Interestingly, the authors have shown that CAR-T cells with the two-step recognition circuit efficiently killed spheroids of HER-2-high tumour cells, kept some killing activity on proximal HER-2-low spheroids but lost this killing activity on more distant HER-2-low cells.1 This characteristic is beneficial as it enables killing of tumour variant with lower target antigen expression in the tumour microenvironment, while sparing more distal cells with low levels of the same target antigen. This evidence concerns the gene ERBB2 and neoplasm.