Table 1 Strategies to overcome challenges in translating CAR therapy to treat T cell malignancies

Fratricide

Targeting downregulated antigens (e.g., CD5)

[59]

Genome editing of target antigen

[45,46,47]

Targeting antigens with limited expression on T cells (e.g., CD30, CD37, TRBC1, CD1a)

[55,56,57,58]

Tet-OFF expression system

[48]

Protein expression blockers (PEBLs)

[49]

Using NK cells or NK-92 cells

[47, 51,52,53,54, 60]

T cell aplasia

Targeting antigens with limited expression on T cells (e.g., CD30, CD37, TRBC1, CD1a)

[55,56,57,58]

mRNA electroporation

Adeno-associated viral (AAV) vector delivery

Using NK cells or NK-92 cells

[47, 51,52,53,54, 60]

Using γδ T cells

Suicide genes and safety switches

Bridge to allogeneic hematopoietic stem cell transplant (HSCT)

Product contamination

Allogeneic CAR T cells with TRAC locus editing

[46, 61]

Using NK cells or NK-92 cells

[47, 51,52,53,54, 60]

Using γδ T cells