NY-ESO-1 tumour antigen mimic epitope and use thereof

A technology of tumor antigens and mimetic epitopes, which is applied in the direction of anti-tumor drugs, special data processing applications, antibody medical components, etc., can solve the problems of inability to achieve anti-tumor effects, achieve easy synthesis and storage, reduce research costs, and widely The effect of applying the foreground

Inactive Publication Date: 2009-03-11
ARMY MEDICAL UNIV
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  • Claims
  • Application Information

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Problems solved by technology

Recent studies have shown that although the modified peptide vaccine based on the epitope MHC binding site can improve the immunogenicity of the vaccine to a certain extent, it cannot achieve the ideal anti-tumor effect in tumor immunotherapy; while the peptide vaccine based on the epitope TCR binding site The modified peptide vaccine is expected to achieve the ideal anti-tumor effect by enhancing the ability to stimulate low-affinity T cells or recruiting a group of new cross-reactive T cells to break tumor immune tolerance

Method used

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  • NY-ESO-1 tumour antigen mimic epitope and use thereof
  • NY-ESO-1 tumour antigen mimic epitope and use thereof
  • NY-ESO-1 tumour antigen mimic epitope and use thereof

Examples

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Embodiment Construction

[0025] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

[0026] 1. Antigen mimotope prediction

[0027] 1. Establishment of TCR-pMHC complex structure model

[0028] With the help of NY-ESO-1 in the US RCSB Protein Data Bank (PDB, protein database) 157-165 The crystal structure (PDB ID: 2BNQ) of the specific TCR and MHC trimolecular complex 1G4-9C-A2, and the structure model of the TCR-pMHC complex 1G4-9C-A2 was established on the Insight II workstation;

[0029] 2. Analysis of epitope TCR binding site

[0030] Binding free energy is an important indicator for evaluating the binding strength between docking molecules in protein interactions, and can accurately evaluate receptor-ligand interactions. According to the TCR-pMHC complex structure model established in step 1, for NY-ESO-1 157-165 Each amino acid on the TCR / pMHC binding interface was subjected to alanine point mutation, and the b...

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Abstract

The invention discloses epitope for an NY-ESO-1 tumor antigen. The amino acid sequence of the mimic epitope is Ser-Leu-Leu- Met-Phe-Ile-Thr-Trp-Cys, namely SLLMFITWC; the mimic epitope can raise a CTL immunity response, can undergo a cross reaction with a natural epitope, has the characteristics of strong immunogenicity, immune tolerance breaking, strong specificity, safety, low cost, and easy synthesis and storage, and can be used to prepare tumor-therapeutic polypeptide vaccine. The invention also discloses a method for predicting the mimic epitope, which comprises steps of the establishment of a structural model of a TCR-pMHC complex, the analysis of TCR binding sites of the epitope, and the analysis of amino acid replacement of the TCR binding sites of the epitope. The method is also applicable to the computer-aided modification of CTL epitopes of other antigens, and can provide a useful tool for the design and research of therapeutic polypeptide vaccine.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a NY-ESO-1 tumor antigen mimic epitope and its application. Background technique [0002] NY-ESO-1 belongs to the cancer-testis antigen (Cancer-Testis Antigen, CTA) family, which can be expressed in testis, ovarian tissue and many different types of tumor tissues, but not in other normal tissues. strong tumor antigens. At the same time, because this antigen can cause the body to produce cellular immunity and humoral immunity, it is considered to be one of the most immunogenic tumor antigens at present. Therefore, NY-ESO-1 is an ideal target for tumor immunotherapy. [0003] With the development of modern immunology, more and more attention has been paid to the important role of cytotoxic T lymphocytes (CTL) in tumors. How to effectively stimulate the specific cellular immune response mediated by CTL and exert anti-tumor efficacy has become an important topic in the field of tumor ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06G06F19/00A61K39/00A61P35/00G06F19/12
Inventor 吴玉章尚小云王莉
Owner ARMY MEDICAL UNIV
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