Downregulation of the CD19 antigen in patients with B cell malignancies is a common mechanism of relapse following anti-CD19 CAR-T cell therapy. Now, Shah et al. report on the first-in-human trial of bispecific anti-CD20, anti-CD19 CAR-T cells in patients with refractory B cell non-Hodgkin lymphoma or chronic lymphocytic leukaemia. In 22 patients, infusion of the bispecific CAR-T cells at a dose of 2.5 × 10⁶ cells per kg achieved a favourable toxicity profile and high efficacy. The overall response rate at day 28 was 82%, with 14 patients achieving a complete remission and 4 exhibiting evidence of progressive disease. Notably, those patients who experienced therapy failure or relapse all retained CD19 expression.