Definition

An anti-ROR1/anti-CD3/anti-PD-L1/anti-4-1BB tetra-specific antibody, with potential immunostimulatory and antineoplastic activities. Upon administration, nebratamig targets and binds to the tumor-associated antigen (TAA) receptor tyrosine kinase-like orphan receptor 1 (ROR1), the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) expressed on tumor cells, the T-cell surface antigen CD3 and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) expressed on a variety of leukocyte subsets including activated T lymphocytes. This may crosslink ROR1-expressing tumor cells and cytotoxic T lymphocytes (CTLs) and result in a potent CTL-mediated cell lysis of ROR1-expressing tumor cells. In addition, 4-1BB binding results in T-cell co-stimulation and enhanced anti-tumor activity. At the same time, GNC-035 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. ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is expressed during embryogenesis and in many types of hematological malignancies. It plays key roles in tumor cell proliferation and survival.