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.

B7 family and their co-inhibitory receptors in T cells. Fig.1 B7 family and their co-inhibitory receptors in T cells. (Flem-Karlsen, 2020)

Function

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.

Reference

  1. Flem-Karlsen, K.; et al. B7-H3 immune checkpoint protein in human cancer. Current medicinal chemistry. 2020, 27(24): 4062-4086.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.