PHILADELPHIA—Three of the top-ten causes of death worldwide are infectious diseases, with billions of people harboring such potentially lethal pathogens as the hepatitis B virus, malaria, tuberculosis, the influenza virus, and HIV. Taking a creative approach to address this problem, Penn Medicine and colleagues at Oxford University and Massachusetts General Hospital have received an additional five-year round of funding totaling $10 million from the National Institutes of Health (NIH) to explore using a promising cancer treatment to combat these dangerous viruses.
E. John Wherry, PhD, the chair of Pharmacology at the Perelman School of Medicine of the University of Pennsylvania, will lead the Penn team in the collaboration to study the impact of an immunotherapy called PD-1 blockade on viral immunity in humans. This grant renewal is part of the NIH’s Cooperative Centers for Human Immunology consortium.
The programmed cell death protein 1 (PD-1) is located on an immune cell’s surface and plays a key role in restraining T cell activity. While this control of immune response can prevent autoimmune diseases, it can also block the immune system’s ability to kill cancer cells. PD-1 inhibitors can thwart PD-1, ramping up the immune system’s capacity to attack tumors.
“These medications have also shown early promise against infectious diseases,” said Wherry. “But there is almost no information in humans about how targeting PD-1 affects immunity to viruses and vaccines.”
The new grant aims to address this crucial gap in knowledge to improve prevention and treatment of infectious diseases. The primary goal is to apply PD-1 blockade in hepatitis B virus infection and flu vaccination, identifying innate and adaptive immune effects controlled by PD-1 signals in response to viruses and vaccines in people.
By studying humans, the new grant will seek to address a common challenge in basic biomedicine: Much research now only takes place in mice, making the translation of insights gained from animal studies to humans limited. “Flu and other respiratory infections alone kill up to half a million people globally each year,” said Wherry. “Vaccines remain only partially effective, especially in the most vulnerable populations. Although we have learned a great deal about human immunology in the past several decades, we still have a long way to go.”
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
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