Researchers have managed to reduce gastrointestinal tumors in mice by using a yeast probiotic to deliver immunotherapy directly to the gut, paving the way for a new approach to tackle challenging gut cancers.
Immunotherapy is an emerging treatment that enlists the body’s immune system to fight cancer; however, it has had limited success for gastrointestinal cancers. Recently, scientists at Washington University School of Medicine in St. Louis have developed a probiotic that can provide immunotherapy straight to the gut, resulting in tumor reduction in mice and suggesting a potentially effective oral medication for cancers that are hard to reach.
The innovative probiotic treatment for cancer was published on November 20 in the journal Cell Chemical Biology. This approach establishes a customizable drug delivery system that could also be adapted for treating other gut-related diseases.
“Gastrointestinal cancers are challenging to treat, partly due to their location,” explained Gautam Dantas, PhD, the senior author of the study and the Conan Professor of Laboratory and Genomic Medicine in the Department of Pathology & Immunology at WashU Medicine. “We’ve created a yeast-based probiotic that targets immunotherapy to the tumor site. We hope that this probiotic could eventually be added to the treatment options available to help reduce tumors in patients.”
Cancers of the gastrointestinal tract, such as those of the stomach, liver, esophagus, pancreas, and colon, account for more than 25% of all cancer cases. Currently, over 5 million individuals are living with these types of cancers—a figure that continues to grow—while 3.7 million succumb to them each year around the globe. The high mortality rate is partly due to late-stage diagnoses that are complicated by the anatomical difficulties in imaging and sampling tissues within the extended and intricate gastrointestinal system. Often, patients require a combination of therapies, including surgery, chemotherapy, radiation, and immunotherapy, among others.
Though there are immunotherapy options for gastrointestinal cancers, these treatments are typically delivered via intravenous injection and often show limited effectiveness. As Dantas describes, safe doses of immunotherapy might not adequately reach the tumor site to have a meaningful impact. Oral immunotherapy pills could potentially direct treatment right to challenging gastrointestinal tumors, but protein-based therapies usually break down in the gut’s acidic and digestive environment before they can reach their target. Probiotics, which include bacteria and yeast, are resilient enough to endure stomach acid and enzymes, making them a promising vehicle for safely delivering protein-based drugs that would otherwise be degraded.
Co-first author Olivia Rebeck, who conducted these studies as a graduate student in Dantas’s lab along with postdoctoral researchers Miranda Wallace, PhD, and Jerome Prusa, PhD, used a specific yeast strain to transport immunotherapy to the gut. The yeast—Saccharomyces cerevisiae var. boulardii—is a well-established and safe probiotic. Unlike bacteria, this yeast is less likely to exchange genetic material with other microorganisms and does not settle in the gastrointestinal tract in a way that could disrupt existing microbial communities. Its naturally occurring anticancer properties, documented to inhibit some cancer cell types in laboratory settings, may provide an added advantage.
The team modified the yeast to act as tiny drug factories that produce immune checkpoint inhibitors—drugs that stimulate immune cells to recognize and attack cancer cells. Tumors often misuse the system that enables healthy cells to evade immune detection, which allows cancer cells to avoid being targeted by the immune system. The researchers determined that the probiotic yeast effectively produced and released the drug, which helps activate the immune system to combat tumors.
In their experiments, the researchers administered either the drug-producing probiotic or an intravenous dose of the immunotherapy drug to mice with colorectal cancer. The results showed that the mice receiving the probiotic had fewer tumors compared to those treated with systemic immunotherapy drugs.
The researchers have filed for two patents—supported by the Office of Technology Management at WashU—related to their engineered probiotic.
This yeast-delivery method could also be modified for other gastrointestinal conditions. Currently, the team is working to adapt this system to target Clostridioides difficile (C. diff), a bacterium known to cause diarrhea and colitis, among other issues. Directly delivering therapeutic agents aimed at this bacterium or its toxins may reduce the need for antibiotics that can also adversely affect beneficial gut bacteria.
