Table 4.

Challenges of CAR-T therapy against T-ALL and strategies to overcome the challenges.

Challenge	Strategy	Target Antigen Studied	Reference
Fratricide	Genetic editing of target antigen	CD3, CD7	[56,59]
	Protein expression blocker (PEBL)	CD7	[57]
	Tet-Off inducible expression system	CD5	[58]
	Using CD8+ T cells only	CD4	[60]
	Using CAR-NK cells	CD3, CD4, CD5, CD7	[71,72,73,74]
Potential contamination of autologous products	Allogeneic CAR-T cells with TCR editing	CD7	[61]
	Using CAR-NK cells	CD3, CD4, CD5, CD7	[71,72,73,74]
Prolonged T cell aplasia	Safety switch	CD4	[60]
	Using CAR-NK cells	CD3, CD4, CD5, CD7	[71,72,73,74]