CN105859865A - Dual anti-tumor polypeptide based on Eps8-EGFR binding domain - Google Patents
Dual anti-tumor polypeptide based on Eps8-EGFR binding domain Download PDFInfo
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- CN105859865A CN105859865A CN201610293675.9A CN201610293675A CN105859865A CN 105859865 A CN105859865 A CN 105859865A CN 201610293675 A CN201610293675 A CN 201610293675A CN 105859865 A CN105859865 A CN 105859865A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
The invention relates to a dual anti-tumor polypeptide based on the Eps8-EGFR binding domain. The amino acid sequence of the polypeptide is Glu-Phe-Leu-Asp-Cys-Phe-Gln-Lys-Phe (SEQ ID No:1). The dual anti-tumor polypeptide can induce toxic T cells, effectively kills HLA-A*2402 positive tumors and Eps8 positive tumors, can directly inhibit proliferation of HLA-A*2402 positive tumor cells and Eps8 positive tumor cells, and can be used for preparing dual anti-tumor medicine.
Description
Technical field
The present invention relates to organic chemistry filed, be specifically related to the polypeptide from mammal, this polypeptide has antitumor activity, suitable
For preparing antineoplastic.
Background technology
Polypeptide drugs have very important Development volue in clinical practice.Part of polypeptide medicine has promotion body's immunity
Effect, referred to as polypeptide vaccine.Induction is strong and the qualification of the novel tumor antigen of specificity antineoplastic immunity response ensure that for
The exploitation of the polypeptide vaccine of all kinds tumour and clinical practice (Reche P, et al.J Immunol Res 2015；2015:
349049；Jazirehi AR,et al.Cancer Res 2011；71(4):1406-1417；Andersen RS,et al.Cancer
Immunol Immunother 2011；60(2):227-234；Gritzapis AD,et al.Cancer Res 2010；70(7):2686-
2696；Klepin HD,et al.Oncologist 2009；14(3):222-232.).Up to now, existing many practical tumours are correlated with
Antigen derives the clinical testing of polypeptide, induces anti-tumor immune response (Walter S, et al.Nat Med the most to varying degrees
2012；18(8):1254-1261；Bae J,et al.Clin Cancer Res 2012；18:4850-60；Slingluff CJ,et al.Clin
Cancer Res 2007；13:6386-95；Slingluff CJ,et al.Clin Cancer Res 2009；15:7036-44；Slingluff CJ,et
al.J Clin Oncol 2011；29:2924-32.)
The Immune Selection driven due to treatment can cause the deletion of tumour antigen, suddenlys change or lower, and then causes tumour cell immunity
Escape, therefore, occur tumour cell to develop the ideal targets that requisite tumor associated antigen is immunotherapy, can be by swollen
The risk of knurl immunologic escape is down to minimum.
Eps8, i.e. EGF-R ELISA path substrate 8 (Epidermal growth factor receptor Pathway
Substrate 8, Eps8), it is that EGF-R ELISA (EGFR, Epidermal Growth Factor Receptor) is important
One of kinase activity substrate.It turned out, Eps8 is up-regulated in many tumour cells, including cervical carcinoma (Chen YJ,
et al.Mol Cancer Ther 2008；7:1376-85.), colorectal cancer (Maa MC, et al.J Biol Chem
2007；282:19399-409.), hypophysoma (Xu M, et al.Endocrinology 2009；150:2064-71.), oral squamous cell carcinomas
(Chu PY,et al.Asia Pac J Clin Oncol 2012；8:e77-81.), Pancreatic neoplasms (Welsch T, et al.Cancer
Lett 2007；255:205-18.), breast cancer (Yao J, et al.Cancer Res 2006；66:4065-78.), thyroid cancer
(Griffith OL,et al.J Clin Oncol 2006；24:5043-51.), the cancer of the esophagus (Bashir M, et al.Cell Commun
Signal 2010；8:13.) and glioblastoma (Ding X, et al.Oncol Rep 2013；29:697-703.) etc. entity tumor,
And Huppert's disease (Li YuhuaDeng. Shandong medicine 2011；51:9-11.), leukaemia (Li YH,et al.Clin Lab 2013；
59(11-12):1261-1269；Li YH,et al.Leuk Res 2015；39(6):575-581；Kang H,et al.Blood
2012；119:1872-81.) etc. hematological system tumor.Analyze discovery further, Eps8 up-regulated promote tumor cell proliferation with
Transfer, suppresses apoptosis of tumor cells, reduces drug susceptibility, (Welsch T, et al. closely related with tumor patient poor prognosis
Cancer Lett 2007；255:205-18；Chen YJ,et al.Mol Cancer Ther 2008；7:1376-85；Ding X,et al.
