Bruce Cree, MD, PhD, MAS, on Overcoming Limitations of Monoclonal Antibodies in Autoimmune Disease With CAR-T

“We know that these [pathogenic B-cells] are present there and are in this privileged location where monoclonal antibodies simply can't get to—or can’t get to easily—and even if the antibody gets there, most of the antibodies kill B-cells through complement-dependent mechanisms... You don't really see complement within the central nervous system. So a cell-based therapy that can cross the blood-brain barrier, get at these tissue-resident B-cells that are embedded deep within the brain and within the meninges has the potential to eradicate these cells.”

A number of autoimmune diseases are driven by the activity of B-cells. As such, B-cell depleting therapies, such as CD20-directed or CD19-directed monoclonal antibodies, are a common standard of care approach to treating these diseases. Although this approach is highly effective for many patients, a subset of the patient population is refractory to these treatments—they may experience some short-term benefit, but eventually disease progression continues. This may be due in part to the inability of monoclonal antibodies to reach active B-cells embedded deep in tissues or in the central nervous system. Research into new therapeutic options to address this unmet need is ongoing. One potential option is the repurposing of chimeric antigen receptor T-cell (CAR-T) therapy, a type of engineered cell therapy originally developed to treat B-cell cancers. Because CAR-T therapies consist of the patients’ own cells, they may be able to reach areas of the body unreachable by monoclonal antibodies.

CGTLive™ spoke to 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 more about the rationale behind using CAR-T to treat autoimmune diseases. In addition to discussing how CAR-T could overcome disadvantages of monoclonal antibody treatments, he also spoke about the promising early research that has been done with CAR-T in lupus and the potential for further research in diseases like multiple sclerosis. He noted that UCSF may have the opportunity to begin a planned study for CAR-T in multiple sclerosis in the near future.