TOPIC 386: ENGINEERING PROBIOTICS TO DELIVER CHEMOPREVENTATIVE AGENTS TO THE HUMAN GUT

Colorectal cancerCRCis the second most common cause of cancer death in the USwith more thanAmericans dying every year from CRCHigh risk populations that have been targeted for preventionwhich include patients with inherited CRC syndromes such as familial adenomatous polyposisFAPand Lynch syndromeThe challenge for chemopreventionis how to provide precision delivery and thus avoid unacceptable toxicityin an otherwise healthy populationTo address thiswe propose the delivery of chemopreventative agents via a widely consumed probiotic strain of bacteriaWe propose a mechanism of delivery whereby the probiotic bacteria release the chemopreventative agents via engineered lysisby utilizing our previously established lysis paradigm for the delivery of therapeutics in vivowhere localized release increases the safety of the approachWe then anticipate that introducing pre screenedin vitro validated engineered bacterial preventatives into a chemoprevention directed mouse model of CRC will result in reduced local tumor growth and prolonged mouse survival in immunocompetent and human tumor mouse modelswithin the colonGiven that the standardyears and older screening population in the US can have an adenoma rate of up tothere is a large opportunity to provide chemoprevention to reduce the future risk of CRC even within the general community