The FDA gave the green light to Novartis's tisagenlecleucel for the treatment of acute lymphoblastic leukaemia (ALL), marking a historic approval for a first-in-modality chimeric antigen receptor (CAR) T cell therapy.

CAR Ts are an ex vivo form of gene therapy, in which T cells are removed from cancer patients, genetically modified to express cancer-cell seeking receptors, and re-infused into patients. Tisagenlecleucel, like many of the first-generation CAR Ts, is modified to target the B cell antigen CD19, depleting these cells for the treatment of various blood cancers. The drug was approved on the basis of a clinical trial in 63 patients with relapsed or refractory B cell precursor ALL, in which the overall remission rate within 3 months of treatment was 83%.

“We're entering a new frontier in medical innovation with the ability to reprogramme a patient's own cells to attack a deadly cancer,” said FDA commissioner Scott Gottlieb.

Several other CAR Ts are on their way to patients, including Kite Pharma's CD19-targeting axicabtagene ciloleucel for refractory aggressive non-Hodgkin lymphoma. The FDA is expected to rule on this application by the end of November. In August, Gilead Sciences agreed to buy Kite for nearly US$12 billion.

Safety issues, however, continue to loom over the field. Tisagenlecleucel carries a black box warning that notes the risk of cytokine release syndrome and neurological events. Other companies have fared worse, and have had to put clinical trials of CAR Ts on hold owing to fatalities. Cellectis — a company that is using gene-editing tools called TALENs to engineer T cells from healthy donors into allogeneic 'off-the-shelf' CAR Ts — suffered such a setback in September, after a patient with a blastic plasmacytoid dendritic cell neoplasm died in a trial of CD123-targeting UCART123. Juno Therapeutics halted a study of its lead CD19-targeting CAR T in 2016 after two patients died from cerebral oedema.

The field is also still struggling to figure out how to use CAR Ts in solid tumours and how to overcome manufacturing issues (Nat. Rev. Drug Discov. 16, 301–304; 2017).

Novartis has priced tisagenlecleucel at $475,000 per treatment, renewing concerns about the high cost of new cancer drugs.