CAR-T researchers have had years to study CD19 protein molecules as a target in their successful leukemia studies. But a small, exploratory study at Stanford underscores that there’s substantial promise in expanding their scope to include CD22, offering a new route to follow for patients who relapse — or never respond — after being treated with the first round of cell therapies now hitting the market.
The research team recruited 15 patients for this trial who had either relapsed or never responded to CD19-targeted CAR-T therapy, which involves extracting a population of T cells from patients and adapting them with a chimeric antigen receptor so they would target a protein commonly found on the surface of leukemia cells. Ten of them had relapsed, with their cancer cells no longer expressing CD19.
After stepping up the dose from the first round, the researchers achieved remission in 11 of the 15 patients — a remarkable 73%. The remissions lasted a median of 6 months with one patient in remission at 21 months, with signs that the cancer cells were able to mutate to stop expressing CD22 and escape the therapeutic assault.
“The take-home message is that we’ve found another CAR T-cell therapy that displays high-level activity in this Phase I trial,” said Stanford’s Crystal Mackall, who led the study. “But the relapse rate was also high. So this forces the field to get even more sophisticated. How much of a target is needed for successful, long-lasting treatment? What happens if we target both CD19 and CD22 simultaneously?”
Stanford’s team reported progress with CD22 four days after investigators at Seattle Children’s launched a combination CAR-T trial using a new cell therapy that could simultaneously attack CD19 and CD22, looking for a more potent and consistent strategy for acute lymphoblastic leukemia that could conceivably cut the relapse rate in half, while also taking another step down a path toward using CAR-T in solid tumors — one of the Holy Grails that has emerged in the field.
(Editor’s note: After we published this story, one of our readers pointed out that Autolus also just started a PhI/II study using a CD19/CD22 CAR-T.)
The small trial at Stanford is significant for a variety of reasons. While Novartis and Gilead/Kite have begun the process of fielding the first new therapies, the emphasis in research circles has shifted to creating a new, safer generation of CAR-Ts that can be far more durable. Also, Mackall told The New York Times, it’s important to understand that CD19, for all its remarkable effect in offering a beacon for cell therapies, is “not some kind of unicorn.”
More targets exist that will work here, she says. And that’s where researchers will turn next.
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