Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the CD276 gene.[5]

CD276
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCD276, 4Ig-B7-H3, B7-H3, B7H3, B7RP-2, CD276 molecule
External IDsOMIM: 605715; MGI: 2183926; HomoloGene: 11892; GeneCards: CD276; OMA:CD276 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001024736
NM_025240
NM_001329628
NM_001329629

NM_133983

RefSeq (protein)

NP_001019907
NP_001316557
NP_001316558
NP_079516

NP_598744

Location (UCSC)Chr 15: 73.68 – 73.71 MbChr 9: 58.43 – 58.46 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

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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). [6] The 4Ig-B7-H3 isoform is predominant in cancer.[7]

Function

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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.[6]

As a possible drug target

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Due to its selective expression on solid tumors, B7-H3 has been the target of several anticancer agents such as enoblituzumab (MGA271),[8] omburtamab, MGD009, MGC018, DS-7300a, and CAR T cells.[6][7] Nanobodies targeting the IgV and IgC domains of B7-H3 have been developed in the laboratory of 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.[7]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000103855Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035914Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: CD276 CD276 molecule".
  6. ^ a b c Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, Ferrone S (March 2021). "B7-H3: An Attractive Target for Antibody-based Immunotherapy". Clinical Cancer Research. 27 (5): 1227–1235. doi:10.1158/1078-0432.CCR-20-2584. PMC 7925343. PMID 33051306.
  7. ^ a b c Li D, Wang R, Liang T, Ren H, Park C, Tai CH, et al. (September 2023). "Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours". Nature Communications. 14 (1): 5920. Bibcode:2023NatCo..14.5920L. doi:10.1038/s41467-023-41631-w. PMC 10517151. PMID 37739951.
  8. ^ "Servier Pays MacroGenics $20M for Option to Anticancer Antibody - GEN". GEN. December 2011.

Further reading

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