Monoclonal antibodies against the receptor programmed cell death protein 1 (PD1) and its ligand PDL1 have shown impressive clinical activity in various cancers. However, the effectiveness of these antibodies is limited by poor tumour penetrance and immune cell depletion. Maute et al. engineer a non-antibody-biologic competitive antagonist of PDL1 — named HAC-PD1 — based on the PD1 ectodomain. Compared with PDL1-specific antibodies, HAC-PD1 exhibited enhanced tumour delivery without depleting peripheral effector T cells, resulting in superior antitumour efficacy in syngeneic mouse tumour models.