An Innovative Research Grant from Stand Up to Cancer will help a University of Texas MD Anderson Cancer Center physician scientist and her team understand how the bacteria in the digestive tracts of melanoma patients affects their response to a common immunotherapy drug.
The $750,000, three-year grant to Jennifer Wargo, M.D., associate professor of Surgical Oncology and Genomic Medicine, is one of 10 nationally announced today at the annual meeting of the American Association for Cancer Research.
"We have encouraging preliminary evidence from a clinical study that the diversity and composition of a patient's gut microbiome may play a significant role in determining how they respond to immune checkpoint blockade - specifically anti-PD-1 therapy," Wargo said.
"This Innovative Research Grant will help us address two important questions: exactly how gut microbes influence the immune system and how we might manipulate that to improve treatment," said Wargo, who also co-leads the Melanoma Moon Shot™, part of MD Anderson's Moon Shots Program™ to reduce cancer deaths by accelerating development of therapies from scientific discoveries.
Anti-PD1 drugs use an antibody to block activation of a brake on immune system T cells, unleashing the immune system to attack cancer.
Wargo and colleagues have presented data at scientific meetings, including the AACR annual meeting, showing that analysis of fecal samples from both responders and non-responders to anti-PD1 therapy had distinct differences in their gut microbiomes. Patients whose melanoma responded to treatment had greater diversity of bacteria overall and also an abundance of the Ruminococcaceae and Clostridiales bacteria. Non-responders had more Bacteriodales bacteria.
"Immuno-oncology is one of the most exciting areas in cancer research today, and we believe these outstanding investigators have the potential to help take the field to the next level," said William Kaelin, Jr., M.D., professor at the Dana-Farber Cancer Institute and Harvard Medical School and chair of the SU2C Innovative Research Grants Committee (IRGC) in the grant announcement. "We want to see more patients benefitting from the science of immuno-oncology, so increasing the types of cancers for which treatment may be effective is critical. These researchers will bring new ideas and fresh energy to that effort."
Wargo's team will expand studies of patient samples to build on existing data and define microbiome-immune system interactions for a broader range of immunotherapies. They also will use experimental mouse models to identify specific microbiome effects. Germ-free mice will have fecal transplants from responding or non-responding patients to colonize their digestive tracts, providing favorable and unfavorable microbiomes to study in detail.
Stand Up To Cancer, a program of the Entertainment Industry Foundation, raises funds to accelerate the pace of research to get new therapies to patients quickly and save lives.
From its inception in 2008, SU2C's Innovative Research Grants were designed to support work that utilizes new ideas and approaches to solve critical problems in cancer research. These innovative projects are characterized as "high-risk" because they challenge existing paradigms, and, if successful, the projects have the potential for "high-reward" in terms of saving lives.
This year's program focused on immunotherapy and is funded by a grant to SU2C by Bristol-Myers Squibb, with grantees selected independently by a committee chaired by Kaelin.
In collaboration with the Parker Institute for Cancer Immunotherapy (PICI), the first immunotherapy-microbiome clinical trial is expected to launch later this year. Research also continues to be funded by MD Anderson's Melanoma Moon Shot™ and PICI, as well as the Melanoma Research Alliance.