2021 Grantee: Shannon Oda, PhD
Seattle Children’s Research Institute, University of Washington
Research Project: Developing Engineered Proteins to Enhance Adoptive Cell Therapy of PDA
Award: 2021 Pancreatic Cancer Action Network Career Development Award made possible by Linda E. Amuso in memory of Susan A. Lombardi
Award Period: July 1, 2021 – June 30, 2023
After receiving her undergraduate degree at Linfield College, Dr. Oda conducted research at a biotech company in Oregon, with a focus on treating diabetes in a mouse model. She completed her doctorate under the guidance of Raul Torres, PhD, at the University of Colorado Anschutz Medical Campus and National Jewish Health, where she described new immune-based pathways to control tumor progression in mice. Dr. Oda worked as a postdoctoral fellow and Research Associate in the lab of Philip Greenberg, MD, recipient of the 2016 PanCAN Translational Research Grant, funded in memory of Abby Sobrato, at the Fred Hutchinson Cancer Research Center and University of Washington. There, she focused on improving the persistence and efficacy of adoptive cell therapy by adding co-stimulatory proteins to T-cell receptor constructs.
Currently an Assistant Professor at the University of Washington and a Principal Investigator at Seattle Children’s Research Institute, Dr. Oda is using advanced technologies to characterize the programming differences in engineered T-cells to understand changes to the tumor microenvironment after a treatment approach known as adoptive cell transfer, and to develop the next generation of engineering strategies to improve adoptive cell transfer efficacy.
One of the biggest barriers to effective immunotherapy is the cancer cells and their surrounding microenvironment’s ability to evade and block an immune attack. This is especially challenging for pancreatic cancer, which has long been known as an immunologically “cold” tumor. One strategy to overcome these challenges could be engineering immune T-cells to target the cancer cells and ignore the inhibitory signals from the tumor and its environment. Using the patient’s own immune cells to generate a “living drug” can avoid the toxic side effects of other common therapies, such as radiation or chemotherapies.
To innovate more effective T-cell therapies for pancreatic cancer patients, Dr. Shannon Oda will develop novel engineered proteins, called immunomodulatory fusion proteins (IFPs), that enable T-cells to mount a more powerful and durable attack on cancer cells. In proof-of-concept studies, Dr. Oda and colleagues have demonstrated that IFPs can be engineered to convert cancer-produced inhibitory signals into T-cell activating boosts, in a process she described as “replacing a T-cell brake with an accelerator.”
IFPs can enhance other versions of engineered T-cells by allowing them to live longer and have improved metabolism (use of nutrients to create energy). IFPs can be tailored to signal in response to different stimuli and deliver different enhancements to T-cells. Dr. Oda and her team have developed critical engineering concepts and screening strategies to support the rapid development of new pancreatic cancer-targeted IFPs. They will use these to identify IFPs and IFP combinations that best enhance therapeutic efficacy. Through this project, they will test the next generation of IFPs in animal tumor models to understand precisely how IFPs work and how they might be further improved. The investigators will advance successful candidate IFP strategies to studies with human T-cells. Overall, Dr. Oda plans to develop a comprehensive dataset by creating a toolbox of IFPs that support personalized therapy options for pancreatic cancer patients.