CiTE antibody for AML

In this issue of Blood, Herrmann et al¹ have developed a novel checkpoint inhibitory T-cell–engaging (CiTE) antibody for acute myeloid leukemia (AML) by fusing the extracellular domain of programmed cell death protein 1 (PD-1_ex) to a CD3 3 CD33 bispecific T-cell engager (BiTE; see figure panels A-B). Incorporation of the PD-1_ex domain increased human T-cell activation and led to efficient cytotoxicity against CD33¹/PD-L1¹ cells in vitro and in a murine xenograft model. Importantly, the PD-1_ex domain is not sufficient to redirect T cells to PD-L1¹ cells lacking the CD33 target. This preferential targeting of CD33¹/PD-L1¹ cells should reduce the immune-related adverse events associated with on-target/off-tumor effects of global checkpoint blockade with anti-PD1/PD-L1 monoclonal antibodies (mAbs).