Parker Institute Scientists at MD Anderson Cancer Center publish findings in Science, Plan Clinical Trial
While cancer immunotherapy has extended the lives of patients who had failed other therapies, two big questions remain:
Why do some patients respond to these breakthrough cancer drugs while others do not, and how can we make immunotherapy work for more types of cancer patients?
New research published Nov. 2 in the journal Science sheds light on one factor that could play a major role: the microbiome.
In this paper, scientists found that melanoma patients who have a greater diversity of bacteria in their gut microbiome responded better to an anti-PD-1 checkpoint inhibitor versus those with less diversity. Anti-PD-1 checkpoint inhibitors target a protein on T-cells, taking the brakes off the immune response so it can better fight off tumors.
The lesson from that data is clear, says senior author Jennifer Wargo, M.D., a Parker Institute physician-scientist at MD Anderson Cancer Center: “Diversity matters.”
Specific bacteria also associated with response to cancer drugs
Dr. Wargo’s team also found that patients on anti-PD-1 checkpoint inhibitors with an abundance of specific bacteria in the Ruminococcaceae family, such as Faecalibacterium prausnitzii, had a longer period of progression-free survival, during which time the diseases stay in check. On the flipside, bacteria in the order Bacteroidales were linked to faster advancing disease and a decrease in patient survival.
Prior research in mice, and more recent work from Dr. Wargo’s lab, has shown that introducing a “favorable” microbiome profile could lead to improved outcomes in response to cancer immunotherapy. Currently, checkpoint inhibitors are effective for 20 to 30 percent of patients.
The next step: testing the hypothesis in humans.
“What if we could change the microbiome and improve responses to cancer therapy? That’s what we were thinking going into this,” Dr. Wargo said during a recent visit to the Parker Institute, based in San Francisco.
Diet, antibiotic use and fecal transplantation have been shown to impact the variety of microbes colonizing the gut.
If it is possible to convert a cancer patient who does not respond to cancer immunotherapy into someone who does by altering the makeup of their gut, that could significantly increase the number of people who can be treated successfully with immunotherapy.
“If this works, it would be a game-changer,” said Fred Ramsdell, Ph.D., vice president of research at the Parker Institute.
Clinical Trial in the Works
On the basis of Dr. Wargo’s work, the Parker Institute is planning, in collaboration with MD Anderson and others, what may be the first-of-its-kind microbiome-cancer immunotherapy clinical trial for advanced melanoma patients.
While details are still being finalized, the phase 1b trial is anticipated to test two types of pills designed to change a person’s microbiome against a placebo in combination with an immune checkpoint inhibitor.
“We believe this is the first such clinical study in oncology, and represents a novel way to try to increase the proportion of patients who respond to existing immunotherapies,” Ramsdell said.
Doctors will evaluate patients along the way to see how their gut microbiome profile changes, before, during and after treatments.
To gain more insight, researchers will also look into how the immune system of patients are changing by following certain biomarkers.
“We are interested in a biomarker-rich study to help establish why or why not this approach works,” Ramsdell said. “We certainly hope it does, but understanding the underlying mechanisms is equally important.”
The trial is expected to open at MD Anderson and expand to additional Parker Institute affiliated sites in the future.
Read the MD Anderson press release.