Oncol Rep 2013；29:697-703；Li YH,et al.Future Oncol 2013；9(10):1587-1594.).More than study
Bright Eps8 is key molecule and the prognostic factor of tumor development.
Part of polypeptide medicine is separately had to play the effect of the suppression BA such as tumor proliferation, transfer, referred to as peptide inhibitor.This
Class polypeptide drugs are for the purpose of blocking rush knurl associated signal paths.The existing multiple antineoplastic polypeptide medicines of last decade go through to list,
As being applied to gonadotropin-releasing hormone (GRH) (GnRH) antagonist abarelix (Abarelix:abarelix-of prostate cancer
depot-F,abarelix-depot-M,abarelix-L,PPI 149,R 3827.Drugs R D 2003；4 (3): 161-166.) and
degarelix(Frampton JE,et al.Drugs 2009；, and be applied to the egg of Huppert's disease 69 (14): 1967-1976.)
White enzyme body inhibitor carfilzomib (McCormack PL.Drugs 2012；72(15):2023-2032.).
The patent application of Publication No. CN 103694333A discloses a kind of EPS8 antitumor CTL epitope peptide, and demonstrates
It promotes the effect of CTL cell killing tumour cell.But, the follow-up study of the present inventor finds, above-mentioned CTL epitope peptide
Cytostatic to tumor cell effect undesirable, inhibiting rate is below 50%.
Therefore, the polypeptide of dual GVT is developed, i.e. this polypeptide both can promote CTL cell killing tumour cell, again
Can directly suppress tumor cell proliferation, Clone formation, the design to antineoplastic is significant.
Summary of the invention
A kind of dual antineoplastic polypeptide based on Eps8-EGFR binding domain of offer of the technical problem to be solved, should
Polypeptide both can cause the CTL of corresponding molecular specificity, can block again Eps8/EGFR signal path, the increasing of suppression tumour cell
Grow.
The present invention solves the technical scheme of the problems referred to above:
A kind of dual antineoplastic polypeptide based on Eps8-EGFR binding domain, the amino acid sequence of this polypeptide is Glu-Phe-Leu-
Asp-Cys-Phe-Gln-Lys-Phe (SEQ ID No:1).
Above-mentioned dual antineoplastic polypeptide sequence as shown in SEQ ID NO:1 can use solid-phase synthesis synthesis to obtain.
Above-mentioned dual antineoplastic polypeptide is positioned in Eps8-EGFR binding domain, had both had immunogenicity, and can block again
EGFR/Eps8 signal path, the propagation of suppression tumour cell, therefore can be used for preparing tumor vaccine, it is also possible to be used for preparing anti-
The medicine of tumour.
Dual antineoplastic polypeptide of the present invention can inducing specific T cell immune response, show as stimulate specificity T thin
Intracrine high level IFN-γ also produces specific killing effect to Eps8 positive tumor cell.Of the present invention dual anti-swollen
Knurl polypeptide also can block the signal path of EGFR/Eps8, directly suppresses tumor cell proliferation, therefore can be with conventional chemotherapeutic drugs
Combination.
Accompanying drawing explanation
Fig. 1 is the mass spectrogram of dual antineoplastic polypeptide of the present invention.
Fig. 2 is the testing result figure of the specific CTL secretion of gamma-IFN ability of dual antineoplastic polypeptide of the present invention induction, its
In, figure A is induction CTL secretion of gamma-IFN microphoto；The bar chart of figure B induction CTL secretion of gamma-IFN spot number.
