Improvement in CAR T-Cell Therapy Removes Severe Side Effects

University of Southern California (USC) scientists have made an advancement in chimeric antigen receptor (CAR) T-cell therapy that seems to eliminate its severe side effects, making the treatment safer and potentially available in outpatient settings.

The study, published on April 22, 2019 online in Nature Medicine, showed that this improved version of CAR T-cell therapy produced no serious side effects in 25 patients who had lymphoma that recurred after previous treatments. Although the study was designed to look at safety-not effectiveness-six out of 11 participants receiving a commonly used dose went into complete remission.

“This is a major improvement,” said Si-Yi Chen of the USC Norris Comprehensive Cancer Center, professor in the department of molecular microbiology and immunology at the Keck School of Medicine of USC, and senior author of the study, in a university press release. “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.”

In CAR T-cell therapy, immune cells called T cells are harvested from a patient’s blood and then modified in the lab to produce CARs on their surface. The altered T cells are reinfused into the patient where the cells’ new receptors enable them to recognize, latch onto, and eliminate cancer cells.

Approved by FDA in August 2017, CAR T-cell therapy is used to treat leukemia and lymphoma and often causes severe side effects, some of which are life threatening, that must be managed by experienced specialists. These side effects occur when CAR T cells rapidly proliferate and release a flood of substances called cytokines. Severe cytokine release syndrome can lead to life-threatening multi-organ damage and brain swelling. In this revised version, researchers edited the sequence and shape of the CAR molecules. As a result, the CAR T cells eliminate cancer cells but produce fewer cytokines and proliferate more slowly, giving 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,” Chen said. “Toxicities are currently the biggest barrier to the use of CAR T-cell therapy. My hope is that this safer version of CAR T-cell therapy could someday be administered to patients in outpatient settings.”

The next step, according to Chen, is to perform a multicenter Phase II study to test safety and effectiveness in a larger group of patients.

Source: University of Southern California