Treatment of Pediatric Acute Myeloid Leukemia (AML) with Chimeric Antigen Receptor (CAR) T-cells

Researchers at the Center for Childhood Cancer Research are creating and testing new CAR T cell immunotherapies for children with relapsed and chemotherapy-refractory AML.

Acute myeloid leukemia (AML) accounts for approximately 20 percent of pediatric leukemias. Current intensive cytotoxic chemotherapy regimens achieve long-term cure in only 60 percent of children.

Relapsed and chemotherapy-refractory AML accounts for more than half of childhood leukemia-related deaths. Additional intensification of chemotherapy with cytotoxic agents to treat these high-risk patients is not feasible because of both short-term and long-term safety risks. CCCR investigators and colleagues are working to develop new treatments for children with high risk AML.

CAR T cells can be engineered to attack specific tumor proteins (antigens) on the surface of cancer cells, including AML. Binding of CAR T cells to these antigens induces T cell expansion and proliferation that results in cancer cell killing.

Studies conducted at the CCCR are focused upon identifying new targets and developing new CAR T cell immunotherapies for children with AML. Members of the Tasian laboratory are currently testing the efficacy of several new anti-AML CAR T cells in specialized AML xenograft models with the goal of continued clinical translation.

Results of earlier preclinical studies by CCCR investigators and collaborators have informed a phase 1 trial to evaluate CD123-redirected CAR T cell (CART123) immunotherapy in adults with relapsed or refractory AML. Phase 1 trials of CAR T cell immunotherapies for children with AML are also currently in development under the leadership of Richard Aplenc, MD, PhD and Sarah K. Tasian, MD.