Jennifer Adair carried out her first gene therapy experiment several years ago. A cancer treatment, it involved collecting blood from a patient, and then adding to these cells a new strand of DNA — a gene — that would protect them from a powerful chemotherapy. The altered cells were then reinfused into their veins.
The study, involving 11 patients, proved fairly successful. But Adair, who runs a gene-therapy lab at the Fred Hutchinson Cancer Research Center in Seattle, says it took three sleepless scientists around 96 hours just to process a single person’s cells in a multimillion-dollar cleanroom. “I said, ‘Wow, we really need to simplify this,’” Adair recalls.
Gene therapy is moving quickly from experiment to medical reality. But with potential treatments for cancer and rare diseases now showing promise, scientists are worried that the technology is so complex that patients will not benefit as quickly as they should because of a shortage of trained technicians and suitable facilities. For the most successful gene therapies, those that require modifying blood cells outside the body, the procedures are offered only by a dozen or so research centers, all in major cities like New York, Seattle, Milan, and Paris.
Bottlenecks and ethical dilemmas are arising already as some patients able to afford it buy plane tickets and travel across the globe to seek out cures, while the vast majority of people have no possibility of accessing these treatments.
Just last week, French scientists working with the U.S. biotech company BlueBird Bio described how they’d fixed the gene for sickle cell disease in a boy at a Paris hospital. It was yet another technical success. But no one asked how it would reach those who need it. Most cases of sickle cell disease — about 57 percent of the 300,000 new cases each year — are in Nigeria, the Democratic Republic of the Congo, or India.
In October, Adair demonstrated a new technology she thinks could democratize access to gene therapy. Tweaking a cell-processing device sold by German instrument maker Miltenyi, she mostly automated the process of preparing blood cells with a gene therapy for HIV that her center is also testing. Cells dripped in one end came out the other 30 hours later with little oversight needed. She even added wheels. Adair calls the mobile lab “gene therapy in a box.”
Adair thinks a key job for the mobile gene-therapy lab is to extend experimental studies to the developing world, including Africa, where most HIV cases are. “We wanted to show that we could make the trial mobile, because we are kidding ourselves that treating someone in Seattle is going to have the same risks and outcomes as in South Africa,” she says.
Helping to drive interest in portable gene-therapy devices is a new form of cancer therapy, known as CAR-T, that reprograms the DNA of immune system sentinels called T cells so they attack tumors. A growing pack of biotech companies has raised billions of dollars to test these treatments, which also require taking a person’s blood and performing the gene addition in a specialized facility.
One of the first CAR-T treatments to reach the marketplace will probably come from Novartis. The Swiss drug giant last year completed a global test of children with leukemia in which 82 percent of the kids saw their tumors evaporate, and many stayed cancer-free.
Novartis will apply for permission to sell the treatment this year, but the company isn’t too happy with how the therapy is made. For its study, Novartis says that it air-shipped patients’ cells back and forth to a single cell-processing factory it owns in Morris Plains, N.J., with the help of Cryoport, a company specializing in shipping frozen cells. It’s logistically complex, labor-intensive, expensive, and potentially unpredictable, since no two people’s cells are the same. What’s more, Novartis isn’t certain how many patients it will actually be able to treat.
“We are limited in the number of patients we can treat given the cumbersome supply chain that we have going,” says Philip Gotwals, chief of exploratory immune-oncology at Novartis. “If we don’t do anything to automate the process, you would have to [build more of] these large factories, and I don’t know if the industry would do that.”
Miltenyi, the German device maker, says its instrument, called Prodigy, can already largely automate CAR-T production, and is now being tested by a few companies. The instrument, which weighs about 150 pounds, looks a little like a machine from Willy Wonka’s factory, with bright pastel casements, neatly placed dials, and twists and turns of disposable tubing covering its surface. Instead of hot chocolate, a patient’s cells move through the tubes, mixing with chemicals that stimulate them and, eventually, a load of DNA-carrying viruses used to alter their genetic code.
The instrument costs about $150,000, and a kit of supplies to process one patient’s cells costs another $12,000. Katharina Winnemöller, a marketing manager based in Germany, says doctors in London will use the box to treat cancer patients with CAR-T cells in coming months. “We want to make cell therapy less elite than it is right now. I don’t think every rural hospital will be able to do it, but it doesn’t have to only be for people able to pay $500,000,” says Winnemöller, citing a potential price for this type of cancer treatment. “I think the price has to go down.”
Novartis’s Gotwals says Miltenyi’s gadget is just one of several devices under development. Last summer, after predicting CAR-T cancer treatments could generate $10 billion in sales by 2021, General Electric acquired a company called Biosafe that specializes in cell handling. MIT’s Draper Laboratories is working on microfluidics devices to prepare CAR-T treatments, and a California startup, Berkeley Lights, has new ways to sort through blood cells to zero in on just the right ones.
Gotwals expects that, at first, gene therapy in a box will be useful to companies that want to expand manufacturing, or to academic centers that want to start offering it. Eventually, it may be that when a person is diagnosed with cancer or born with sickle cell disease, doctors in Lagos, Mumbai, or Seattle simply go online and order the right gene-therapy kit. “The aspiration is to have a device by the bedside. You would just plug the patient in and give them whatever makes sense,” says Gotwals.