Abstract

Bacterial Extracellular Vesicles as Next-Generation Cancer Immunotherapy

Tae Ryong Lee, Chief Scientific Officer, Rosetta Exosome

Coley’s toxin is a mixture of bacterial species developed as a treatment for cancer by Dr. William Coley in the late 19th century and there have been many attempts to develop modern versions of Coley's toxins since then. These attempts were not so successful until the recent development of ‘cancer immunotherapy’ especially due to the toxic side effects. Extracellular vesicles (EVs) are considered to represent the characteristics of their origin, so we assumed that bacterial EVs can be key components of Coley’s toxin with reduced side effects. Therefore, we investigated bacterial EVs as a therapeutic agent for treating cancer. Several different cancers were grafted subcutaneously to mice and these mice were treated with EVs obtained from several Gram-negative and Gram-positive bacterial species including toxicity-reduced EVs from the msbB-deleted or LTA-mutant bacterial strains. Treatments of all EVs significantly reduced the tumor volumes in all tested cancers. In vivo IVIS imaging analyses showed that EVs were highly enriched in tumor tissue rather than spreading out the other organs. Cytokine analyses have revealed that IL12p40, IFN-? and CXCL10 cytokines increased in blood and tumor tissue upon EVs treatment. These results suggest that bacterial EVs are promising immunotherapeutic agents to treat various cancers and these could bring a new insight in the development of novel cancer immunotherapy.