Oncolytic virus and neoantigen combined tumor vaccine and preparation method thereof

Abstract

The invention discloses an oncolytic virus and neoantigen combined tumor vaccine and a preparation method thereof. The combined vaccine can be implemented through the following two ways: in the firstway, an immune response reaction generated from an oncolytic virus reagent is used for improving the efficiency for phagocytizing a polypeptide reagent by an antigen presenting cell, increasing the number of T cells which can specifically identify a neoantigen and improving the tumor invasion performance of the T cells so as to enhance the anti-cancer curative effect; and in the second way, a genecoding a tumor neoantigen is inserted into an oncolytic virus vector to massively express the tumor neoantigen, and is combined with the tumor killing performance of the oncolytic virus to further enhance the immune response reaction of a tumor focus local part and improve the invasion degree of the killing type T cell in a tumor tissue, so that the local part can generate an immune response reaction, and generation of an effector cell is stimulated to achieve an anti-cancer effect. Experiment comparison discovers that the first combined vaccine and the second combined vaccine have an excellent tumor inhibition effect, and the second combined vaccine has a remarkable tumor inhibition effect.

Description

technical field [0001] The invention relates to the field of genetic engineering, in particular to a tumor vaccine combined with an oncolytic virus and a neoantigen and a preparation method thereof. Background technique [0002] For a long time, finding effective ways to attack tumors has been the goal pursued by researchers. One of the biggest difficulties lies in the widespread heterogeneity of tumors. Not only within the tumor tissue, even within the same tumor type, there are great differences among different patients. During the rapid growth and proliferation of cancer cells, it is often too late to repair the errors that occur during DNA replication, so many new mutant proteins will appear, which are called neoantigens (Neoantigen). Early studies believed that the mutations carried by most tumor neoantigens had no effect on the growth of tumor cells and were negligible by-products. With the deepening of research, scientists have recently discovered that even if the m...

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Problems solved by technology

[0008] In order to solve the deficiencies in the prior art, the object of the present invention is to provide a tumor vaccine combined with oncolytic virus and neoantigen and its preparation method. The combined vaccine can be realized in two ways. The first is to use oncolytic The tumor killing of viral reagents produces a local immune response in tumor lesions, improves the phagocytosis efficiency of neoantigen polypeptide vaccines by antigen-presenting cells, and the number of T cells that can specifically recognize tumor neoantigens and tumor infiltration ability, thereby enhancing the anticancer effect The second is to insert the gene encoding tumor neoantigen into the oncolytic virus vector to improve the problem that the antigenic peptide cannot directly enter the tumor, and combine the tumor killing ability of the oncolytic virus to further enhance the local immune response of the tumor lesion. Increase the degree of infiltration of killer T cells in tumor tissue, generate local immunogenic responses, stimulate the production of effector cells, and transform "cold" tumors into "hot" tumors to achieve anti-cancer effects

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