CD19-specific chimeric antigen receptor (CD19 CAR)

The CD19-specific chimeric antigen receptor (CAR) is a synthetic fusion protein engineered to redirect T-cell specificity toward the CD19 antigen, a transmembrane protein expressed throughout almost all stages of B-cell development (June et al., 2018). The receptor typically consists of an extracellular single-chain variable fragment (scFv) for antigen recognition, a hinge and transmembrane region, and intracellular signaling domains such as CD3-zeta and costimulatory molecules like 4-1BB or CD28 (Miliotou and Papadopoulou, 2018). Upon binding to CD19 on the surface of normal or malignant B cells, the CAR triggers robust T-cell activation, proliferation, and cytotoxic effector functions, leading to the destruction of the target cell (Neelapu et al., 2017). This technology has been successfully commercialized in several FDA-approved therapies for B-cell malignancies, including acute lymphoblastic leukemia and various types of non-Hodgkin lymphoma (FDA, 2017). While highly effective in treating refractory diseases, the use of CD19 CARs is associated with significant toxicities, most notably cytokine release syndrome (CRS) and neurotoxicity, which result from the massive systemic release of inflammatory cytokines (Maude et al., 2014).

Other names

Anti-CD19 CARCD19-directed chimeric antigen receptorCD19-CAR19-28z19-bbzFMC63-derived CAR

The CD19-specific chimeric antigen receptor (CAR) functions by providing T cells with a non-MHC-restricted ability to recognize the CD19 antigen on B cells. Binding of the extracellular scFv domain to CD19 induces clustering of the CAR molecules, which initiates signaling through the intracellular CD3-zeta and costimulatory domains (e.g., 4-1BB or CD28). This signaling cascade leads to T-cell activation, secretion of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha, and the release of cytotoxic granules containing perforin and granzymes, which induce apoptosis in the target CD19-positive cell (June et al., 2018; Miliotou and Papadopoulou, 2018).