Definition

An antibody-drug conjugate (ADC) composed of a human immunoglobulin (Ig) G1 monoclonal antibody directed against the T-cell checkpoint ligand B7-H4 (V-set domain-containing T-cell activation inhibitor 1; VTCN1; B7x; B7S1) linked to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), via a protease-cleavable peptide linker, with potential antineoplastic activity. Upon administration of anti-B7-H4 ADC SGN-B7H4V, the anti-B7-H4 monoclonal antibody moiety targets and binds to B7-H4 expressed on tumor cells. Upon binding, internalization and linker cleavage, MMAE binds to tubulin and inhibits tubulin polymerization, which results in G2/M phase arrest and apoptosis specifically in B7-H4-expressing tumor cells. B7-H4, a member of the B7 family of immune modulators, is upregulated in a variety of tumor cell types and tumor-associated macrophages (TAMs). It negatively regulates T-cell immune responses. In addition, SGN-B7H4V may also kill B7-H4-expressing tumor cells through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).