anti-EGFRvIII/CD3/PD-L1/4-1BB tetra-specific antibody GNC-039

A tetra-specific antibody directed against the tumor-associated antigen (TAA) and epidermal growth factor receptor (EGFR) mutant EGFR variant III (EGFRvIII), the T-cell surface antigen CD3, the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), and the immune co-stimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9), with potential immunostimulatory and antineoplastic activities. Upon administration, anti-EGFRvIII/CD3/PD-L1/4-1BB tetra-specific antibody GNC-039 targets and binds to EGFRvIII, CD3, 4-1BB and PD-L1. The binding of GNC-039 to EGFRvIII expressed on tumor cells and CD3 expressed on T-cells may crosslink EGFRvIII-expressing tumor cells and cytotoxic T-lymphocytes (CTLs) and result in a potent CTL-mediated cell lysis of EGFRvIII-expressing tumor cells. In addition, the binding of GNC-039 to 4-1BB expressed on a variety of leukocyte subsets including activated T-lymphocytes results in T-cell co-stimulation and enhanced anti-tumor activity. At the same time, GNC-039 binds to PD-L1 and prevents PD-L1 from binding to and activating its receptor, programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances CTL-mediated tumor cell lysis, which may lead to a reduction in tumor growth. PD-L1 binding to PD-1 on activated T-cells inhibits the expansion and survival of CD8-positive T-cells, suppresses the immune system and results in immune evasion. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity. EGFRvIII, a mutant form of EGFR expressed in certain tumor cell types, plays a key role in tumor cell proliferation and survival.