The human microbiome naturally includes fungi, which live on and in our bodies, usually causing no harm. But in patients whose immune systems are compromised, like those receiving chemotherapy for cancer or medications for severe autoimmune disease, fungi can overgrow and cause life-threatening infections. Up to 25% of patients die as a result of these infections, which are responsible for more than 1.6 million deaths globally per year. Antifungal drugs exist to treat these infections, but they themselves can be toxic and extremely painful. They are generally administered intravenously to address an infection, and can wreak havoc on the body’s healthy organs in the process. A better solution needs to be developed to treat severe fungal infections effectively while reducing harm to patients.
Researchers at the Wyss Institute and infectious disease physicians at Massachusetts General Hospital are developing a solution called FeCILL, short for “Fungicidal endovascular Controlled-release Iron-binding Lectin Liposomes.” FeCILL is a novel delivery vehicle that consists of a lipid-based vesicle coated with FcMBL, a modified version of a naturally occurring protein called mannose-binding lectin. FcMBL binds directly to all fungi, but not to healthy human cells, allowing the vesicle to release its antifungal drug cargo only where the infection is present. In addition, FeCILL incorporates a mechanism to sequester iron in its local environment, starving the fungi of this crucial growth nutrient and making them more susceptible to the antifungal drug. This platform therapy could increase efficacy while reducing toxicity and side effects in patients who take traditional antifungal drugs.
FcMBL was originally developed by Mike Super and Don Ingber within the Institute’s Bioinspired Therapeutics and Diagnostics Platform to treat infectious diseases and sepsis. When attached to magnetic beads and incorporated into a “biospleen” device, FcMBL could effectively bind to virtually any foreign pathogen and filter it out of the blood as a solution to save the lives of patients with severe sepsis. In 2019, that technology was licensed to BOA Biomedical, which is working to commercialize it.
But Super knew that FcMBL had great potential for other applications as well, and kept working on it in the lab. In 2020, Alex Tatara joined Massachusetts General Hospital as a clinical fellow in the Division of Infectious Diseases. As a physician scientist with a background in biomaterials, he was interested in conducting research alongside his clinical practice and joined David Mooney’s group as a postdoctoral research fellow. At the Wyss Institute, he was introduced to Mike Super given their shared interests in the challenge of fungal infection. The subsequent collaboration has produced FeCILL, a project strategically combining engineered immunoproteins and clinically available therapeutics to disrupt fungal defenses and metabolism while limiting patient side effects.
In recognition of its potential to dramatically improve the fates of patients with fungal infections, FeCILL was named a Wyss Validation Project in 2022. The team is currently validating their results using in vitro microfluidic platforms and physiologically relevant animal models of disease.