FLT3 Receptor-Redirected Chimeric Antigen Receptor T Cells for AML and ALL

Background:

Many children with acute myeloid leukemia (AML) and infants with acute lymphoblastic leukemia (ALL) relapse or are resistant to current best available therapies, resulting in significant mortality. New treatments are needed to prevent relapses and to improve cures. However, drug discovery research for these high risk leukemias has made little progress to date in bringing new treatments to the clinic. Our team at the Children's Hospital of Philadelphia (CHOP) recently published our tremendous clinical success with a new T cell immunotherapy called CART19 for children with relapsed ALL. We are working in the laboratory to develop similar approaches for other pediatric leukemias.

Project Goal:

The FLT3 receptor (FLT3R) protein is mutated in a subset of high-risk AML and expressed at high levels in many infants with ALL. The FLT3R thus may be a potential therapeutic target for both AML and ALL. Our proposal focuses upon testing the effectiveness of new FLT3R-targeted engineered T cell immunotherapy using specialized mouse models of childhood FLT3R-mutant AML and of FLT3R-overexpressing infant ALL. Given our clinical expertise in the care of children with high-risk leukemias and our experience with T cell immunotherapy development in the laboratory and in the clinic, we are uniquely poised at CHOP to conduct these research studies. Results from our preclinical work will help us to identify innovative therapies for potential testing in children with high-risk AML and ALL who otherwise have no remaining treatment options.