Bacterium-Mimicking Vector with Enhanced Adjuvanticity for Cancer Immunotherapy and Minimized Toxicity

Bacteria are utilized as adjuvants for anticancer immunotherapy. However, immunotherapy with bacteria or their extracts is limited due to their toxicity. On the basis of the innate molecular interactions of foreign molecules from the bacterial components with the host pattern recognition receptors (PRRs), a synthetic adjuvant vector morphologically mimicking the bacterium is engineered, which comprises an optimal combination of components derived from bacterial cell wall, flagellum, and nucleoid. The bacterium-mimicking vectors (BMVs) cooperatively trigger multiple signaling pathways of PRRs and display superior antitumor therapeutic and prophylactic effects to either that of the reported synthetic or bacterium-derived adjuvant. Significantly, BMVs improve the efficacy of photothermal ablation therapy to eradicate 50% of large established tumor in mice that completely reject tumor rechallenge. The synthetic BMVs with the detoxified and controllable composition exhibit minimized toxicity. Such a bacterium-mimicking engineering strategy provides a rational approach to select pathogen-associated molecular patterns, which drives the desired antitumor immune response. The engineered BMVs offer a promising alternative to the bacterial adjuvant for cancer immunotherapy.