CN107325172A - Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer - Google Patents

Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer Download PDF

Info

Publication number
CN107325172A
CN107325172A CN201710546363.9A CN201710546363A CN107325172A CN 107325172 A CN107325172 A CN 107325172A CN 201710546363 A CN201710546363 A CN 201710546363A CN 107325172 A CN107325172 A CN 107325172A
Authority
CN
China
Prior art keywords
antigenic peptide
lung cancer
medicine
cell
cell lung
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201710546363.9A
Other languages
Chinese (zh)
Inventor
张超
冷晓燕
常菁
曹巍
虞强
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiangsu Maijian Biotechnology Development Co Ltd
Original Assignee
Jiangsu Maijian Biotechnology Development Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Jiangsu Maijian Biotechnology Development Co Ltd filed Critical Jiangsu Maijian Biotechnology Development Co Ltd
Priority to CN201710546363.9A priority Critical patent/CN107325172A/en
Publication of CN107325172A publication Critical patent/CN107325172A/en
Pending legal-status Critical Current

Links

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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
    • 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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Oncology (AREA)
  • Biophysics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Toxicology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Application the invention provides Antigenic Peptide T790M 2 and its in the medicine for preparing treatment non-small cell lung cancer, the amino acid sequence of the Antigenic Peptide T790M 2 is as shown in SEQ ID NO.1.The Antigenic Peptide has the effect that non-small cell lung cancer cell is killed in T cell targeting that activates, and can be the non-small cell lung cancer patient for preventing and/or treating EGFR T790M mutation（EGFR TKIs therapies）A kind of new, promising immunotherapy method is provided.

