B7-H3, also known as CD276, is a membrane protein belonging to the B7-CD28 family of immunomodulatory proteins that act as immune checkpoint molecules. B7-H3 is expressed at low levels in normal human tissues but is abnormally high in various tumors and cancers. It plays a critical role in tumor development, progression, and immune evasion, and its expression is associated with poor prognosis.
Studies have shown that B7-H3 is a co-stimulatory/co-inhibitory molecule that induces cellular immunity and promotes the secretion of cytokines IFN-γ, IL-8, and TNF-α. It enhances the cytotoxic effect of CD8+ T cells and inhibits Treg cells, thus avoiding tumor immune escape. The underlying mechanism involves signaling pathways through T cell surface receptors, including NFAT, NFkB, and AP-1 factors, but the signaling pathway and receptor of B7-H3 remain unidentified.
Due to its regulatory effect on the immune system and high expression in tumor cells, B7-H3 is a promising target for immunotherapy strategies. BCG001, an afucosylated monoclonal antibody developed in collaboration with Mabworks Biotech, has a higher affinity to tumor cells than enoblituzumab and shows more significant ADCC on tumor cells. The candidate molecule is more specific than enoblituzumab, as shown by negative B7-H3 cell line staining and membrane protein array analysis. It did not bind to any target other than B7-H3, indicating greater therapeutic efficacy and safety than enoblituzumab.
AACR 2023: *Novel Preclinical Candidates Targeting B7-H3, 6B5 and 10F7, Are Suitable for Development Into Various Drug Modalities