The New Pancreatic Cancer Convergence Dream Team
Posted on April 2, 2014, 3:16 AM
In the US, cancer of the pancreas is the fourth-leading cause of cancer deaths in both men and women. Pancreatic cancer is distinct among the top-five cancer killers (lung, colorectal, breast, pancreas and prostate) in that both the incidence rate and death rate are unfortunately increasing. It’s often a “silent killer” – difficult to detect until it’s too late, due to a lack of specific symptoms.
That is why Stand Up To Cancer (SU2C) and the Lustgarten Foundation, along with the American Association for Cancer Research (AACR), SU2C’s Scientific Partner, are proud to announce the formation of a Dream Team dedicated solely to pancreatic cancer research. The team will be supported in part by a gift to SU2C from the Fox Family Cancer Research Funding Trust. The SU2C-Lustgarten Pancreatic Cancer Convergence Dream Team Translational Research Grant will provide $8 million in funding over three years for this innovative project that will develop new therapies to exploit patients’ own immune cells to treat their cancers.
Elizabeth M. Jaffee, M.D., co-director of the Gastrointestinal Cancers Program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, will lead the Dream Team. Robert H. Vonderheide, M.D., D.Phil., associate director for Translational Research at the Abramson Cancer Center of the University of Pennsylvania, will co-lead the project, which is titled, “Transforming Pancreatic Cancer from Death Sentence to Treatable Disease.”
“Pancreatic cancer suppresses the body’s antitumor immune response,” said Dr. Jaffee. “These tumors do not allow immune cells that can recognize and kill them to even enter the pancreas. We think we can use vaccination to activate antitumor immune cells and then use other agents to get those cells into the pancreas, where they can attack the tumor.”
Pancreatic ductal adenocarcinoma (PDA) is resistant to most forms of therapy and is one of the most fatal types of cancer. The environment that surrounds cancer cells is referred to as the tumor microenvironment, and studies in mice and humans have shown that the PDA tumor microenvironment has unique characteristics that are thought to limit the efficacy of treatment. By understanding the obstacles that prevent the tumor from responding to treatments, it should be possible to develop therapeutic agents to eliminate these barriers resulting in the effective treatment of PDA.
T cell-based cancer immunotherapy has shown promise for the treatment of a variety of cancer types and was hailed as “Breakthrough of the Year” in 2013 by the journal Science. Despite its emerging promise, clinical efforts for immune therapy in PDA have lagged behind. Recent advances in PDA mouse models and in technologies to study cancer-associated immune processes at tumor sites have revealed that major anti-PDA immune responses can occur if antitumor T cell-generating approaches are combined with drugs that block immune suppression in the tumor. Based on promising initial clinical trials, this Dream Team’s goal is to “re-program” the tumor microenvironment to fuel clinically meaningful anticancer immune responses in patients with PDA.
The Dream Team will use a “convergence” approach by bringing together leading individuals in the fields of immunotherapy, genetics, informatics, biostatistics, regulatory/clinical trials, cancer biology, and pathology. This group of experts will apply their efforts toward understanding and treating PDA. According to co-leader Dr. Vonderheide, “We believe that we are on the cusp of developing and delivering care that has the potential to make real headway. We have a new understanding that the immune system can be a powerful therapy for cancer and we know that to exploit it to treat pancreatic cancer, we need to activate the immune system in better and more robust ways.”
As with each of the SU2C Dream Teams, researchers on the newest team represent a variety of institutions, including Johns Hopkins University; the Abramson Cancer Center of the University of Pennsylvania; Washington University in St. Louis; University of California, San Francisco; Oregon Health & Science University; and New York University Langone Medical Center. They will conduct combination clinical trials and establish biomarkers of tumor microenvironment reprogramming. Trials will focus on novel immune suppressive pathways within the tumor, either in combination with a T cell-activating vaccine or chemotherapy. These trials will also establish a national PDA biobank for identification of immune biomarkers. Preclinical studies in PDA mouse models will be conducted to establish novel multi-agent approaches and develop biomarkers that will drive the next generation of clinical trials. The project is estimated to start July 1, 2014, with clinical trials scheduled to open within the first year.
“While we are making progress with many other forms of cancer, breakthroughs are needed in pancreatic cancer to improve survival time and allow people to live their lives as normally as possible,” said Sung Poblete, Ph.D., R.N., SU2C’s president and chief executive officer. “The SU2C-Lustgarten Foundation Dream Team is bringing together some wonderfully talented researchers from top cancer centers who will work collaboratively to bring us closer to the day when pancreatic cancer can be managed if not cured.”
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