Description

Antigenic Peptide T790M-2 and its prepare treatment non-small cell lung cancer medicine in Using
Technical field
The invention belongs to biomedicine technical field, and in particular to Antigenic Peptide T790M-2 and its non-small thin preparing treatment Application in the medicine of born of the same parents' lung cancer.
Background technology
Lung cancer is the main cause of global cancer mortality.And non-small cell lung cancer accounts for the 80% of cases of lung cancer.Although controlling now Treatment means have to develop on a large scale very much, but the prediction of lung cancer patient still is apparent not enough.But nearest people are to this disease in treatment method Achieve important progress.Particularly EGF-R ELISA-tyrosine kinase inhibitor (EGFR-TKIs), is replaced as Ji is non- Buddhist nun, Erlotinib have been developed the new therapeutic modality being used as specific non-small cell lung cancer, these patients The tyrosine kinase domain of EGFR gene is mutated.Using EGFR-TKI medicines to EGFR saltant type non-small cell lung carninomatosis People is (such as
DelE746-A750 and L858R) implement preclinical research, show higher clinical response rate, about 80%.However, with the passage of time, most patient generates acquired drug resistance to EGFR-TKIs.To non-small cell lung The further investigation of cancer is identified in the EGFR-TKIs resistance sufferers that secondary mutation T790M appears in 50%.But for there is this For the non-small cell lung cancer sufferer for planting mutation, there is presently no effective therapeutic modality.
In recent years, due to the identification of kinds of tumors related antigen, tumor immunology field achieves noticeable progress. The especially research and development and clinical test of kinds of tumors immunotherapy, using tumor correlated albumen or the tumor vaccine of peptide fragment. Although immunotherapy shows feasibility and hypotoxicity, the random experiment in later stage, except minority in early clinic experiment In addition, compared to existing therapeutic modality, fail to show beneficial therapeutic effect.These unexpected results may return Because in being at least partly due to the type of vaccine antigen.At present, what most vaccine antigen was isolated from not undergoing mutation is autologous Antigen, due to the presence of Central immunotolerance and/or peripheral immune tolerance mechanism, they do not show high immunogenicity.Phase Than under, the neoantigen of tomour specific, due to the amino acid sequence containing mutation, with immunogenicity, because they can be by place Main immune system is recognized as exotic.Particularly, the vaccine antigen for carrying out self-driven mutation is probably one of immunization therapy Promising target, because they can seldom lose from tumour cell.Although there is some research reports to point out to target exempting from for mutant antigen Epidemic disease treatment have feasibility, but up to now only have sub-fraction mutant antigen be identified be immunization therapy potential target spot.
In non-small cell lung cancer, some t cell epitopes from mutant antigen have been reported.But in our research In, we predict the t cell epitope of HLA-A*0201 (A2) restricted antigen from EGFR T790M drug resistant mutants, it Have very strong immunogenicity to the T cell of people, the t cell epitope predicted can be to prevent and/or treatment EGFR T790M dash forward The non-small cell lung cancer patient (EGFR-TKIs therapies) of change provides a kind of new, promising immunotherapy method.
The content of the invention
The technical problem of solution：Non-small cell is treated it is an object of the invention to provide Antigenic Peptide T790M-2 and its preparing Application in the medicine of lung cancer, the Antigenic Peptide has the effect of activation T cell targeting kill non-small cell lung cancer cell.
Technical scheme：Antigenic Peptide T790M-2, its amino acid sequence is as shown in SEQ ID NO.1.
Further, the amino acid sequence of the Antigenic Peptide T790M-2 has the amino acid sequence as shown in SEQ ID NO.1 Replace, lack or add the amino acid sequence that one or more amino acid residues are obtained in row.
A kind of medicine for being used to treat non-small cell lung cancer, the medicine contains above-mentioned Antigenic Peptide T790M-2.
Medicines of the above-mentioned Antigenic Peptide T790M-2 in the non-small cell lung cancer for preparing prevention and/or treatment EGFR T790M mutation Application in thing.
Above-mentioned Antigenic Peptide T790M-2 is being prepared for inducing to exempting from the EGFR T790M non-small cell lung cancers being mutated Application in the medicine of epidemic disease.
Applications of the above-mentioned Antigenic Peptide T790M-2 in the medicine for induced tumor reaction-ive T cell is prepared, the tumour Reaction-ive T cell is the T cell for the non-small cell lung cancer cell growth that can have EGFR T790M to be mutated with targeted inhibition.
Beneficial effect：There is the Antigenic Peptide T790M-2 of the present invention activation T cell targeting to kill non-small cell lung cancer cell Effect, provides a kind of new to prevent and/or treating the non-small cell lung cancer patient (EGFR-TKIs therapies) of EGFR T790M mutation , promising immunotherapy method.
Brief description of the drawings
Fig. 1 is that the CTL cells of maturation DC inductions in embodiment 2 are united to H1975-A2 and H1975 cytotoxic activity column Meter figure；
Fig. 2 is the nude mice body weight column statistical chart of CTL killing experiments in embodiment 2；
Fig. 3 is the nude mice pathologic section-H＆E coloration results of CTL killing experiments in embodiment 2.
Embodiment
Invention is described in further detail below by embodiment.But it will be understood to those of skill in the art that under Row embodiment is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.
Embodiment 1
Antigenic Peptide T790M-2 is predicted and synthesis
Recent motif method analysis display, SYFPEITHI hyper-base sequence methods are effective HLA-A2 binding peptides forecasting systems.Cause This is used for the HLA-A2 binding peptides for predicting the 9-mer from EGFR-T790M.Using HLA-s of the SYFPEITHI to EGF-T790M A*02:01 restricted CTL epitope carries out remotely predicting, obtains the nonapeptide (L I M Q L M P F G) of score value higher (13 points).
Above-mentioned Antigenic Peptide is prepared using the method for chemical synthesis, i.e., highly developed solid-phase peptide well known in the art is closed Into method, both Fmoc methods can also be used using Boc methods.Specific practice is exactly that protected amino acid is even one by one It is linked to inertia solid phase carrier up, is then cleaved from carrier peptide chain using strong acid, while removes side chain protected.Prepare Obtain the peptide that amino acid sequence is L I M Q L M P F G.
Embodiment 2
1. PMBC separating experiment
