The SU2C-NSF-LF Cancer Convergence Dream Team Progress Update
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The SU2C-National Science Foundation-Lustgarten Foundation Cancer Convergence Dream Team Progress Report
“Liberating T-cell Mediated Immunity to Pancreatic Cancer”
Grant Funded: January, 2016
Convergence Team Leader:
• Jeffrey Drebin, MD, PhD - University of Pennsylvania
• Jedd D. Wolchok, MD, PhD – Memorial Sloan Kettering Cancer Center
• David T. Ting, MD – Massachusetts General Hospital/Harvard Medical School
• Curtis G. Callan, PhD – Princeton University
• Harlan Robins, PhD – Fred Hutchinson Cancer Research Center
• Benjamin D. Greenbaum, PhD – Ichan Medical School at Mount Sinai
Through collaboration of research scholars in distinct disciplines, convergence grants offer a novel model research meant to spur innovation in new ways of combating cancer. By taking advantage of advances in information technology, nanotechnology, new material research, imaging, optics, quantum physics, and other physical sciences, often considered outside the realm of traditional biomedical research, the subsequent convergence grants may provide critical outcomes to advance the fight against cancer.Project Background
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death and is expected to become the second most common cause of death in the United States within the next five years. Although there have been anecdotal reports of response to immune-based therapies, they have not been shown to be generally effective, likely because immune cells generally do not infiltrate the tumor and because the tumor creates immunosuppressive factors.
There is evidence that vitamin D can increase the effectiveness of standard chemotherapies in pancreatic cancer, and it has been observed that the treatment results in an increased number of immune cells in the tumor perhaps helping to kill the tumor cells. The Team is building on these results, exploring the potential for immunologic therapies for pancreatic cancer. To that end, the Team has two specific aims:
1. Characterization of Vitamin D effects on the immune cell repertoire and immunologic milieu in human pancreatic cancer. The Team is analyzing tumor samples from patients who have had Vitamin D treatment, focusing on the diversity of epitopes on immune cells. It is the epitopes that allow immune cells to identify cells as health or not, and cancers often masquerade as healthy cells. In addition, the Team is investigating the makeup of the tumor microenvironment in order to understand the immunosuppressive properties and to develop biomarkers that can indicate whether an immunotherapy will work.
2. Exploratory study of chemoimmunotherpay in pancreatic cancer. The team is conducting a clinical trial in which the standard chemotherapy is combined with Vitamin D and immunotherapy. Correlative studies will be done to understand the immune response and develop biomarkers to more effectively measure the efficacy of the therapy.
The Team has received IRB approval to conduct the clinical trial investigating whether the addition of immunotherapies can increase the patient’s immune cells’ ability to kill the tumor. Studies of the immune cell diversity have begun and computational approaches to understanding the microenvironment have yielded early results.