Vaccine based on simulating human blood vessel endothelial cell growth factor VEGF epitope and preparation method thereof

Abstract

The invention provides a vaccine based on an epitope simulating human vascular endothelial growth factor VEGF, as well as a preparation method thereof. A VEGF mimic epitope which is specifically affinitive with human-mouse chimeric monoclonal antibody Avastin is screened out by use of a phage random presentation technique, and the amino acid sequence of the mimic epitope is Asp-His-Thr-Leu-Tyr-Thr-Pro-Tyr-His-Thr-His-Pro; the mimic epitope has no homology with the protein sequence of VEGF. A vaccine which can induce a polypeptide epitope aiming at VEGF molecular autoantibody in vivo is constructed on the basis of the mimic epitope. The invention provides a strategy for developing and designing the tumor therapeutic vaccine, which is targeted at the VEGF. The VEGF is one of molecules which has the strongest effect of promoting vascular growth, and is an ideal target for resisting angiogenesis and treating tumors. Therefore, the vaccine replaces or replenishes monoclonal antibody passive immunotherapy with an active immunity mode, so as to lay foundations for overcoming the defects of monoclonal antibody therapy.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and specifically relates to a mimetic epitope based on simulating human vascular endothelial cell growth factor VEGF and a polypeptide epitope vaccine capable of inducing autoantibodies against VEGF molecules in vivo constructed by using the mimetic epitope and its Preparation. Background technique [0002] 1. Research on VEGF molecules and their monoclonal antibodies [0003] 1.1 VEGF molecules [0004] The relative molecular weight of VEGF is 34-42KD, which is composed of homodimers with a molecular weight of 17-22KD linked by disulfide bonds. The gene structure of human VEGF is located at chromosome 6p21.3. The gene is 28kb in length, and the gene encoding VEGF is about 14,000 base pairs long, consisting of 8 exons and 7 introns alternately. There are five isoforms of VEGF due to the different splicing modes of VEGF mRNA. According to the size of amino acids, they are named VEGF206 (in...

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Problems solved by technology

In fact, there are three mechanisms that lead to immune tolerance: cell line knockout, that is, specific lymphocytes are completely eliminated from the lymphocyte population; immune anergy, that is, specific lymphocytes exist, but their functions cannot be activated; immune Neglect, that is, immune function lymphocytes are present, but cannot be activated because they have not encountered self-antigens in the form of antigens

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