes the present invention in detail with reference to the accompanying drawings and embodiments.
Fig. 1 is the Space structure simulation figure of E1 epitope peptides.
Fig. 2 is the Space structure simulation figure one that E1 epitope peptides and MHC-I molecules combine.
Fig. 3 is the Space structure simulation figure two that E1 epitope peptides and MHC-I molecules combine.
Fig. 4 is the Space structure simulation figure of E2 epitope peptides.
Fig. 5 is the Space structure simulation figure one that E2 epitope peptides and MHC-I molecules combine.
Fig. 6 is the Space structure simulation figure two that E2 epitope peptides and MHC-I molecules combine.
Fig. 7 is the mass spectral analysis figure of E1 epitope peptides.
Fig. 8 is the high-efficient liquid phase chromatogram technique analysis figure of E1 epitope peptides.
Fig. 9 is the mass spectral analysis figure of E2 epitope peptides.
Figure 10 is the high-efficient liquid phase chromatogram technique analysis figure of E2 epitope peptides.
Specific implementation mode
A kind of restricted antitumor CTL epitope peptide of MHC-I classes can be combined with the binding site of people's MHC-I class molecules,
The epitope peptide of the cytotoxic T lymphocyte of specificity can be activated, 2 epitope peptides are with following amino acid sequences：
E1, Tyr Ile Met Phe Val Asp Pro Ser Leu；
E2, Tyr Leu Val Ala Leu Ser Tyr Thr Leu.
The epitope peptide combined with people's MHC-I class molecules, for the sequestered polypeptide with the amino acid sequence, fusion
Type polypeptide and mosaic type polypeptide；And the various forms of condensates that one of 2 kinds of polypeptides described above are monomer.
The restricted targeting anti-tumor CTL epitope peptides of the MHC-I classes can by artificial synthesized, or by prokaryotic cell or
Eukaryotic cell expression purifying obtains.
The restricted antitumor CTL epitope peptide of MHC-I classes is according to the machine of epitope peptide and MHC-I class interactions of molecules
Reason, prediction obtains epitope peptide, and can effectively be combined with MHC-I class molecules according to it and can activate the spy of T lymphocyte specific
Property is accredited as effective epitope peptide, and the epitope peptide length only 9 amino acid sequences are readily synthesized in vitro, facilitate clinical application.
Epitope peptide involved by the restricted antitumor CTL epitope peptide of MHC-I classes and egg known to function or property
White matter is merged or is fitted into, i.e., these protein molecules or chimeric molecule contain polypeptid acid sequence of the present invention, tool
There is the same or similar activity of these polypeptides.
Following embodiment will be helpful to the understanding to the present invention, but these embodiments are only for being illustrated the present invention,
The present invention is not limited to these contents.
Embodiment one
Epitope peptide is verified with people's MHC-I class molecule affinity：
1, the method combined with quantitative motif method by hyper-base sequence method, the polypeptide sequence and MHC-I that the verification present invention designs
Class molecule binding characteristic.
Hyper-base sequence method is based on anisotropic point of the same race of the HLA in same human leucocyte antigen (HLA) (HLA) family, or even different families
There is the Antigenic Peptide that son is received the peptide motif that same or analogous anchor point residue is constituted, the anchor point residue of hyper-base sequence main function to be
Positioned at 9 (P9) amino acid residues of 2 (P2) amino acid residues of peptide chain and carboxyl terminal.When P2, P9 residue be A, I, L, M,
V, when T, and second is aromatic amino acid, and the 9th is hydrophobic amino acid, has higher affinity with HLA-A2 molecules.
The particular sequence of these amino acid is the active site that peptide molecule is combined with MHC-I molecules or crucial acidic amino acid, is determined
With the living features of MHC-I class molecule combination polypeptides.
Usinghttp://www.syfpeithi.de/bin/MHCServer.dll/ EpitopePrediction.htm is carried
The analysis of hyper-base sequence method is carried out to polypeptid acid sequence for analysis software.
