Bruce Cree, MD, PhD, MAS, on Misconceptions About CAR-T in Autoimmune Disease

“As promising as these drugs are and as amazing as the technology is, we have a very, very long road and a difficult road to navigate to prove that CD19 CAR-T therapy can substantially attenuate or even potentially cure autoimmune disease.”

In September 2022, a paper covering a compassionate use study that treated 5 patients with systemic lupus erythematosus with a CD19-directed chimeric antigen receptor T-cell (CAR-T) product was published in Nature Medicine. The study found that the patients experienced deep depletion of B-cells and improvement of clinical symptoms following treatment with the CAR-T product. Since then, interest has been growing in both the clinical community and among industry leaders for the potential of CAR-T therapy to treat B-cell driven autoimmune diseases.

CGTLive® recently sat down with Bruce Cree, MD, PhD, MAS, a professor of neurology and the clinical research director of the University of California San Francisco (UCSF) Multiple Sclerosis Center, to learn about some of the misconceptions arising about CAR-T for autoimmune disease during this flurry of initial enthusiasm. Cree pointed out that this early open-label clinical study and others like it have been uncontrolled, and that without more rigorous trial design, proof of efficacy has not yet been established. He emphasized the importance of clinical trial designs that utilize controls and noted that several important factors are at play. For example, current CAR-T therapy options require a lymphodepletion regimen consisting of fludarabine and cyclophosphamide prior to administration, which may have its own impact on patients’ disease outcomes. Furthermore, he stressed that future trials will have to compare CAR-T therapies against monoclonal antibody treatments administered after lymphodepletion in order to determine whether lymphodepletion and CAR-T provides substantial superiority over lymphodepletion and moncolonal antibodies. Cree noted that rigorous testing like this is of the utmost importance when considering the high costs of developing CAR-T products.

REFERENCES
1. Mackensen A, Müller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022;28(10):2124-2132. doi:10.1038/s41591-022-02017-5