Table 1.

Resistance mechanisms to CD19 and CD22 CAR-T cells.

	Proposed Mechanism	Ref.
T-Cell Failure
Production failure	Failure of T-cell expansion and transduction in culture
Primary T-cell failure	Low memory/stem-cell memory T cells in the leukapheresis	[21]
	Lack of multi-cytokine producing cells	[22]
	Increased exhaustion of cells	[21,23–25]
	Increased regulatory T cells	[26]
Secondary T-cell failure	Nature of the costimulatory domain	[27,28]
	Anti-CAR immune response	[10,13]
	Suppressive microenvironment in extramedullary leukemia	[15,29]
Target Antigen Modulation
Loss of CD19 expression	Mutations in CD19	[30,31]
	Splice variants of CD19	[30]
	Lineage switch to myeloid leukemia	[32–35]
	Defective trafficking to the cell membrane	[36]
	Leukemia transduction by CAR masking CD19 expression	[37]
CD22 down modulation	Unknown posttranscriptional effects	[7]

Abbreviation: CAR-T cells: chimeric-antigen receptor expressing T cells.