Background on CD19-CAR T Cells
CAR (Chimeric Antigen Receptor) T cells are T cells that have been engineered with additional receptors to identify specific proteins, called antigens, present on the surface of other cells. CAR-enabled targeting is the basis of numerous immuno-oncology treatments across the biotechnology industry, where CAR T cell therapy has shown remarkable clinical success.
Most CARs have a similar structure that includes an extracellular target binding domain derived from antibodies and an intracellular signaling domain derived from the natural T cell receptor complex. The extracellular domain is typically a single-chain variable fragment (scFv) that binds specifically to a target antigen on cancer cells, such as CD19. More recent CARs include additional costimulatory domains, such as 4-1BB (CD137), to increase the engineered cells’ cytokine production and self-replication for a more durable and potent clinical result.
Two CD19-specific CAR T cell products, Kymriah® and Yescarta®, achieved regulatory approval in 2017 for types of cancers, including acute lymphoblastic leukemia (ALL) and diffuse large B cell lymphoma (DLBCL).
In September 2022, an academic group published findings Nature Medicine that showed the potential of CD19-CAR T to transform the course of autoimmune disease. In five patients with severe systemic lupus erythematosus (SLE), one-time treatment with a 4-1BB-containing CD19-CAR T cell therapy induced clinical remission of all five patients within three months after treatment, with mild CRS in 3/5 patients and no neurotoxicity observed. Healthy B cells repopulated in all patients within 5 months of treatment, and responses remained durable off all SLE-associated medications with 5-17 months of follow-up.1 Similar results were observed in a case report of a patient with anti-synthetase syndrome, a subtype of myositis, as published The Lancet in February 20232. These findings demonstrate the potential for CD19-CAR T to “reset the immune system,” potentially eliminating the cause of autoimmune disease with restoration of the healthy immune system.
- Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
- Müller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023).
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