MIT Team Develops New Preservation Method for CAR-T Cells

CAR-T cells are used to treat some types of blood cancer, but only about 5 percent of hospitals in the United States can generate and deliver them. For many patients, this means the cells must be frozen and shipped long-distance. To make this therapy more accessible, researchers at MIT have developed a new way to protect the cells from damage that occurs during freezing and storage, significantly reducing the use of a chemical preservative currently required for the process. 

To make CAR-T cells, doctors isolate T cells from patient blood, engineer them to express a chimeric antigen receptor that targets specific cancer proteins, and let them proliferate for several weeks before infusion. Because only a small number of hospitals can generate and administer these cells, most are produced at centralized facilities, frozen, and shipped. To protect them from damaging ice crystals, the cells are treated with DMSO, which must be removed before transfusion, a step most hospitals lack the expertise to perform and one that can itself harm the cells.

The MIT team’s new method replaces most of the DMSO with sugars previously shown to help cells survive cold temperatures, delivered into the cells using electroporation, a technique that applies a small electrical current to briefly open holes in the cell membrane. The researchers still needed a small amount of DMSO, but not enough that it had to be removed afterward.

“With this approach, you could theoretically just thaw the cells and then inject them, without any extra processing steps. We think that could allow a lot more cancer treatment centers to be able to give CAR-T cell therapy,” says Ana Jaklenec, one of the lead authors on the study published in Trends in Biotechnology.

The researchers tested the method on CAR-T cells and mesenchymal stem cells, finding higher survival rates after freezing and thawing compared with DMSO. Thawed CAR-T cells preserved this way were also used to treat lymphoma and glioblastoma in mice, with higher survival rates than mice treated with cells preserved using DMSO. “We believe that our cryopreservation strategy can truly improve the cell therapeutic accessibility because with our strategy, you don’t need to remove the cryoprotectants. You could use the cells upon thawing,” says lead author Amy Lee.

The researchers now hope to work with hospitals to explore whether the new technique could be integrated into the process of producing and thawing CAR-T cells, and Jaklenec says a small patient trial could follow if cell viability and functionality hold up.