Our goal is to develop a potent therapy for pancreas cancer – an incurable disease that is resistant to traditional cancer treatments. Challenges involved in treating this disease include: i) a barrier that surrounds the cancer cells (“tumor stroma”) and limits drug access, ii) diversity among cancer cells, making it hard to find a single means of killing all cells, and iii) the harsh cancer milieu, which prevents immune cells from working. Thus, new therapies to beat these barriers are vital and T cell therapy may meet this need. We plan to collect immune cells, called T cells, from patients and in the laboratory we will train them to find and kill tumor cells that display “tumor associated antigens – TAAs” on their surface. We plan to use cells that have been trained to look for tumor cells expressing 5 different TAAs in a clinical trial where we will gauge if this therapy is both safe and active in patients. Next, to ensure that our cells retain their ability to kill in the tumor milieu we will equip them with a special switch that allows them to convert bad signals into ones that are good for our T cells. Hence, we will turn an “off” switch into an “on”. By using this tactic, we hope to boost the activity of our therapy.