Accelerating Production of CAR T Cells

If anything ever seemed like a miracle in cancer treatments, it might be therapies based on chimeric antigen receptor (CAR) T cells. As Monica Casucci, PhD, group leader, innovative immunotherapies at IRCCS Ospedale San Raffaele in Milan, Italy, and her colleagues wrote: “CAR T-cell therapy has considerably changed the landscape of treatment options for B cell malignancies, leading to the recent approval of the first CAR T-cell products for treating cancer.”

Nonetheless, the production of these treatments faces a crucial bottleneck.

“Cell expansion is the rate-limiting step defining the cycle time of the production process,” says David Backer, CEO at Curate Biosciences in Carlsbad, CA. “This bottleneck is driven by having significant losses of the patient-sourced cells, and the expansion process adds days or even weeks to the production of marketed autologous cell therapies.”

Consequently, this lag prevents broader availability of these treatments. “Although there are tens of thousands of patients technically eligible for CAR T-therapies today, only a small fraction of them actually receive it, in part because the time to production limits manufacturing capacity,” Backer explains.

Many scientists and companies seek improvements in making CAR T cells. It’s not just that production needs to be accelerated to make enough cells, but also enough healthy cells. “There is a growing body of evidence that the therapeutic suitability of the cells diminishes over the course of cell expansion,” Backer says.

Tackling the challenge of expansion

The challenge of expansion can be addressed in various ways. As previously reported, for example, Backer’s team developed a system that maximizes the number of healthy cells available at the start of the process. As Backer explains, this system “reduces the time and number of cell divisions required to achieve a dose.”

As an alternative, some scientists explore ways to bypass the expansion step. For example, Michael C. Milone, MD, PhD, associate professor of pathology and laboratory medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia, and his colleagues described a method in which “functional CAR T cells can be generated within 24 hours from T cells derived from peripheral blood without the need for T-cell activation or ex vivo expansion.”

Any approach that speeds up the production of CAR T-therapies—while maintaining or even improving efficacy—promises to get these treatments to more patients. Accelerating or bypassing expansion could reduce the cost and expand the availability of these treatments, and the results might create the miracle that cancer patients seek.

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