Heidi Ledford in Scientific American:
A groundbreaking treatment that arms immune cells called T cells to battle cancer is barrelling towards regulators, fuelled by unprecedented clinical success and investor exuberance. But progress of the therapy, called CAR-T, has been marred by its toxicity; several deaths have been reported in clinical trials. Even as the first company readies its application to the US Food and Drug Administration (FDA)—expected by the end of the year—researchers are hard at work to make the supercharged T cells safer. Doing so is crucial to expanding the use of the therapy to more people, says Anthony Walker, a managing partner at Alacrita, a consulting firm in London. “Right now it is heroic medicine,” he says—a gruelling treatment deployed only in people for whom all else has failed. “Patients are taken sometimes to within an inch of their lives.”
Most CAR-T procedures begin by harvesting a patient’s white blood cells and sifting out the T cells. Those T cells are engineered to recognize cancer cells, and then infused into the patient, ready to do battle. The approach has shown remarkable success against leukaemias and lymphomas: in one study, all traces of leukaemia disappeared in 90% of the patients who received the treatment (S. L. Maude et al. N. Engl. J. Med. 371, 1507–1517; 2014). Results such as those have fuelled an investor frenzy. “It set the field on fire,” says Walker. Swiss pharmaceutical giant Novartis invested in the technique in 2012. In 2014, CAR-T firm Kite Pharma of Santa Monica, California, raised US$128 million when it went public. A few months later, one of its competitors, Juno Therapeutics of Seattle, Washington, yielded $264 million in its initial public offering. Now Kite is racing to be the first to bring a CAR-T therapy to the market. On October 18, the company will update investors on its plans to manufacture and sell the complex therapy, which it hopes to launch in 2017. But the treatment’s toxicity has discouraged some investors. On September 26, Kite released interim clinical-trial results—widely seen as successful—in people with aggressive non-Hodgkin’s lymphoma (see go.nature.com/2djdqen). Yet about one-third of the patients developed serious neurological side effects, and 18% developed a deadly condition called cytokine release syndrome, which can cause organ failure. Two of the 62 patients died as a result of the treatment.