Double-modified engineering bacterium and application thereof

Abstract

The invention belongs to the field of biological medicines, and relates to a dual-modified engineered bacterium and application thereof, in particular to an engineered bacterium externally coupled with an immune checkpoint inhibitor and internally coded with a tyrosinase gene, a pharmaceutical composition containing the dual-modified engineered bacterium and application of the pharmaceutical composition. Wherein the engineered bacterium is preferably escherichia coli. By utilizing the engineered bacteria, melanin expression and distribution which are controllable in space and time are obtained, melanin is similar to an inhibitor in distribution, and the melanin and the inhibitor are combined to enhance a dual-immune activation effect and synergistically reprogram a tumor immune microenvironment. The engineered bacterium can significantly inhibit tumor growth and prolong the lifetime by being singly used or combined with a conventional tumor treatment mode or medicine. The pharmaceutical composition containing the bacteria or the application of the pharmaceutical composition not only overcomes the difficult tumor inner barrier, but also has good permeability, and can uniformly and enduringly disperse the anti-tumor drug into the whole tumor.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to an engineered bacterium encoding a tyrosinase gene, in particular to a double-modified engineered bacterium and its application. The bacterium is an externally coupled immune checkpoint inhibitor and an internally An engineered bacterium encoding a tyrosinase gene, a pharmaceutical composition containing the bacterium and applications thereof. Background technique [0002] In terms of cancer therapy, approaches that enable the uniform and durable distribution of anticancer drugs throughout tumors are of great interest for maximizing their therapeutic efficacy, but have proven to be extremely challenging. At present, anticancer drugs have limited accumulation in tumor tissue and poor penetration ability, which often affects their curative effect. Various mildly loaded nanoparticles have been developed for concentrating drugs at tumor sites through the high-osmotic long-retention EPR effe...

AI Technical Summary

Problems solved by technology

Although this can increase local exposure, the release of the drug is also limited by intratumoral barriers (including dense extracellular matrix and tumor interstitial pressure), resulting in high concentrations only around the point of injection.

Furthermore, other forms of drugs, such as antibody-drug conjugates, polymer prodrugs, and ligand-drug conjugates, are also poorly permeable within solid tumors due to the presence of unavoidable and troublesome biological barriers

Therefore, methods capable of uniformly and durably dispersing antitumor drugs throughout tumors in order to maximize their therapeutic effects have long been desired by researchers but have proven difficult.

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