The approach is called chimeric antigen receptor (CAR) T-cell therapy, which uses specially modified immune cells to find and destroy cancerous cells. A version of CAR T-cell therapy was recently endorsed by an advisory committee to the Food and Drug Administration for treatment of advanced leukemia. Despite great success against certain types of leukemia and lymphoma, it has been difficult to apply CAR T-cell therapy to solid tumors.
The Stand Up To Cancer–Lustgarten Foundation Chimeric Antigen Receptor T Cell (CART) Translational Research Team is headed by three investigators at the University of Pennsylvania’s Perelman School of Medicine who have been pioneers in CAR T-cell therapy development: Carl H. June, MD, the Richard W. Vague professor in immunotherapy; Shelley L. Berger, PhD, the Daniel S. Och university professor; and E. John Wherry, PhD, Richard and Barbara Schiffrin president’s distinguished professor of microbiology, and director, Institute for Immunology.
The team will receive $2 million in funding, with $1 million coming from SU2C and $1 million from the Lustgarten Foundation for Pancreatic Cancer Research, the largest private foundation dedicated solely to funding pancreatic cancer research.
The study will focus in large part on epigenetics, which are factors that influence the way genes are expressed rather than changes in the underlying genetic code itself.
“We will investigate CAR T-cell therapy for pancreatic cancer in combination with analysis of the epigenetics of patients who respond to the treatment as well as those who fail to respond, with the goal of finding ways to increase the response rate and explore new therapies against this terrible disease,” June said.
Phase I clinical trials will help identify epigenetic changes that are common to patients who don’t respond to immunotherapy, compared to those who do.
“Identification of mechanisms of resistance is the central question facing the field of immuno-oncology,” June added.
Another objective is to explore the use of CAR T cells that will target mesothelin, a protein that is overexpressed in pancreatic cancer, providing a target for CAR T cells.
Cancer of the pancreas is one of the deadliest forms of cancer, with a five-year survival rate of only 8 percent, according to the National Cancer Institute (NCI). Some 53,670 people will be diagnosed with pancreatic cancer this year, the NCI estimates, and about 43,000 deaths will occur.
The Stand Up To Cancer–Lustgarten Foundation Chimeric Antigen Receptor T Cell (CART) Translational Research Team is one of four SU2C-sponsored research teams addressing pancreatic cancer. In collaboration with the Lustgarten Foundation, SU2C and the AACR have initiated a review process in which all four teams come together on a semi-annual basis to share their progress and data.
“The fact that we are bringing four teams together twice a year is a sign of the enormous commitment by Stand Up To Cancer and its collaborators to new research in pancreatic cancer,” said David A. Tuveson, MD, PhD, director of the Cold Spring Harbor Laboratory Cancer Center in Cold Spring Harbor, New York, a member of the SU2C Scientific Advisory Committee, and research director for the Lustgarten Foundation. “Given the dearth of treatment options, new approaches are desperately needed. The teams learn from each other by sharing findings and discussing challenges as they pursue their particular lines of research,” he said.
The other teams are:
• SU2C-Lustgarten Foundation Pancreatic Cancer Dream Team: Transforming Pancreatic Cancer to Treatable Disease, led by Elizabeth M. Jaffee, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and Robert H. Vonderheide, MD, DPhil, of the University of Pennsylvania.
• SU2C-Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team: Reprogramming of Transcriptional Circuitry to Control Pancreatic Cancer, led by Daniel D. Von Hoff, MD, of The Translational Genomics Research Institute (TGen), Ronald M. Evans, PhD, of the Salk Institute for Biological Studies, and Gerard I. Evan, PhD, of the University of Cambridge.
• SU2C-National Science Foundation-Lustgarten Foundation-V Foundation Convergence Team: Liberating T-cell Mediated Immunity to Pancreatic Cancer, led by Jeffrey A. Drebin, MD, PhD, chairman of the Department of Surgery at Memorial Sloan Kettering Cancer Center in New York.
The CAR T cell team is the seventh Translational Research Team that SU2C has launched since its inception in 2008. SU2C has also launched 20 larger Dream Teams and has made 46 Innovative Research Grants and 18 Phillip A. Sharp Innovation in Collaboration Awards.