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CD47

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2943

Nomenclature: CD47

Family: CD molecules

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 5 323 3q13.12 CD47 CD47 molecule
Mouse 5 303 16 B5 Cd47 CD47 antigen (Rh-related antigen, integrin-associated signal transducer)
Rat 5 303 11q21 Cd47 Cd47 molecule
Gene and Protein Information Comments
There are four alternatively spliced isoforms of human CD47 that differ only in the length of their cytoplasmic tail [9]. Although the functional significance of the alternate splice variants is poorly understood., evidence of the highly conserved nature of the isoforms between mouse and man, suggests an important role for the cytoplasmic domains in CD47 function. Isoform 2 is the most widely expressed form that is found in all circulating and immune cells.
Previous and Unofficial Names Click here for help
CD47 antigen | CD47 antigen (Rh-related antigen, integrin-associated signal transducer) | CD47 antigen (Rh-related antigen | integrin associated protein IAP | integrin-associated signal transducer | MER6
Database Links Click here for help
Alphafold Q08722 (Hs), Q61735 (Mm), P97829 (Rn)
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL3714583 (Hs)
Ensembl Gene ENSG00000196776 (Hs), ENSMUSG00000055447 (Mm), ENSRNOG00000001964 (Rn)
Entrez Gene 961 (Hs), 16423 (Mm), 29364 (Rn)
Human Protein Atlas ENSG00000196776 (Hs)
KEGG Gene hsa:961 (Hs), mmu:16423 (Mm), rno:29364 (Rn)
OMIM 601028 (Hs)
Pharos Q08722 (Hs)
RefSeq Nucleotide NM_198793 (Hs), NM_010581 (Mm), NM_019195 (Rn)
RefSeq Protein NP_942088 (Hs), NP_034711 (Mm), NP_062068 (Rn)
UniProtKB Q08722 (Hs), Q61735 (Mm), P97829 (Rn)
Wikipedia CD47 (Hs)

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Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
magrolimab Peptide Immunopharmacology Ligand Hs Binding 8.1 – 11.1 pKd 7
⤷ pKd 11.1 (Kd 8x10-12 M) [7]
Description: Binding affinity for bivalent human CD47 in vitro, determined by surface plasmon resonance
pKd 8.1 (Kd 8x10-9 M) [7]
Description: Binding affinity for monomeric human CD47 in vitro, determined by surface plasmon resonance
Immunopharmacology Comments
CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). It is a ubiquitously expressed membrane protein that is a 'marker of self', and which is involved in self tolerance. Binding to SIRPα produces an anti-phagocytic signal. CD47 expression is hijacked by cancer cells to evade immune surveillance and macrophage-mediated removal. Anti-CD47 monoclonal antibodies are being investigated as novel immuno-oncology agents [7]. Efficacy of this strategy has been demonstrated in malignant pediatric brain tumours, in vitro and in vivo in patient-derived orthotopic xenograft models [5]. A novel engineered dual-targeting bispecific antibody format, called κλ bodies [4] that selectively block the CD47-SIRPα interaction and simultaneously bind a tumour specific antigen (e.g. CD19 or mesothelin) and mediate immune activation via the Fc portion of the antibody have been shown to effectively kill cancer cells in vitro and in vivo, whilst sparing normal cells [3]. This approach is postulated to be applicable to targeting of other ubiquitously expressed therapeutic proteins. Intratumoural delivery of an anti-CD47 nanobody using engineered, non-pathogenic Escherichia coli has produced local and systemic anti-tumour effects in mouse syngeneic tumour models [2].
Several pharma companies have anti-CD47 therapeutics under early clinical evaluation (tabulated below)

