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eukemia bubbling in her veins. She’d had bags and bags of chemotherapy and a bone marrow transplant. But the cancer still thrived. By last June, the 12-month-old was desperately ill. Her parents begged—wasn’t there anything?
There was. In a freezer at her hospital—Great Ormond Street, in London—sat a vial of white blood cells. The cells had been genetically altered to hunt and destroy leukemia, but the hospital hadn’t yet sought permission to test them. They were the most extensively engineered cells ever proposed as a therapy, with a total of four genetic changes, two of them introduced by the new technique of genome editing.
Where the technology stands, it’s a pretty radical treatment.
Soon a doctor from Great Ormond was on the phone to Cellectis, a biotechnology company with French roots that is now located on the East Side of Manhattan. The company owned the cancer treatment, which it had devised using a gene-editing method called TALENs, a way of making cuts and fixes to DNA in living cells. “We got a call. The doctors said, ‘We’ve got a girl who is out of T cells and out of options,’” André Choulika, the CEO of Cellectis, remembers. “They wanted one of the vials made during quality-control testing.”
The doctors hoped to make Layla a “special,” a patient who got the drug outside a clinical trial. It was a gamble, since the treatment had been tried only in mice. If it failed, the company’s stock and reputation could tank, and even if it succeeded, the company might get in trouble with regulators. “It was saving a life versus the chance of bad news,” Choulika says.
Immune Engineering
Breakthrough
Killer T cells programmed to wipe out cancer.
Why It Matters
Cancer, multiple sclerosis, and HIV could all be treated by engineering the immune system.
Key Players in Immune Therapies
– Cellectis
– Juno Therapeutics
– Novartis
Cellectis began developing the treatment in 2011 after doctors in New York and Philadelphia reported that they’d found a way to gain control over T cells, the so-called killer cells of the immune system. They had shown that they could take T cells from a person’s bloodstream and, using a virus, add new DNA instructions to aim them at the type of blood cell that goes awry in leukemia. The technique has now been tested in more than 300 patients, with spectacular results, often resulting in complete remission. A dozen drug firms and biotechnology companies are now working to bring such a treatment to market.
The T cells created by Cellectis could have even broader applications. The previous treatments use a person’s own cells. But some patients, especially small children like Layla, don’t have enough T cells.
Foreseeing this problem, Cellectis had set out to use gene editing to create a more highly engineered but ultimately simpler “universal” supply of T cells made from the blood of donors. The company would still add the new DNA, but it would also use gene editing to delete the receptor that T cells normally use to sniff out foreign-looking -molecules.
“The T cell has a huge potential for killing. But the thing you can’t do is inject T cells from Mr. X into Mr. Y,” Choulika says. “They’d recognize Mr. Y as ‘non-self’ and start firing off at everything, and the patient will melt down.” But if the T cells are stripped down with gene editing, like the ones that were sitting in Great Ormond’s freezer, that risk is mostly eliminated. Or so everyone hoped.
In November, Great Ormond announced that Layla was cured. The British press jumped on the heartwarming story of a brave kid and daring doctors. Accounts splashed on front pages sent Cellectis’s stock price shooting upward. Two weeks later, the drug companies Pfizer and Servier announced they would ante up $40 million to purchase rights to the treatment.
Although many of the details of Layla’s case have yet to be disclosed, and some cancer experts say the role of the engineered T cells in her cure remains murky, her recovery pointed a spotlight on “immune engineering,” and on the way that advances in controlling and manipulating the immune system are leading to unexpected breakthroughs in cancer treatment. They also could lead to new treatments for HIV and autoimmune diseases like arthritis and multiple sclerosis.
[“Source-technologyreview”]