Douglas Mitchell, PhD

The immune system normally protects us from cancer by finding and removing abnormal cells before they grow. Many solid tumors develop when they learn how to hide from the immune system. Frequently, immune cells cannot enter the tumor because the tumor builds a strong barrier around itself. A major part of this barrier comes from a signal called TGF-beta. Tumors use proteins called integrins as “on-switches” that turn on TGF-beta. When TGF-beta is active, it creates conditions that keep immune cells out. If we can safely turn off this switch inside the tumor, the immune system may be able to enter and attack the cancer. Our research develops very small and stable proteins called lasso peptides that are designed to turn off this TGF-beta switch in tumors. By blocking the switch, these lasso peptides may open the door for immune cells to enter and may help existing drugs work better to kill the cancer cells.  We will test these new agents in models of solid tumors to see how they change the tumor environment and support immune responses.We are also creating an imaging tool that lets doctors see whether the drug appropriately reaches a patient’s tumor. This information will guide future clinical studies and help match patients with the right treatment. If successful, this work will make immunotherapy effective for many more people with solid tumors and give patients a better chance at longer and healthier lives.