Quantitative motif method is based on IBS it is assumed that i.e. in the combination of Antigenic Peptide and HLA-A2 molecules, and the side chain of Antigenic Peptide is imitated
(anchoring, inhibition or neutral) is answered to rely primarily on residual by adjacent amino acid the location of in peptide with corresponding amino acid residue
Base influences smaller.This assume that in a certain range in a polypeptide sequence, each amino acid residue independently of each other and
The combination of entire peptide and MHC-I class molecules is influenced, and the combination of the Antigenic Peptide can be exactly each position amino acid residue combination energy
Synthesis.On the basis of this assumption, Parker in 1993 etc. analyzes the affine of 154 nonapeptides and HLA-A2 molecules with peptide Binding experiment
Power, and an associate(d) matrix for including 180 coefficients is obtained, wherein each coefficient has reacted corresponding amino acid residue in the position
Energy is accordingly combined when setting.In conjunction with can be bigger, epitope peptide be combined closer with HLA-A2 molecules.Polypeptide each position is measured to Mr. Yu
Corresponding amino acid residue attachment coefficient is multiplied multiplied by typical coefficient 0.151, as the binding force of the peptide and HLA-A2, is when combining
When number is greater than or equal to 5, it may be determined that be combined stabilization with HLA-A2 molecules, otherwise regard as combining unstable.According to above-mentioned
Principle, using http:The analysis software that //www.bimas.com is provided carries out quantitative motif method point to polypeptid acid sequence
Analysis.
Although hyper-base sequence method prediction CTL epitopes overcome the previous false negative result being also easy to produce using Simple motif method, but
Due to this predicted method and motif method weakness having the same, i.e., the influence of two, nine residues is only only accounted in prediction and is neglected
, easily there are false positive results in the residue combination situation for having omited other sites, therefore it is pre- to combine quantitative motif method raising CTI. epitopes
The accuracy (table 1) of survey.Table 1 shows that hyper-base sequence method and quantitative motif method show two epitope peptide E1 and E2 and HLA-A2 points
Son has good binding ability；Table 2 is the abbreviations table of amino acid in 20.
Table 1 integrates hyper-base sequence method and quantitative motif method obtains the scoring that polypeptid acid sequence is combined with HLA-A2
2 amino acid abbreviations table of table
2, the combination of computer simulation epitope peptide and people's MHC-I class molecules：
To ChemDraw Ultra, ChemDraw 3D of the above-mentioned gained epitope peptide in ChemOffice software packages
Ultra establishes the 2 and 3 dimensional organization of epitope peptide respectively；With MOE softwares to epitope peptide and and HLA-A2.1 energy and structure
It is modified, the three-dimensional structure that both simulations combine, carries out molecular dynamics and combine simulation and physiological activity and applying value
It estimates, includes mainly following methods：(1) epitope peptide molecular model is built.With the ChemDraw in ChemOffice software packages
Ultra builds epitope peptide molecule two-dimensional structure, then the two-dimensional structure of epitope peptide is imported ChemDraw 3D Ultra and obtains three-dimensional
Model simultaneously saves as Mol2 formats, imports in MOE softwares three-dimensional structure in docking simulation link, selects drop-down menu successively
There is the energy level optimization that Minimize dialog boxes carry out peptide molecule, is allowed to energy level and reaches in Compute-Minimize-Molecule
To the minimum energy and configuration state for being most suitable for carrying out molecular docking with the compound of HLA-A2.1, then by the epitope after optimization
Peptide exports as MOL2 formats, in case the engagement groove groove with HLA-A2.1 carries out three-dimensional docking.(2) compound of HLA-A2.1 into
Prepare before row molecular dynamics simulation.The initial coordinate of HLA-A2.1 comes from the exclusive website of protein structureshttp:// www.rcsb.org/pdb/, the HLA-A2.1 structured datas of acquisition are imported in MOE softwares, select drop-down menu successively
, there are Docking dialog boxes in Applications-Docking Suite-Docking Ligands, the right side on the columns Filename
Side selects Define to carry out docking pre-structure modification (repairing side chain, dehydration hydrogenation) to HLA-A2.1 structures, and structural modification is completed
Post analysis obtains the engagement groove groove three-dimensional information of HLA-A2.1, preserves in case being docked with epitope peptide.(3) model is docked
Structure.It opens Applications-Docking Suite-Docking Ligands successively in MOE softwares, occurs
Docking dialog boxes, the engagement groove groove three-dimensional letter for the HLA-A2.1 that selection obtains on the columns Docking Mode and Filename
Breath selects Mole 2File in the columns Ligand Sourse and selects each optimized of MOL2 formats and be in energy level most
Low epitope peptide data, is docked and is finally obtained the scoring of docking simulation respectively, by the score value of docking simulation to table
Position peptide molecule and the binding force of HLA-A2.1 are estimated, due between Antigenic Peptide and MHC molecule mainly by hydrophobic effect, H keys,
The weak interactions such as sat linkage carry out intermolecular identification, and the effect of these secondary keys is stronger, in conjunction with then closer.Computer simulation knot
Fruit shows that E1, E22 epitope peptide can be combined (such as Fig. 2,4) with HLA-A2.1 well.