Fig. 3 is that the specific CTL of dual antineoplastic polypeptide of the present invention induction is to the Eps8 positive, HLA-A*2402 is positive
The curve map of colon cancer cell SW620 Cytotoxicity in vitro ability, the abscissa in figure represents effector cell (CTL) and target cell
(SW620) ratio (effect target ratio), ordinate represents killing rate (%).
Fig. 4 is that the specific CTL of dual antineoplastic polypeptide of the present invention induction is to the Eps8 positive, HLA-A*2402 is positive
The curve map of colon cancer cell Colo320 Cytotoxicity in vitro ability, the abscissa in figure represents effector cell (CTL) and target cell
(Colo320) ratio (effect target ratio), ordinate represents killing rate (%).
Fig. 5 is that the specific CTL of dual antineoplastic polypeptide of the present invention induction is to the Eps8 positive, HLA-A*2402 is positive
The curve map of non-small cell lung cancer cell A549 Cytotoxicity in vitro ability, the abscissa in figure represents effector cell (CTL) and target
The ratio (effect target ratio) of cell (A549), ordinate represents killing rate (%).
Fig. 6 is that the specific CTL of dual antineoplastic polypeptide of the present invention induction is to the Eps8 positive, HLA-A*2402 is positive
The curve map of hepatocellular carcinoma H22 Cytotoxicity in vitro ability, the abscissa in figure represents effector cell (CTL) and target cell
(HepG2) ratio (effect target ratio), ordinate represents killing rate (%).
Fig. 7 is that dual antineoplastic polypeptide effect 48h of the present invention is to the Eps8 positive, HLA-A*2402 positive tumor cells increase
Growing the curve map of inhibiting rate, the abscissa in figure represents that peptide concentration, ordinate represent proliferation inhibition rate (%).
Fig. 8 is that dual antineoplastic polypeptide of the present invention is to the Eps8 positive, HLA-A*2402 positive tumor cell Clone formation
The bar chart of inhibiting rate, the abscissa in figure represents that peptide concentration, ordinate represent Clone formation inhibiting rate (%).“*”
Represent compared with corresponding solvent control group (0 μM), P < 0.05；In figure "**" represent and corresponding solvent control group
(0 μM) is compared, P < 0.01；In figure "***" represent compared with corresponding solvent control group (0 μM), P < 0.001.
Fig. 9 be Publication No. CN 103694333A patent application described in CTL epitope peptide is positive to Eps8, HLA-
A*The curve map of the SW480 cell proliferation inhibition rate of 0201 positive.
Detailed description of the invention
Embodiment 1 (screening of Eps8-EGFR binding domain polypeptide)
The antineoplastic polypeptide in Eps8-EGFR domain of the present invention source, is the primary structure according to antigen, and employing is exempted from
Epidemic disease informatics means, use online biological software SYFPEITHI
(http://www.syfpeithi.de/bin/MHCServer.dll/EpitopePrediction.htm) (this algorithm is recorded in
Rammensee H,et al.Immunogenetics 1999；50 (3-4): 213-219.) and BIMAS (http://www-
Bimas.cit.nih.gov/molbio/hla_bind/) (this algorithm is recorded in Parker KC, et al.J Immunol 1994；152(1):
163-175.) the HLA-A to Eps8 molecule EGFR binding domain*2402 restricted being predicted are analyzed, and filter out amino acid sequence
It is classified as the polypeptide shown in SEQ ID No:1, and is designated as Eps8-327.Polypeptide shown in SEQ ID No:1 is raw by peptide in Hangzhou
Change the sequence that Co., Ltd is provided according to the present inventor, use the synthesis of the Fmoc solid phase method of peptide synthesis.Use reversed phase high-pressure liquid phase
Its target product synthesized is purified and purity analysis by chromatograph, and result shows its purity > 95%, then use mass spectrography to enter
Row is identified and molecular weight determination, obtains mass spectrogram as shown in Figure 1.
Following embodiment 2-7 dual antitumous effect to the polypeptide Eps8-327 (SEQ ID No:1) obtained by this example respectively
Verify.
