A new device greatly simplifies cell-based gene therapy, turning it from a clean room to a desktop operation.
The device, which its developers have named "gene therapy in a box," is based on the commercially available Clinimacs Prodigy device (Miltenyi Biotec GmbH) and is "an ahead-of-the-game approach to scale up what we see working now," Jennifer Adair told BioWorld Today.
"Gene therapy, and this type of bone marrow blood stem cell gene therapy in particular, is really taking off," she said. Numerous early stage trials are currently testing such therapies for both rare and common inherited diseases.
And stem cells are not the only type of blood cell being edited. T-cell editing to generate chimeric antigen receptor (CAR) T cells is generating much excitement in oncology, and editing helper T cells to be resistant to infection with HIV is a strategy being pursued as part of an HIV cure.
Between them, those approaches, if they are ultimately successful, could benefit tens of millions of patients globally.
Given those numbers, Adair said, "in the back of everyone's mind is the question 'What's it going to take to scale this up?'"
Currently, ex vivo clinical gene editing of stem cells can only be done in highly specialized facilities, and the process requires near constant human attention.
Even in the U.S., there are not many such facilities. And in poorer countries, using gene editing to treat conditions such as sickle cell anemia or HIV is a nonstarter with current technologies.
Adair is an assistant member of the Fred Hutchinson Cancer Research Center's Clinical Research Division and a research assistant professor of medical oncology at the University of Washington School of Medicine. In the Oct. 20, 2016, online issue of Nature Communications, Adair and her co-authors described automating the Clinimacs Prodigy so that it was able to transduce blood progenitor cells that were derived from either the blood or the bone marrow with what they termed "minimal user input."
The machine, they wrote in their paper, produced "yield, purity and rates of transduction of the CD34 [progenitor] cells are comparable to current cGMP practices, and pass cGMP standards for human transduced products."
The team also tested the staying power of the cells in animal models. The researchers showed that transduced human progenitor cells were able to engraft into the bone marrow of immunodeficient mice, and, in monkeys that received an autologous stem cell transplant, the transduced cells also engrafted and produced all types of blood cells.
Adair said that the method worked whether the cells were harvested from the blood or the bone marrow, and could also be used with other cell types. "The machine doesn't know whether you're processing stem cells or T cells," she said. "What it's doing is adding fluid or culturing cells on the user's demand."
In their paper, Adair and her team used a lentiviral vector to deliver the gene to cells, but she said the approach would also work using different types of gene editing such as CRISPR or zinc finger nucleases.
Adair and her colleagues currently have FDA approval to use the device in a trial for Fanconi anemia.
They are also working on the device to "make it as user-friendly as possible," she said, in order to develop a machine that would enable clinically trained staff to use it for gene editing in combination with specific kits.
The next step toward developing the machine, she said, is to get approval from the FDA for a protocol in the U.S.
Ultimately, she wants the device to be cheap enough to be a realistic option in middle- and low-income countries as well.
"We really need to be able to move these therapies to all these regions of the world," she said. "I think that's imperative when we're talking about diseases" – such as HIV – "where the bulk of the burden lies outside of the U.S."