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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

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 [14]. 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
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
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Antibody Sp. Action Value Parameter Reference
magrolimab Peptide Immunopharmacology Ligand Hs Binding 8.1 – 11.1 pKd 9
pKd 11.1 (Kd 8x10-12 M) [9]
Description: Binding affinity for bivalent human CD47 in vitro, determined by surface plasmon resonance
pKd 8.1 (Kd 8x10-9 M) [9]
Description: Binding affinity for monomeric human CD47 in vitro, determined by surface plasmon resonance
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
thrombospondin 1 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Binding - - 6
[6]
Immunopharmacology Comments
CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin 1 (THBS1) and signal-regulatory protein alpha (SIRPα). It is a ubiquitously expressed membrane protein that is a 'marker of self', and it is involved in self tolerance. Binding to SIRPα produces an anti-phagocytic signal.

The CD47/THBS1 axis has been implicated in wound healing, and in the pathological progression of immune thrombocytopenia (ITP) [17].

Cancer cells that express CD47 expression are able to evade immune surveillance and macrophage-mediated removal. Anti-CD47 monoclonal antibodies are being investigated as novel immuno-oncology agents [9]. Efficacy of this strategy has been demonstrated in malignant pediatric brain tumours, in vitro and in vivo in patient-derived orthotopic xenograft models [7]. A novel engineered dual-targeting bispecific antibody format, called κλ bodies [5] 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 [4]. 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 [3].
Several pharma companies have anti-CD47 therapeutics under early clinical evaluation (tabulated below)

NameCompanyComment
Hu5F9-G4Forty SevenMaximun development Phase 2 in advanced cancers. Ph1 results published [16]
CC-90002/INBRX-103Celgene/InhibrxPhase I in AML was terminated in October 2018 (NCT02641002)
Evorpacept (ALX148)ALX Oncology (previously Alexo)Maximun development Phase 3 (NCT05002127)
SRF231 [11]Surface OncologyMaximun development Phase 1 monotherapy (NCT03512340)
AO-176[13]Arch OncologyMaximun development Phase 1
IBI188 [10]Innovent BiologicsMaximun development Phase 1/2

Trillium Therapeutics have two anti-SIRPα fusion proteins in Phase 2 (TTI-621 and TTI-622), and other companies have additional CD47/SIRPα-disrupting agents in their oncology development pipelines: TG-1801(NI-1701) a CD47/CD19 bispecific in Ph1, NI-1801 a mesothelin/CD47 bispecific in Ph1, BI 765063/OSE-172 a SIRPα monoclonal in Ph1, and the bi-functional SIRPα/4-1BB ligand fusion protein DSP107 [2] that has reached Ph1/2.
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 (THBS1), 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 [15].

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. Cendrowicz E, Jacob L, Greenwald S, Tamir A, Pecker I, Tabakman R, Ghantous L, Tamir L, Kahn R, Avichzer J et al.. (2022) DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity. J Exp Clin Cancer Res, 41 (1): 97. [PMID:35287686]

3. 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]

4. 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]

5. 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]

6. Gao AG, Lindberg FP, Finn MB, Blystone SD, Brown EJ, Frazier WA. (1996) Integrin-associated protein is a receptor for the C-terminal domain of thrombospondin. J Biol Chem, 271 (1): 21-4. [PMID:8550562]

7. 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]

8. 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]

9. 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]

10. Ni H, Cao L, Wu Z, Wang L, Zhou S, Guo X, Gao Y, Jing H, Wu M, Liu Y et al.. (2022) Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody. Cancer Immunol Immunother, 71 (2): 353-363. [PMID:34165607]

11. Peluso MO, Adam A, Armet CM, Zhang L, O'Connor RW, Lee BH, Lake AC, Normant E, Chappel SC, Hill JA et al.. (2020) The Fully human anti-CD47 antibody SRF231 exerts dual-mechanism antitumor activity via engagement of the activating receptor CD32a. J Immunother Cancer, 8 (1). [PMID:32345627]

12. 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]

13. Puro RJ, Bouchlaka MN, Hiebsch RR, Capoccia BJ, Donio MJ, Manning PT, Frazier WA, Karr RW, Pereira DS. (2020) Development of AO-176, a Next-Generation Humanized Anti-CD47 Antibody with Novel Anticancer Properties and Negligible Red Blood Cell Binding. Mol Cancer Ther, 19 (3): 835-846. [PMID:31879362]

14. 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]

15. 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]

16. Sikic BI, Lakhani N, Patnaik A, Shah SA, Chandana SR, Rasco D, Colevas AD, O'Rourke T, Narayanan S, Papadopoulos K et al.. (2019) First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers. J Clin Oncol, 37 (12): 946-953. [PMID:30811285]

17. Ye QD, Jiang H, Liao XL, Chen K, Li SS. (2017) Identification and Validation of Gene Expression Pattern and Signature in Patients with Immune Thrombocytopenia. SLAS Discov, 22 (2): 187-195. [PMID:27554456]

How to cite this page

CD molecules: CD47. Last modified on 22/02/2024. Accessed on 24/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2943.