Embodiment 2 [induction of external primed antigen presenting cells (APC)]
Use the BMDC (DC) that PMNC derives as APC, (Nakahara with reference to described in other places
S, et al.Cancer Res 2003Jul 155,63 (14): 4112-8) induce DC in vitro.Specifically, Ficoll-is utilized
Plaque density gradient method separating health volunteer (HLA-A*2402 is positive) peripheral blood separates mononuclearcell
(PBMCs), separate original DC by adherent method, PRMI-1640,1000U/ml granulocyte containing 10%FBS-
The nutrient solution of macrophage colony stimulatory factor (GM-CSF) and 1000U/ml IL-4 (IL-4) is cultivated.Cultivating
7th day, in the culture medium containing 3 μ g/ml B2Ms, utilize each synthetic peptide (20 μ g/ml) impulse through cell because of
The DC of son induction 3 hours.The cell generated is at cell surface expression DC correlation molecule, such as CD80, CD83, CD86
With HLA-II molecule (data do not show).
Embodiment 3 (induction of external CTL)
The above-mentioned DC mitomycin C (MMC) through polypeptide impulse inactivates (30 μ g/ml, 30min), with 1:20 ratio
With autologous CD8+T cell (by CD8 positive separating kit by just selecting acquisition) mixing, in containing IL-7 10ng/ml's
Culture medium is cultivated.3rd day, add IL-2 to final concentration of 20U/ml in the medium.At the 7th day and the 14th day, use
Through peptide impulse, inactivation autologous DC stimulate T cell further.Within 21st day, collect cell detection CTL function (Olson
BM,et al.Cancer Immunol Immunother 2011；60(6):781-792；Andersen RS,et al.Cancer
Immunol Immunother 2011；60(2):227-234.).
Embodiment 4 (CTL secretion of gamma-IFN function)
IFN-γ-ELISPOT is utilized to detect above-mentioned CTL activity.Specifically, by kit operating instruction, in 96 hole nitric acid
Cellulose membrane culture plate preincubate capture antisera overnight, counts and adjusts above-mentioned effector cell next day to 1 × 106/ ml, is inoculated in training
Support plate, every hole 100 μ l, hatch 24h, wash plate, hatch respectively one anti-, two resist, colour developing, finally use ELISPOT plate reader
Spot is counted.Packet includes: positive control group: effector cell+10 μ l PHA, final concentration 1～4 μ g/ml；Experimental group:
Effector cell；Background negative control group: the Lympho-Spot serum free medium of 100 μ l.
Result: as in figure 2 it is shown, compared with solvent control group, the T cell secretion of gamma-IFN digital display of Eps8-327 induction writes and increases
Add, P < 0.001.
Embodiment 5 (CTL killing tumor cell function)
Utilize the ability of lactic dehydrogenase (LDH) method for releasing detection CTL killing tumor cell.Specifically, according to CytoNon-Radioactive Cytotoxicity Assay kit operating instruction, with above-mentioned CTL as effector cell, with
Each tumour cell (SW620, Colo320, A549 and HepG2) is target cell, and detection specific T-cells is to tumour cell
Killing ability.Arrange experimental group, effector cell's spontaneous release group, target cell spontaneous release group, target cell maximum release group,
Ground control group and volume correction group.Effector cell and target cell are hatched altogether, after reaction 4h, add substrate colour developing 30min,
After terminating reaction, ELIASA measures absorbance (A) value of wavelength 490nm, calculates the CTL killing rate to tumour cell.
Killing rate (%)=[(the relative A value of the relative A value of experimental group-target cell spontaneous release group-effector cell's spontaneous release group
A value relatively)/(the relative A value of the relative A value of target cell maximum release group-target cell spontaneous release group)] × 100%.Its
In, experimental group, target cell spontaneous release group and effector cell's spontaneous release group are individually subtracted medium controls A value and obtain it
Corresponding A value relatively；Target cell maximum release group deducts fixing fabric structure group and obtains its corresponding A value relatively.
Result: as shown in figures 3 to 6, compared with solvent control group, derives from the polypeptide Eps8-of Eps8-EGFR binding domain
The specific T-cells of 327 inductions significantly kills the Eps8 positive, HLA-A*The tumour cell SW620 of 2402 positives,
Colo320 (colon cancer), A549 (non-small cell lung cancer) and HepG2 (liver cancer).
