The semi-automated “point of care” delivery system developed by Adair’s team using instrumentation available from Miltenyi Biotec reduces the space required to produce the modified cells from 500 square feet to less than 5 square feet and the staffing from five or 10 people to one or two, according to oncologist Dr. Hans-Peter Kiem, a Fred Hutch and University of Washington cell and gene therapy researcher and the paper’s senior author. It does the job in less than half the time.

“This is truly transformative,” Kiem said. “It will change the way we manufacture and deliver cell and gene therapy products and will have a major impact on making stem cell gene therapy and transplantation and likely also immunotherapy available to patients with genetic diseases, HIV and cancer worldwide.”

An idea takes root

In 2008, Kiem hired Adair to run a clinical trial for a gene therapy to treat glioblastoma, the deadliest form of brain cancer. The study called for extracting a patient’s blood stem cells and inserting a special “resistance” gene designed in the laboratory to protect blood cells from damage by chemotherapy drugs. Infused back into the patient, the resistant cells would multiply and allow glioblastoma patients to receive higher doses of the cancer-killing chemo than they otherwise could withstand.

Stem cell–based gene therapy involves removing blood or bone marrow from patients, separating out the stem cells — which give rise to all blood and immune cells in the body — and using a deactivated virus to transfer genetic instructions for treating or preventing a disease into the cells. (Scientists also are investigating the use of targeted nucleases such as CRISPR to edit genes, but most gene therapies now being tested in humans rely on viral vectors.) After being infused back into the patient, the stem cells propagate new cells that carry the modification.

For Adair, the idea for gene therapy in a box was planted in 2009. She was on her way home in a taxi at 1 a.m. after having delivered genetically modified cells to the first patient in the newly launched brain cancer trial. Snatching only a few hours for sleep, Adair spent most of four days in a strictly regulated clean room where every bathroom break meant having to wash and suit up again in sterile clothing. The 96-hour marathon of time-sensitive, near-constant work left her physically and mentally exhausted.

“How are we ever going to be able to do this for more than one cancer patient a week?” she remembered thinking. “It just seemed harrowing.”

Fast-forward five years, and blood stem cell–based gene therapy, though still experimental, was exploding. Patients in that early-phase brain cancer trial were living months or even years longer than most people with glioblastoma survive. Adair was running additional clinical trials, including one for a rare blood disorder called Fanconi anemia, and Kiem got a grant to investigate cell and gene therapy for curing HIV, the virus that causes AIDS — once considered unimaginable.

It was at a 2014 conference on that HIV cure research that Adair had her second epiphany, this time about costs.

More than 25 million of the estimated 36.7 million people worldwide living with HIV are in sub-Saharan Africa, according to the World Health Organization. No country there could support multimillion-dollar clean rooms or afford the sky-high costs of whatever therapies might come out of them.

Adair remembers sitting at the conference and thinking, “If we cure HIV in a patient in the U.S., how are we ever going to get this to the countries that need it?’”

‘Why not now?’

Adair wasn’t the only person asking these questions. As recently as July, researchers and activists at the International AIDS conference in Durban, South Africa, pointed out that lifesaving antiretroviral treatment to suppress HIV reached sub-Saharan Africa years after the drugs were available in developed countries and worried that the same thing could happen with a future cure.

“HIV cure research is still in its infancy. For now, it’s mainly restricted to the North and high-income countries,” said Dr. Paula Munderi of the Medical Research Council/Uganda Virus Research Institute at a symposium on global HIV cure research. “My appeal today is that low-income countries — Africa in particular, which has the bulk of the patients — not be left out of the research agenda.”

Adair had heard other gene therapy researchers dismissing questions about accessibility by saying, “First we have to show gene therapy works, and then we’ll worry about that.”

She wasn’t buying it.

“Why not now?” she remembered thinking. “Is there a way we could do this, in a simplified fashion?”

With Kiem’s encouragement, when Adair became head of her own lab in 2014, she used her Fred Hutch start-up funding to work on finding a way to make these still experimental therapies available and affordable wherever they are needed.

‘I want to make this device do everything’

In the brain cancer clinical trial, Adair used a first-generation device made by Miltenyi Biotec to separate the stem cells from other blood cells. It involved adding specialized metal beads to bone marrow removed from patients, then using a magnet to pull out the stem cells.

But when she started working on a clinical trial for Fanconi anemia, a rare genetic disorder that leads to bone marrow failure, she needed something faster. Such patients have a tiny number of stem cells to begin with, and those are very susceptible to damage from exposure to ambient oxygen. To limit their exposure time, Adair had to find a way to speed up the process of separating and modifying the cells.