Why is this research question important?
This dismal prognosis of pancreatic cancer is largely due to two critical factors:
(1) the dense layers of non-cancer cells known as stromal cells, which prevent immune cells and therapeutics from effectively reaching and attacking cancer cells, and
(2) the nonclinically relevant models used for drug development, which are mostly artificial laboratory conditions that fail to reflect the complexity of real human tumours, resulting in treatments that either do not work well in patients or cause unintended side effects.
Dr Peter Wan at the University of Oxford is applying to Pancreatic Cancer UK’s Career Foundation Fellowship to explore novel strategies that directly address these challenges. He aims to simultaneously eliminate the cancer and stromal cells, and significantly enhance treatment outcomes for pancreatic cancer patients.
What is this project going to do?
Peter aims to develop bispecific T cell engagers that target stress-related molecules present on both pancreatic cancer cells and the surrounding stromal supportive cells. His study will develop and optimise the T cell engagers using real pancreatic cancer samples taken directly from patients, a method being demonstrated for the first time. This approach will allow him to select the most translational antibodies that have high cancer-targeting ability.
Additionally, he will test the effectiveness of these T cell engagers in patient-derived tissues (both pancreatic cancer tissues and adjacent healthy tissues) that closely replicate real human physiology to ensure that they are potent while sparing healthy tissues. Throughout the project, he will get patient and public involvement by seeking their input on the research design and sharing progress in accessible formats.
How could the outcomes of this project make a difference to people with pancreatic cancer?
This research will pave the way for a new class of therapeutics capable of overcoming the unique barriers in pancreatic cancer. By directly addressing the limitations of existing therapeutics through testing and optimisation in patient-derived biopsy models Peter can ensure the T cell engager is highly cancer-selective and potent.
This approach not only enhances safety but also improves the ability of immune cells to attack both cancer and stromal cells, potentially extending survival and improving the quality of life for pancreatic cancer patients. The project will also generate strong data supporting further urgent development of this therapeutic approach towards clinical evaluation.
Next steps
No scientific background or prior experience is needed to take part in this opportunity.
If you would like to give your feedback on this project, please contact the Research Team (research@pancreaticcancer.org.uk) quoting the involvement reference ‘Wan’. We will then email you the project summary and specific questions Peter would like you to consider.
Please return your responses to the research team by Sunday 9th February 2025.