NameCompanyComment
Hu5F9-G4Forty SevenPhase 1/2 evaluations in combination with cetuximab or rituximab (NCT02953782, NCT02953509)
CC-90002/INBRX-103Celgene/InhibrxPhase I in AML was terminated in October 2018 (NCT02641002)
ALX148ALX Oncology (previously Alexo)Phase 1 in combination with pembrolizumab, trastuzumab or rituximab (NCT03013218)
SRF231Surface OncologyPhase 1 monotherapy trial began in March 2018 (NCT03512340)
Trillium Therapeutics have two anti-SIRPα fusion proteins in Phase 1 (TTI-621 and TTI-622), and other companies have additional CD47/SIRPα-disrupting agents in preclinical testing (e.g. TG-1801 (NI-1701), NI-1801, OSE-172, AO-176, IBI188 and DSP107).
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Immuno Process:  Cytokine production & signalling
General Comments
CD47 is a ubiquitously expressed membrane protein that is a 'marker of self'. It is a ligand of SIRPα. The CD47/SIRPα anti-phagocytic axis is important for self-tolerance. CD47 binds thrombospondin-1 (TSP-1), an interaction with a role in the regulation of angiogenesis and inflammation, and in cellular functions including cell migration, adhesion, proliferation and apoptosis. CD47 also binds several membrane integrins [1] (e.g. αvβ3) which is likely involved in modulation of cellular adhesion, spreading and migration. CD47 is an immuno-oncology drug target [10].

References

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1. Brown EJ, Frazier WA. (2001) Integrin-associated protein (CD47) and its ligands. Trends Cell Biol, 11 (3): 130-5. [PMID:11306274]

2. Chowdhury S, Castro S, Coker C, Hinchliffe TE, Arpaia N, Danino T. (2019) Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nat Med, 25 (7): 1057-1063. [PMID:31270504]

3. Dheilly E, Moine V, Broyer L, Salgado-Pires S, Johnson Z, Papaioannou A, Cons L, Calloud S, Majocchi S, Nelson R et al.. (2017) Selective Blockade of the Ubiquitous Checkpoint Receptor CD47 Is Enabled by Dual-Targeting Bispecific Antibodies. Mol Ther, 25 (2): 523-533. [PMID:28153099]

4. Fischer N, Elson G, Magistrelli G, Dheilly E, Fouque N, Laurendon A, Gueneau F, Ravn U, Depoisier JF, Moine V et al.. (2015) Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG. Nat Commun, 6: 6113. [PMID:25672245]

5. Gholamin S, Mitra SS, Feroze AH, Liu J, Kahn SA, Zhang M, Esparza R, Richard C, Ramaswamy V, Remke M et al.. (2017) Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med, 9 (381). [PMID:28298418]

6. Kauder SE, Kuo TC, Harrabi O, Chen A, Sangalang E, Doyle L, Rocha SS, Bollini S, Han B, Sim J et al.. (2018) ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile. PLoS One, 13 (8): e0201832. [PMID:30133535]

7. Liu J, Wang L, Zhao F, Tseng S, Narayanan C, Shura L, Willingham S, Howard M, Prohaska S, Volkmer J et al.. (2015) Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS ONE, 10 (9): e0137345. [PMID:26390038]

8. Petrova PS, Viller NN, Wong M, Pang X, Lin GH, Dodge K, Chai V, Chen H, Lee V, House V et al.. (2017) TTI-621 (SIRPαFc): A CD47-Blocking Innate Immune Checkpoint Inhibitor with Broad Antitumor Activity and Minimal Erythrocyte Binding. Clin Cancer Res, 23 (4): 1068-1079. [PMID:27856600]

9. Reinhold MI, Lindberg FP, Plas D, Reynolds S, Peters MG, Brown EJ. (1995) In vivo expression of alternatively spliced forms of integrin-associated protein (CD47). J Cell Sci, 108 ( Pt 11): 3419-25. [PMID:8586654]

10. Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L. (2012) CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. Br J Pharmacol, 167 (7): 1415-30. [PMID:22774848]

How to cite this page

CD molecules: CD47. Last modified on 02/05/2023. Accessed on 30/11/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2943.