3, the combination of T2 affinity experiment detection epitope peptide and people's MHC-I class molecules：
The present embodiment utilizes the characteristics of T2 cell lines, detects the affinity of epitope peptide and people's MHC-I class molecules.T2 cells can
MHC- class Ⅰmolecules are expressed, but because of antigen polypeptide transport protein (TAP) defect necessary in its endogenous antigen presentation approach, therefore
Endogenous antigen cannot be transported, can only be by unloaded HLA-A2 molecular presentations in cell surface, and unloaded HLA-A2 molecules exist
Cell surface is unstable, degrades or return cell interior quickly.But the antigen polypeptide that external source gives is combined into HLA-A2 molecules
After compound, the stability of cell surface HLA-A2 molecules can be enhanced, and stay in cell surface.The combination of Antigenic Peptide and HLA-A2
Power is stronger, then the expression quantity of T2 cell surfaces HLA-A2 molecules is higher.So the T2 cell surfaces of detection antigen polypeptide processing
The increase of HLA-A2 developed by molecule amounts can intuitively reflect binding force and the combination of foreign antigenic polypeptide and HLA-A2 molecules
Stability can further prove the validity of the polypeptide of the present invention.
In embodiment, T2 cells wash 2 times through PBS, and after being resuspended with serum-free IMDM culture mediums, 1 is pressed on 6 well culture plates
×106The density in/hole is planted, and after each antigen polypeptide is dissolved with dimethyl sulfoxide (DMSO) (DMSO), T2 is added to the concentration of 50 μ g/ml
In the culture solution of cell, and blank control group and positive controls are set, 30 μ g/ml Influenza matrix are added in positive controls
Polypeptide.3 μ g/ml people β are added in each hole2Microglobulin.T2 cells are at 37 DEG C, 5%CO2, cultivate under the conditions of saturated humidity
After for 24 hours.After incubation, T2 cells centrifuge 5min with 1000rpm, and sedimentation cell is washed 3 times with ice PBS, then with 100 μ l ice
PBS is resuspended, and the 5 anti-human HLA-A2.1-FITC monoclonal antibodies of μ l mouse, 4 DEG C of incubation 15min are added, and centrifugation is abandoned after supernatant with 300 μ l ice PBS
It is resuspended, average fluorescent strength (MFI) is detected on flow cytometer.It is the affinity of epitope peptide and MHC-I molecules shown in table 3
Experimental result.
As a result using fluorescence coefficient (FI) as measurement index, calculation formula is：Fluorescence coefficient (FI)=(polypeptide mean fluorecence
Intensity-β2Microglobulin average fluorescent strength)/β2Microglobulin average fluorescent strength, criterion：FI>1.5 for polypeptide with
HLA-A2.1 molecular binding affinities are high, and 1.0<FI<1.5 be medium binding force, FI>0.5 is low combination power.
The affinity experimental result of 3 epitope peptide of table and MHC-I molecules
The experimental results showed that：Two epitope peptide E1 and E2 have very high binding force with MHC-I classes molecule.
Embodiment two
Synthesis, purifying and the molecular weight determination of epitope peptide：
Using standard Fmoc schemes, the conjunction of polypeptide is carried out using the ABI43IA type Peptide synthesizers of PE companies of U.S. production
At being summarized as follows：So that peptide chain is extended from c-terminus to aminoterminal according to polypeptide sequence, after synthesis, TFA/DCM is selected to be cut
It cuts, epitope peptide collection liquid is dried under reduced pressure at normal temperatures to 1-2mL, then with the pre- cold ether precipitations of at least 50mL, is then filtered, is obtained
The polypeptide crude product arrived.After the epitope peptide crude product of acquisition is dissolved with a small amount of DMSO, it is diluted with water to required volume, it is a concentration of
10mg/mL is purified and is carried out pure on Waters, US product Delta600 types HPLC after 0.22 μm of Fibrous membrane filtration
Degree analysis.Mobile phase selects aqueous solution containing 0.1%TFA and the cyanogen solution of second containing 0.1%TFA.The purifying of each peptide selects C18 to prepare column
The purity analysis of (Waters, US, 7.0 μm, 100A, 7.8mm × 150mm), each peptide selects the C18 analytical columns (U.S.
