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HER3-dimerized-interface antigen peptide, recombinant antigen peptide, coding gene and application of HER3-dimerized-interface antigen peptide

A technology for recombining antigens and encoding genes, which is applied in the fields of HER3 dimerization interface antigen peptides, encoding genes and their applications, and recombinant antigen peptides. problem, to achieve the effect of low cost of treatment

Pending Publication Date: 2020-09-11
WANNAN MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The former may be shielded by potentially effective target epitopes due to the large size of the immunogen molecule, making it difficult to stimulate the body to produce an effective immune response; the latter stimulates the body to produce antibodies whose binding sites are basically the same as those of the marketed antibodies, and it is difficult to avoid competitive binding disadvantages or off-targets of the marketed antibodies disadvantages, all have limitations

Method used

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  • HER3-dimerized-interface antigen peptide, recombinant antigen peptide, coding gene and application of HER3-dimerized-interface antigen peptide
  • HER3-dimerized-interface antigen peptide, recombinant antigen peptide, coding gene and application of HER3-dimerized-interface antigen peptide
  • HER3-dimerized-interface antigen peptide, recombinant antigen peptide, coding gene and application of HER3-dimerized-interface antigen peptide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0104] Selection of HER3 183-227aa, HER3 236-308aa, HER3 559-591aa dimerized B cell epitopes:

[0105] Retrieve the full-length amino acid sequence of HER3 in the NCBI database, combine with the 3D structure diagram of HER3, and select peptides that are exposed on the surface of the dimerization structure and are easily accessible ( figure 1 , figure 2 with image 3 ), using the online B cell epitope prediction tool to evaluate and select the peptide with the highest comprehensive score in each segment as the HER3 2 Polymeric B cell epitope peptide ( Figure 4 ).

Embodiment 2

[0107] Preparation of antigenic peptides in the form of MVF-GPSL-B cell epitopes

[0108] Among the recombinant B cell epitope peptides MVF-GPSL-HER3 183-227aa, MVF-GPSL-HER3 236-308aa and MVF-GPSL-HER3 559-591aa, MVF is "universal Th epitope sequence", and GPSL is a flexible linker ( Figure 5 ). These recombinant peptides can be produced by either direct chemical synthesis or genetic engineering. In this example, the recombinant peptide is produced by genetic engineering. First, the gene of the recombinant peptide is synthesized and cloned in a prokaryotic or eukaryotic expression system. After induced expression, a certain method is used to separate and purify the obtained product. Due to the high cost of chemically synthesizing long peptides, it is difficult to ensure the correctness of the structure. The invention adopts the genetic engineering method based on the expression system of Escherichia coli to produce.

[0109] 1) Obtaining the target gene

[0110] Accordin...

Embodiment 3

[0141] Immunogenicity analysis of three recombinant anti-HER3 dimerization antigen peptides and preparation of polyclonal antibodies. Rats were immunized with the above-mentioned purified recombinant antigenic peptides as antigens, immunogenicity was analyzed and recombinant antigenic peptide antiserum was prepared.

[0142] 1) Recombinant anti-HER3 dimerization antigen peptide immunization

[0143] The three recombinant peptides MVF-GPSL-HER3 183-227aa, MVF-GPSL-HER3 236-308aa and MVF-GPSL-HER3 559-591aa powders obtained by lyophilization were weighed and redissolved by adding 1ml of normal saline for every 2mg. After several times of gentle blowing, it was found that the three recombinant peptide powders could not be completely dissolved and were in a suspended state. Take 100 microliters of each recombinant peptide suspension and centrifuge at 18,000 rpm for 10 minutes. Undissolved peptide precipitates are found at the bottom of the centrifuge tube. The concentrations of t...

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Abstract

The invention provides an HER3-dimerized-interface antigen peptide, a recombinant antigen peptide, a coding gene and application of the HER3-dimerized-interface antigen peptide. Compared with the prior art, the antigen peptide provided by the invention is selected based on structural functions of HER3 and has better pertinency to blocking of an HER3 signal conduction function. The antigen peptideprovided by the invention is located in a dimerization interface region of a non-HER3-ligand-bonded area, whereas, a majority of the existing antibodies target to a ligand-bonded area or a conformation changed area after ligand bonding, and competing of a bonded site with a ligand can be avoided through targeting to the dimerization interface region; and the antigen peptide provided by the invention is a linear B-cell epitope antigen peptide and can be free of a target missing effect caused by conformational change of the HER3. The antigen peptide is applied to preparation of drugs for preventing and treating HER3-overexpression tumors and reversing EGFR-HER2-targeting drug resistance, is mainly used for preparing therapeutic vaccines, the therapy cost is much lower than that of antibodies, and the side effect is lower than that of antibodies required to be used by large dose.

Description

technical field [0001] The invention relates to the field of preparation of polypeptides and drug carriers, in particular to a HER3 dimerization interface antigen peptide, recombinant antigen peptide, coding gene and application thereof. Background technique [0002] Human epidermal growth factor receptor 3 (HER3, human epidermal growth factor receptor 3) and human epidermal growth factor receptor (EGFR / HER1, human epidermal growth factor receptor), human epidermal growth factor receptor 2 (HER2, human epidermal growth factor receptor 2) belongs to the epidermal growth factor receptor family, which plays an important regulatory role in the growth and development of embryos and normal tissues. However, EGFR and HER2 expression up-regulation or activating mutations can be found in colorectal cancer, lung cancer and some breast cancers, respectively, and are closely related to tumor proliferation, metastasis and anti-apoptosis, etc., and are definite tumor therapeutic target mo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/82C07K14/71C07K19/00C12N15/62C12N15/10C07K16/32C07K16/06A61K39/00A61P35/00
CPCC07K14/82C07K14/71C12N15/10C07K16/32C07K16/06A61K39/001106A61P35/00C07K2319/40C07K2317/73C12Q2531/113
Inventor 朱磊孙金琳张叶明沈学彬章圣朋
Owner WANNAN MEDICAL COLLEGE