GRANTEE: Ann Leen, PhD
Baylor College of Medicine
Co-Principal Investigator: William Fisher, MD
Research Project: T-Cell Therapy for Pancreatic Cancer
Award: 2016 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2016 – June 30, 2018
Dr. Leen is an immunologist with an extensive background in immunotherapy for cancer and post-transplant viral infections. For the past 15 years, she has developed and clinically tested a variety of novel immune-based therapies to treat both patient groups. Dr. Leen works at the Center for Cell and Gene Therapy at Baylor College of Medicine, where she is an associate professor. Her undergraduate studies took place at University College Cork, Ireland, and she earned her PhD in immunology at CRC Institute for Cancer Studies in Birmingham, U.K.
Dr. Fisher is the chief of the division of general surgery, a professor of surgery and the director of the Elkins Pancreas Center at Baylor College of Medicine. He attended medical school at the University of Cincinnati and conducted his residency and fellowship training at Mount Carmel Medical Center and Ohio State University, both in Columbus. Dr. Fisher has focused his career on pancreatic cancer as a surgeon, basic scientist and clinical researcher. At the Elkins Pancreas Center, he directs all the clinical care for a large population of pancreatic cancer and chronic pancreatitis patients. He coordinates the basic science, tissue banking and clinical research related to pancreatic cancer that is performed at Baylor.
Drs. Leen and Fisher are teaming up to test an immunotherapeutic approach to treating pancreatic cancer. Their goal is to introduce a modified type of immune cells, called T cells, into the pancreatic tumor environment that can selectively and effectively kill the cancer cells. The researchers identified two major challenges that could impede this type of immunotherapeutic approach. First, pancreatic cancer cells are very heterogeneous, which means that the cells within the tumor have different features from one another. Also, the stroma, or tissue surrounding the tumor, includes cells that serve to protect the tumor from an immune attack.
Drs. Leen and Fisher have developed strategies to overcome these two challenges. T-cells function by recognizing an antigen, or protein present on the outside of other cells, which signals the T-cells to kill only the cells expressing that antigen. Because all cells within the pancreatic tumor do not express the same antigen, the research team will generate T-cells that recognize five different antigens that are commonly expressed on the surface of pancreatic cancer cells. In addition, the specially designed T-cells will be subsequently engineered to thrive on factors secreted by pancreatic cancer cells and the surrounding stroma – instead of being impeded by those same factors.
During their two-year funded period, Drs. Leen and Fisher will test the safety and antitumor effects of T-cells targeting five tumor antigens in a phase 1 trial in patients with metastatic pancreatic cancer. In addition, experiments will be conducted to ascertain whether these T-cells can remain within and around the tumor or stroma, maintain their function and induce an antitumor response in patients. Finally, the researchers will evaluate the added benefit of engineering the T-cells to be stimulated, rather than inhibited, by the pancreatic cancer cells and surrounding stroma. Drs. Leen and Fisher’s research team is uniquely positioned to translate the proposed studies to the clinic given their knowledge, experience in performing “first in man” clinical trials and specialized infrastructure, which allow them to make and modify killer T-cells that are suitable for administration to patients.