A new CAR takes a test drive in DLBCL

In this issue of Blood, Roddie et al report results from the phase 1 ALEXANDER trial using a novel bicistronic anti-CD19 and anti-CD22 dual-targeted autologous chimeric antigen receptor (CAR) T-cell product, AUTO3, in combination with pembrolizumab, as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphomas (LBCLs).(1) Currently available CAR T cells directed at the single CD19 antigen produce durable remissions in approximate to 40% of patients with relapsed/refractory LBCL as third-line or later therapy,(2,3) so most patients will progress despite access to this major treatment advance. Targeting a second tumor antigen with the same CAR T cell represents a novel and appealing strategy to try to overcome a mechanism of resistance and enhance efficacy.