GRANTEE: Steven Leach, MD
Memorial Sloan-Kettering Cancer Center
Co-Principal Investigator: Douglas Fearon, MD, Weill Cornell Medical College
Research Project: Eliminating T cell barriers in pancreatic cancer patients
Award: 2015 Celgene Corporation – Pancreatic Cancer Action Network – AACR Research Acceleration Network Grant
Award Period: July 1, 2015 – June 30, 2018
Dr. Leach currently holds the David M. Rubenstein Chair, and is the inaugural director of Memorial Sloan-Kettering’s new Rubenstein Center for Pancreatic Cancer Research. Prior to this, he served as Professor of Surgery, Oncology and Cell Biology, and the Paul K. Neumann Professor in Pancreatic Cancer at Johns Hopkins. Dr. Leach received his BA at Princeton University and MD at Emory University, and then completed his postdoctoral training at Yale University. His laboratory has a long track record of research productivity in the field of pancreatic cancer biology, and is known for establishing important links between pancreatic development and pancreatic cancer. Dr. Leach is a member and chair-elect of the Pancreatic Cancer Action Network’s Scientific and Medical Advisory Board.
Dr. Fearon has a joint appointment at Weill Cornell Medical College as the Walter B. Wriston Professor in Pancreatic Cancer Research, and as professor at Cold Spring Harbor Laboratory. He has a broad background in studies of innate and adaptive immunity, including CD8+ T cell biology. More recently, he has contributed to the understanding of the immune suppressive mechanisms in the tumor microenvironment. Dr. Fearon earned his BA at Williams College and his MD at Johns Hopkins University. His medical training took place at Johns Hopkins and Harvard Medical School.
To date, immunotherapeutic approaches (training the patients’ immune system to fight off their tumors) that have worked in other cancer types have not been effective against pancreatic cancer. One of the reasons is that pancreatic cancer cells are able to avoid an immune attack by emitting signals to the cells of the immune system. One of these signals is via a secreted protein called CXCL12. CXCL12 is secreted from the cancer cells and then binds to a protein called CXCR4 on the surface of the immune cells, inhibiting the immune system from attacking the cancer cells. In experiments conducted in mice, a drug blocking CXCL12 (AMD3100) sensitizes pancreatic tumors to immune attack, leading to rapid tumor destruction. Based on these findings, the research team has obtained funding to initiate a clinical trial investigating the safety and effectiveness of AMD3100 in pancreatic cancer patients. Next, they will investigate new versions of AMD3100 that last longer, as well as drugs that target CXCR4 on the immune cells themselves. Plans are in place to test these new immune-targeting treatment strategies in patients with metastatic pancreatic cancer and before surgery in patients with earlier stage disease.