Genetic engineering of a probiotic-based drug delivery system for colorectal cancer therapy

Abstract

Food-grade bacteria, including lactic acid bacteria (LAB), are safe to ingest and are not associated with development of disease. The impact of LAB on health has been studied in depth from a clinical perspective. Evidence suggests that LAB benefit health in several ways, including improving the balance between probiotic and harmful bacteria in the intestine, protecting against pathogen infections, and modulating host immunity in the gut. Recent publications show that LAB are safe biotherapeutics that exert positive effects against various cancer types, including colorectal cancer (CRC). CRC develops in intestine and, unless treated early, will invade the surrounding tissue and spread to other parts of the body. One intrinsic advantage of food-grade LAB is that they can be applied easily as oral medications and act as vehicles for bio-therapeutics, which can be delivered directly to the mucosal surface of the intestine. Consequently, a LAB-based drug delivery system (DDS) can have synergistic effects: the patient derives benefit from both the LAB and the therapeutic cargo. Furthermore, the localized effect of LAB-based DDS in the intestine would ensure targeted treatment at the site of disease; this has the benefits of requiring a lower dose of a drug, with fewer systemic side effects. In this review, we discuss the evidence supporting the beneficial effects of LAB-based DDS and its application to CRC.

Anti-Cancer Roles of Probiotic-Derived P8 Protein in Colorectal Cancer Cell Line DLD-1

“…Probiotic organisms may act as biopharmaceutical factories and have been screened for potential therapeutic agents [ 10 , 13 , 19 ]. Probiotics can be successfully engineered to secrete anti-CRC biopharmaceuticals [ 14 , 18 ]. One protein derived from probiotics, P8, was found to have anti-CRC therapeutic properties, inducing G 2 cell cycle arrest [ 14 , 15 , 17 ].…”

“…Additionally, probiotics have not been reported to be pathogens in any disease [ 11 ]. Due to their safety [ 12 , 13 ] and potency [ 14 , 15 , 16 , 17 ], probiotics may be utilized as drug delivery vehicles, including for the treatment of CRC [ 14 , 18 ].…”