CD276, also known as B7 homolog 3 protein (B7-H3), is a member of the B7 superfamily and acts as an immune checkpoint molecule and a costimulatory/coinhibitory immunoregulatory protein1. CD276 influences innate and adaptive immunity, regulates the aggressiveness of cancer cells, and is thought to play an important role in tumor development and cancer immunity. CD276 has been studied in many cancers, including breast, lung, ovarian, brain, gastric, and squamous cell carcinoma.
Human CD276 exists as either a soluble isoform or as a ~45–66 kDa type I transmembrane protein that is composed of an extracellular domain, a transmembrane domain, and a short intracellular domain1. In murine CD276, the extracellular domain is composed of a single pair of immunoglobulin variable and constant domains. Soluble CD276 is produced by cleavage from the cell surface or via alternative intron splicing and has been found in the secretomes of exosomes and other extracellular vesicles.
In normal human tissues, CD276 mRNA is widely and abundantly expressed but protein abundance is low1. miR-124 is thought to cause translational repression of CD276 by targeting its 3’-UTR, while other miRNAs are known to affect CD276 expression. In contrast, in tumor cells, CD276 mRNA and protein are abundant, and its presence is correlated with worsened prognosis, poor survival, recurrence rate, and enhanced invasive and migratory properties. CD276 blocking with monoclonal antibodies has been shown to reduce tumor growth and prolong survival in mouse models of various cancers. TREM-like transcript 2 (TLT-2) has been identified as a potential receptor2.
MJ18 was generated by immunizing Sprague Dawley rats with aa 1–242 of mouse CD276 extracellular domain linked to the Fc portion of mouse IgG2a3. After immunization, lymph node cells were fused with P3U1 myeloma cells, hybridomas were selected by flow cytometry, and MJ18 was purified from ascites.