Embodiment 6 [suppression tumor cell proliferation (CCK-8 method)]
Take the logarithm cells rinsed with PBS in growth period, be resuspended in after counting and train containing volume fraction 10% hyclone RPMI 1640
Support in base to density be 5 × 104/ ml, is inoculated in 96 orifice plates with 100 μ l/ holes, is placed in incubator overnight, changes into after cell attachment
Serum free medium carries out 4h Nature enemy, abandons nutrient solution, washes twice with PBS, is subsequently adding the respective concentration prepared
The polypeptide solution of (25,50,75,100,125,150,175 μMs), after cultivating 48h respectively, every hole adds 10 μ l CCK-
8 solution, continue in incubator to cultivate 3h.It is placed in ELIASA, reads absorbance at 450nm wavelength.Experiment repetition three
Secondary, it is all provided with 3 multiple holes, averages as final result.
Result: as it is shown in fig. 7, the polypeptide Eps8-327 being derived from Eps8-EGFR binding domain significantly inhibits HLA-A*2402 Hes
The propagation of colon cancer cell SW620, Colo320, HT-29 that Eps8 is positive.The half of SW620 is suppressed by Eps8-327
Concentration (IC50) it is 26.79 μMs (95%CI:17.34-41.38), the IC to Colo320 cell50It it is 108.3 μMs
(95%CI:101.8-115.2), the IC to HT-29 cell50It is 149.3 μMs (95%CI:129.7-171.9).
Embodiment 7 [suppression tumor cell clone forms (plate clone experiment)]
Taking the logarithm each tumour cell in growth period, the complete culture solution containing 10%FBS is resuspended, adds candidate polypeptide to the most final concentration of
100 μMs, 200 μMs, it is inoculated in 6 orifice plates with 500 cells/well, puts 37 DEG C, 5%CO2Incubator is cultivated 7-14 days, shape
Become after the visible clone of naked eyes (more than 50 cells), with PBS rinsing cell once, exhaust residual liquid.Add
4% paraformaldehyde room temperature fixes 20min, abandons fixer, and PBS rinsing cell once, adds 0.5% crystal violet dye
Liquid, room temperature dyeing 10-20min, abandons dyeing liquor, dries after distilled water flushing, calculate Cell colonies assay=(clone's number/connect
Plant cell number) × 100%.
Result: as shown in Figure 8, be derived from Eps8-EGFR binding domain polypeptide Eps8-327 suppression tumour cell HT-29,
SW620, Colo320 and HepG2 Clone formation.
Embodiment 8 (contrast experiment)
This example uses CCK-8 method to four CTL epitope peptides described in the patent application of Publication No. CN 103694333A
The ability of EPS8-101, EPS8-276, EPS8-360 and EPS8-455 suppression tumor cell proliferation is verified, concrete steps
As follows: SW480 cells rinsed with PBS in growth period of taking the logarithm, it is resuspended in after counting containing volume fraction 10% hyclone
In RPMI 640 culture medium to density be 5 × 104/ ml, is inoculated in 96 orifice plates with 100 μ l/ holes, is placed in incubator overnight, treats cell
Change serum free medium after adherent into and carry out 4h Nature enemy, abandon nutrient solution, wash twice with PBS, be subsequently adding and prepare
The polypeptide solution of respective concentration, after cultivating 48h respectively, every hole adds 10 μ l CCK-8 solution, continues to cultivate 3h in incubator.
It is placed in ELIASA, reads absorbance at 450nm wavelength.Experiment in triplicate, is all provided with 3 multiple holes, average into
Final result.
Result: as it is shown in figure 9, four CTL epitope peptide EPS8-101, EPS8-276, EPS8-360 and EPS8-455 exist
0-100 μM of concentration ranges does not has inhibitory action to SW480 cell proliferation, only reveals at high concentration 150-200 μM interval table and presses down
Make use, but its inhibiting rate is still below 50%.Fig. 9 with Fig. 7 is compared visible, four CTL epitope peptide EPS8-101,
The ability of EPS8-276, EPS8-360 and EPS8-455 suppression SW480 cell proliferation is markedly less than polypeptide of the present invention
Eps8-327 (SEQ ID No:1).
