Jump-starting innovative projects exploring pathogen-associated cancers

Pathogen-Associated Malignancies Integrated Research Center awards first round of pilot funding supporting researchers studying H. pylori, EBV and the microbiome
Drs. Neelendu Dey, Nina Salama and Andrew McGuire
Inaugural PAM IRC pilot-award recipients include Drs. Neelendu Dey, Nina Salama and Andrew McGuire. Fred Hutch file photos

Worldwide, as many as one in five cancer patients can trace their disease — directly or indirectly — to a pathogen. The good news is that this gives researchers a firm target to aim at when developing strategies to prevent or treat these cancers. The Pathogen-Associated Malignancies Integrated Research Center, Fred Hutchinson Cancer Research Center’s most recently established IRC, was created to facilitate these studies. Directed by Dr. Denise Galloway, its goal is to support collaborative, multidisciplinary research into pathogen-associated cancers. Now, the PAM IRC has handed out its first pilot awards to jump-start innovative research.

The inaugural recipients of the PAM IRC Innovation Awards are principal investigators Dr. Neelendu Dey of the Clinical Research Division, Dr. Nina Salama of the Human Biology Division, and Drs. Andrew McGuire and Martin Prlic of the Vaccine and Infectious Diseases Division.

Dey will receive $200,000 over two years to investigate the role that the gut microbiome may play in the development of colorectal cancer through its effects on intestinal nerves. These nerves, termed the enteric nervous system, or ENS, influence gut motility, which in turn may play a role in the development and spread of colorectal cancer. Activity of the ENS is influenced by bile acids, which are modified by gut bacteria. Different gut bacteria modify bile acids various ways, producing products that can stimulate the ENS dissimilarly.

Dey already has shown that in mice, diet can affect gut motility through the microbiome by altering the spectrum of bile-acid products that different bacteria produce to stimulate the enteric nervous system.

In a preclinical model of colorectal cancer with a clearly defined microbiome, Dey will test the idea that the microbiome influences colorectal cancer development through bacteria-produced bile acid products, and examine whether the ENS is central to this phenomenon.

Salama will receive $100,000 over one year to examine how the stomach pathogen Helicobacter pylori may influence the development of gastric cancer subtypes and the immune response to gastric cancer by altering the tumor microenvironment. Gastric cancer, closely linked to H. pylori infection in the stomach, is the third leading cause of cancer death worldwide. Patients with this cancer lack effective chemotherapies and need better treatment options.

Dr. Martin Prlic
Dr. Martin Prlic is principal investigator, along with Dr. Andrew McGuire, of a PAM IRC award that aims to develop CAR T cells to combat tumor cells arising from Epstein-Barr virus infection. Fred Hutch file photo

Recent studies have demonstrated that the bacterium often persists even after cancerous tumors have formed, suggesting that it may shape how stomach cancer both develops and progresses. Salama will study whether H. pylori influences the molecular subtype of stomach tumors and how the immune system responds to them. The work may also help reveal whether — and in whom — to deploy immunotherapy to treat stomach cancer.

McGuire and Prlic will receive $200,000 over two years to work toward developing chimeric-antigen receptor, or CAR, T cells that can combat tumor cells arising from Epstein-Barr virus infection. EBV proteins are expressed on the surface of some tumor types, providing potential targets for CAR T cells. However, the use of CAR T cells to combat EBV-positive tumors is currently hampered by two issues. First, there are currently no antibodies that recognize the EBV surface proteins that can form the foundation of an EBV-targeting CAR. Second, several EBV-positive tumors are found in mucosal tissues, such as the lining of the gut. Most T cells typically do not home to these areas. McGuire and Prlic will work to find EBV-specific antibodies that can be used to generate CARs and work to engineer a subtype of T cell that homes to areas where many EBV-positive tumors are found.

Read more about Fred Hutch achievements and accolades.

Sabrina Richards, a staff writer at Fred Hutchinson Cancer Center, has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a PhD in immunology from the University of Washington, an MA in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.

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