anti-c-Met/anti-TROP2/anti-CD3/anti-CD28 tetra-specific antibody MDX2001

A tetra-specific antibody targeting the tumor-associated antigens (TAAs) proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) and trophoblast cell surface protein 2 (trophoblast antigen 2; calcium signal transducer 2; TROP2; TROP-2; TACSTD2; GA733-1; M1S1), the T-cell surface antigen CD3, and the T-cell specific surface glycoprotein and co-stimulatory molecule CD28, with potential immunostimulating and antineoplastic activities. Upon administration, anti-c-Met/anti-TROP2/anti-CD3/anti-CD28 tetra-specific antibody MDX2001 targets and binds to both CD3 and CD28 on T cells, and c-Met and TROP2 expressed on tumor cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte (CTL) response against c-Met and/or TROP2-expressing tumor cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis. TROP-2 is a transmembrane protein overexpressed in various tumors. Its expression is associated with enhanced tumor aggressiveness, metastasis, drug resistance and increased tumor cell survival. The simultaneous binding of MDX2001 to two T-cell receptors (TCRs) and two TAAs may optimize T-cell function while preventing tumor antigen escape, and may result in an increased T-cell-mediated tumor cell killing as compared to antibodies that target one TCR and one TAA.