The major challenges of CAR-T therapy in T-cell malignancies. (A) Fratricide, in which CAR-T expressing the target antigen are “self killed” by fellow CAR-T. (B) T-cell aplasia, in which normal T cells that also express the target antigen are killed by the CAR-T in “on-target, off-tumor” toxicity. (C) Product contamination, the risk that T lymphoblasts contaminate the final CAR-T product.