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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 1 | 534 | 15q24.1 | CD276 | CD276 molecule | 11 |
| Mouse | 1 | 316 | 9 B | Cd276 | CD276 antigen | 11 |
| Rat | 1 | 316 | 8q24 | Cd276 | Cd276 molecule | |
| Gene and Protein Information Comments | ||||||
| Multiple transcript variants and protein isoforms are produced from the human gene. Human B7-H3b (an isoform with four Ig-like domains that results from gene duplication and differential splicing) is the major isoform expressed in several tissues [11]. | ||||||
| Database Links |
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| Alphafold | Q5ZPR3 (Hs), Q8VE98 (Mm), Q7TPB4 (Rn) |
| CATH/Gene3D | 2.60.40.10 |
| ChEMBL Target | CHEMBL3712879 (Hs) |
| Ensembl Gene | ENSG00000103855 (Hs), ENSMUSG00000035914 (Mm), ENSRNOG00000033608 (Rn) |
| Entrez Gene | 80381 (Hs), 102657 (Mm), 315716 (Rn) |
| Human Protein Atlas | ENSG00000103855 (Hs) |
| KEGG Gene | hsa:80381 (Hs), mmu:102657 (Mm), rno:315716 (Rn) |
| OMIM | 605715 (Hs) |
| Pharos | Q5ZPR3 (Hs) |
| RefSeq Nucleotide | NM_001024736 (Hs), NM_133983 (Mm), NM_182824 (Rn) |
| RefSeq Protein | NP_001019907 (Hs), NP_598744 (Mm), NP_877976 (Rn) |
| UniProtKB | Q5ZPR3 (Hs), Q8VE98 (Mm), Q7TPB4 (Rn) |
| Wikipedia | CD276 (Hs) |
Download all structure-activity data for this target as a CSV file 
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| Antibody Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| A radio-iodinated monoclonal called [131I]-omburtomab (humanized from a mouse monoclonal designated 8H9) [1,9] that targets B7-H3 expressing cancer cells is being developed by Y-mAbs Therapeutics. It has been granted FDA breakthrough therapy designation for pediatric relapsed/refractory metastatic neuroblastoma with central nervous system or leptomeningeal metastasis. A Phase 2/3 clinical trial (NCT03275402) in neuroblastoma is underway (as of March 2019). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| B7-H3 is an immunoregulatory receptor involved in T cell activation and IFN-γ production [5-6]. B7-H3 is primarily expressed on the cell membranes of solid tumours, with limited expression by normal tissues [3]. It is reported to protect cancer cells from NK cells effector functions [2,4]. B7-H3 is an actively pursued immuno-oncology molecular target [3,12]. Anti-BH-73 assets in clinical pipelines include: Omburtamab (phase 2; Y-Mabs Therapeutics) Enoblituzumab (MGA271; Phase 2; Macrogenics) Orlotamab (MGD009, CD3/B7-H3 bispecific; Phase 1; Macrogenics) and preclinical leads MGC018 (ADC; Macrogenics), DS-7300 (ADC; Daiichi Sankyo), HuB7-H3 and omburtamab-DTPA (Y-Mabs Therapeutics). |
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| General Comments |
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B7-H3 is a molecular target for oncology drug development [8,10]. This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590. |
1. Ahmed M, Cheng M, Zhao Q, Goldgur Y, Cheal SM, Guo HF, Larson SM, Cheung NK. (2015) Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3. J Biol Chem, 290 (50): 30018-29. [PMID:26487718]
2. Bottino C, Dondero A, Bellora F, Moretta L, Locatelli F, Pistoia V, Moretta A, Castriconi R. (2014) Natural killer cells and neuroblastoma: tumor recognition, escape mechanisms, and possible novel immunotherapeutic approaches. Front Immunol, 5: 56. [PMID:24575100]
3. Calabrò L, Sigalotti L, Fonsatti E, Bertocci E, Di Giacomo AM, Danielli R, Cutaia O, Colizzi F, Covre A, Mutti L et al.. (2011) Expression and regulation of B7-H3 immunoregulatory receptor, in human mesothelial and mesothelioma cells: immunotherapeutic implications. J Cell Physiol, 226 (10): 2595-600. [PMID:21792917]
4. Castriconi R, Dondero A, Augugliaro R, Cantoni C, Carnemolla B, Sementa AR, Negri F, Conte R, Corrias MV, Moretta L et al.. (2004) Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci USA, 101 (34): 12640-5. [PMID:15314238]
5. Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, Dong H, Sica GL, Zhu G, Tamada K et al.. (2001) B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol, 2 (3): 269-74. [PMID:11224528]
6. Dong C, Nurieva RI, Prasad DV. (2003) Immune regulation by novel costimulatory molecules. Immunol Res, 28 (1): 39-48. [PMID:12947223]
7. Johnson LS, Huang L, Moore PA, Loo DT, Chen FZ. (2014) Antibodies reactive with B7-H3 and uses thereof. Patent number: US8802091B2. Assignee: Macrogenics Inc. Priority date: 04/05/2012. Publication date: 12/08/2014.
8. Loo D, Alderson RF, Chen FZ, Huang L, Zhang W, Gorlatov S, Burke S, Ciccarone V, Li H, Yang Y et al.. (2012) Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent antitumor activity. Clin Cancer Res, 18 (14): 3834-45. [PMID:22615450]
9. Modak S, Kramer K, Gultekin SH, Guo HF, Cheung NK. (2001) Monoclonal antibody 8H9 targets a novel cell surface antigen expressed by a wide spectrum of human solid tumors. Cancer Res, 61 (10): 4048-54. [PMID:11358824]
10. Nygren MK, Tekle C, Ingebrigtsen VA, Fodstad O. (2011) B7-H3 and its relevance in cancer; immunological and non-immunological perspectives. Front Biosci (Elite Ed), 3: 989-93. [PMID:21622107]
11. Sun M, Richards S, Prasad DV, Mai XM, Rudensky A, Dong C. (2002) Characterization of mouse and human B7-H3 genes. J Immunol, 168 (12): 6294-7. [PMID:12055244]
12. Zhou Z, Luther N, Ibrahim GM, Hawkins C, Vibhakar R, Handler MH, Souweidane MM. (2013) B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma. J Neurooncol, 111 (3): 257-64. [PMID:23232807]
Other immune checkpoint proteins: B7-H3 (CD276). Last modified on 11/04/2023. Accessed on 09/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2938.
target has curated data in GtoImmuPdb
