Although clinical trials in ALL patients treated with CD28- or 4-1BB-co-stimulated CD19-specific CAR-T cells revealed comparable initial response rates, CAR-T cells with 4-1BB co-stimulatory domains appear to outperform those with CD28 in terms of clinical efficacy in CLL trials (29, 30). The gene discussed is CD28; the disease is B-cell chronic lymphocytic leukemia.