SBIR PHASE II, TOPIC 016: DEVELOPMENT OF A BACTERIAL SYNCHRONIZED LYSIS CIRCUIT PLATFORM TO DELIVER THERAPEUTICS

Despite advances in surgery and systemic immunotherapies, many cancers that result in solid tumors and distant organ metastasis still represent a major unmet need in oncology. Certain genetically amenable bacteria, such as E. coli and Salmonella, have been shown to specifically colonize solid tumors agnostic of tumor type. We are leveraging 15 years of progress in Synthetic Biology to engineer widely consumed probiotic E. coli for cancer therapy. We propose the delivery of therapeutic proteins via engineered bacteria to greatly enhance safety and localization of therapy using our synchronized lysis circuit (SLC). Here, we will develop IND-enabling capabilities to translate our SLC bacteria to the clinic. Specifically, we focus on developing stable strains, a manufacturing process, and demonstrating safety. Our proposed engineered probiotic delivery system has commercial applications as a therapeutic agent for patients with colorectal cancer (CRC) and/or liver metasteses. Colorectal cancer (CRC) is the second most common cause of cancer death in the US, with more than 50,000 Americans dying every year from CRC. Liver metastasis occurs in up to 50% of patients with colorectal cancer and in these patients, their 5 year survival is only 10%.