HLA-A*02 is taken under aseptic condition:01 positive normal health donor limosis vein blood 20mL, uses separation of lymphocytes Liquid separates monocyte, cell suspension is prepared, using whole mass concentration as 2 × 109/ L is placed in blake bottle, is placed in 37 DEG C, 5%CO2 Incubator is incubated after 2h, washes away non-adherent cell；Collect adherent cell (monocyte) standby.
2. maturation DC is induced and antigen load
Above-mentioned monocyte presses whole mass concentration and adds human granulocyte-macrophage colony stimulating factor (rhGM-CsF) 1000mg/L, recombinant human interleukin--4 (rhIL-4) 500mg/L, add the cell factor of 1/2 concentration first, culture is extremely every other day (A groups) Antigenic Peptide is added within 5th day, (B groups) only adds culture medium as a control group, in 37 DEG C, 5%CO2Under the conditions of cultivate 2 days, more Nutrient solution is changed, TNF (TNF)-α (10mg/L) is added, continues to cultivate 48h, cell is collected and supernatant is standby.
3.DC surface markers are detected
Collect the DC cells of different antigen inductions and 10min is centrifuged with 1500r/min, extract cell precipitation and slow with phosphate Fliud flushing (PBS) is washed 3 times, and 30min is incubated at room temperature, reuse PBS wash after 1 time add FITC- mouse anti-human CD80, CD83, CD86, CDla, HLA DR sites (HLA-DR), using the Ig of isotype fluorescent staining as control, use flow cytometer The expression of cell surface molecule is analyzed, one is shown in Table.
The Antigenic Peptide of table one loads analysis %, the n=3 of DC cell surface molecule marks,)
Group CD1a CD 80 CD 83 HLA-DR CD86
A 37.5±2.3 59.0±4.3 51.3±2.9 73.8±2.2 72.6±4.2
B 25.2±2.1 50.7±2.3 38.5±4.4 64.2±3.9 70.9±4.1
4. the CTL cells of maturation DC inductions
Peripheral blood comes from same blood donor.The autologous anticoagulations of 4mL are added to the centrifuge tube of T lymphocyte separation mediums, layering Centrifugation, draws monocyte.By 2 × 108The DC of/L monocyte and Antigen co-cultures 5d, then to remove attached cell standby With.
5.MTT determination of color CTL killing activity
(1) the CTL cells for inducing ripe DC are used as effector cell, Non-small cell lung carcinoma cell H1975 (HLA-A2- T790M+), H1975-A2 (H1975transfected with HlA-A2, HLA-A2+T790M+) it is used as target cell.Adjustment effect Cell is answered, the effect target ratio of target cell is 3:1、10:l.
(2) using 96 well culture plates (advance ultraviolet irradiation 20min).Experimental group adds effector cell per hole and the thin liquid of target is each 100 μ L are mixed, and three multiple holes are added altogether；Laying effect cell and target cell control, are all provided with three wells, respectively take 100 μ L, all simultaneously It is each in control wells to add the μ L of RPMI-1640 (containing 10% hyclone) nutrient solution 100,37 DEG C, 5%CO2Under the conditions of educate 24h altogether.
(3) after 24h, the μ L of supernatant 100 are abandoned in suction, and adding MTT liquid storages, (5mg/mL is dissolved in 0.02M, pH7.4,0.05% Portugal In the PBS of grape sugar) 20 μ L, 37 DEG C, 5%CO2Under the conditions of, then 2~4h is educated altogether.
(4) carefully inhale and abandon the addition μ L of dimethyl sulfoxide (DMSO) 150 after supernatant, place 20min.
(5) OD490nm values are determined in enzyme mapping.
Killer cell activity is represented with killing cytotoxic activity percentage, is calculated as follows：
As a result as shown in Table 2：
The CTL cells of the maturation of table two DC inductions to H1975-A2 and H1975 cytotoxic activity (%, n=3,)
Result above shows that the CTL cells of maturation DC inductions are higher than H1975 to H1975-A2 cytotoxic activity, shows this The CTL cells of Maturation induction are recognized in mode restricted a kind of HLA-A2 with the non-small of EGFR T790M mutation in invention Cell lung cancer cell.The gap of each group more can intuitively be compared by Fig. 1 cytotoxic activity columns statistical chart.
6.CTL killing experiments：
(1) foundation of non-small cell lung cancer nude mice model：Cellar culture mouse source non-small cell lung cancer cell (H1975-A2), In exponential phase 1 × 10 is made using physiological saline7/ mL cell suspension, and cell tail vein was transplanted in 5~8 weeks Female BAl BIc/c nude mices, interval is transplanted once for 3 days again, continuous 2-3 weeks, and modeling is successful on the whole after the 1-2 months.The side of blood is taken with eye socket Formula obtains nude mice venous blood, monocyte is separated, according to " PMBC separating experiment " and " detection of DC surface markers " Method induction CTLs.
(2) experiment packet：It is randomly divided into 5 groups (body weight state is homogeneous), every group 5：(A groups) blank control group：Do not appoint The control group of where reason；(B groups) model control group：Transplant mouse source non-small cell lung cancer cell (H1975-A2), later stage injection life Reason salt solution does negative control；(C groups) CTL groups, transplanting mouse source non-small cell lung cancer cell (H1975-A2), later stage injection load is anti- The CTLs of the DC inductions of former peptide, daily can defeated 1 × 106Individual cell, continuous processing one week；(D groups) pure medicine group：Transplant mouse source non- Small cell lung cancer cell (H1975-A2), later stage injection Gefitinib medicine, injects a 50mg/kg, continuous processing one daily Week；(E groups) medicine+CTL groups, transplanting mouse source non-small cell lung cancer cell (H1975-A2), later stage per injection Gefitinib CTLs1 × 10 of the DC inductions of 50mg/kg and Loading peptides6, continuous processing one week.
(3) Testing index：After medicine and CTL are handled 2 weeks, observation nude mice changes of weight and nude mice lung pathologies change feelings Condition.As knowable to the data of table three, the nude mouse of normal nude mice control group, model control group and treated with gefitinib group is done with blank group Weight substantially mitigates；And CTL treatment groups and CTL+ treated with gefitinib groups nude mouse weight relative drop are less.By Fig. 2 body weight columns Statistical chart more can intuitively compare the gap of each group.As shown in Figure 3, the disease of the nude mice of model control group and treated with gefitinib group Manage result and understand that various pulmonary lesions are more obvious, there is obvious focus, and invade the substantial amounts of tumour cell of profit in the tissue；CTL Treatment group and CTL+ treated with gefitinib group nude mice focuses are considerably lighter, and the tumor cell number in tissue is substantially reduced.
The model of table three after naked two weeks weight ratio compared with
SEQUENCE LISTING
<110>Jiangsu Mai Jian biotechnologies Development stock Co., Ltd
<120>Antigenic Peptide T790M-2 and its application in the medicine for preparing treatment non-small cell lung cancer
<130> 20170629
<160> 1
<170> PatentIn version 3.3
<210> 1
<211> 9
<212> PRT
<213>Artificial sequence
<400> 1
Leu Ile Met Gln Leu Met Pro Phe Gly
1 5

