Recent research has shown that certain forms of E.coli bacteria tend to colonise hypoxic areas of the body, including tumours, suggesting they might be playing a role in cancer therapeutics.

A team of researchers at Dana-Farber Cancer Institute led by Dr. Romee in collaboration with Dr. Jiahe Li at the University of Michigan engineered gut derived E.coli bacteria to express immune-activating cytokines on their surfaces, with the idea that the bacteria would move into the tumour and induce potent immune responses.

E.coli displaying murine decoy resistant IL18 demonstrated superior anti-tumour responses compared to immune checkpoint inhibitor therapy, with a 50-60% cure rate in mice.

The team also observed synergy between treatment with the engineered bacteria and immune checkpoint inhibitor therapy.

Treated tumour tissues revealed increased activity and infiltration of CD8+ T cells and NK cells.

The therapy also enhanced the therapeutic efficacy of mesothelin targeting CAR NK cells in mice, suggesting the bacteria act as a “tumour GPS” for the systemically infused NK cells.

The study also demonstrated the safety and efficacy of this approach in multiple hard to treat tumours including mesothelioma.

The findings make a strong case for evaluation of the approach alone or in combination with other immunotherapeutic strategies in early-phase clinical trials.

Immunotherapeutic approaches have substantially improved the treatment of patients with advanced malignancies.

However, most advanced and metastatic malignancies remain incurable and therefore represent a major unmet need.

This study uses genetically engineered live bacteria to strongly stimulate immune responses and enhance the effects of immunotherapy.

Source: Dana-Farber Cancer Institute