Recombinant oncolytic vaccinia virus and preparation method and application thereof

Abstract

The invention discloses a recombinant oncolytic vaccinia virus and a preparation method and application thereof. The thymidine kinase (TK) region of the virus comprises a coding sequence of a PD1 full-length antibody shown in the formula of SEQ ID NO.1. Through effective combination of the anti-tumor effect of gene therapy and the oncolytic effect of virus treatment, the oncolytic vaccinia virus for efficiently expressing the PD1 full-length antibody gene is prepared. When the oncolytic vaccinia virus produces the oncolytic effect of splitting tumor cells, the PD1 full-length antibody is efficiently expressed, the activity of PD1 on the surfaces of T cells is inhibited, the T cell immune response is activated and the dual antitumor effects are produced. Compared with the single gene therapy or viral therapy, the method using the recombinant oncolytic vaccinia virus improves the effects of killing malignant B cell lymphoma. Through virus replication-related gene deletion, the TK regionof the vaccinia virus genome is deleted so that specific replication of the viruses in the abnormally proliferating tumor cells is ensured and the viruses can not replicate in normal cells, so that the safety of the oncolytic vaccinia virus vector is greatly improved.

Description

technical field [0001] The invention belongs to genetic engineering, immunology and oncology, and relates to a recombinant oncolytic vaccinia virus and its preparation method and application. Background technique [0002] The incidence of malignant lymphoma accounts for 3-5% of all cancer patients, with 452,000 new patients every year. More than 90% of adult patients are derived from mature B cells, suggesting that B cell lymphoma is one of the important diseases that threaten human health. [0003] Immunotherapy is another new method of cancer treatment after surgery, radiotherapy, chemotherapy, and molecular targeted therapy. Among various cancer immunotherapy methods, immune checkpoint inhibitors are one of the drugs that have achieved outstanding efficacy in recent years. Immune checkpoints are inhibitory pathways that prevent excessive activation of the immune system. There are some proteins such as CTLA4 and PD1 on the surface of activated immune cells that act as "b...

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Problems solved by technology

[0007] However, immune checkpoint inhibitors also have their limitations: (1) Most patients cannot achieve a durable complete response; (2) About 25-30% of patients experience severe immune-related side effects (irAEs) after PD-1 monoclonal antibody treatment; ( 3) The characteristics of the PD-1 / PD-L1 pathway in the tumor microenvironment affect the efficacy of PD-1 monoclonal antibody

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