Table 2.

The comparison between the different CAR-armed cells

Variable	CAR-T cells	CAR-NK cells	CAR-NKT cells	Ref.
Features/ Population	• Express TCR. • Heterogeneous. • Cellular-immune system. • MHC-I/II-restricted. • Thymus-dependent.	• Lack TCR. • Homogenous. • Innate immune system. • Non-MHC restricted. • Has NCR (KIR and NKGD2).NK1.1+. • Thymus independent.	• Express αβTCR and NK cell markers. • Homogenous. • Innate immune system. • Recognize α-GalCer. • Non-MHC restricted. • TCR & CD1d restricted. • Thymus-dependent.	[8, 95, 101]
Cell sources	• Autologous PBMCs. • UCB (rarely). • iPSCs.	• PBMCs. • UCB. • hPSC/iPSCs. • NK cells line.	• PBMCs. • UCB. • hPSC/iPSCs.	[102, 103]
Function	Effector	Effector	Adjuvant	-
Preparation/ expansion	• Active with anti-CD3/CD28 beads. • Do not need to feeder cells.	• Enrichment magnetic T-cell depletion CD56+ selection. • Using of IL-2. • Do not need to feeder cell.	• Activation with α-GalCer-pulsed PBMCs. • Using of IL-2.	[104, 105]
Activation and cytotoxic manner	• TCR manages processed antigens with MHC content in intra-cellular. • Complete activation by costimulatory signals. • Inducing apoptosis.	• Performance by ADCC, perforin, and granzyme secretion. • Expression apoptosis-inducing ligands. • Cytotoxic function regulates by stimulatory and inhibitory signals. • Cytotoxicity without sensitization or HLA-matching.	• Ability to recognize and destroy CD1d+ cells. • Regulate the immune system and activation of other cells. • Activation is required for costimulatory signals.	[75, 106]
CARs action	• When armed with CAR, only work CAR-dependent. • Useless in losing tumor antigen.	• Cytotoxic property by dependent and independent CAR. • Activation by CAR without requiring stimulator/inhibitor signals.	• Cytotoxicity dependent and independent-CAR. • The indirect anti-tumor function.	[4, 107]
Side effects	• On target-off tumor. • CRS. • GVHD. • Neurotoxicity. • TLS.	• Lower GVHD. • Lower CRS. • Fever and fatigue.	• Maybe limit cytotoxicity ability. • Not reported anything in interim reports.	[108, 109]
Suicide gene required	Required for limiting on-target off-tumor.	Not be required.	Not be required commonly.	[67]
Pre/clinical functions	Very functional in pre/clinical evaluation.	Very functional in pre/clinical evaluation.	Very functional in pre/clinical evaluation.	[15, 95]
Off-the-shelf approach	Autologous cells needed the development of an allogeneic approach.	Potential off-the-shelf CAR-cell products.	Potential off-the-shelf CAR-cell products.	[110]
Primary Location	Tissue or blood.	Blood.	Tissue or blood.	[111]
Proliferation post-activation	Yes	No	Yes
Memory/ Persistence	Yes (αβ T)	No	Yes	[111]