Waters companies, 5.0 μm, 100A, 3.9mm × 150mm).The Measuring Molecule Weight of each polypeptide after purification is in API 2000
Pacify conventional method on type (Waters, US) mass spectrograph to carry out.Its mass spectral analysis figure is referring to Fig. 5, Fig. 7, HPLC analysis charts ginseng
See Fig. 6, Fig. 8, it can be seen that the molecular weight theoretical value of 2 polypeptides is close with measured value, within the scope of allowable error, and it is pure
Degree illustrates that synthetic effect is good, can be used for testing in next step 95% or more.It is put in -70 DEG C after the freeze-dried processing of aforementioned polypeptides
It preserves, is spare.
Embodiment three
Targeting immunologic cytotoxicity effect of calcium flavin (Calcein-AM) the release experiment epitope peptide to tumour cell：
1, the preparation of effector cell
People's DC cells of induced maturation, after being cleaned with PBS, serum-free IMDM culture mediums are resuspended, and add 50 μ g/ml epitope peptides,
37 DEG C of overnight incubations.DC cells are cleaned through PBS, are counted, and mitomycin C, 37 DEG C of incubation 30min are added by the concentration of 30 μ g/ml.
DC cells press 1 after ice PBS cleanings, counting with breeding period T cell:20 ratios co-culture, and the IL-2 of 50U/ml is added, with
Stimulate T cell.Stimulation in 1 week 1 time, totally 3 times, by induced t cell at cytotoxic T cell (CTL), i.e. effector cell.
2, the preparation of target cell
Recovery breast cancer cell MCF7, MBA-MD-231 and OS-732 cells MG-63, U-2OS, normal culture pass
Generation.Wherein two cell strain of MCF7, MG-63 is HLA-A2.1 negative, and two cell strain of MBA-MD-231, U-2OS is HLA-A2.1 sun
Property.
3, calcium flavin release experiment
Target cell, cleaning is marked to be resuspended with the Calcein-AM of 10mM concentration；Effector cell and the tumour cell after label
According to 1:1、10:1、20:1、40:1、80:1 effect target ratio, 37 DEG C of co-cultivation 4h；Then culture solution, 1000rpm centrifugations are collected
5min is taken 100 μ l supernatants to measure average fluorescent strength and is added using simple target cell as spontaneous release with simple target cell
Detergent is as maximum burst size.
Effector cell indicates the killing rate of target cell with cell dissolution rate：Cell dissolution rate=(experimental release-is spontaneous
Burst size)/(maximum burst size-spontaneous release).Table 4 is that the effector cell of epitope inducing peptide kills the targeting of tumour cell
Hinder result.
Target killing percentage (%) of the effector cell of 4 epitope inducing peptide of table to tumour cell
Note：Lethal effect is indicated with killing rate (% has been omitted from).
The experimental results showed that：Human breast cancer cell MBA-MD-231 and people's bone of two polypeptides of E1, E2 to the HLA-A2 positives
Sarcoma cell U-2OS all has lethal effect；E1, E2 are thin to the human breast cancer cell line Bcap-37 and human osteosarcoma of HLA-A2 feminine genders
Born of the same parents' MG-63 lethal effect unobvious are killed restricted with MHC-I molecules.
Claims (2)
1. a kind of restricted antitumor CTL epitope peptide of MHC-I classes, it is characterised in that：The MHC-I classes are restricted antitumor
CTL epitope peptides can be combined with the binding site of people's MHC-I class molecules, can activate the cytotoxic T lymphocyte of specificity,
The amino acid sequence of epitope peptide is：
E1, Tyr Ile Met Phe Val Asp Pro Ser Leu；
Or E2, Tyr Leu Val Ala Leu Ser Tyr Thr Leu.
