Definition

A trispecific antibody targeting the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), human vascular endothelial growth factor (VEGF) and human transforming growth factor beta (TGF-beta), with potential immune checkpoint inhibitory, anti-angiogenic and antineoplastic activities. Upon administration, anti-PD-L1/VEGF/TGF-beta trispecific antibody DR30206 targets and simultaneously binds to both PD-L1 and VEGF expressed on tumor cells, and also neutralizes TGF-beta. This prevents both TGF-beta- and PD-L1-mediated immuno-suppressive pathways signaling, which increases natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activities, restores and enhances anti-tumor responses, and inhibits tumor cell proliferation in susceptible tumor cells. The binding of DR30206 to VEGF prevents the binding of VEGF to its receptor VEGFR, abrogates VEGF/VEGFR-mediated signaling and may lead to the inhibition of vascular endothelial cell proliferation. The inhibition of tumor angiogenesis may further decrease tumor cell proliferation and prevent metastasis. VEGF is overexpressed in a variety of cancers and is associated with increased invasiveness and decreased survival. TGF-beta and PD-L1 are both upregulated in certain types of cancers; their overexpression is associated with increased evasion of immune surveillance and contributes to poor prognosis.