CN-110684743-B - Virus for specifically killing tumor cells and tumor therapeutic drug

Abstract

The invention discloses a virus and tumor therapeutic drug for specifically killing tumor cells, and relates to the technical field of biology. The virus is a recombinant oncolytic virus, and has an exogenous promoter on the genome, which is located upstream of the essential gene of the virus, so that the natural promoter of the essential gene is replaced to drive the essential gene to be expressed in tumor cells and not expressed in normal cells. The virus can specifically kill various tumor cells, and has higher killing efficiency on tumor cells and safety on non-tumor cells.

Inventors

• WU ZETANG

Assignees

• 伍泽堂

Dates

Publication Date

20260505

Application Date

20190716

Claims (6)

1. 1. A virus for specifically killing tumor cells is characterized in that the virus is an oHSV-BJTT virus or a oHSVBJGMCSF virus, the preservation number of the oHSV-BJTT virus is CCTCC NO: V201922, and the preservation number of the oHSVBJGMCSF virus is CCTCC NO: V201921.
2. 2. A tumor therapeutic agent comprising the virus which specifically kills tumor cells according to claim 1.
3. 3. The tumor therapeutic agent according to claim 2, further comprising a pharmaceutically acceptable carrier.
4. 4. A nucleic acid molecule has a sequence shown as SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3 or SEQ ID NO. 4.
5. 5. A vector comprising a nucleic acid molecule having a sequence as set forth in SEQ ID NO.1, SEQ ID NO.2, or SEQ ID NO. 4.
6. 6. The vector according to claim 5, wherein the vector comprises a nucleic acid molecule having the sequences shown in SEQ ID NO.2 and SEQ ID NO. 3.

Description

Virus for specifically killing tumor cells and tumor therapeutic drug Technical Field The invention relates to the technical field of biology, in particular to a virus and tumor therapeutic drug for specifically killing tumor cells. Background Overcoming cancer is a worldwide problem. The current treatment of cancer relies mainly on traditional chemotherapy and radiotherapy in combination with CAR T and antibody therapies developed in recent years. However, various treatments are not very effective or have serious side effects or potential safety risks. Development of novel safe and efficient treatment schemes is imperative. Research shows that the development of oncolytic viruses has broad prospects in treating cancers. Oncolytic viruses are a class of replication-competent tumor-killing viruses that replicate in tumor cells to kill tumor cells and enhance the ability to kill cancer cells in situ or attack migrated cancer cells by eliciting a cancer-specific immune response from the lysed tumor cell debris. By utilizing the characteristic of oncolytic virus, the application of oncolytic virus in treating tumor of patients is a treatment strategy with broad prospect. Oncolytic viruses are genetically engineered to selectively expand and kill cancer cells. A number of oncolytic viral targeting strategies have been intensively studied. One widely used design principle is to delete the unnecessary genes of the virus that encode the antiviral pathways that antagonize normal cells, making them unable to replicate in normal cells, while cellular canceration alters the signaling pathways, with oncolytic viruses maintaining replication and killing activity in cancer cells. It is well established that WNT signaling pathway genes such as RAS, TP53, RB1, PTEN, etc. and some other tumor-associated genes and signaling pathways such as critical viral defenses in mammalian cells are mediated by interferons and cytokines, but cancer cells disable this pathway, which provides free space for replication and propagation of the virus in the cancer cells. The first oncolytic virus drug Imlygic (T-vec), approved by the FDA, derived from herpes simplex virus type 1 (HSV-1), was engineered to delete both ICP34.5 and ICP47 genes, the former preventing normal cell shutdown protein synthesis machinery to facilitate virus propagation, the latter inhibiting antigen presentation to evade antiviral immune responses. At present, pexa-Vec in clinical stage 3 deletes thymic kinase gene so that it can only be replicated in high kinase activity cell, such as liver cancer. However, the existing oncolytic viruses have weak killing effect on cancer cells and extremely poor broad spectrum. To increase oncolytic virus effectiveness and broad spectrum, it should be a better design choice to keep the viral genes intact. In view of this, the present invention has been made. Disclosure of Invention The invention aims to provide a virus and a tumor therapeutic drug for specifically killing tumor cells, which have higher killing efficiency on tumor cells and are safe to non-tumor cells, and in addition, the virus genome has a complete structure and can kill various types of tumor cells. The invention is realized in the following way: In a first aspect, the invention provides a virus that specifically kills tumor cells, the virus being a recombinant oncolytic virus having an exogenous promoter on its genome that is located upstream of an essential gene of the virus to drive expression of the essential gene in tumor cells and not in normal cells. The virus provided by the invention is recombinant oncolytic virus, an exogenous promoter is introduced at the upstream of an essential gene on a genome, the exogenous promoter replaces a natural promoter of the essential gene, the expression of the downstream essential gene is driven to be expressed in tumor cells, the oncolytic virus can normally replicate, and the tumor cells are killed through the replication specificity of the oncolytic virus, when the oncolytic virus is in normal cells, the exogenous promoter does not drive the expression of the essential gene, so that the replication of the oncolytic virus is influenced, and the oncolytic virus has better safety to the normal cells. In addition, the original genes in the genome of the recombinant oncolytic virus provided by the invention are not deleted or destroyed, so that the recombinant oncolytic virus provided by the invention can replicate with stronger replication capacity, kill tumor cells with higher killing rate, has strong killing effect and certain broad spectrum, and can kill various types of tumor cells. Further, in some embodiments of the invention, the exogenous promoter is a tumor cell specific promoter; Further, in some embodiments of the invention, the tumor cell specific promoter is selected from any one of the group consisting of a telomerase reverse transcriptase promoter (hTERT), a human epidermal growth factor receptor-2 promoter (H