SAN FRANCISCO—The future of CAR-T is off the shelf, according to Cellectis CEO André Choulika. Allogeneic CAR-T therapy, which uses donor T cells, has the potential to clear the hurdles that come with autologous CAR-T, which uses a patient’s own T cells. Those challenges include the cost, complexity and time-consuming nature of autologous treatments, as well as distribution and market access. Some patients can’t benefit from autologous CAR-T because they don’t have enough T cells or T cells of good enough quality to make those treatments.
“With off-the-shelf CAR, you don’t ask patients to provide part of the raw materials for their treatment,” Choulika said at the J.P. Morgan Healthcare Conference. And the allogeneic approach could expand the reach of CAR-T treatments beyond certain indications, namely those in which patients don’t need that particular tissue to survive.
Take the blood cancers for which CAR-T therapies have already been approved—two different forms of B-cell lymphoma. If the CAR-T cells remain in the body for a long time, “that’s OK,” Choulika said. “The patient can survive without B cells.”
They’re not as harmless if they persist in the body and their target is expressed on a different type of cell.
“If the target is expressed on myeloid progenitor cells … the patient cannot rebuild blood, even red blood cells,” Choulika said. “You don’t want the CAR to stay there forever, so it doesn’t really make sense to make an autologous CAR.”
Founded nearly 20 years ago as a gene-editing company, Cellectis found validation—and “a bit of cash”—in a deal with Servier in 2014.
“[It] was a really difficult decision for us … If we’d had the same amount of cash [in 2014] that we have today, I wouldn’t have licensed any of our targets to anyone,” Choulika said.
But at the time, the autologous treatments Kymriah and Yescarta hadn’t been approved and no one really believed in allogeneic CAR-Ts, Choulika said. So the company licensed out its lead asset, UCART19, to gain some credibility and to be able to move it forward. Later in 2014, Cellectis licensed another 14 assets to Pfizer.
Between them, Cellectis, Servier and Pfizer had programs with 31 targets, though some of the disease areas overlap. Working in the same indications doesn’t necessarily spell out competition, though. Combining these treatments could make them more effective, reducing relapse in patients.
Four years later, in 2018, Pfizer spun out its CAR-T portfolio, the assets finding their way to Arie Belldegrun and David Chang’s Allogene.
It was a good decision, Choulika said.
“We are excited to be working with very experienced people such as Belldegrun and Chang … It’s great for UCART19 that has been licensed from Servier to Allogene and it’s good for us because we benefit from this experience that the Allogene team had in past in our current development.”
Choulika sees autologous CAR-T therapies as something to be used in a hospital setting, like a bone marrow transplant, with off-the-shelf versions being the way forward. He also sees the technology being applied to not just T cells, but other immune cells, such as natural killer cells, to tackle other diseases, expanding its utility from liquid cancers into solid tumors and then into other areas, such as autoimmune diseases.