Definition

A bifunctional antibody fusion protein targeting both vascular endothelial growth factor (VEGF) and the pro-inflammatory cytokine human transforming growth factor beta (TGF-beta; TGFb), with potential antineoplastic activity. Upon administration, anti-VEGF/TGF-beta bispecific antibody fusion protein ZGGS18 targets, binds to and neutralizes both VEGF and TGF-beta. This prevents VEGF- and TGF-beta-mediated signaling and abrogates VEGF/VEGFR-induced angiogenesis and TGF-beta-mediated induction of VEGF, which further inhibits angiogenesis. It also inhibits TGF-beta-mediated immunosuppression, thereby enhancing anti-tumor immunity in the tumor microenvironment (TME) and promoting a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. VEGF is upregulated in a variety of cancer cell types and plays a crucial role in angiogenesis. TGF-beta, dysregulated in many types of cancer, plays a key role in immunosuppression in the TME, enhances tumor cell proliferation, and promotes cancer progression.