Anti-CD19 Orexi CAR T cells, secreting a CD47-SIRPα checkpoint inhibitor (CV1), potentiate antibody-mediated (anti-CD20; rituximab) tumor cell lysis via enhancing macrophage-mediated ADCP/ADCC. On administration of anti-CD19 Orexi CAR T cells and therapeutic anti-CD20 mAb rituximab, anti-CD19 CAR engages CD19 on the tumor cell surface (1). Local CV1 secretion by Orexi CAR T cells is enhanced because of CAR stimulation by CD19-positive tumor cells (2). CV1 binds to CD47 expressed by tumor cells and blocks the signaling pathway between inhibitory SIRPα on macrophages and tumor-CD47, enabling increased macrophage-mediated ADCP/ADCC (3). Overall, this synergistic approach of combining CAR T-cell therapy, local CD47 blockade, and mAb therapy results in increased tumor cell lysis (4). Figure created with BioRender.com.