Genetically engineered B cells are used for gene therapy

Until now, B cells have not received the same attention—in fact, genetically engineered versions have never been tested in humans. That’s partly because “engineering B cells is not that easy,” says Virginia Tech professor Xin Luo, who in 2009 showed how to generate B cells with the added gene.

That early work at Caltech investigated whether the cells could be directed to make antibodies against HIV, potentially leading to a new type of vaccine.

While that idea didn’t pan out, now biotech companies like Immusoft, Be Biopharma and Walking Fish Therapeutics are looking to use the cells as molecular factories to treat serious rare diseases. “These cells have the power to secrete protein, so that’s what they want to use,” Luo said.

Immusoft has licensed the Caltech technology and made an early investment from Peter Thiel’s biotech fund Breakout Labs. Matthew Scholes, the founder of the software developer company, boldly predicted that an experiment would start immediately in 2015. But the technology, which the company calls “immune-system programming,” isn’t as simple as coding a computer.

Ainsworth says Immusoft first had to spend years working out safe ways to add genes to B cells. Instead of using viruses or gene editing to make genetic changes, the company uses transposons, molecules that like to cut and paste segments of DNA.

It also took time to convince the FDA to approve the experiment. That’s because it’s known that if DNA is added near cancer-promoting genes, it can sometimes turn them on.

“Is the FDA concerned that if you’re doing this in B cells, you might get leukemia? That’s something Dr. Paul Orchard, who is recruiting patients at the University of Minnesota and conducting the study, is watching closely.

B-cell factories

The first human test may address some open questions about the technology. One is that the modified cells take up long-term residence in people’s bone marrow, where B cells normally reside. In theory, the cells could survive for decades—even the patient’s entire life. Another question is whether they can sufficiently supplement the missing enzyme to help stop MPS, a progressive disease.