Developing a pediatric B-ALL model to uncover epigenetic mechanisms of relapse from CAR-T cell immunotherapy
Project Goal: To develop more effective CAR-T immune therapy treatments to prevent relapse in poor-prognosis leukemia.
Institution: Human Immunology and Immunotherapy Initiative at University of Colorado School of Medicine and Children’s Hospital of Colorado
Researchers: Dr. Patricia Ernst and Dr. Terry Fry
Year Awarded: 2018
Type of Childhood Cancer: Acute B Lymphoblastic Leukemia
Dr. Patricia Ernst and Dr. Terry Fry at the Human Immunology and Immunotherapy Initiative at University of Colorado School of Medicine and Children’s Hospital of Colorado, whose project is entitled “Developing a pediatric B-ALL model to uncover epigenetic mechanisms of relapse from CAR-T cell immunotherapy,” and focuses on developing more effective CAR-T immune therapy treatments to prevent relapse in poor-prognosis leukemia. The improvement in the survival of children diagnosed with leukemia represents one of the most inspiring cancer treatment success stories in the last 50 years. However, certain types of poor-prognosis childhood leukemias do not respond to current therapies. In addition to optimized use of conventional chemotherapy, a promising new strategy utilizing the patient’s own genetically engineered immune cells (termed chimeric antigen receptor or CAR T cell therapy) has remarkably improved prognoses of children with a type of leukemia called “B cell acute lymphocytic leukemia”, or B-ALL. However, the same poor-prognosis B-ALL also has a remarkable propensity to evade chemotherapy or CAR T cell therapy resulting in a high relapse rate. This proposal will focus on how this leukemia evades CAR T cell therapy by developing new model systems in which we can study how this immune evasion occurs. In this proposal, we will establish a childhood B-ALL model system in which we can determine how the leukemia escapes CAR T cell treatment and explore effective combinations of immune therapy and other therapeutic modalities to prevent relapse in young patients that suffer from this poor-prognosis leukemia.