An engineered PD1-Fc fusion produced in N. benthamiana plants efficiently blocks PD1/PDL1 interaction

• DOI: 10.1007/s00299-025-03475-0
• Publication Date: 2025-03-23T09:49:27Z
• Authors: Shiva Izadi; Rafaela Abrantes; Simon Gumpelmair; Vinny Kunnummel; Henrique O. Duarte; Peter Steinberger; Celso A. Reis; Alexandra Castilho
• Keywords: Ectodomain; Immune checkpoint; Fc receptor; Blocking antibody; Cancer Immunotherapy

Abstract Key message Plant-made PD1–Fc fusions engineered for optimized glycosylation and Fc-receptor engagement are highly efficient in blocking PD1/PDL1 interactions can be cost-effective alternatives to antibody-based immune checkpoint inhibitors. Immune inhibitors (ICIs) antibodies receptors that have pivotal roles during T-cell activation processes. The programmed cell death 1 (PD1) regarded as the primary targeting PD1 or its ligand PDL1 revolutionized immunotherapy of cancer. However, majority patients fail respond, treatment resistance well immune-related adverse events commonly associated with this therapy. Alternatives ICIs pathway may bear potential overcome some these shortcomings. Here, we used a plant expression platform based on tobacco relative Nicotiana benthamiana generate immunoglobulin fusion proteins harboring wild type an affinity-enhanced ectodomain. We exploited versatility our system variants differed regarding their profile capability engage Fc-receptors. Unlike wild-type counterpart, versions showed strongly augmented capabilities both protein- cell-based assays. Moreover, contrast clinical antibodies, binding is not affected by status PDL1. Importantly, could demonstrate plant-made inhibitory signaling T reporter assay. Taken together, study highlights utility plant-based protein biologics therapeutic potential. Targeting derived reduce overstimulation therapies while retaining favorable features such long serum half-life.