In some ways, drug development is like any other kind of highly competitive tech product. You're off and running on version 2.0 while the 1.0 prototype is still in beta testing. So it's no wonder that in the sizzling hot CAR-T field, some of the pioneering scientists who helped blaze the trail to the clinic are now at work on the new-and-improved model.
Stan Riddell, a scientist at the Fred Hutchinson Cancer Research Center--which is allied with Juno Therapeutics ($JUNO), where Riddell is a scientific founder--has published new work in Nature Biotechnology on an amped-up T-cell design. Using a small protein tag, Riddell's group says it can purify and track the T cells after they've been modified in the lab and then injected into patients.
Investigators at Juno, Kite and elsewhere are hard at work in the clinic with T-cells that have been reengineered with chimeric antigen receptors, so they can hunt and destroy cancer cells. In this new study, Riddell says he's demonstrated in mice that the protein tag helps whip up potency, spur the proliferation of cells that fight cancer, cut back on manufacturing time from 14-20 days down to 9 days, and add a "kill switch" that can be used to deactivate the therapy if it threatens the patient.
That last bit about the safety switch is particularly significant, as the CAR-T approach is well known to spur cytokine release syndrome, also called a cytokine storm, which can and has killed patients.
Just days ago Riddell and a group of colleagues from several institutions tied to Juno captured the global spotlight with a small human study demonstrating the improved efficacy of a subset of cells called memory T cells.
In a small group of dying, late-stage patients given just months to live, this approach eliminated symptoms of acute lymphoblastic leukemia in 94% of the group. Patients with a variety of blood cancers saw an 80% response rate.
"This is unprecedented in medicine, to be honest, to get response rates in this range in these very advanced patients," Riddell told reporters at the meeting.
This kind of scientific tinkering will be key to distinguishing the leaders in the field. CAR-T using patient cells also faces a challenge from investigators using off-the-shelf cells that should be easier to make and less expensive once on the market. And the potential multibillion-dollar payoff is keeping researchers focused squarely on advancing new wrinkles that may well provide a crucial edge in the market war to come.