Until now, B cells have not received the same attention—indeed, genetically engineered versions have never been tested in humans. That’s partly because “engineering B cells is not that easy,” says Xin Luo, a professor at Virginia Tech who in 2009 showed how to create B cells that have an extra gene.
That early work, done at Caltech, investigated whether cells could be directed to make antibodies against HIV, potentially becoming a new form of vaccination.
Although that idea failed, now biotech companies like Immusoft, Be Biopharma, and The Walking Fish Therapeutics they want to use cells as molecular factories to treat serious rare diseases. “These cells are protein-secreting powerhouses, so that’s something they want to take advantage of,” says Luo.
Immusoft has licensed the Caltech technology and received an early investment from Peter Thiel’s biotech fund, Breakout Labs. Company founder Matthew Scholz, a software developer, boldly predicted in 2015 that the trial could begin immediately. But the technology, which the company calls “programming the immune system,” hasn’t turned out to be as simple as computer coding.
Ainsworth says Immusoft first had to spend several years working on reliable ways to add genes to B cells. Instead of using viruses or gene editing to make genetic changes, the company now uses a transposon – a molecule that likes to cut and paste segments of DNA.
It also took time to convince the FDA to allow the trial. That’s because it’s known that if the added DNA ends up near cancer-promoting genes, it can sometimes trigger them.
“The FDA is concerned if you do this in a B cell, could you develop a leukemia situation? That’s something they’re going to be watching pretty closely,” says Paul Orchard, a doctor at the University of Minnesota who will be recruiting patients and conducting the study.
The first human test could solve some open questions about the technology. One is whether the improved cells will reside long-term in people’s bone marrow, where B cells normally live. In theory, the cells could survive for decades—even the patient’s lifetime. Another question is whether it will produce enough of the missing enzyme to help stop MPS, which is a progressive disease.