In a word, the present invention identifies the novel polypeptide being derived from Eps8-EGFR binding domain, and on the one hand these polypeptide can induce
CTL killing tumor cell, on the other hand can significantly inhibit tumor proliferation, Clone formation, have dual GVT, suitable
For tumour immunotherapy and cancer target therapy.
Above-described embodiment 2-8 illustrates, polypeptide of the present invention polypeptide of the present invention Eps8-327 (SEQ ID No:1) is with public
The number of opening is four CTL epitope peptide EPS8-101, EPS8-276, EPS8-360 described in the patent application of CN 103694333A
With the function of EPS8-455 and effect, there is following difference: 1, polypeptide of the present invention is HLA-A*2402 restricted polypeptide,
It is applicable to HLA-A*2402 Positive Populations；Four CTL epi-positions described in the patent application of Publication No. CN 103694333A
Peptide is HLA-A*0201 restricted polypeptide, it is adaptable to HLA-A*0201 Positive Populations；2, polypeptide of the present invention is except swashing
Live outside anti tumor immune response, also there is the effect directly suppressing the BA such as tumor cell proliferation, Clone formation, and public
The number of opening is only capable of activating anti tumor immune response for four CTL epitope peptides described in the patent application of CN 103694333A.
Claims (3)
1. a dual antineoplastic polypeptide based on Eps8-EGFR binding domain, the amino acid sequence of this polypeptide is Glu-Phe-
Leu-Asp-Cys-Phe-Gln-Lys-Phe (SEQ ID No:1).
A kind of dual antineoplastic polypeptide based on Eps8-EGFR binding domain the most according to claim 1, its feature exists
In, this dual antineoplastic polypeptide is to use solid-phase synthesis synthesis.
3. the polypeptide described in claim 1 promotes anti-tumor immune response in preparation and suppresses the double of cellular biology of tumor activity
Application in weight anti-tumor drug.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106279402A (en) * | 2016-08-28 | 2017-01-04 | 苏州普罗达生物科技有限公司 | A kind of carcinoembryonic antigen immunogen polypeptide and application thereof |
| CN106367406A (en) * | 2016-08-28 | 2017-02-01 | 苏州普罗达生物科技有限公司 | UDP glycosyl transferase immunogen polypeptide and applications thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005116051A3 (en) * | 2004-05-25 | 2006-03-02 | Immatics Biotechnologies Gmbh | Tumor-associated peptides that bind to mhc-molecules |
| CN1883709A (en) * | 2005-06-21 | 2006-12-27 | 南京大学 | Bi-functional targeting antineoplastic polypeptide and application thereof |
| CN103992382A (en) * | 2014-05-14 | 2014-08-20 | 南方医科大学 | Oligopeptide formed by combining targeted EPS8 (Epidermal Growth Factor Receptor pathway substrate No.8) with EGFR (Epidermal Growth Factor Receptor) and application of oligopeptide |
-
2016
- 2016-05-05 CN CN201610293675.9A patent/CN105859865B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005116051A3 (en) * | 2004-05-25 | 2006-03-02 | Immatics Biotechnologies Gmbh | Tumor-associated peptides that bind to mhc-molecules |
| CN1883709A (en) * | 2005-06-21 | 2006-12-27 | 南京大学 | Bi-functional targeting antineoplastic polypeptide and application thereof |
| CN103992382A (en) * | 2014-05-14 | 2014-08-20 | 南方医科大学 | Oligopeptide formed by combining targeted EPS8 (Epidermal Growth Factor Receptor pathway substrate No.8) with EGFR (Epidermal Growth Factor Receptor) and application of oligopeptide |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106279402A (en) * | 2016-08-28 | 2017-01-04 | 苏州普罗达生物科技有限公司 | A kind of carcinoembryonic antigen immunogen polypeptide and application thereof |
| CN106367406A (en) * | 2016-08-28 | 2017-02-01 | 苏州普罗达生物科技有限公司 | UDP glycosyl transferase immunogen polypeptide and applications thereof |
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