A newly approved treatment is a milestone in gene therapy for cancer
An illustration depicting the life cycle of a cancer cell
Dimas Padilla, a 44-year-old sales representative who lives near Orlando, hoped he had seen his last battle with non-Hodgkin’s lymphoma. But while driving one day, he felt his seatbelt pressing against his neck more tightly than usual.
“Right then my worst fear came into my mind,” Padilla says. “I didn’t want to say it, but I knew it.” One of his lymph nodes had swollen to the size of a golf ball—his cancer was back for the third time, and all his therapy options were exhausted. Or so he thought until he met Frederick Locke, an oncologist who leads the immune cell therapy initiative at Moffitt Cancer Center in Tampa.
Locke was studying an experimental treatment called chimeric antigen receptor T-cell therapy (CAR T-cell therapy for short), in which a patient’s own immune-system cells are genetically enhanced to fight cancer. Padilla first had his T-cells harvested from his blood. Technicians then inserted a novel gene into those cells, which responded by producing new surface receptors that would seek and latch onto a specific protein target on his lymphoma cells. Doctors put these customized T-cells back into Padilla’s bloodstream.
“It really was remarkable,” Locke says. “His tumor on his neck just shrunk away within a week or two.”
A year later, the tumor still hadn’t returned. Padilla marked the anniversary by taking his family to the beach to “celebrate life.” He has now been tumor-free for 18 months. About half of the 101 patients involved in the study had a complete remission—a success rate four or five times higher than could be expected with existing treatments. The results convinced the Food and Drug Administration this past October to approve this version of the treatment, called Yescarta, for certain types of B-cell lymphoma. It’s only the second gene therapy the agency has greenlighted for cancer.
“These are patients with an abysmal prognosis, really without hope,” says Locke. “And now with this therapy we’re really able to give them a chance.”
Such success doesn’t come without risk. For the time being, Yescarta is available only for patients for whom at least two other forms of therapy have failed. Like other forms of immunotherapy, it can produce dangerous side effects, including neurological toxicity. Three patients in the Yescarta trial died from severe cases of cytokine release syndrome (CRS), which can occur when proteins called cytokines are released by active white blood cells and cause life-threatening inflammation.
This syndrome is typically reversible, Locke says. Padilla experienced a high fever and temporary memory loss. At one point, he was unable to recall the year of his birth or write his own name. Yet he was back to normal in about two weeks.
The treatment was worth the discomfort, according to Padilla. “The other option, if I didn’t do anything,” he says, pausing—“That was it.”
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