Photo of Shannon Sirk.
Urbana, Ill. – Therapeutic antibodies have revolutionized the treatment of many diseases, including cancer. However, these drugs can be prohibitively expensive and are not an option for every patient. Shannon Sirk, Cancer Center at Illinois researcher and assistant professor of bioengineering, is working to address this issue by engineering alternative production and delivery systems for these cancer-fighting drugs.
The overarching goal of Sirk’s research group is to modify human commensal microbial species to generate therapeutic antibodies from inside the body, circumventing the need for costly manufacturing and providing a means for long-term, low-cost treatment of cancer patients.
Microbes are everywhere, living symbiotically on nearly every surface of our bodies including the gut. They play an integral role in our bodily functions, aiding digestion and even helping to fight cancer. Understanding how to manipulate commensal microbial communities can benefit human health, but Sirk aims to go one step further by engineering certain bacteria to perform additional, beneficial functions.
“Traditionally, therapeutic antibodies can be very costly to make, so they are not available to everyone. My lab is trying to make this really powerful class of drugs more accessible by changing how we manufacture them — specifically, by engineering bacteria that live in the gut to directly produce the antibodies within the body,” Sirk said. “These bacterial species are already perfectly suited to grow in their native niche — our guts; what remains is to take advantage of their ability to serve as robust biochemical factories.”
Sirk and her research group are working to engineer microbes to produce many kinds of disease-fighting antibodies, including several cancer targets. While initial efforts are focused on engineering gut commensal microbes to target diseases of the gastrointestinal tract, Sirk is working to expand the reach of intestinally-produced drugs beyond the gut. Such studies include efforts to modify the antibodies themselves to enable them to escape the gut and enter the bloodstream, thereby accessing tumors at other sites in the body.
Still, Sirk’s lab is not naive; while this work could significantly improve access to costly treatments, and even revolutionize the management of chronic conditions, they are in the early stages of research and have much to explore, discover, and optimize. One key concern centers on the safety of introducing genetically modified bacteria into a patient.
“We’re proposing permanent changes to a person’s gut microbiota, which means we have to be really careful. What we’re attempting requires extensive safety and efficacy studies,” said Sirk. “Something we would also consider is whether a person has a lifelong requirement for treatment. Some bacteria will colonize the gut permanently, whereas others pass through our system quickly. All of this would influence decisions made in the clinic, and we keep these parameters in mind as we develop our platform in the lab.”
Sirk’s lab is not limiting their “in vivo antibody factory” approach to microbes. With support from the Cancer Center at Illinois and in collaboration with colleagues on campus, Sirk is using in vivo gene editing to drive antibody production from the liver, in an approach similar to the microbial production platform but which would co-opt a patient’s own cells rather than those of microbes to fulfill their antibody manufacturing needs.
– Written by Lisa Mei, CCIL Communications Intern
Shannon Sirk is a Cancer Center at Illinois (CCIL) researcher, assistant professor of bioengineering, and co-leader of the CCIL Cancer and Microbes Working Group with Sayeepriyadarshini Anakk, also a CCIL researcher and associate professor of molecular and integrative physiology.