Chimeric antigen receptors (CARs) combine a binding fragment of an antibody with intracellular signaling domains. We have reported exciting data on CTL019 cell therapy expressing an anti-CD19 CAR. Infusion of these cells results in 100 to 100,000x in vivo proliferation, durable anti-tumor activity, and prolonged persistence in patients with B cell tumors, including sustained complete responses (CRs) in adults and children with acute lymphoblastic leukemia (ALL; Grupp et al., NEJM 2013, Maude et al., NEJM 2014). This talk will update the audience on pediatric engineered cell therapy. Recent updates of our data in ALL show a 93% complete response rate and 79% overall survival at 1 year.
In addition, we will discuss potential other application in pediatric diseases such as neuroblastoma, which may be targeted with GD2 CARs. Preclinical data from ongoing studies will be presented showing the potential efficacy of alternative targets that may extend this therapy outside of B cell malignancy.
CTL019 cells can undergo robust in-vivo expansion and can persist for over 4 years in patients with relapsed ALL, allowing for the possibility of long-term disease response without subsequent therapy such as transplant. This approach also has promise as a salvage therapy for patients who relapse after allo-SCT with a low risk of GVHD. CTL019 therapy is associated with a significant CRS that responds rapidly to IL6-targeted anti-cytokine treatment. This therapy has received Breakthrough Therapy designation from the FDA, and phase II multicenter trials are underway and have been completed.