Acute myeloid leukemia (AML) is the second most common type of leukemia in children and remains very deadly in patients with treatment-resistant disease. A novel type of therapy where patient’s infection-fighting cells (“T cells”) are engineered in a laboratory with a cancer-fighting protein called a chimeric antigen receptor, or a CAR, has shown great promise in patients with another type of leukemia that arises from B cells.

Diffuse midline gliomas (DMGs) are one of the deadliest forms of childhood cancer. Most children with DMG die within a year of being diagnosed with the disease. Immunotherapy with anti-GD2 CAR T cells extended survival in mouse models and induced tumor shrinkage in a pilot study in DMG patients. However, tumors inevitably recurred and caused patient death, pointing to the need for strategies that enhance response to therapy.

The NRAS and KRAS genes encode small proteins (N-Ras and K-Ras) that act as molecular switches. In normal cells, Ras proteins transiently bind to GTP wheh they are turned on - this stimulates growth through other proteins called effectors. Ras proteins are then turned off when GTP is converted to GDP. The NRAS and KRAS genes are mutated in many pediatric and adult cancers. These mutations result in the production of Ras proteins that can no longer efficiently convert GTP to GDP and behave like a switch that is on and can’t be turned off.