Disease relapse in paediatric patients with B cell acute lymphoblastic leukaemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cells is generally associated with loss of CAR T cell persistence and/or loss of CD19 expression. To overcome this limitation, several sequential or combinatorial approaches using CD22-targeted CAR T cells have been tested; however, responses are usually not durable. Now, data from a phase II trial reveal that co-administration of CD19-targeted and CD22-targeted CAR T cells is safe and effective in relapsed and/or refractory (R/R) B-ALL.