Escherichia coli Nissle 1917 anti-tumor targeted engineering bacterial strain as well as construction method and application thereof

Abstract

The invention discloses an escherichia coli Nissle 1917 anti-tumor targeted engineering bacterial strain as well as a construction method and application thereof. The escherichia coli Nissle 1917 anti-tumor targeted engineering bacterial strain is collected in China Center For Type Culture Collection on June 26, 2018, with the culture collection number of CCTCC NO: M 2018403; the classification name thereof is escherichia coli EcN (Tum 5-p53), and the Latin scientific name thereof is Escherichia coli Nissle (Tum 5-p53). The constructed escherichia coli EcN (Tum 5-p53) contains an anti-tumor hypoxic expression vector pET28a-Pvhb-SUMO-Tum 5-MMP-p53, can efficiently express bifunctional protein Tum 5-p53, can transmit an antiangiogenic factor Tum-5 and tumor suppressor protein p53 to a solidtumor, and plays a good anti-tumor therapeutic effect. The tumor inhibiting rate of the anti-tumor targeted engineering bacterial strain on a human liver cancer SMMC-7721 nude mouse is as high as 69.47%.

Description

technical field [0001] The present invention relates to a strain of anti-tumor targeting engineering bacteria, in particular to a strain of Escherichia coli Nissle 1917 anti-tumor targeting engineering bacteria and its construction method and application. Background technique [0002] Cancer seriously threatens human life and health. Conventional cancer treatments, such as surgery, radiotherapy, and chemotherapy, usually cannot completely eliminate tumor cells in the tumor anaerobic microenvironment. Using targeted delivery vectors to deliver anti-cancer genes or anti-tumor drugs to tumor hypoxic regions for cancer treatment is a cancer treatment method that has developed rapidly in recent years and has the most clinical application prospects. [0003] E. coli Nissle 1917 (EcN) was originally isolated by military surgeon Alfred Nissle from the feces of a soldier who did not develop diarrhea during an outbreak of severe shigellosis. In recent years, the intestinal probiotic...

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Problems solved by technology

[0005] At present, Escherichia coli EcN is highly targeted to solid tumors, can specifically colonize tumor hypoxic areas, and can be used as a delivery vehicle to deliver anti-tumor active proteins to tumor areas; however, eukaryotic anti-tumor proteins are expressed in prokaryotic bacteria Difficulties exist: poor protein soluble expression, easy formation of inclusion body proteins, and difficulty in obtaining active proteins with normal spatial structures; in addition, due to the development of drug resistance in tumor cells, the therapeutic effect of drugs may be poor when used again; single gene therapy for tumors There are also defects such as poor efficacy persistence

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