IRB sythesises probiotic bacterium that could improve cancer immunotherapy

A new step forward in the fight against tumours with immunotherapeutic approaches has been taken in the laboratories of the Institute for Research in Biomedicine (IRB, affiliated to USI) with the development of a synthesised strain of the bacterium Escherichia coli, which 'colonises' tumours and converts ammonia, a metabolic waste product that accumulates in tumours, into L-arginine, an amino acid that enhances the anti-tumour functions of T-cells. The work, led by the Roger Geiger lab at the IRB, was published in the prestigious scientific journal Nature.

Numerous metabolites influence cancer cell growth and tumor infiltrating immune cells. One potential therapeutic intervention is to tune the concentrations of these metabolites in favor of an effective anti-tumor response. However, methods to locally control metabolite concentrations in tumors are challenging. 

Certain bacterial strains colonize tumors where they survive and thrive in the necrotic core. In collaboration with Synlogic, Cambridge (USA), we engineered tumor-homing bacteria such that they convert the metabolic waste product ammonia into L-arginine, an immunomodulatory metabolite that enhances anti-tumor functions of T cells. 

The engineered bacteria colonize tumors, increase intratumoral L-arginine, enhance T cell activity, and synergize with PD-L1 blocking antibodies. Thus, engineered microbial therapies enable metabolic modulation of tumors leading to enhanced efficacy of immunotherapies. 

This bacteria-based therapy is suitable for the development of human therapeutics. The non-pathogenic bacteria have an intrinsic “kill-switch” as they are susceptible to antibiotics and possess desirable engineerability, safety and manufacturability features. Intratumoral injections of probiotic bacteria were previously found safe in clinical studies. 

The full article published in Nature with the title Metabolic modulation of tumours with engineered bacteria for immunotherapy is available online at: 
www.nature.com/articles/s41586-021-04003-2