Grant: Project Grant

Pediatric high-grade gliomas are aggressive brain tumors that affect children and adolescents. Even with surgery, radiation, and chemotherapy, many patients still have limited options and poor outcomes. New approaches are thus urgently needed. One promising approach uses the patient's own immune system to fight the tumor. In particular, tumor infiltrating lymphocytes, which are immune cells already found inside the tumor, can be expanded in the lab and returned to the patient to target and destroy tumor cells. However, high-grade gliomas often create a hostile environment that prevents tumor infiltrating lymphocytes from entering and eradicating tumor cells. Our overall goal is to deliver a safe and effective immune-based therapy option for children and adolescents with high-grade gliomas. Our project tests whether adding of a class of drugs with immune-changing properties can remove these roadblocks and make tumor infiltrating lymphocytes more practical and effective for children. These drugs are designed to weaken cancer cell survival defenses and to "wake up" anti-tumor immunity. There are three goals: (1) make high-grade glioma tumors more receptive to attack by tumor infiltrating lymphocytes, (2) increase the yield and quality of tumor infiltrating lymphocytes derived from these tumors, and (3) test whether expanded tumor infiltrating lymphocytes can eliminate high-grade gliomas.