B7-H3 Immune Checkpoint Molecule for Drug Development
Introduction to B7-H3
B7-H3, also known as CD276, belongs to the B7 family of immune checkpoint proteins. B7-H3 is a transmembrane protein expressed on the surface of different kinds of cells such as antigen-presenting cells (APCs), natural killer cells (NKs), tumor endothelial cells. B7-H3 can also be present in intra- and extracellular vesicles. Besides, B7-H3 may be present as circulating soluble isoforms in serum and other body fluids. Human B7-H3 exists as three isoforms containing: two Ig-like soluble isoforms (sB7-H3), two IgV- and two IgC-domains (4IgG B7-H3), and one IgV- and one IgC-domain (2IgG B7-H3). Among them, the 4IgG B7-H3 isoform is the predominant form in humans. It consists of a heavily N-linked glycosylated type 1 transmembrane protein of 534 amino acids with an apparent molecular weight (MW) around 100 kDa.
Fig.1 B7 family and their co-inhibitory receptors in T cells. (Flem-Karlsen, 2020)
B7-H3 is recognized as a co-stimulatory molecule for immune reactions such as T cell activation and IFN-γ production. Besides its immunoregulatory role, B7-H3 has intrinsic pro-tumorigenic activities related to enhanced cell proliferation, migration, invasion, angiogenesis, metastatic capacity, and anti-cancer drug resistance. B7-H3 has also been found to regulate key metabolic enzymes, promoting the high glycolytic capacity of cancer cells. However, B7-H3 receptors are still not identified, and little is known about the molecular mechanisms underlying B7-H3 functions.
Immunotherapy Targeting B7-H3
B7-H3 is overexpressed in a variety of tumor types cancers, including breast, pancreatic, hepatocellular, renal, lung, and colorectal cancer, but the limited expression in normal tissues. Thus, it is a promising new immunotherapy target for anti-cancer immune response and a potential biomarker.
Different anti-B7-H3 approaches have been studied in preclinical or clinical trials. Anti-B7-H3 monoclonal antibodies (mAbs) have been studied with promising results. Several antibody-drug conjugates (ADCs) have shown effective selective destruction of tumor vasculature in multiple tumor xenografted models. Moreover, anti-B7-H3 CAR-T cell therapy exhibits potent efficacy in preclinical models of tumors, including pediatric tumors, glioblastoma, melanoma, and hematologic malignancies.
Studies have provided strong evidence for the value of B7-H3 as a target in immune-based antitumor therapies since its overexpression across various cancer cells but seldom in normal cells. Verification of the receptor for B7-H3 and better elucidation of the B7-H3 pathway in immune response and cancer development is crucial and may help provide the rationale for the therapeutic application of anti-B7-H3 agents. Creative Biolabs offers a comprehensive set of immune checkpoint molecule research services for worldwide clients to support your project. For any questions, please do not hesitate to contact us for more information.
Flem-Karlsen, K.; et al. B7-H3 immune checkpoint protein in human cancer. Current medicinal chemistry. 2020, 27(24): 4062-4086.
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