c-Met-targeting tri-specific natural killer cell engager ABBV-303

An engineered immune modulating agent based on tri-specific natural killer (NK) cell engager therapy (TriNKET) that is targeting c-Met (hepatocyte growth factor receptor; HGFR), with potential immunostimulating and antineoplastic activities. Upon administration, c-Met-targeting tri-specific NK cell engager ABBV-303 targets and binds to c-Met on tumor cells and simultaneously binds to NK cells via the receptors CD16 and NKG2D (natural killer group 2D; killer cell lectin-like receptor K1; KLRK1), thereby bringing c-Met-expressing tumor cells and NK cells together. This activates NK cells and results in the selective NK cell-mediated killing of c-Met-expressing tumor cells. In addition, the NK cells activate T and B cells, and enhance a cytotoxic T-lymphocyte (CTL)-mediated immune response against c-Met-expressing tumor cells. C-Met, a receptor tyrosine kinase that is overexpressed or mutated in many tumor cell types, plays a key role in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis. Its expression is associated with poor prognosis in many tumor types.