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

From: Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions

Challenge Strategy Reference
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