San Antonio Express-News (Sunday)
MD Anderson team using poop to develop cancer treatment
Ongoing efforts to improve cancer therapy have turned Texas scientists’ attention to one possible solution: poop.
More specifically, the complex assortment of viruses, bacteria and other bugs found in human waste.
Recent studies show these microorganisms can help people respond to immunotherapy, which stimulates a person’s immune system to detect and destroy cancer cells more effectively.
A new partnership between MD Anderson Cancer Center and biopharmaceutical company Federation Bio aims to expand this research, to develop drugs that help patients benefit from a type of treatment that so far has only limited success. Immunotherapy response rates vary widely depending on the type of cancer, with diseases such as prostate cancer and glioblastoma so far proving resistant.
“Who would have thought that poop matters so much?” said Dr. Jennifer Wargo, professor of genomic medicine and director of microbiome research at MD Anderson.
Wargo, who heads the institution’s Platform for Innovative Microbiome and Translational Research (PRIME-TR), is a national leader in understanding how bacteria living in the intestinal tract can affect responses to immunotherapy and other cancer treatments.
About six years ago, she helped discover that patients with metastatic melanoma — a severe form of skin cancer that spreads from the original tumor site to other parts of the body — benefited more from immunotherapy if they had a more diverse population of bacteria in their gut. Follow-up research found a link between a high-fiber diet and improved immunotherapy responses.
More recent clinical studies have focused on the potential benefits of fecal transplantation for cancer patients, a process some researchers colloquially term “rePOOPulating.” The treatment involves replacing unfavorable bacteria in the digestive tract with healthier bacteria from a donor, through a medical procedure or a pill.
Fecal transplants are considered experimental, with a significant risk of infection. However, for decades they has been effective at treating Clostridium difficile, also known as C. diff, which infects the bowel and causes diarrhea and colitis. The Food and Drug Administration last year issued its first approval of a fecal transplant-based therapy. And recent studies into the use of fecal transplants for cancer patients have shown promise, MD Anderson researchers say.
In the early stages of two clinical trials, the results of which were published in 2020, cancer patients who did not benefit from previous rounds of immunotherapy received the treatment again, this time with fecal material from a healthy donor who had benefited from immunotherapy. About 30 percent of the participants responded to the treatment, the studies found.
“That made us all think, OK, so if we understand that there’s an association between the composition of the gut microbiome, and someone’s ability to respond to immunotherapy, can we modify the gut microbiome to give many more patients the ability to respond to immunotherapy?” said Dr. Nadim Ajami, director of research for MD Anderson’s PRIME-TR.
Through the partnership with Federation Bio, MD Anderson will study fecal samples from people who previously benefited from immunotherapy to narrow down the properties that influence the treatment. From there, the San Francisco company, formed in 2019, will use its specialized technology to engineer a synthetic material that can be manipulated and manufactured at a large scale.
Federation Bio already has used the technology to design a treatment, currently in clinical trials, for a disease known as enteric hyperoxaluria, a complication of gastrointestinal disorders.
In a statement, Federation Bio CEO Emily Drabant Conley said the collaboration with MD Anderson “enables us to explore (the technology’s) potential in oncology, where there is both high unmet need and evidence supporting the critical role of the microbiome in driving therapeutic response.”
The drug development process will take years, followed by FDA hurdles, but Wargo thinks the research could offer benefits beyond cancer care. MD Anderson already sponsors a study of the association between gut microorganisms and vaccine responses.
“What if the same bugs that promote immunotherapy response could improve response to flu vaccines or COVID vaccines?” she said. “I think that’s a ways down the road. Right now our focus is, first and foremost, we want to make cancer history.”