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Tumor related gene PDGFRalpha mutation related antigen short peptide and application thereof

A tumor-related gene, short peptide technology, applied in the direction of anti-tumor drugs, receptors/cell surface antigens/cell surface determinants, specific peptides, etc., can solve the problems of uncontrolled cell proliferation and differentiation, and achieve clear effects and good clinical transformation. and disease prevention prospects, the effect of good application potential

Inactive Publication Date: 2020-05-19
维塔恩(广州)医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The mutation of PDGFRα will lead to the continuous activation of KIT tyrosine kinase, and the uncontrolled cell proliferation and differentiation

Method used

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  • Tumor related gene PDGFRalpha mutation related antigen short peptide and application thereof
  • Tumor related gene PDGFRalpha mutation related antigen short peptide and application thereof
  • Tumor related gene PDGFRalpha mutation related antigen short peptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Prediction of T cell epitopes of PDGFRα gene mutant peptides and design of PDGFRα short peptides

[0042] 1. Through the comprehensive platform of T cell epitope prediction data (http: / / www.cbs.dtu.dk / services / NetCTL) and bioinformatics technology, analyze and predict T cell epitope receptor (TCR) and MHC class I Molecular high-affinity peptide sequences. A series of PDGFRα mutation-related antigen short peptides were obtained through research.

[0043] 2. Screen out 50 polypeptide fragments with high predicted scores and low predicted toxicity from the above polypeptides for further research. The specific experiment is as follows:

[0044] The method for establishing PDGFRα mutant short peptide-specific CTL clones is as follows:

[0045] 10 by Flow Sorting of Healthy Donors 5 CD8 + T cells, added Mo-DCs10 loaded with PDGFRα mutant short peptide 4 were stimulated twice at intervals of 1 week, and then mitomycin C-treated autologous peripheral blood monon...

Embodiment 2

[0051] Embodiment 2 Inhibition of tumor growth test

[0052] Example 1 obtained 20 PDGFRα mutant short peptides with specific immune response effects and capable of activating T lymphocytes. Five short peptides were randomly selected from them, and further verification experiments were continued.

[0053] The gastrointestinal stromal tumor cells GIST-430 were cultured with the cell culture supernatants induced by the five short peptides. The control group was divided into two groups: no short peptide loading and nonsense short peptide loading.

[0054] The results showed that, compared with the control group, the supernatants induced by the five short peptides could significantly inhibit tumor growth and significantly increase the tumor inhibition rate (such as figure 2 shown).

[0055] Experimental results show that the CTL epitope established by the present invention is extremely effective. By presenting the PDGFRα mutant short peptide shown in any one of SEQ ID NO: 1-2...

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Abstract

The invention discloses a platelet-derived growth factor receptor alpha (PDGFRalpha) mutation related antigen short peptide and an application thereof. The sequence of the PDGFRalpha mutation relatedantigen short peptide is shown in any one of SEQ ID NO:1-20. The short peptide has high affinity with the MHC I molecule on dendritic cells (DCs), can effectively stimulate and induce production of specific cytotoxic T lymphocytes (CTLs), and can be used for immune clearance of PDGFRalpha gene mutant cells, thereby preventing the occurrence of PDGFRalpha gene mutation-related diseases, especiallypreventing PDGFRalpha gene mutation-related tumor diseases; therefore, the PDGFRalpha antigen short peptide provided by the invention has the potential of good polypeptide vaccine and DC vaccine, andhas good clinical transformation and disease prevention potential. Moreover, the PDGFRalpha antigen short peptide provided by the invention has a shorter length and low chemical synthesis difficulty,can be directly used to synthesize a high-purity product, and has greatly reduced application costs, a clear effect, and very good application prospects.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to a tumor-related gene PDGFRα mutation-related antigen short peptide and its application. Background technique [0002] Platelet-derived growth factor receptor α (platelet-derived growth factor receptoralpha, PDGFRα) is located on chromosome 4q12, and when combined with the ligand PDGFS, it can promote tumor angiogenesis. Studies have reported that PDGFRA is highly expressed in 8.7% of squamous cell carcinoma of the lung. In various tumor studies on the expression of PDGFRα, comparing tumor cells and normal epithelial cells, almost consistent results appeared, indicating that PDGFRα is closely related to the degree of malignancy of tumors, and the mutant isoforms of PDGFRα have been widely used in tumor research in recent years. PDGFRα has a high mutation rate in lung cancer and gastrointestinal tumors. The mutation of PDGFRα will lead to the continuous activ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/71C12N5/0783A61K39/00A61P35/00A61P37/02
CPCA61K2039/5154A61P35/00A61P37/02A61K39/001108C07K14/71C12N5/0638
Inventor 李许锋黄燕花赵乙木罗夫·辛克纳吉孙晨
Owner 维塔恩(广州)医药有限公司
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