anti-programmed cell death protein 1 + anti-vascular endothelial growth factor + interleukin-21 variant tri-specific fusion protein

αPD-1/αVEGF/IL-21v is a novel tri-specific fusion protein designed to overcome resistance to immune checkpoint inhibitors (ICIs) by simultaneously targeting three pathways within the tumor microenvironment (TME). It consists of an anti-PD-1 component to sustain T cell activation, an anti-VEGF component to normalize tumor vasculature and enhance the recruitment of tumor-infiltrating lymphocytes (TILs), and an engineered interleukin-21 variant (IL-21v). The IL-21v is specifically designed to minimize peripheral toxicity while selectively promoting the expansion and differentiation of effector and memory CD8+ T cells within the TME. Preclinical studies indicate that this tri-specific construct induces PD-1-dependent STAT3 activation with high selectivity for PD-1+ cells, leading to superior antitumor efficacy and long-lasting immunity in ICI-resistant models compared to PD-1/VEGF bispecific therapies.

Other names

αPD-1/αVEGF/IL-21v tri-specific fusion protein