Bacterial nanoparticles as a potent and safe alternative to BCG for bladder cancer immunotherapy.

Bladder cancer is the second most common malignancy of the urogenital system, with non-muscle-invasive forms being the most prevalent. While therapy with intravesical instillation of Bacillus Calmette-Guérin (BCG) is widely used, it shows variable efficacy and notable side effects, which prompts the need for new treatments. This study introduces a nanoscale biotherapy against bladder cancer using bacterial extracellular vesicles (bEVs) from Escherichia coli. In an orthotopic syngeneic rat model of bladder cancer with luciferase-tagged tumour cells, intravesical bEVs treatment significantly inhibited tumour growth compared to the gold standard therapy: BCG. Indeed, compared to BCG, bEVs treatment led to superior tumour regression, with 60% of treated animals showing complete tumour clearance versus 20% in the BCG-treated group. Moreover, we observed strong local immune activation, namely T cell infiltration and mucosal lymphoid aggregates, which negatively correlated with tumour size, suggesting that bEVs efficacy is due, at least in part, to their ability to induce a strong antitumor immune response. Notably, bEVs caused no mortality or systemic toxicity. Altogether, the present study constitutes a striking illustration of translational medicine, where the properties of a bacterial compound can be harnessed for patient benefit.