CD276 (B7-H3), 4Ig isoform (B7-H3)

B7-H3 (CD276) is a type I transmembrane glycoprotein and a member of the B7 family of immune regulatory proteins [1.3.2]. The 4Ig isoform is the predominant form found in humans, characterized by an extracellular domain containing four immunoglobulin-like domains (two pairs of IgV-IgC) resulting from an exon duplication [1.2.1, 1.2.4]. While its physiological role remains partially elusive, it is widely recognized as an immune checkpoint molecule that primarily exerts co-inhibitory effects on T-cell responses, thereby facilitating tumor immune evasion [1.1.1, 1.3.2]. B7-H3 is significantly overexpressed in numerous solid tumors—including lung, prostate, breast, and ovarian cancers—as well as in the tumor vasculature, while maintaining very limited expression in normal tissues [1.2.5, 1.3.3]. This differential expression makes the 4Ig isoform an attractive target for various therapeutic modalities, such as antibody-drug conjugates (ADCs), monoclonal antibodies, and CAR-T cell therapies [1.3.2, 1.3.3]. Clinical development of B7-H3-targeted agents, such as ifinatamab deruxtecan and enoblituzumab, aims to exploit its role in promoting tumor proliferation, metastasis, and resistance to therapy to improve patient outcomes in advanced malignancies [1.3.3, 1.3.5].

Other names

CD276B7 homolog 3B7H34Ig-B7-H3B7-H3b

Antibody-dependent cellular cytotoxicity (ADCC), delivery of cytotoxic payloads via antibody-drug conjugates (ADCs), T-cell redirection and activation (bispecific antibodies and CAR-T cells), and radioligand-mediated cell death [1.3.2, 1.3.3, 1.4.1].