Development of natural killer cell–based precision immunotherapy for pancreatic cancer

Each person with pancreatic cancer has a unique tumour, but each person has a unique immune system too. Dr Jeanette Boudreau and her team are studying how the immune system and the tumour interact, work together and oppose each other in order to decide whether the tumour will continue to grow or be eliminated by the immune system. Dr Boudreau plans to use this information to teach every pancreatic cancer patient’s immune system to effectively eliminate their tumour. Pancreatic cancer has a poor survival rate because the tumour often remains undetected before it spreads to other tissues or it regrows after surgical removal. The immune system can be used to find tumours hiding throughout the body, and the researchers expect that this could be a good approach to treat pancreatic cancer. However, methods to accomplish this have not yet been developed. Dr Boudreau studies a type of immune cell called the natural killer (NK) cell, which is known to be good at controlling cancer. Researchers lack the detailed knowledge needed to precisely deploy NK cells against cancer. The team will be building on their previous work, where they developed technology to analyze NK cell function in greater detail than was previously possible. They showed how NK cell function is programmed in different people based on the genes they carry. In this project, the researchers will use model systems to develop and test a method for matching NK cells to tumours in a way that best facilitates their killing, toward the goal of developing immunotherapies for pancreatic cancer. Immunotherapy is a promising new way to treat cancer. In immunotherapy, a person’s immune system is used to stop their cancer. Unfortunately, immunotherapy is challenging to apply because every tumour is different. Moreover, it has not been developed yet for pancreatic cancer, where treatment options are limited and survival is poor. The team thinks that natural killer (NK) cells could be ideal to exploit as a new kind of immunotherapy that could be made available to all people with pancreatic cancer. They will study how NK cells interact with pancreatic cancer to learn how to predict when and how they lead to tumour killing. Using lab experiments, genetic studies and computer analyses, they will figure out how to predict which NK cells are the best for each person’s individual pancreatic tumour. They will test how different NK cells kill tumour cells in order to build a computer program that selects the best NK cells for each person. They will also test its accuracy using a new mouse model of pancreatic cancer. Mortality is decreasing among many types of cancer, but for pancreatic cancer, 5 year survival remains at less than 10%. With an expected increase in pancreatic cancer incidence, there is an urgent need for improved approaches to treating this disease. The researchers are developing NK cell–based immunotherapies for cancer. Natural killer cells have several properties that make them good for immunotherapy, including being able to use cells isolated from third party donors that are grown in the lab. The function of NK cells is controlled by many signals that are triggered by proteins on target cells, including cancer cells. The number of signalling triggers is limited. By studying their role in NK activation, the researchers expect to be able to design personalized immunotherapies to treat people with pancreatic tumours. Additional ICR-CIHR partnership funding: $98,000