Tumor-related gene FBXW7 mutation-related antigen short-peptide and application thereof

A tumor-related gene and short peptide technology, applied in the field of biomedicine, can solve the problem of weak affinity between CDP and FBXW7, and achieve the effect of good clinical transformation and disease prevention prospects, good application potential, and low difficulty in chemical synthesis.

Inactive Publication Date: 2020-04-24
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

However, the CDP of some substrates has weak affinity with FBXW7 and requires FBXW7 dimer to degrade

Method used

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  • Tumor-related gene FBXW7 mutation-related antigen short-peptide and application thereof
  • Tumor-related gene FBXW7 mutation-related antigen short-peptide and application thereof
  • Tumor-related gene FBXW7 mutation-related antigen short-peptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1 Prediction of T cell epitope of FBXW7 gene mutant peptide and design of FBXW7 short peptide

[0043] 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 FBXW7 mutation-related antigen short peptides were obtained through research.

[0044] 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:

[0045] The method for establishing FBXW7 mutant short peptide-specific CTL clones is as follows:

[0046] 10 by Flow Sorting of Healthy Donors 5 CD8 + T cells, added Mo-DCs10 loaded with FBXW7 mutant short peptide 4 Stimulated twice at intervals of 1 week, and then treated with mitomycin C-loaded FBXW7 short peptide autologous per...

Embodiment 2

[0052] Embodiment 2 Inhibition of tumor growth test

[0053] Example 1 obtained 20 FBXW7 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.

[0054] Lung cancer cells A549 were cultured with the cell culture supernatants induced by the 5 short peptides respectively. The control group was divided into two groups: no short peptide loading and nonsense short peptide loading.

[0055] The results showed that, compared with the control group, the supernatants induced by the five short peptides could significantly inhibit the growth of tumor cells and significantly reduce tumor activity (such as figure 2 shown).

[0056] Experimental results show that the CTL epitope established by the present invention is extremely effective. By presenting the FBXW7 mutant short peptide shown in any one of SEQ ID NO: 1-20 through dendritic...

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Abstract

The invention discloses an FBXW7 mutation-related antigen short-peptide and application thereof. The sequence of the FBXW7 mutation-related antigen short-peptide is shown as any one of SEQ ID NO: 1-20. The short-peptide has high affinity with MHC I molecules on DC cells, can effectively stimulate and induce to generate specific cytotoxic T lymphocytes (CTLs), and can be used for immune clearance of FBXW7 gene mutation cells so as to prevent the occurrence of FBXW7 gene mutation related diseases, especially to prevent FBXW7 gene mutation related tumor diseases. Therefore, the FBXW7 antigen short-peptide provided by the invention has good potential of polypeptide vaccines and DC vaccines, and has good clinical transformation and disease prevention potential. Moreover, the FBXW7 antigen short-peptide is short in length and low in chemical synthesis difficulty, a high-purity product can be directly synthesized, the application cost is greatly reduced, and the effect is definite. Therefore,the FBXW7 antigen short-peptide has application prospects.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to a tumor-related gene FBXW7 mutation-related antigen short peptide and its application. Background technique [0002] The FBXW7 gene is located at 4q31 in the human chromosome, and consists of 1 specific exon and 10 shared exons. After splicing, three transcripts of FBXW7a, FBXW7β and FBXW7γ are produced. The composition of the FBXW7 gene is highly conserved in humans: ① FBXW7 contains several conserved domains for protein interaction, which can directly bind SCF to S-phase-associated protein 1 (skp1) and recruit other components of SCF; ② The N-terminal of FBXW contains 8 repeats of WD40, which constitute substrate binding These repeated sequences may be the binding points for direct interaction with substrates; ③The other domain of FBXW7 is called D domain, which can promote the dimerization of FBXW7. Although it is not important for substrate recognition, u...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C12N5/0783A61K39/00A61P35/00
CPCA61K39/0011A61K2039/5154A61K2039/57A61P35/00C07K14/4703C12N5/0638C12N2501/727C12N2501/998C12N2502/11
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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