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A GAS7 tumor antigen and applications thereof

An antigenic peptide and anti-tumor immune technology, applied in the field of immunology, can solve the problems of drug resistance, damage, and drug resistance caused by antagonistic drugs

Inactive Publication Date: 2017-11-17
SHANGHAI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, small molecule targeted therapy has the following problems: 1. Drug resistance, patients develop resistance to antagonistic drugs after a period of drug treatment; 2. Adverse reactions, joint pain in patients during drug treatment , nausea and other issues
[0005] Passive immunotherapy of tumors has the following problems: 1. Blocking CTLA4 may cause the body's immune response to cause certain damage to normal tissues, causing autoimmune diseases; 2. The emergence of immune-related adverse reactions is accompanied by the accumulation of organs , severe cases may be life-threatening
Although tumor neoantigens are the most ideal targets, due to the heterogeneity of tumors and the complexity of interactions with the body, the probability of tumor cell mutations producing a certain neoantigen is low

Method used

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  • A GAS7 tumor antigen and applications thereof
  • A GAS7 tumor antigen and applications thereof
  • A GAS7 tumor antigen and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0186] Example 1 Synthesis of GAS7 Antigen Peptide and Measurement of Binding Affinity with MHC Molecule HLA-A2

[0187] Through a large number of screening, a series of natural antigen peptides targeting CD8+ T cell epitopes of GAS7 were screened out, and certain amino acid positions of the natural antigen peptides were mutated to obtain corresponding mutant peptides. The binding affinities of these natural antigenic peptides and mutant antigenic peptides to HLA-A2 were predicted by IEDB T cell epitope analysis tool. Afterwards, GAS7 mutant peptides and natural antigen peptides were synthesized by Biological Peptide Synthesis Company (GenScript).

[0188] The information of the synthesized GAS7 antigen peptide and the predicted binding affinity between the antigen peptide and HLA-A2 are shown in Table 3.

[0189] table 3

[0190]

[0191]

[0192] Among them, G1, G2, G3, G4, G7-1, G7-2 are original peptides, G1-1, G1-2, G2-1, G2-2, G2-3, G3-1, G3-2, G4 -1, G4-2, G7-1...

Embodiment 2

[0194] Example 2 Using different immunization strategies to immunize HLA-A2 transgenic mice to detect the immune response of the mice

[0195] Strategy A

[0196] Using the adjuvant Al(OH) 3 Immunize the mice twice after mixing with the antigen peptide, and detect the immune response of the mice at a fixed time point (the seventh day after the second immunization) after the second immunization, and the test results are as follows: figure 1 shown.

[0197] The results showed that the response levels of mutant antigenic peptides G3-1 and G7-22 were significantly higher than those of other antigenic peptides. The results showed that the mutant antigen peptides G3-1 and G7-22 belonged to a class of mutant antigen peptides with better response, which could be used for further research and analysis.

[0198] Strategy B

[0199] After the inventor loaded the mutated peptide on DC (dendritic cells), the original peptide and the adjuvant Al(OH) 3 After the mice were mixed immunize...

Embodiment 3

[0205] Example 3 Detection of Different Immunization Strategies for Improving the Cross Reaction of Antigenic Peptides

[0206] The proportion of CD8-positive cells producing IFNγ after stimulating spleen cells with antigenic peptides in vitro was analyzed by flow cytometry, and the original peptides of the following three groups (G3 A / G72A, G3 B / G72B, G3 C / G72C) The cross-reactivity of G3 and G7-2 was detected.

[0207] G3 A / G72A: After the DC-loaded mutant peptide was immunized once, the cross-immune reaction of the mice to the original peptide G3 and G7-2 was detected.

[0208] G3 B / G72B: After DC-loaded mutated peptide immunization, the original peptide and adjuvant Al(OH) were used 3 After the mice were mixed and immunized twice, the specific immune responses of the mice to the original peptides G3 and G7-2 were detected.

[0209] G3 C / G72C: Adjuvant Al(OH) 3 After the mice were immunized twice with the mutant peptide, the specific immune responses to the original pept...

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Abstract

The present invention provides GAS7 tumor antigen and its application. Specifically, the present invention provides an antigenic peptide of GAS7 protein, the antigenic peptide is composed of 7-25 amino acids, and the antigenic peptide is a T cell recognition epitope. The antigenic peptide of the present invention can effectively activate T cells that recognize natural tumor antigens, effectively increase their affinity, and induce stronger cross-immune reactions to natural peptides.

Description

technical field [0001] The present invention relates to the field of immunology, in particular, to the GAS7 tumor antigen and its application. Background technique [0002] With the change of environmental conditions and the increase of the aging population, the incidence of cancer has gradually increased in recent years. Tumor has become an important factor threatening human health. At present, tumor immunotherapy has become a research hotspot all over the world. Immunotherapy of tumors refers to the use of the body's immune system to fight tumors. The body's anti-tumor immune response is mainly mediated by CD8-positive cytotoxic T lymphocytes (CD8+CTL). Active immunotherapy is to combine tumor antigens (proteins, polypeptides, DNA, RNA) and even tumor cell lysates with appropriate carriers, supplemented by appropriate adjuvant Al(OH) 3 , the immune body aims to induce a lasting immune response in the body. Passive immunotherapy mainly uses tumor-specific antibodies or...

Claims

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Application Information

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IPC IPC(8): C07K14/82C07K19/00C12N15/12C12N5/0784G01N33/68G01N33/574A61K39/00A61P35/00
CPCC07K14/82A61K39/0011A61K2039/55505C07K14/765C07K14/795C07K2319/00C07K2319/33C07K2319/55C12N5/0639G01N33/5743G01N33/57484G01N33/68
Inventor 冷启彬胡广罗开明崔瑛
Owner SHANGHAI UNIV
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