Grant: Canada Postdoctoral Research Award (CPRA) program

Pancreatic cancer (PCa) is notoriously difficult to treat and has poor survival outcomes, and would therefore benefit from next generation immune therapies. A new strategy for anti-cancer immune therapy involves harvesting immune cells from within tumours, called tumour infiltrating lymphocytes (TIL). These TILs can be grown up in the lab and then given back to the patient in huge numbers, upon which they can find the tumour once against and overwhelm it in numbers leading to strong anti-tumour responses. Another exciting immunotherapeutic strategy is cancer vaccines, which entail administering a highly inflammatory dose of biological substances that can alert the immune system about the presence of cancer, effectively removing the cancer's ability to avoid immune detection. Both TILs and cancer vaccines can be effective treatment strategies, but PCa has a unique architecture that can allow it to suppress immune responses. To enhance the ability of these two therapies and make them effective for PCa, I will be using a novel class of drugs that effectively remove the brakes on the immune system, allowing certain types of immune cells, including T-cells, to become hyperactivated in a controlled fashion. These drugs are called HPK1 inhibitors, where HPK1 is a central suppressor of immune cell activity that normally acts to prevent autoimmunity but can often be exploited by cancers. By inhibiting the activity of this suppressive HPK1, I can allow immune activation to continue freely. In sum, by combining two different immunotherapies with HPK1 inhibitors, I aim to amplify immune activation to create a more effective and therapeutic anti-tumour reaction that will overpower PCa and lead to tumour destruction. This work will act as a demonstration that this exciting class of drugs has significant potential to improve therapeutic outcomes in difficult-to-treat cancers, such as PCa.