Engineered yeast cells deliver PD-1 inhibitors that shrink intestinal tumors in mice

Delivering drugs to gut tumors can be tricky. Researchers at Washington University in St. Louis have engineered an oral probiotic yeast to do the work for them, with the fungal cells able to release immune checkpoint inhibitors that shrank intestinal tumors in mice with colorectal cancer.

The results were published in Cell Chemical Biology on Nov. 20.

“We have engineered a yeast-based probiotic that delivers immunotherapy directly to the tumor site,” study senior author Gautam Dantas, Ph.D., said in a Nov. 20 release. “Our hope is that one day the probiotic could be added to the arsenal of therapies to help shrink tumors in people.”

The researchers have filed two patents related to the technique, and they are working to tweak the method to treat infections by the bacterium Clostridioides difficile, or C. diff, according to the release.

Through gene editing, the yeast cells were engineered to essentially function as mini-factories for antibodies targeting programmed death ligand 1 (PD-1), a protein expressed on the surface of T cells that is a common cancer immunotherapy target. Binding to PD-1 can coax T cells to attack cancer cells, which normally evade detection by the immune system.

PD-1 inhibitor therapies include blockbusters such as Merck’s Keytruda and Bristol Myers Squibb’s Opdivo.

The effects of the probiotic on tumor size and immune modulation were small but statistically significant, which indicates room for the method to be improved, the authors noted in the paper.

Yeast isn’t the only living entity engineered to deliver drugs lately. In July, researchers used the protozoan parasite Toxoplasma gondii to shuttle drugs across the blood-brain barrier in mice.