FMC63-derived chimeric antigen receptor (FMC63 CAR) (FMC63 CAR)

The FMC63-derived chimeric antigen receptor (FMC63 CAR) is a synthetic, engineered receptor designed to redirect T-cell specificity toward the CD19 protein, which is ubiquitously expressed on the surface of B-lineage cells (Zola et al., 1991). The receptor's extracellular binding domain consists of a single-chain variable fragment (scFv) derived from the FMC63 mouse monoclonal antibody (Nicholson et al., 1997). Upon binding to CD19 on target cells, the CAR initiates a signaling cascade through its intracellular CD3-zeta domain and a costimulatory domain, typically CD28 or 4-1BB (Kochenderfer et al., 2009; Milone et al., 2009). This activation leads to the proliferation of the engineered T cells and the release of cytotoxic granules and cytokines, resulting in the lysis of both malignant and healthy B cells. The FMC63 CAR is the most widely utilized antigen-binding domain in commercially approved CAR-T cell therapies, including Tisagenlecleucel and Axicabtagene ciloleucel (FDA, 2017). It is primarily indicated for the treatment of relapsed or refractory B-cell malignancies, such as acute lymphoblastic leukemia and various non-Hodgkin lymphomas. However, its high potency can lead to severe adverse effects, most notably cytokine release syndrome (CRS) and neurotoxicity (ICANS), requiring careful clinical management.

Other names

CD19-specific chimeric antigen receptor (FMC63)FMC63-scFv CARAnti-CD19 CAR (FMC63)

The FMC63-derived scFv binds to the CD19 antigen on B-cells, triggering intracellular signaling through the CD3-zeta and costimulatory domains (CD28 or 4-1BB), resulting in T-cell activation, proliferation, and cytotoxic destruction of the target cell.