My lab is working to develop treatments for pancreatic cancer by activating the body's immune cells to fight against the tumor. Patients with pancreatic cancer have exceptionally poor prognoses partly because the tumors are extremely dense and impenetrable to therapy. I want to investigate the role of immune cells in the tumor environment, specifically, how to activate and recruit these cells to destroy the tumor. I propose a two-pronged strategy to tackle this question: 1) Disable a key signaling mechanism driving tumor growth, and 2) Attract immune cells to the tumor site where they can destroy the tumor. Based on a novel technology pioneered by Hidde Ploegh, I will use alpaca-derived antibodies to target PD-L1, a protein commonly expressed in pancreatic cancer but not in healthy tissues. Further, I will couple these alpaca antibodies with cytokines—chemicals that will attract immune cells to extinguish the tumor. Notably, these specialized alpaca antibodies are quite small and can penetrate dense tissues. Already, I have shown that an IL-2-antibody fusion can reduce pancreatic tumor growth by 50% in a mouse model. I will now determine whether other types of cytokine-antibody fusions can evoke equal, if not better, therapeutic responses. Together, these studies could define a new strategy for a well-coordinated immunological response against pancreatic cancer.