2. a kind of preparation method of restricted antitumor CTL epitope peptide of MHC-I classes according to claim 1, feature exist
In：The restricted antitumor CTL epitope peptide of MHC-I classes can be by artificial synthesized, or passes through prokaryotic cell or eukaryocyte
Expression and purification obtains.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610076778.XA CN105504015B (en) | 2016-02-02 | 2016-02-02 | A kind of restricted antitumor CTL epitope peptide of MHC-I classes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610076778.XA CN105504015B (en) | 2016-02-02 | 2016-02-02 | A kind of restricted antitumor CTL epitope peptide of MHC-I classes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105504015A CN105504015A (en) | 2016-04-20 |
| CN105504015B true CN105504015B (en) | 2018-09-25 |
Family
ID=55712370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610076778.XA Active CN105504015B (en) | 2016-02-02 | 2016-02-02 | A kind of restricted antitumor CTL epitope peptide of MHC-I classes |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105504015B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106589105B (en) * | 2017-01-23 | 2020-09-15 | 中国医科大学 | HLA-A2-restricted ECM 1-specific CTL epitope peptide and application thereof |
| CN106589106B (en) * | 2017-01-23 | 2020-09-15 | 中国医科大学 | HLA-A24-restricted ECM 1-specific CTL epitope peptide and application thereof |
| CN110305209B (en) * | 2019-07-09 | 2022-09-13 | 福建医科大学附属第一医院 | Polypeptide for treating malignant tumor and application thereof as vaccine |
| CN113105527B (en) * | 2020-01-13 | 2024-04-26 | 沈阳医健生命科技有限责任公司 | Anti-tumor dominant CTL epitope peptide of HLA-A2 restrictive tumor associated antigen E protein and application |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101092450A (en) * | 2007-01-10 | 2007-12-26 | 中国人民解放军第三军医大学第一附属医院 | Heparinase polypeptide epitope combined to molecules in human MIIC -I category |
| CN101580540B (en) * | 2009-06-19 | 2012-05-23 | 中国人民解放军第三军医大学第二附属医院 | Mouse HCV (hepatitis C virus) polypeptide epitope combined with MHC-I molecule and application thereof |
| CN104163852B (en) * | 2013-12-04 | 2016-09-28 | 魏敏杰 | The ECM1 polypeptide epitope being combined with people's MHC-I quasi-molecule |
| CN104163862B (en) * | 2013-12-04 | 2017-02-08 | 魏敏杰 | GRP78 peptide epitopes combined with human MHC-I (Major Histocompatibility Complex-I) molecule |
-
2016
- 2016-02-02 CN CN201610076778.XA patent/CN105504015B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105504015A (en) | 2016-04-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105504015B (en) | A kind of restricted antitumor CTL epitope peptide of MHC-I classes | |
| AU2007340679B2 (en) | HLA-A*1101-restricted WT1 peptide and pharmaceutical composition comprising the same | |
| DK2518149T3 (en) | HLA-A * 3303-LIMITED WT1 PEPTIDE AND PHARMACEUTICAL COMPOSITION INCLUDING THE SAME | |
| CN104163852B (en) | The ECM1 polypeptide epitope being combined with people's MHC-I quasi-molecule | |
| CN103570818B (en) | Tumor antigenic polypeptide and the purposes as tumor vaccine thereof | |
| CN105026422B (en) | SH2 domain variants | |
| CN106589105A (en) | HLA-A2-restricted ECM1-specific CTL epitope peptide and applications thereof | |
| CN102123731A (en) | Immunogenic peptides derived from the midkine protein, as an anticancer vaccine | |
| Bojko et al. | Design, synthesis and biological evaluation of PD-1 derived peptides as inhibitors of PD-1/PD-L1 complex formation for cancer therapy | |
| CN104163862B (en) | GRP78 peptide epitopes combined with human MHC-I (Major Histocompatibility Complex-I) molecule | |
| CN107936109A (en) | Tumour antigen small peptide derived from SAGE1 | |
| CN106478797B (en) | Tumour antigen small peptide from SAGE1 | |
| CN109890957A (en) | The enveloped virus of non-genetic modification | |
| Taylor et al. | Calmodulin binds a highly extended HIV-1 MA protein that refolds upon its release | |
| Rafnar et al. | Expression and analysis of recombinant Amb a V and Amb t V allergens. Comparison with native proteins by immunological assays and NMR spectroscopy. | |
| CN112409449B (en) | HLA-A 0201-limited KIF15 specific anti-tumor CTL dominant epitope peptide and application | |
| CN108218977A (en) | Small peptide from tumour antigen SAGE1 | |
| Bayó‐Puxan et al. | Combined use of oligopeptides, fragment libraries, and natural compounds: a comprehensive approach to sample the druggability of vascular endothelial growth factor | |
| Hossain et al. | HLA class II defects in Burkitt lymphoma: bryostatin-1-induced 17 kDa protein restores CD4+ T-cell recognition | |
| CN108250289A (en) | Tumour antigen small peptide from MAGE B6 | |
| Li et al. | Discovery of modulators for the PD-1/PD-L1 interaction by molecular simulation and bioassay | |
| CN106754805A (en) | A kind of antineoplastic polypeptide and its production and use | |
| Gomme et al. | Characterization of epitope regions of thyrotropin β‐subunit recognized by the monoclonal antibodies mAb279 and mAb299: a chimeric peptide approach | |
| CN101233149A (en) | Complement C3a derived peptides and uses thereof | |
| CN108203459A (en) | Tumour antigen small peptide from PRAME |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |