Project 466638

Pancreatic cancer is one of the deadliest human cancers, with a 5-year survival rate of only 8%. Pancreatic tumours tend to go undiagnosed until they are quite advanced, at which point they are unresectable and require systemic treatment. Though traditional chemotherapy has been a cornerstone of systemic cancer treatment for decades, its nonspecific nature often results in off-target killing of healthy cells. Thus, there is a need for more specific, effective, and safe late-stage treatment options for pancreatic cancer.Cancer cells carry certain surface markers, which are not present on healthy cells. So, to treat tumours more specifically, one strategy is to direct toxic molecules to cells carrying these markers. Immunotoxins make up one class of such targeted therapeutic molecules, and are constructed by combining the highly potent killing portion of a bacterial toxin with a homing portion that seeks out certain cancer markers. Despite the success of this technology, there are currently no immunotoxins approved to treat pancreatic cancer. Our lab has recently generated an immunotoxin from diphtheria toxin that targets two different pancreatic cancer markers. We have shown this immunotoxin to be very potent against multiple pancreatic cancer cell lines, warranting further investigation into its efficacy and safety in advanced tumour models. In this proposal, we are asking for funding from CIHR to test the efficacy of this immunotoxin in more than 25 pancreatic cancer patient-derived organoids (3D tissue constructs mimicking organs). We also propose to examine the safety profile and anti-tumour effects of this therapeutic agent in mouse models. These studies represent a huge step forward in the development of urgently needed treatment options for pancreatic cancer.