Neoantigen cancer vaccines hold great promise for cancer treatment but are often limited by the immunosuppressive tumor environment. Now, as described in Nature, Redenti et al. have overcome this issue by harnessing the natural capacity of bacteria to colonize tumors and trigger immune responses. They have developed a microbial system that produces and delivers distinct sets of neoantigens to elicit potent killing of solid tumors.

Redenti et al. engineered the probiotic Escherichia coli Nissle 1917, introducing several modifications that enhance therapeutic use. First, the authors removed E. coli cryptic plasmids and deleted the Lon and OmpT proteases, which enhanced the production of synthetic neoantigen constructs by 80-fold. This engineered vector was four times more susceptible to phagocytosis than the wild type, increasing uptake by antigen-presenting cells. Next, the authors co-expressed listeriolysin O, a Listeria-derived pore-forming protein that permeabilizes the phagolysosomal membrane, to induce cytosolic delivery of neoantigens for enhanced presentation to CD8+ T cells and to promote T helper 1 cell immunity.