Genomeweb review of CAR T-cell Therapies: Sangamo Mention

The
Genomeweb website has an excellent review of the CAR-T landscape. It also delves into the benefits of various gene editing techniques. The article can be found here:
https://www.genomeweb.com/gene-silencinggene-editing/gene-editing-drives-development-cancer-t-cell-therapies
Here are some relevant quotes:
With numerous receptors to target, CAR T cells could be engineered every which way to target many kinds of cancer — there's even evidence they could be used to treat solid tumors. But so far they only work as an autologous treatment, where the T cells are isolated from the patient, engineered ad hoc, grown to great numbers, and reintroduced to that same patient. Otherwise, if the T cells came directly from another patient, they would likely turn against the body, inducing graft versus host disease (GVHD).
"From an operational standpoint, it's almost a nightmare," Friesen said of autologous CAR T cell treatment. "It's very difficult and commercially that's not a very viable proposition."

Both Janssen and Cellectis, a Paris-based firm that recently opened a CAR T-cell research center in New York, are pursuing development of an off-the-shelf, or allogeneic, CAR T-cell product that would not cause GHVD. To do this, they'll need to engineer cells so that they don't attack the cells in the body and vice versa, and to make it happen they've both made bold decisions on genome-editing technologies.  Janssen recently partnered with Transposagen to use CRISPR/Cas9, while Cellectis is going a different route with transcription activator-like effector nucleases (TALENs).

Other companies that have announced CAR T cell projects include Kite, Bluebird, and Sangamo Biosciences. Sangamo is trying to engineer T cells to eliminate HIV, using its exclusive zinc finger nuclease gene-editing technology.

But Janssen — and anybody else who is using CRISPR to engineer T cells — may run into problems, André Choulika, CEO of Cellectis, told GenomeWeb.
"It's a new technology for underfunded academic labs, but it's not a technology for industrial therapeutic labs," he said. "The technology is not ready yet."
Cellectis plans to use TALENs in its CAR T cell development, a technology for which it has acquired an exclusive license from the University of Minnesota. Dan Voyntas, a professor there and inventor of TALENs, is the head of Cellectis' plant sciences division.
But Choulika said the company has done its due diligence and prefers TALENs for a variety of reasons. "We've tried them all — Meganucleases, ZFNs, CRISPR. We benchmarked them, comparing all the different technologies," he said, adding that TALENs come out on top in a number of important metrics for engineering CAR T cells.
Choulika said Cellectis can routinely get TCR alpha knockout efficiency of 80 to 95 percent with TALENs. Cellectis measured CRISPR/Cas9 knockout efficiency at around 25 percent, thus any cost savings would be partially lost due to lower effectiveness.
Another problem at this stage in CRISPR/Cas9 technology development is the off-target effects. "You can get your knockouts, but the T cell will lose one thing, which is t-cell expansion. Most of the cells won't be able to amplify," Choulika said.