Transcatheter Bacteriolytic Therapy with Iron Oxide Labeled Clostridium novyi-NT Spores

Bacteriolytic therapy as a form of cancer treatment has generated much attention in recent years. Clostridium novyi-NT (C. novyi-NT) stands out specifically for its obligate anaerobic properties, which allows the bacteria to specifically colonize the necrotic cores of solid tumors, leading to subsequent destruction and shrinking of tumor size. Despite the efficacy of this bacteria observed in a variety of studies, a major area of concern regarding bacteriolytic therapy is the possible toxicity that could accompany the presence of large numbers of spores injected into the bloodstream, which is the current method of delivery. Out of these millions of spores, only a minute subset actually finds the target tumors, with the rest being dispersed throughout the animal. Therefore, a safer and more reliable method of bacterial delivery to the target site is still necessary before bacteriolytic therapy can be applied to the clinical environment. We aim to utilize interventional techniques with magnetic resonance imaging (MRI) to study and develop the use of bacteriolytic therapy with C. novyi-NT for the treatment of hepatocellular carcinoma (HCC). We hypothesize that arterial intracatheter delivery of the bacteria will reduce potential systemic toxicity compared to intra-venous administration. To this end, we will first generate iron-oxide labeled bacterial spores which will improve therapy by allowing MRI detection and confirmation of proper delivery. It will also allow for a better understanding of the mechanism of therapy. Spores will be evaluated with viability studies, fluorescence microscopy, and MRI imaging. We will then perform in vivo studies in a well-established N1-S1 HCC rat model to verify the feasibility of direct delivery of bacterial spores, first through a direct injection approach and then comparing it with an intra-arterial, transcatheter infusion approach. We will utilize both quantitative MRI measurements and histological assays to assess the efficacy of treatment while monitoring for potential toxicities throughout the treatment process. Our goal is to validate the safety and potential efficacy of this approach for the treatment of patients with HCC. Long term, we hope this work will contribute in promoting this therapeutic avenue for use in the clinical environment. As the medical student, I have been trained and will be performing the majority of the laboratory work including, optimizing iron oxide labeling, animal husbandry, MR imaging, and treatment procedures. The scientific advisor will help guide experimental design and provide input regarding troubleshooting and data analysis.