Tisagenlecleucel

Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy that involves genetically modified autologous T cells isolated from each individual patient. The reprogramming of the patient's T cells uses a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains from 4-1BB (CD137) and CD3 zeta. These intracellular costimulatory signaling domains increase the expansion, longer-term persistence and potency of CAR T cells; the CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of tisagenlecleucel. Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the tisagenlecleucel cells.