CD276 (B7-H3) (B7-H3)

CD276, widely known as B7-H3, is a type I transmembrane glycoprotein and a member of the B7 family of immunoregulatory proteins (UniProt Q5ZPR3). It functions as an immune checkpoint molecule that predominantly inhibits T-cell activation and proliferation, thereby playing a critical role in tumor immune evasion (PubMed: 31100115). While B7-H3 mRNA is found in various normal tissues, the protein expression is highly restricted in healthy cells but significantly upregulated in a broad spectrum of solid tumors, including lung, prostate, and breast cancers. This differential expression pattern correlates with advanced disease stage, increased metastasis, and poor clinical prognosis, making it a highly attractive therapeutic target. HS-20093 (also known as GSK5764227) is an investigational antibody-drug conjugate (ADC) that specifically targets B7-H3 to deliver a potent topoisomerase I inhibitor payload directly to malignant cells (ClinicalTrials.gov: NCT05276609). By binding to the B7-H3 antigen on the tumor surface, the ADC is internalized, releasing the cytotoxic agent and inducing DNA damage and cell death. Beyond ADCs, B7-H3 is being explored as a target for monoclonal antibodies, CAR-T cell therapies, and bispecific antibodies, aiming to overcome the immunosuppressive microenvironment of refractory solid tumors (GSK Press Release, 2023).

Other names

CD276 antigenB7 homolog 34Ig-B7-H32Ig-B7-H3Costimulatory molecule

Antibody-drug conjugate (ADC) mediated delivery of cytotoxic payloads (e.g., topoisomerase I inhibitors); Antibody-dependent cellular cytotoxicity (ADCC); Blockade of co-inhibitory signaling to restore T-cell activity.