Experts to Explain Why CAR-T Cell Therapy Is Promising But Not a Cure-All

Chimeric antigen receptor T-cell (CAR-T) therapy has the potential to be the most important breakthrough in autoimmune disease treatment. But early clinical trial data do not always hold up.

“CAR-T offers an extraordinary possibility — long-term, drug-free remissions — but we need to do the work to prove that this new therapeutic modality is effective and safe in treating rheumatic diseases,” said Anca Askanase, MD, MPH, Professor of Medicine at Columbia University Irving Medical Center. “CAR-T is a novel way of looking at the treatment of autoimmune diseases, but we need to do our due diligence. The mechanism of action makes sense, but it’s a little premature to celebrate.”

Dr. Askanase is Founder and Director of the Columbia University Lupus Center and Director of Rheumatology Clinical Trials and an active participant in both investigator-initiated and manufacturer-sponsored CAR-T trials. She is one of the speakers for Are We Putting the CAR-T Before the Horse? on Monday, Nov. 18, from 1–2 p.m. ET in Ballroom A of the Walter E. Washington Convention Center. The session will be available on demand within 48 hours for registered ACR Convergence 2024 participants.

Most current approaches to CAR-T therapy are based on autologous T-cells that are engineered from the patient’s own T-cells to target specific antigens, then reinfused into the patient. Autologous T-cells are tremendously effective against leukemias, lymphomas, and some solid tumors, as well as systemic lupus erythematosus (SLE) and other autoimmune diseases. Autologous T-cells also are expensive to produce, which can limit access to treatment.

“There are other approaches using allogenic, off-the-shelf T-cells, regulatory CAR-T cells, and CAR-T or natural killer T-cells (NKT cells) produced from induced pluripotential stem cells,” said George Tsokos, MD, Professor of Medicine at Harvard Medical School and Chief of Rheumatology and Clinical Immunology at Beth Israel Deaconess Medical Center. “With proper manipulation, we can use them off the shelf for any individual. You don’t have to pull T-cells from every patient and process them individually, which is the expensive part of CAR-T therapy.”

Another approach is the T-cell engager that “teaches” T-cells how to attack pathogenic B-cells. Bispecific T-cell engager (BiTE) agents have been approved for leukemia and show promise in other B-cell malignancies as well as autoimmune diseases.

“All of these options are being evaluated by manufacturers, by patients, and academic investigators,” Dr. Askanase said. “It feels like we could be on the precipice of a transformation, a revolution. It feels like we are about to see extraordinary progress.”

That is not to say CAR-T therapy is without risk. Immunotherapy was initially developed in cancer, Dr. Tsokos noted, and the cancer literature shows the potential for side effects from CAR-T treatment.

One of the key questions is the durability of CAR-T response in autoimmune diseases.

“How long do these cells exist in the blood of patients?” Dr. Tsokos asked. “There are reports they can survive for months. And there is the prospect of CAR-T cells growing out of control to become leukemia. It’s rare, but it can happen.”

Dr. Askanase said she is expecting multiple abstracts detailing early experience with CAR-T therapy in autoimmune diseases at this year’s ACR Convergence.

“We need proof in controlled trials that cell therapy is effective in autoimmune diseases and that the risks are much less than the benefits,” she said. “When I last counted, there were at least 25 CAR-T protocols underway. Whether there will be 25 going into later-phase development, I don’t know. But as rheumatologists, we should do the clinical and the bench work to understand the role of CAR-Ts, define who they work for, and determine how safe and effective they really are for our patients.”