Figure 1.

A representative figure of an armored 3rd generation CAR in a T cell and a schematic of the transgene, which includes the extracellular scFv, two intracellular costimulatory domains (4-1BB and CD28), the ζ chain, a 2A linker, and the gene of interest to be coexpressed (61, 62). Examples of “armor” added to the CAR T cell are the CCR2 receptor (63), which has been shown to increase T cell migration and homing to the tumor site (64, 65) or constitutive secretion of the cytokine IL-7 and chemokine CCL19, which are important to memory differentiation and T cell migration, respectively (66). CARs that constitutively secrete IL-12 have also been used in several studies to boost survival and cytotoxicity (67). Also depicted is an example of an inducible suicide gene, tEGFR, which consists of the truncated transmembrane and extracellular portion of the EGFR protein. When targeted by the antibody Cetuximab, the receptor triggers apoptosis in the cell, providing a safety switch to protect against potential toxicity (68). Inducible caspase 9 (iC9) and HSV-TK are other common suicide genes that have been coexpressed with CARs.