B7-H3 (CD276) | Other immune checkpoint proteins | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

B7-H3 (CD276)

target has curated data in GtoImmuPdb

Target id: 2938

Nomenclature: B7-H3 (CD276)

Family: Other immune checkpoint proteins, CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
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
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein

Download all structure-activity data for this target as a CSV file

Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
enoblituzumab Monkey Binding 7.7 pKd 7
pKd 7.7 (Kd 2.25x10-8 M) [7]
Description: By surface plasmon resonance (SPR) assay.
enoblituzumab 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 2 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0042110 T cell activation IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0050776 regulation of immune response IBA
GO:0050852 T cell receptor signaling pathway IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0045078 positive regulation of interferon-gamma biosynthetic process IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 3 GO processes
GO:0042102 positive regulation of T cell proliferation IDA
GO:0042110 T cell activation IDA
GO:0050852 T cell receptor signaling pathway IBA
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.


Show »

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. U.S.A., 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 23/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2938.