Claims (6)

1. Antigenic Peptide T790M-2, it is characterised in that：Its amino acid sequence is as shown in SEQ ID NO.1.
2. Antigenic Peptide T790M-2, it is characterised in that：Its amino acid sequence is in the amino acid sequence as shown in SEQ ID NO.1 Replace, lack or add the amino acid sequence that one or more amino acid residues are obtained.
3. a kind of medicine for being used to treat non-small cell lung cancer, it is characterised in that：The medicine contains described in claim 1 or 2 Antigenic Peptide T790M-2.
4. the Antigenic Peptide T790M-2 described in claim 1 or 2 is preparing prevention and/or is treating the non-small of EGFR T790M mutation Application in the medicine of cell lung cancer.
5. Antigenic Peptide T790M-2 described in claim 1 or 2 prepare be used to inducing to EGFR T790M be mutated it is non- Application in the immune medicine of ED-SCLC.
6. the Antigenic Peptide T790M-2 described in claim 1 or 2 is in the medicine for induced tumor reaction-ive T cell is prepared Using, it is characterised in that：The tumor-reactive T cells are can have EGFR T790M to be mutated with targeted inhibition non-small thin The T cell of born of the same parents' lung cancer cell growth.
CN201710546363.9A 2017-07-06 2017-07-06 Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer Pending CN107325172A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710546363.9A CN107325172A (en) 2017-07-06 2017-07-06 Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710546363.9A CN107325172A (en) 2017-07-06 2017-07-06 Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer

Publications (1)

Publication Number Publication Date
CN107325172A true CN107325172A (en) 2017-11-07

Family

ID=60196616

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710546363.9A Pending CN107325172A (en) 2017-07-06 2017-07-06 Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer

Country Status (1)

Country Link
CN (1) CN107325172A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109887553A (en) * 2019-01-29 2019-06-14 杭州纽安津生物科技有限公司 For the polypeptide vaccine and its design method in tumor-targeting drug drug resistance site

