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2023 Grantee: William Freed-Pastor, MD, PhD
Dana-Farber Cancer Institute
Research Project: Immunopeptidomics to Accelerate Immunotherapies in Pancreas Cancer
Award: 2023 Pancreatic Cancer Action Network Career Development Award in memory of Llewellyn Bixby IV, through a gift made by his family
Award Period: July 1, 2023 – June 30, 2025
Amount: $250,000
Biographical Highlights
Dr. William Freed-Pastor is a physician-scientist at Dana-Farber Cancer Institute (DFCI) and Harvard Medical School, specializing in gastrointestinal oncology and immuno-oncology. He is an investigator within the Division of Molecular and Cellular Oncology and the Hale Center for Pancreatic Cancer Research at DFCI. The Freed-Pastor laboratory develops and utilizes sophisticated preclinical models of pancreatic cancer to dissect mechanisms of immune escape and tumor-immune crosstalk.
Dr. Freed-Pastor has been a Young Investigator on a Stand Up To Cancer (SU2C)-Lustgarten Foundation Pancreatic Cancer Interception Dream Team, and he was recently awarded the SU2C Golden Arrow Early Career Scientist Award, a SU2C Sharp Award for Innovation in Collaboration (with Dr. Philip Greenberg), a Conquer Cancer Foundation American Society of Clinical Oncology (ASCO) Young Investigator Award and a Burroughs Wellcome Career Award for Medical Scientists for his work to understand the role of the immune system during pancreatic tumor development and offer insights into therapeutic approaches that leverage the immune system for the treatment of pancreatic cancer.
Project Overview
While immunotherapies – therapies that harness a patient’s immune system to fight disease – have shown remarkable promise for some tumor types, like melanoma, they have been less successful in treating pancreatic cancer. This is because pancreatic tumors and their surrounding microenvironment are notorious for hiding from and avoiding immune recognition and attack. Through his PanCAN Career Development Award, Dr. Freed-Pastor seeks to overcome this immunosuppression through stimulation of the immune system.
Under normal conditions, the cells in the body “display” small pieces of proteins, known as peptides, on their surface via a protein family called MHC. A peptide that is recognized by the immune system is known as an antigen. Immune cells circulate in the body and look for foreign antigens – such as pieces of proteins originating from a bacterial or viral infection – and then kill the infected cell.
The Freed-Pastor lab’s previous work has focused on evaluating which antigens are presented by MHC proteins on pancreatic cancer cells. They’ve taken this approach using pancreatic cancer organoids, which are 3D models of pancreatic tumors grown in the lab, generated from patients’ tumor tissue samples. Analyses of these organoids have revealed both “canonical” (expected) and “noncanonical” (unusual) antigens that can be presented by MHC proteins to the immune system. The noncanonical antigens are of special interest to the investigators as potential features of the cancer cells that may be recognizable by the immune system as foreign.
Dr. Freed-Pastor’s PanCAN Career Development Award will allow him and his team to continue to identify canonical and noncanonical antigens associated with a panel of pancreatic cancer patient-derived organoids and determine whether they are also expressed by healthy cells. They will also evaluate the “innate” (naturally occurring) immune response that occurs in response to these antigens, as well as explore strategies to experimentally trigger an immune response to the antigens presented by the pancreatic cancer cells. Dr. Freed-Pastor shared, “The PanCAN Career Development Award will provide crucial support during this pivotal time and catalyze a successful career in pancreatic cancer research.”
