Tumor-associated antigen B7-H3 (B7-H3)

Tumor-associated antigen B7-H3 (CD276) is a type I transmembrane protein and member of the immunoglobulin superfamily predominantly functioning as an immune checkpoint molecule. In normal tissues, B7-H3 is expressed at low levels and mainly acts to regulate immune responses, often suppressing T-cell activation and proliferation. In malignancies, B7-H3 is widely overexpressed across many solid and hematologic tumors, correlating with poor clinical prognosis. B7-H3 modulates the tumor microenvironment by promoting immunosuppression, inducing polarization of tumor-associated macrophages to the pro-tumorigenic M2 phenotype, and contributing to tumor progression, metastasis, angiogenesis, and chemoresistance. Its largely cancer-restricted, high, and homogeneous expression makes B7-H3 an attractive candidate for targeted immunotherapies, including monoclonal antibodies, antibody-drug conjugates, and CAR T-cell therapies. While its role as a ligand in immune regulation is established, the physiological B7-H3 receptor remains unknown. Multiple preclinical and clinical studies are ongoing to explore and validate B7-H3 as a therapeutic target in oncology.

Other names

CD276B7 homolog 3B7H3B7-H3 ligand4Ig-B7-H3TAA B7-H3

Antibody-dependent cell-mediated cytotoxicity (ADCC); Complement-dependent cytotoxicity (CDC); Antibody-dependent cellular phagocytosis (ADCP); Immune checkpoint blockade (modulation of immune response); Direct cytotoxicity (via antibody-drug conjugates or CAR T-cell targeting)