Table 2.

The strengths and weaknesses of various safety strategies of CAR-T cells

Safety strategy		Strengths	Weaknesses
Suicide switch	HSV-TK	1. powerful effect 2. extensive clinical experience	1. immunogenicity 2. clinical incompatibility 3. slow onset 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells
	iCasp9	1. no immunogenicity 2.clinical compatibility 2. rapid onset	1. no preventive effect for toxicity 2. premature eradication of CAR-T cells
	CD20	1. no immunogenicity 2. rapid onset	1. antibody biodistribution 2. on-target toxicity from antibody 3. prodrug infusion reaction 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells
	EGFRt	1. no immunogenicity 2. rapid onset 3. in vivo tracking	1. antibody biodistribution 2. on-target toxicity from antibody 3. prodrug infusion reaction 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells
Endogenous switch	synNotch	1. control the expression of the CARs 2. Specific recognition of tumor sites	1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult
	iCAR	1. antigen-selectively regulate T cell responses 2. protect normal tissue from CAR-T cells	1. uncontrolled activation of CAR-T cells 2. potential “on-target, off-tumor” effect
	Combinatorial Target-Antigen Recognition	1. precise killing of CAR-T cells 2. overcome antigen loss	1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult 3. potential “on-target, off-tumor” effect
Exogenous switch	Bispecific T Cell Engager	1. controlled activation of CAR-T cells 2. simplify manufacturing of CAR-T cells	1. The choice of small molecules needs more consideration
	On-switch CAR	1. controlled activation of CAR-T cells	1. The choice of small molecules needs more consideration