Cluster of Differentiation 276 (B7 homolog 3) (B7-H3 (CD276))

Cluster of Differentiation 276 (B7 homolog 3; B7-H3; CD276) is a 316-amino-acid type I transmembrane protein belonging to the B7 family of immune checkpoint molecules. It exists in two major isoforms, 2IgB7-H3 and 4IgB7-H3, based on the number of extracellular immunoglobulin-like domains; the 4Ig form predominates in humans and especially in cancer tissue. B7-H3 is encoded by the CD276 gene on human chromosome 15. Physiologically, it functions as a negative regulator in adaptive immunity, suppressing T cell activation. In cancer, B7-H3 acts as a key immune checkpoint ligand inhibiting tumor antigen-specific immune responses, supporting tumor cell proliferation, migration, invasion, angiogenesis, and resistance to therapy. Its high expression in a broad range of tumors and limited normal tissue expression have made it an attractive target for antibody-based therapies, CAR T cell therapies, and other immunotherapy modalities. Several agents targeting B7-H3 are in clinical development, and B7-H3 expression serves as a biomarker for patient selection and monitoring efficacy. Notable safety concerns include possible off-tumor toxicities and incomplete understanding of its full physiological roles.

Other names

B7-H3CD276Cluster of Differentiation 276B7 homolog 3

Antibody-dependent cell-mediated cytotoxicity (ADCC); Immune checkpoint blockade (enhancing antitumor T cell activity); Direct cytotoxicity via drug conjugates; CAR T cell-mediated tumor cell lysis; Disruption of B7-H3 ligand-mediated tumor-promoting signals