. 2019 Mar 14;20(6):1283. doi: 10.3390/ijms20061283

Table 1.

Summary of the various approaches employed to regulate CAR T cell activity, and to enhance their selectivity and killing potential.

Aim	Modulation	Approaches
Enhancing selectivity	Simultaneous targeting of multiple antigens	Tandem CAR [130]
	Simultaneous targeting of multiple antigens	iCAR (inhibitory CAR) [129]
	scFv modulation	Fine-tune scFv affinities [113]
	Inducible CARs	synNotch CAR [124]
Enhancing killing potential	Co-stimulatory domains	JAK-STAT CAR [82]
	Co-stimulatory domains	3rd generation ICOS CAR [128]
	Cytokine production	TRUCK system [86]
	Checkpoint Blockade	Secretion of PD-1 scFv [125]
	Targeted delivery of CAR cDNA to disrupt a locus	CRIPSR guided to Fas, endogenous TCR, PD-1, and LAG-3 [131,132,133]
	Targeted delivery of CAR cDNA to disrupt a locus	TALEN-mediated multi-drug resistant CARs [134]
	Immune cell recruitment	7 × 19 CAR (co-expressing IL-7 and CCL 19) [126]
Regulating activity	Suicide Gene	Inducible Caspase9 [135]
	Suicide Gene	Antibody-mediated depletion via marker antigen [43]
	Switchable CAR	Tumor targeting anti- or nanobody (UniCAR, SUPRA CAR) [85,136]
	Switchable CAR	Dimerization through small molecules [137]