Biosynthetic neoantigen displayed on bacteria derived vesicles elicit systemic antitumour immunity

Neoantigens derived from mutant proteins in tumour cells could elicit potent personalized anti-tumour immunity. Nevertheless, the layout of vaccine vehicle and synthesis of neoantigen are pivotal for stimulating robust response. The power of synthetic biology enables genetic programming bacteria to produce therapeutic agents under contol of the gene circuits. Herein, we genetically engineered bacteria to synthesize fusion neoantigens, and prepared bacteria derived vesicles (BDVs) presenting the neoantigens (BDVs-Neo) as personalized therapeutic vaccine to drive systemic antitumour response. BDVs-Neo and granulocyte-macrophage colony-stimulating factor (GM-CSF) were inoculated subcutaneously within hydrogel (Gel), whereas sustaining release of BDVs-Lipopolysaccharide (LPS) and GM-CSF recruited the dendritic cells (DCs). Virtually, Gel-BDVs-Neo combined with the programmed cell death protein 1 (PD-1) antibody intensively enhanced proliferation and activation of tumour-infiltrated T cells, as well as memory T cell clone expansion. Consequently, BDVs-Neo combining with checkpoint blockade therapy effectively prevented tumour relapse and metastasis.