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B7-H3 (CD276)

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2938

Nomenclature: B7-H3 (CD276)

Family: Other immune checkpoint proteins, CD molecules

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 534 15q24.1 CD276 CD276 molecule 10
Mouse 1 316 9 B Cd276 CD276 antigen 10
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 [10].
Database Links Click here for help
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
enoblituzumab Peptide Immunopharmacology Ligand Monkey Binding 7.7 pKd 7
pKd 7.7 (Kd 2.25x10-8 M) [7]
Description: By surface plasmon resonance (SPR) assay.
enoblituzumab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 7.6 pKd 7
pKd 7.6 (Kd 2.45x10-8 M) [7]
Description: By surface plasmon resonance (SPR) assay
Antibody Comments
A radio-iodinated monoclonal called [131I]-omburtomab (humanized from a mouse monoclonal designated 8H9) [1,8] 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 [3,11].

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).
Cell Type Associations
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
Comment:  B7-H3 expression is induced in NK cells by inflammatory cytokines and by phorbol myristate acetate/ionomycin exposure [5].
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
Comment:  B7-H3 expression is induced in monocytes by inflammatory cytokines and by phorbol myristate acetate/ionomycin exposure [5].
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 3 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0042110 T cell activation IDA
GO:0042130 negative regulation of T cell proliferation IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 5 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0042130 negative regulation of T cell proliferation IDA
GO:0050728 negative regulation of inflammatory response IMP
GO:0050776 regulation of immune response IBA
GO:0050852 T cell receptor signaling pathway IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0001817 regulation of cytokine production IBA
GO:0032729 positive regulation of interferon-gamma production IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0042130 negative regulation of T cell proliferation IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 4 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0042110 T cell activation IDA
GO:0042130 negative regulation of T cell proliferation IDA
GO:0050852 T cell receptor signaling pathway IBA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0050728 negative regulation of inflammatory response IMP
General Comments
B7-H3 is a molecular target for oncology drug development [7,9].
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.

References

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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. 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]

8. 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]

9. 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]

10. 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]

11. 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]

How to cite this page

Other immune checkpoint proteins: B7-H3 (CD276). Last modified on 07/08/2019. Accessed on 12/04/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2938.