Novel CAR T-cell therapy removes the risk of severe side effects

Written by Mike Gregg

A ground-breaking study, carried out by USC (University of Southern California, CA, US) and published in Nature Medicine, appears to have removed the severe side effects caused by CAR T-cell therapy. This has made the treatment safer and potentially opened doors for expanding its availability to outpatient settings.

CAR T-cell therapy involves harvesting immune cells called T-cells from a patient’s blood and altering them in a lab by adding chimeric antigen receptors to their cell membranes. The chimeric antigen receptors allow the T-cells to identify and latch to cancer cells, killing them, when they are reinfused into the patient.

However, current CAR T-cell treatments cause severe side effects which can be life threatening. The side effects are caused by the reintroduction of CAR T-cells, which proliferate rapidly and produce cytokines. This results in cytokine release syndrome, which can cause multi-organ damage and brain swelling if not managed properly by specialists.

To prevent these side effects the researchers from University of Southern California (USC; CA, US) altered the sequence and shape of the CAR molecules added to the T-cells. This resulted in the CAR T-cells still killing cancer cells but not proliferating as fast and producing less cytokines, allowing the patient’s body more time to clear cytokines in the blood.

“The improved CAR T-cells proliferated and differentiated into memory cells in the patients, thus producing a potent and long-lasting anti-tumor effect without causing toxicities,” explained Si-Yi Chen (USC).

The researchers tested their improved CAR T-cell therapy on 25 patients that had lymphoma which had recurred after previous treatments. The results were positive with none of the patients experiencing any serious side effects. They also discovered that the new treatment was effective with six out of the 11 participants going into complete remission after receiving a commonly used dose on the trial.

“This is a major improvement, we’ve made a new CAR molecule that’s just as efficient at killing cancer cells, but it works more slowly and with less toxicity,” concluded Chen.

Sources: Ying Z, Huang XF, Liu Y et al. A safe and potent anti-CD19 CAR T cell therapy. Nat Med. https://doi.org/10.1038/s41591-019-0421-7 (2019); www.news.usc.edu/156066/car-t-cell-therapy-side-effects/