Epidermal growth factor receptor and Programmed cell death protein 1 (EGFR/PD-1)

The dual target comprising the Epidermal Growth Factor Receptor (EGFR) and Programmed Cell Death Protein 1 (PD-1) represents a strategic approach to overcome resistance in solid tumor immunotherapy. EGFR is a transmembrane receptor tyrosine kinase that drives essential cellular processes such as proliferation and survival, and its overexpression or mutation is a primary oncogenic driver in non-small cell lung cancer (NSCLC) and head and neck cancers (UniProt P00533). PD-1 is a key immune checkpoint receptor on T cells that, when activated by its ligands, induces immune tolerance and allows tumors to escape T-cell mediated destruction (UniProt Q15116). Bispecific therapeutic agents, often constructed by fusing an EGFR-targeting single-chain variable fragment (scFv) to a PD-1 antibody, are designed to simultaneously disrupt tumor-promoting signaling and reactivate the local immune environment (PMID: 34153344). This dual-action mechanism is particularly promising for "cold" tumors that do not respond to PD-1/PD-L1 inhibitors alone, as the EGFR-binding component can help localize the checkpoint blockade to the tumor site, potentially increasing efficacy while minimizing systemic immune-related adverse events (PMID: 31430443).

Other names

EGFR-PD-1 bispecificPD-1/EGFR bispecificEGFR scFv-PD-1 fusion proteinPD-1 x EGFR

Simultaneous inhibition of EGFR-mediated signaling pathways and blockade of the PD-1/PD-L1 inhibitory checkpoint to enhance T-cell mediated anti-tumor activity.