On Jun. 3, 2019, the University of Pennsylvania (Penn) announced it had received a $12 million grant from The Mark Foundation for Cancer Research to study the connection between cellular therapies and new methods of radiation therapy. The grant from The Mark Foundation for Cancer Research will establish The Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation at the University of Pennsylvania, which will seek to better understand the interconnected relationship between novel forms of radiation therapy, important signaling pathways between cancer and immune cells, and the immune system’s ability to kill cancer. Five specific projects will bring together multidisciplinary teams of basic science and clinical researchers to answer these key questions.

Each of the five projects will converge on understanding the role of interferon (IFN) and pattern recognition receptor (PRR) signaling in enabling the immune system to fight cancer. IFNs normally protect cells from viruses – named for their ability to literally interfere with a virus’ ability to spread. PRRs are molecules that act as an alarm system that typically recognizes invaders. Two projects will identify the genetics behind IFNs and PRRs, including how they signal in cancer and immune cells, how they can be corrupted to do the bidding of cancer cells, and how vulnerabilities can be manipulated to improve response to immunotherapy.

Two other projects involve a concept called FLASH radiation, a super-concentrated form of radiation that can deliver an entire course of radiation therapy – which would typically be given over the course of weeks – in less than a second. Researchers will determine whether FLASH can more favorably impact IFN and PRR signaling compared to traditional radiation. They will then study whether FLASH makes a tumor more susceptible to attack by the immune system, yet decreases side effects normally associated with conventional radiation therapy.

The fifth project seeks to engineer chimeric antigen receptor (CAR) T cells capable of influencing IFN signaling in the tumor. The aim is to improve both the CAR T cells themselves as well as initiate something called the “bystander effect” – engaging other immune cells that have not yet jumped into the fight against the tumor.

“The results of this exciting project could have enormous significance for cancer patients,” said The Mark Foundation CEO Michele Cleary, PhD. “This multidisciplinary effort is well positioned for success, and we expect these leading researchers will uncover novel insights into cancer biology that will substantially expand the options for treatments with better efficacy and minimal toxicities. We look forward to working with this powerhouse team over the next five years and beyond.”