Engineered yeast deliver colorectal cancer immunotherapy

Saccharomyces cerevisiae var. boulardii is a yeast strain that has been designed for a new purpose: treating colorectal cancer.

Researchers have previously engineered Escherichia coli bacteria that produce and release immune checkpoint inhibitors when injected into tumors in mice. In a new study, a team led by microbiologist Gautam Dantas at Washington University in St. Louis designed a system based on S. cerevisiae var. boulardii, (also called S. boulardii) to make and deliver immune checkpoint inhibitors to gastrointestinal tumors in mice after it’s ingested (Cell Chem. Biol. 2024, DOI: 10.1016/j.chembiol.2024.10.013).

Dantas’ team inserted plasmids into the yeast that encode miniature antibody variants, which then block PD-1, a checkpoint protein found on T cells. Cancer cells can shield themselves from the immune system by binding to checkpoint proteins. When checkpoint proteins or the ligands they bind to are blocked, T cells can destroy the tumors.

Mice with colorectal cancer who were fed the engineered yeast had fewer tumors than mice who were given no treatment and mice who received conventional immunotherapy. Dantas suggests that the difference may be due to both the immune checkpoint inhibitors and the yeast itself, since S. boulardii may have innate therapeutic properties that suppress cancer cells.

“Overall, the study is well executed,” Morten Sommer, a microbiologist at the Novo Nordisk Foundation for Biosustainability at the Technical University of Denmark who was not involved in the research, writes in an email. He adds that the study serves as a proof of concept for the use of S. boulardii to deliver immune checkpoint inhibitors.