Type: Translationaldfdhd

Funded by the Dick Vitale Pediatric Cancer Research Fund and the Stuart Scott Memorial Cancer Research Fund

This project studies a rare brain tumor (ependymoma) that affects young children and grows in the back of the brain, where it can cause problems with balance, movement, and thinking. Surgery and radiation therapy are the main treatments. Even with these treatments, the tumor often comes back. When it returns, there are very few options to help children survive.We study how tumor cells survive radiation therapy. We have learned that many of these cancer cells depend on special “survival proteins” that protect them from dying. These proteins help the tumor grow back after treatment. There are drugs that can block these survival proteins. These drugs already help patients with other types of cancer. However, they have not worked well for brain tumors. One reason is that the brain has a protective barrier that keeps many drugs out. Another reason is that these drugs can cause side effects when they affect healthy cells. This project combines two ideas. First, we will learn when and how tumor cells become most dependent on their survival proteins during treatment. Second, we will use a new drug delivery system designed to carry these drugs across the brain’s protective barrier and release them mainly inside the tumor. If successful, this work could help radiation therapy kill more tumor cells while sparing healthy brain tissue. This could slow tumor growth, reduce side effects, and help children feel better and live longer. The knowledge gained may also help researchers design better treatments for other hard‑to‑treat brain cancers.

T cell therapies use T cells as “living drugs.” They work very well when used to treat some blood cancers, but do not work well for treating most types of solid tumors, partly because not enough T cells find and get into the tumor. We found a way to guide T cells to tumors. Tumors release certain types of small chemicals. We can give T cells special sensors on their surface that act like “chemical antennas.” With these sensors, T cells detect tumor chemicals and follow them like a scent trail. This helps T cells to find, attack, and, in turn, destroy tumors. Now we want to use what we found to create a new class of cell therapies. To do that, we will first test this new treatment very comprehensively in mice to examine whether it is ready to be tested in patients. Second, while we are currently using sensors that already exist in nature, we will create new types of synthetic sensors to make T cells even better. Finally, because different tumors may release different chemicals, we will test multiple sensors across different tumor types and develop a simple test that doctors could potentially use one day to match the right sensor for a given tumor or patient. If successful, this work will be a critical step toward powerful and potentially curative treatments for patients with solid tumors.