Fig. 1.

Construction of conventional CARs. A conventional CAR consists of an Ab-based extracellular domain, a transmembrane domain and intracellular signaling domains. The extracellular domain is directed against the tumor-associated antigen (TAA) on the surface of the target cell. It can be constructed from the variable domains of the heavy and light chains of a mAb. After transduction of the T cell with the CAR gene, the resulting CAR T cell can recognize tumor cells via its extracellular Ab domain. Cross-linkage of the tumor cell with a CAR T cell leads to the formation of a synapse-like structure by clustering of the CAR receptors and thereby to an activation of the CAR T cell via its signaling domain(s) and finally to the destruction of the target cell. Both CD4- and CD8-positive T cells work equally well as killer cells though CD4-positive T cells need longer time for cytotoxic activity [29]