Gene Therapy

Parker Institute scientists herald a cell therapy breakthrough in the lab, using next-gen CRISPR tech to engineer T cells

The two pioneering CAR-T therapies on the market — Kymriah and Yescarta — rely on viral vectors to complete the engineering work needed to make a cancer patient’s T cells into a therapy. But a group of Parker Institute for Cancer Immunotherapy-backed scientists at UCSF and UCLA say they have perfected a new approach using CRISPR gene editing tech that they believe will transform the field — opening the door to a range of cell therapies that can be built and manufactured far more easily than the first-gen crowd.

Antoni Ribas

There’s nothing new about CRISPR, of course. The simple, somewhat blunt gene editing technology — generally focused on cutting into genes while struggling with pasting DNA — has taken academic labs, and quite a few commercial ones, by storm in recent years. But the scientists involved in this project, including noted UCLA researcher Antoni Ribas, say they’ve come up with some new techniques that could make it a widely used alternative to viral vectors — which have sometimes been in short supply.

Fred Ramsdell

And they say it fits all the hallmarks of a tech advance: Faster, better, cheaper.

“What takes months or even a year may now take a couple weeks using this new technology,” noted Fred Ramsdell, vice president of research at PICI. “If you are a cancer patient, weeks versus months could make a huge difference.”

The same goes for the companies involved.

The researchers say this new approach makes it possible to insert long stretches of DNA into genes, opening the door to more precise therapies that could be far more effective in tackling cancer or some other T cell targeted disease.

Alex Marson

Up to now, says Alex Marson, associate professor of microbiology and immunology at UCSF, CRISPR has been effective in knocking genes out — by cutting and interrupting. “You could change a few nucleotides at a time,” he noted, “but if you put in bigger data, it would kill the cells.”

This new development of theirs uses electroporation to condition cell membranes and has been used in the lab to go much further — not just pasting into random places, but being far more precise. 

“This is sort of a flexible thing to change the way T cells work,” Marson adds, and the teams involved used it in the lab to work ex vivo on a rare and severe form of pediatric autoimmune disease, correcting mutations. A second project used the technology to create a new T cell therapy for melanoma, successfully testing it in mice.

Theo Roth

Now the focus will shift to moving this into humans.

“This is something we’re very actively working toward now,” says Marson, who’s pursuing conversations with the FDA as well as commercial partners to lay out the next steps of getting this moved toward the clinic.

“There has been thirty years of work trying to get new genes into T cells,” said UCSF student and lead author Theo Roth, who’s been doing much of the fine tuning work in the lab. “Now there should no longer be a need to have six or seven people in a lab working with viruses just to engineer T cells, and if we begin to see hundreds of labs engineering these cells instead of just a few, and working with increasingly more complex DNA sequences, we’ll be trying so many more possibilities that it will significantly speed up the development of future generations of cell therapy.”

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
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Atlas Venture Cambridge, MA

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