Biology:CD276
 Generic protein structure example |
Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the CD276 gene.[1]
Structure
B7-H3 is a 316 amino acid-long type I transmembrane protein, existing in two isoforms determined by its extracellular domain. In mice, the extracellular domain consists of a single pair of immunoglobulin variable (IgV)-like and immunoglobulin constant (IgC)-like domains, whereas in humans it consists of one pair (2Ig-B7-H3) or two identical pairs (4Ig-B7-H3) due to exon duplication. B7-H3 mRNA is expressed in most normal tissues. In contrast, B7-H3 protein has a very limited expression on normal tissues because of its post-transcriptional regulation by microRNAs. However, B7-H3 protein is expressed at high frequency on many different cancer types (60% of all cancers). [2] The 4Ig-B7-H3 isoform is predominant in cancer.[3]
Function
In non-malignant tissues, B7-H3 has a predominantly inhibitory role in adaptive immunity, suppressing T cell activation and proliferation.
In malignant tissues, B7-H3 is an immune checkpoint molecule that inhibits tumor antigen-specific immune responses. B7-H3 also possesses non-immunological pro-tumorigenic functions such as promoting migration, invasion, angiogenesis, chemoresistance, epithelial-to-mesenchymal transition, and affecting tumor cell metabolism.[2]
As a possible drug target
Due to its selective expression on solid tumors, B7-H3 has been the target of several anticancer agents such as enoblituzumab (MGA271),[4] omburtamab, MGD009, MGC018, DS-7300a, and CAR T cells.[2][3] Nanobodies targeting the IgV and IgC domains of B7-H3 have been developed in the laboratory of Dr Mitchell Ho at the NCI, NIH (Bethesda, US). The nanobody-based CAR T cells are active in preclinical models of pancreatic cancer and neuroblastoma and show efficacy against large tumors in mice.[3]
See also
References
- ↑ "Entrez Gene: CD276 CD276 molecule". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80381.
- ↑ 2.0 2.1 2.2 "B7-H3: An Attractive Target for Antibody-based Immunotherapy". Clinical Cancer Research 27 (5): 1227–1235. March 2021. doi:10.1158/1078-0432.CCR-20-2584. PMID 33051306.
- ↑ 3.0 3.1 3.2 "Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours". Nature Communications 14 (1): 5920. September 2023. doi:10.1038/s41467-023-41631-w. PMID 37739951. Bibcode: 2023NatCo..14.5920L.
- ↑ "Servier Pays MacroGenics $20M for Option to Anticancer Antibody - GEN". December 2011. http://www.genengnews.com/gen-news-highlights/servier-pays-macrogenics-20m-for-option-to-anticancer-antibody/81246017/.
Further reading
- "B7-H3: An Attractive Target for Antibody-based Immunotherapy". Clinical Cancer Research 27 (5): 1227–1235. March 2021. doi:10.1158/1078-0432.CCR-20-2584. PMID 33051306.
- "B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production". Nature Immunology 2 (3): 269–274. March 2001. doi:10.1038/85339. PMID 11224528.
- "Characterization of mouse and human B7-H3 genes". Journal of Immunology 168 (12): 6294–6297. June 2002. doi:10.4049/jimmunol.168.12.6294. PMID 12055244.
- "Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss". Genomics 82 (3): 365–377. September 2003. doi:10.1016/S0888-7543(03)00126-5. PMID 12906861.
- "Molecular characterization of human 4Ig-B7-H3, a member of the B7 family with four Ig-like domains". Journal of Immunology 172 (4): 2352–2359. February 2004. doi:10.4049/jimmunol.172.4.2352. PMID 14764704.
- "Human recombinant B7-H3 expressed in E. coli enhances T lymphocyte proliferation and IL-10 secretion in vitro". Acta Biochimica et Biophysica Sinica 36 (6): 430–436. June 2004. doi:10.1093/abbs/36.6.430. PMID 15188059.
- "Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis". Proceedings of the National Academy of Sciences of the United States of America 101 (34): 12640–12645. August 2004. doi:10.1073/pnas.0405025101. PMID 15314238. Bibcode: 2004PNAS..10112640C.
- "B7-H3 promotes acute and chronic allograft rejection". European Journal of Immunology 35 (2): 428–438. February 2005. doi:10.1002/eji.200425518. PMID 15682454.
- "Constitutive and inducible expression of b7 family of ligands by human airway epithelial cells". American Journal of Respiratory Cell and Molecular Biology 33 (3): 280–289. September 2005. doi:10.1165/rcmb.2004-0129OC. PMID 15961727.
- "The immunomodulatory proteins B7-DC, B7-H2, and B7-H3 are differentially expressed across gestation in the human placenta". The American Journal of Pathology 167 (2): 465–473. August 2005. doi:10.1016/S0002-9440(10)62990-2. PMID 16049332.
- "B7-H3: another molecule marker for Mo-DCs?". Cellular & Molecular Immunology 2 (4): 307–311. August 2005. PMID 16274630.
- "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research 12 (2): 117–126. 2007. doi:10.1093/dnares/12.2.117. PMID 16303743.
- "Single-nucleotide polymorphisms in the B7H3 gene are not associated with human autoimmune myasthenia gravis". Journal of Genetics 85 (3): 217–220. December 2006. doi:10.1007/BF02935335. PMID 17406098.
External links
- CD276+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human CD276 genome location and CD276 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q8VE98 (CD276 antigen) at the PDBe-KB.
 |  |
