anti-PD-1 mAb3 × R9E:R76A

Anti-PD-1 mAb3 × R9E:R76A is an experimental bifunctional immunocytokine developed by Amgen. It consists of a bivalent anti-PD-1 monoclonal antibody (mAb3) fused to a highly attenuated interleukin-21 (IL-21) cytokine mutein containing dual amino acid substitutions (R9E and R76A). The drug is designed to simultaneously block the PD-1/PD-L1 inhibitory checkpoint pathway and deliver IL-21-mediated immune stimulation directly to PD-1-expressing T cells (cis-targeting). The R9E and R76A mutations significantly reduce the cytokine's affinity for the IL-21 receptor (IL-21R), which minimizes off-target activation of bystander cells such as dendritic cells and improves the serum half-life. In preclinical studies, this fusion protein demonstrated superior anti-tumor activity and enhanced CD8+ T cell effector function compared to anti-PD-1 monotherapy, particularly in models refractory to standard checkpoint inhibition.

Other names

anti-PD-1-IL21 mutein fusion proteinanti-PD1-IL21 mutein fusion proteinanti-PD 1-IL21 mutein fusion proteinPD-1-targeted IL-21 R9E:R76A monomeranti-PD-1 mAb3 x R9E:R76A fusion protein monomer