Figure 2.

Strategies to improve the safety (e.g., tumor-sensing strategies) as well as to augment the anti-tumor efficacy of CAR T cells are shown. Genetic engineering can be accomplished using viral (e.g., lentiviruses, retroviruses) and non-viral (e.g., CRISPR/Cas9) approaches to endow CAR T cells with gain-of-function or loss-of-function alterations. The overall aim of these approaches is to improve intrinsic T cell fitness and allow these cells to elicit optimal effector activity in the setting of several extrinsic barriers operative within solid tumors, as shown in Figure 1.