Science Fiction Made Real: Kerry Rogers, MD, on How CAR T Works

In this interview, Kerry Rogers, MD, associate professor at The James—The Ohio State University Comprehensive Cancer Center, walked through how chimeric antigen receptor (CAR) T-cell therapy works from start to finish, describing the process as still feeling “like science fiction” despite how established it has become in treating blood cancers such as chronic lymphocytic leukemia (CLL).

She explained that the process begins with leukapheresis, an outpatient procedure that collects a patient’s T cells from the blood using a machine that separates cell components, similar to how blood donation centers collect platelets. The collected T cells are then sent to a manufacturing lab where they undergo genetic modification, typically via a viral vector, to insert CAR that redirects the cell to attack a specific marker, most commonly CD19, found on many B-cell cancers. This process usually takes between 5 and 6 weeks.

Once manufactured and run through quality checks, the modified cells are shipped back to the treatment site. Patients first receive lymphodepletion chemotherapy, typically fludarabine and cyclophosphamide, to create space in the immune system for the new cells. After infusion, the T cells expand and attack the cancer. However, this can trigger serious adverse effects, including cytokine release syndrome and CAR T-cell therapy–specific neurotoxicity, which can cause speech difficulty or confusion, or even death, in rare cases. Rogers noted that management of these complications has significantly improved, with anticytokine therapies, steroids, and earlier intervention reducing the risk of severe outcomes.

Patients require a 24-hour caregiver, cannot drive for a period due to seizure risk, and must remain near the treatment center for about 14 days after their infusion. This is down from 30 days in earlier protocols. Disease response is typically assessed at 30 and 90 days to evaluate how effectively the therapy eliminated the cancer.

“You have to have an experienced center that knows what these complications are that can manage them,” Rogers emphasized, “to have some of these drugs like tocilizumab, which is an anti–IL-6, on-site to treat people. People have to know what to look for.”