Cluster of differentiation 276 (CD276) (CD276)

Cluster of differentiation 276 (CD276), also known as B7-H3, is a type I transmembrane protein belonging to the B7 family of immune checkpoint molecules (UniProt Q5ZPR3). While CD276 mRNA is widely expressed across various tissues, the protein expression in normal, non-malignant tissues is generally low and restricted to specific sites such as the liver, adrenal glands, and prostate (PMID: 31110040). In contrast, CD276 is significantly overexpressed in many solid tumors, including neuroblastoma, melanoma, and carcinomas of the lung and breast, where it is associated with tumor progression and poor clinical outcomes (PMID: 33500230). It functions primarily as an immunomodulatory molecule, often exerting inhibitory effects on T-cell activation and proliferation, thereby facilitating tumor immune evasion. Therapeutic strategies targeting CD276 include monoclonal antibodies like enoblituzumab, which utilizes antibody-dependent cellular cytotoxicity (ADCC), and antibody-drug conjugates (ADCs) like ifinatamab deruxtecan that deliver potent cytotoxics directly to tumor cells. The presence of CD276 on normal tissues, albeit at lower levels, remains a critical safety consideration for on-target, off-tumor toxicity in the development of high-potency agents like CAR-T cells and ADCs.

Other names

B7-H3B7 homolog 34Ig-B7-H3B7RP-2Costimulatory molecule

Antibody-dependent cellular cytotoxicity (ADCC), Antibody-drug conjugate (ADC) mediated delivery of cytotoxic payloads, and CAR-T cell-mediated targeted cell lysis.