Stand Up To Cancer (SU2C) has partnered with the Lustgarten Foundation for Pancreatic Cancer Research to sponsor a translational research team focused on applying chimeric antigen receptor T-cell (CAR-T) therapy to fighting pancreatic cancer.

The Stand Up To Cancer–Lustgarten Foundation Chimeric Antigen Receptor T Cell (CAR-T) Translational Research Team will seek to apply to a solid tumor cancer the CAR-T approach that has seen success in blood cancers such as leukemia.

The team has been awarded $2 million. Half will come from SU2C, a 501(c)(3) funder of cancer research established in 2008 by film and media leaders.

The other half will come from the Lustgarten Foundation, which has directed $132 million to research since its inception and is the largest private foundation dedicated solely to funding pancreatic cancer research.

Leading the team are three pioneers in CAR-T therapy development based at the University of Pennsylvania’s Perelman School of Medicine: Carl H. June, M.D., Shelley L. Berger, Ph.D., and E. John Wherry, Ph.D.

“We will investigate CAR-T 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,” Dr. June said in a statement.


Studying Epigenetic Changes

The research team is planning Phase I trials aimed at identifying epigenetic changes common to patients who do not respond to immunotherapy, and comparing those to changes in patients who do respond. Researchers also aims to explore the use of CAR-T against a potential target—mesothelin, a protein that is overexpressed in pancreatic cancer.  

“Identification of mechanisms of resistance is the central question facing the field of immuno-oncology,” Dr. June added.

Dr. June is the Richard W. Vague Professor of Immunotherapy, director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine and director of the Parker Institute for Cancer Immunotherapy at Penn. Dr. Berger is the Daniel S. Och university professor, while Dr. Wherry is director of the Institute for Immunology and the Richard and Barbara Schiffrin president’s distinguished professor of microbiology.

Earlier this month, Dr. June and colleagues won an FDA advisory committee’s unanimous recommendation of approval for Novartis’ leukemia-fighting treatment CTL019 (tisagenlecleucel), a CAR-T therapy developed through a collaboration between Penn and the pharma giant. CTL019 is indicated for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).

In 2012, Penn and Novartis launched their global collaboration to further research, develop, and commercialize CAR-T therapies, including CTL019, for the investigational treatment of cancers. Since then, Novartis and Kite Pharma have emerged as leading developers of CAR-T therapies, Brad Loncar, CEO of Loncar Investments, told GEN shortly after the unanimous vote by FDA’s Oncologic Drugs Advisory Committee.

The new team is one of four pancreatic cancer research teams sponsored by SU2C. The other three are:

  • SU2C–Lustgarten Foundation Pancreatic Cancer Dream Team: Transforming Pancreatic Cancer to Treatable Disease, led by Elizabeth M. Jaffee, M.D., of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University and Penn’s Robert H. Vonderheide, M.D., D.Phil.
  • SU2C–Cancer Research UK-Lustgarten Foundation Pancreatic Cancer Dream Team: Reprogramming of Transcriptional Circuitry to Control Pancreatic Cancer, led by Daniel D. Von Hoff, M.D., of The Translational Genomics Research Institute (TGen), Ronald M. Evans, Ph.D., of the Salk Institute for Biological Studies, and Gerard I. Evan, Ph.D., 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, M.D., Ph.D., chairman of the Department of Surgery at Memorial Sloan Kettering Cancer Center.

“Given the dearth of treatment options, new approaches are desperately needed,” stated David A. Tuveson, M.D., Ph.D., director of the Cold Spring Harbor Laboratory Cancer Center, a member of the SU2C Scientific Advisory Committee, and research director for the Lustgarten Foundation.