Antitumor cytotoxic T lymphocyte (CTL) epitope peptide analog derived from COX-2

A COX-2, anti-tumor technology, applied in the direction of peptides, etc., can solve the problem of inability to achieve anti-tumor effect

Inactive Publication Date: 2011-08-17
ZHENGZHOU UNIV
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  • Abstract
  • Description
  • 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 point-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 new group of cross-reactive T cells to break tumor immune tolerance

Method used

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  • Antitumor cytotoxic T lymphocyte (CTL) epitope peptide analog derived from COX-2
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  • Antitumor cytotoxic T lymphocyte (CTL) epitope peptide analog derived from COX-2

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Embodiment Construction

[0016] The anti-tumor CTL epitope peptide analogue derived from COX-2 of the present invention is based on the primary structure of the antigen, using immunoinformatics means, and using the SYFPEITHI, BIMAS and NetCTL 1.2 databases to analyze the HLA of the COX-2 protein antigen. - The A*0201 restricted CTL epitope was predicted and analyzed, and the epitope peptide P321 was screened. Then, the 1-position and 9-position amino acids of the epitope peptide P321 that were initially screened out were replaced with Y and L, respectively, to obtain the epitope peptide analog P321-1Y9L of the present invention, which is a nonapeptide, and its amino acid sequence is: Tyr-Leu- Ile-Gly-Glu-Thr-Ile-Lys-Leu is YLIGETIKL with a molecular weight of 1049.3.

[0017] The epitope peptide analogue P321-1Y9L of the present invention was synthesized using a standard Fmoc protocol. After HPLC purification, its purity was greater than 90%, and mass spectrometry analysis confirmed that its molecular...

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Abstract

The invention discloses an antitumor cytotoxic T lymphocyte (CTL) epitope peptide analog derived from COX-2. The amino acid sequence of the analog is Tyr-Leu-Ile-Gly-Glu-Thr-Ile-Lys-Leu. In the invention, according to a primary structure of an antigen, an immune informatics means is adopted, and SYFPEITHI, BIMAS and NetCTL1.2 databases are applied so as to carry out predictive analysis on HLA-A*0201 restriction CTL epitope of COX-2 protein antigen, and then an epitope peptide P321 is obtained by selection; and then 1-site and 9-site amino acids of the epitope peptide P321 are respectively replaced by using Y and L so as to obtain the epitope peptide analog P321-1Y9L. In the invention, the candidate CTL epitope peptide analog which has a strong bonding capability with a major histocompatibility complex molecular and is derived from the COX-2 can be modified and initially identified by adopting a method combining a theory and an experiment; and because the identified nonapetide is not reported in documents, a theory base is provided for developing tumor therapeutic polypeptide vaccine based on the COX-2 and a foundation is established for constructing subsequent multivalent antigen peptide vaccine according to the invention.

Description

technical field [0001] The present invention relates to an anti-tumor CTL epitope peptide, in particular to an anti-tumor CTL epitope peptide analogue derived from COX-2. Background technique [0002] Cyclooxygenase-2 (COX-2) is a protein highly expressed in esophageal cancer cells discovered by Zimmermann in recent years (91% in squamous cell carcinoma, 78% in adenocarcinoma), and it has an excess in tumor tissue, especially in esophageal cancer tissue expression, but is difficult to detect in normal tissues. COX-2 is an inducible enzyme, its expression is highly restricted in certain tissues under normal physiological conditions, such as brain tissue, kidney and eyes, and it is not easy to detect, but it is not easy to detect in growth factors, cytokines, endotoxins, haste, tumor-promoting agents and Under the action of various stimulating factors such as oncogenes, it can be rapidly induced to express, and may participate in the proliferation, metastasis and differentiat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06
Inventor 祁元明吴亚红高艳锋吴宗胤李璐刘伟朱宇皇孙萌
Owner ZHENGZHOU UNIV
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