Tisagenlecleucel, an approved anti-CD19 chimeric antigen receptor T-cell therapy for the treatment of leukemia.

On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients. Conventional standard therapies for B-ALL have high failure rates, thus developing new therapies is crucial for patients with B-ALL. Results from clinical trials indicate that anti-CD19 CAR T-cell therapies could successfully induce high response rates in B-ALL patients. However, related toxicities, such as cytokine release syndrome and CAR T-cell-related encephalopathy syndrome, may be severe or even fatal, and the management of such toxicities is therefore vital. This review will focus on the clinical application of anti-CD19 CAR T-cell therapy in B-ALL treatment, including design features of CAR constructs, therapeutic use of tisagenlecleucel, CAR T-cell therapy clinical trials and related toxicity, and prospects for cancer immunotherapy.