Review Article

Chimeric Antigen Receptor-T (CAR-T) Cells as “Living Drugs”: A Clinical Pharmacist Perspective

Figure 2

CAR-T cell architecture. The CAR construct is composed of four domains which support its functionality. The single chain variable fragment (scFv) domain is the extracellular domain which is involved in recognition and binding. It also can induce immunogenicity if obtained from murine sources. The hinge domain gives flexibility to the CAR enhancing binding and homing. The transmembrane domain provides stability and cytokine release and enables incorporation into exogenous TCR. The intracellular domain has two regions, the costimulation and activation regions, which together initiate a signalling cascade to induce proliferation and activation of T-effector functionality. These domains function synergistically to reprogram the T cell to specifically bind tumour-associated antigens (TAAs) and execute their cytotoxic functions. Key: VH = variable heavy chain, VL = variable light chain, IL-2 = interleukin 2, IFNy = interferon gamma, TNF-α = tumour necrosis factor alpha, TCR = T cell receptor, MHC = major histocompatability complex, TAA = tumour-associated antigen, and CAR = chimeric antigen receptor.