This invention discloses the application of a glutamine-depleting engineered bacterium and its pharmaceutical composition. The engineered bacteria use attenuated bacteria with tumor-targeting capabilities as vector strains. The genome or plasmid of the vector strain integrates a therapeutic gene encoding glutaminase. This method achieves deep and continuous depletion of glutamine in the tumor, avoiding drug resistance caused by tumor metabolic compensation. The inhibition rate against c-Myc-overexpressing soft tissue sarcomas is significantly higher than that of small molecule inhibitors. Enzyme production is only carried out locally in the tumor, with no effect on normal tissues and no systemic toxicity. The engineered bacteria can penetrate the dense tumor matrix and colonize the tumor, solving the problem of poor tissue penetration of small molecule inhibitors. The engineered bacteria continuously multiply and produce enzymes in the tumor, achieving continuous release of glutaminase. The half-life is significantly longer than that of recombinant enzymes, eliminating the need for frequent dosing. The glutaminase optimized by proteinengineering has significantly reduced immunogenicity.
The present invention relates to live attenuated bacteria which persist in a subject and their use in vaccine compositions. In particular, the invention is directed to mutant strain E.coli vaccines which are useful for poultry, and especially chickens.