Editor’s note: RheumMadness is the place for everyone crazy about rheumatology to connect, collaborate, compete and learn together. During RheumMadness, rheumatology concepts represent teams that compete against each other in a tournament, much like basketball teams do in the NCAA’s March Madness tournament. In a series for The Rheumatologist, readers will get a chance to read the scouting reports for each concept team. These reports are written by rheumatology fellows from 13 programs throughout the U.S.
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Region: Cells Team: CAR-T Cells
Chimeric antigen receptor T (CAR-T) cells are made by combining T cell receptor constant variant domains and antibody variable domains. Anti-CD19-targeted CAR-T cells have been shown to be a power forward in the destruction of B cell malignancies, even in patients boxed out of other therapies.
Inspired by this success with CAR-T cell therapy in hematologic malignancies, CD19 CAR-T cell therapy is actively being recruited as the next MVP for B cell depletion therapy in patients with autoimmune disease. It’s hypothesized this elite therapy can better access—within lymphatic organs and inflamed tissues for example—and persistently deplete autoreactive B cells than current players, such as rituximab.
Given that CD19 is expressed during all major states of B cell maturation, it’s speculated that anti-CD19 therapy may lead to depletion of pro-B cell plasmablasts secreting pathologic autoantibodies and some plasma cells. A case report by Mougiakakos et al. in which a severe case of refractory systemic lupus erythematosus (SLE) was swiftly knocked out by CD19 CAR-T cell therapy illustrates the immense power of this emerging, immunosuppressive all-star in the treatment of rheumatic diseases.1
CAR-T cell therapies have been tested in mouse models for type 1 diabetes, lupus, multiple sclerosis, colitis and other diseases with at least some measurable benefit. Additionally, pre-clinical CAR-T studies have been completed or are ongoing for rheumatoid arthritis (RA), SLE and systemic sclerosis. Other potential applications include CAR-T cells expressing citrullinated antigens to target anti-citrulline B cells to treat RA and CAR-T reg cell therapies.2
Implications
CAR-T cells represent a major shift in the nature of therapeutics for rheumatology—possibly more profound than the addition of biologic disease-modifying anti-rheumatic drugs (DMARDs) to the conventional synthetic DMARD playbook in the late 1990s and early 2000s.