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102153644A (en) * 2010-12-31 2011-08-17 广东药学院 Antigenic peptide for dimerization of epidermal growth factor receptor
EP2883884A1 (en) * 2012-08-10 2015-06-17 Kanagawa Prefectural Hospital Organization Antigen peptide originated from t790m point-mutated sequence of epidermal growth factor receptor
CN109310739A (en) * 2016-03-31 2019-02-05 内恩疗法公司 Neoantigen and its application method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102153644A (en) * 2010-12-31 2011-08-17 广东药学院 Antigenic peptide for dimerization of epidermal growth factor receptor
EP2883884A1 (en) * 2012-08-10 2015-06-17 Kanagawa Prefectural Hospital Organization Antigen peptide originated from t790m point-mutated sequence of epidermal growth factor receptor
CN109310739A (en) * 2016-03-31 2019-02-05 内恩疗法公司 Neoantigen and its application method

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KAZUYA OFUJI ET AL: "A peptide antigen derived from EGFR T790M is immunogenic in non‑small cell lung cancer", 《INTERNATIONAL JOURNAL OF ONCOLOGY》 *
TEPPEI YAMADA ET AL: "EGFR T790M Mutation as a Possible Target for Immunotherapy; Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the EGFR T790M Mutation", 《PLOS ONE》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109887553A (en) * 2019-01-29 2019-06-14 杭州纽安津生物科技有限公司 For the polypeptide vaccine and its design method in tumor-targeting drug drug resistance site
CN112687325A (en) * 2019-01-29 2021-04-20 杭州纽安津生物科技有限公司 Polypeptide vaccine composition for targeted drugs Aleptinib, Ceritinib and crizotinib and design method thereof
CN112687325B (en) * 2019-01-29 2024-01-26 杭州纽安津生物科技有限公司 Polypeptide vaccine composition aiming at targeted drugs of alatinib, ceritinib and crizotinib and design method thereof

Similar Documents

Publication Publication Date Title
CN103898051B (en) Improve immunoreactive method
US11466053B2 (en) Polypeptide and use thereof
CN104262459B (en) Acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and vaccine and pharmaceutical application of acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide
CN106222141B (en) NK cell culture fluids and cell culture processes
CN106554416A (en) A kind of anti-PD-L1 Humanized monoclonal antibodies combine interferon gene stimulatory protein(SP)（STING）Application of the agonist in antitumor
CN106397574A (en) Antigen epitope peptide and application thereof
CN107557337A (en) A kind of immunocyte of safety-type Chimeric antigen receptor modifications of anti-ROR1 and its application
CN107699547A (en) The targeting CD133 of the gene silencings of PD 1 CAR T cells and its application
US11213563B2 (en) Polypeptide and use thereof
CN102532269B (en) Dominant sequence of delta 1 chain complementary determining region (CDR) 3 in gamma delta T lymphocytes, and T cell receptor (TCR) transfected cells and application thereof
CN107106578A (en) Treat the bisphosphonate compound of E Positan epstein-Barr virus relevant diseases and the therapy of gamma delta T cells mediation
CN107325172A (en) Antigenic Peptide T790M 2 and its application in the medicine for preparing treatment non-small cell lung cancer
CN107188955A (en) Antigenic Peptide T790M 3 and its application in the medicine for preparing treatment non-small cell lung cancer
CN107188957A (en) Antigenic Peptide T790M 1 and its application in the medicine for preparing treatment non-small cell lung cancer
CN107325171A (en) Antigenic Peptide T790M 7 and its application in the medicine for preparing treatment non-small cell lung cancer
CN105233280A (en) DC-based glioma holoantigen vaccine and preparation method thereof
US20190263863A1 (en) Polypeptide and use thereof
CN111777677A (en) EGFR T790M new antigen epitope peptide and application thereof in treating tumors
US11820836B2 (en) Polypeptide and use thereof
CN107188958A (en) Antigenic Peptide T790M 5 and its application in the medicine for preparing treatment non-small cell lung cancer
CN107188959A (en) Antigenic Peptide T790M 6 and its application in the medicine for preparing treatment non-small cell lung cancer
CN110205293A (en) A kind of preparation method and application of the NK immunocyte of reinforced efficient treatment lung cancer
CN107188956A (en) Antigenic Peptide T790M 4 and its application in the medicine for preparing treatment non-small cell lung cancer
CN108392627A (en) The preparation method of DC-TAA tumor vaccines
CN101778639B (en) Proteinases destroy cancer tumor&#39;s solid structure and kill cancer cells locally

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
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20171107