Definition

A T-cell engaging bispecific antibody and Conditional Bispecific Redirected Activation (COBRA) protein targeting both the tumor-associated antigen (TAA) epidermal growth factor receptor (EGFR; HER1; ErbB1) and the T-cell surface antigen CD3, and containing a protease cleavable linker and a human serum albumin (HSA) binding part, with potential immunostimulating and antineoplastic activities. Upon administration, EGFR/CD3-targeting T-cell engaging molecule TAK-186 is cleaved by proteases in the tumor microenvironment (TME). Upon cleavage, TAK-186 dimerizes to form the active molecule and binds to both CD3 on cytotoxic T lymphocytes (CTLs) and EGFR on EGFR-expressing tumor cells. This activates and redirects CTLs to EGFR-expressing tumor cells, leading to CTL-mediated killing of EGFR-expressing tumor cells. EGFR, upregulated and/or mutated in a variety of tumor cell types, plays a key role in tumor cell proliferation. The albumin-binding domain targets and binds to serum albumin, thereby extending the serum half-life of the inactivated TAK-186. Upon cleavage of the HSA-binding component, the activated TAK-186 dimer will be eliminated after cancer cell killing; this improves the safety profile of this agent by reducing its ability to cause damage to healthy cells.