CD19 Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B cell acute lymphoblastic leukemia.
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen binding domains of an antibody fused to T cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable. CD19 targeted CAR T cells have induced complete remissions of disease in up to 90% of patients with relapsed or refractory B cell acute lymphoblastic leukemia (B ALL) who have an expected complete response rate of 30% in response to chemotherapy. The high efficacy of CAR T cells in B ALL suggests that regulatory approval of this therapy for this routinely fatal leukemia is on the horizon. We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed.
Clinical advances in hematology oncology H&O