Definition

A T-cell engaging bispecific antibody and Conditional Bispecific Redirected Activation (COBRA) protein targeting both the tumor-associated antigen (TAA) and immunoregulatory protein B7-homologue 3 (B7-H3, CD276) and the T-cell surface antigen CD3, with potential immunostimulating and antineoplastic activities. Upon intravenous administration, B7H3/CD3-targeting T-cell engaging molecule TAK-280 is cleaved by proteases in the tumor microenvironment (TME). Upon cleavage, TAK-280 is activated and binds to both CD3 on cytotoxic T lymphocytes (CTLs) and B7H3 on B7H3-expressing tumor cells. This activates and redirects CTLs to B7H3-expressing tumor cells, leading to a CTL-mediated killing of B7H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis.