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CD33

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2601

Nomenclature: CD33

Abbreviated Name: SIGLEC3

Family: Other immune checkpoint proteins, CD33-related SIGLECs, CD molecules

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 364 19q13.41 CD33 CD33 molecule
Mouse 1 403 7 28.25 cM Cd33 CD33 molecule
Rat - - 1q22 Cd33 CD33 molecule
Previous and Unofficial Names Click here for help
CD33 antigen | SIGLEC3
Database Links Click here for help
Alphafold P20138 (Hs), Q63994 (Mm)
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL1842 (Hs)
DrugBank Target P20138 (Hs)
Ensembl Gene ENSG00000105383 (Hs), ENSMUSG00000004609 (Mm), ENSRNOG00000037331 (Rn)
Entrez Gene 945 (Hs), 12489 (Mm), 690492 (Rn)
Human Protein Atlas ENSG00000105383 (Hs)
KEGG Gene hsa:945 (Hs), mmu:12489 (Mm), rno:690492 (Rn)
OMIM 159590 (Hs)
Pharos P20138 (Hs)
RefSeq Nucleotide NM_001772 (Hs), NM_001111058 (Mm)
RefSeq Protein NP_001763 (Hs), NP_001104528 (Mm)
UniProtKB P20138 (Hs), Q63994 (Mm)
Wikipedia CD33 (Hs)

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
lintuzumab Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding ~10.0 pKd 2
⤷ pKd ~10.0 (Kd ~1x10-10 M) [2]
vadastuximab talirine Peptide Primary target of this compound Immunopharmacology Ligand Hs Binding 9.3 pKd 5
⤷ pKd 9.3 (Kd 5x10-10 M) [5]
Description: Saturation binding in HEL 92.1.7 cells endogenously expressing human CD33.
gemtuzumab ozogamicin Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding - - 1
⤷ [1]
Antibody Comments
Evidence of the effectiveness of gemtuzumab ozogamicin centers on the drug's ability to inhibit the growth of leukemic cells in vitro and in vivo [3,6-7].
Immunopharmacology Comments
CD33 (SIGLEC3) is a myeloid cell I-type (Ig-type) lectin that binds glycans containing sialic acids [4]. Most SIGLECs inhibit immune cell activation, via immunoreceptor tyrosine-based inhibitory (ITIM) motifs in their cytosolic domains. Hence, blockade of SIGLEC interactions restores immune cell activation, which is of interest for the treatment of myeloid leukemias. As such, CD33 is the target of approved monoclonal antibody-drug conjugate gemtuzumab ozogamicin (for CD33-positive acute myeloid leukemia) and investigational mAb lintuzumab which was a clinical candidate biologic for refractory or relapsed acute myelogenous leukemia.
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   granulocyte (CL:0000094)
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
General Comments
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. Bernstein ID. (2000) Monoclonal antibodies to the myeloid stem cells: therapeutic implications of CMA-676, a humanized anti-CD33 antibody calicheamicin conjugate. Leukemia, 14 (3): 474-5. [PMID:10720144]

2. Caron PC, Co MS, Bull MK, Avdalovic NM, Queen C, Scheinberg DA. (1992) Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res, 52 (24): 6761-7. [PMID:1458463]

3. Frankel AE, Sievers EL, Scheinberg DA. (2000) Cell surface receptor-targeted therapy of acute myeloid leukemia: a review. Cancer Biother Radiopharm, 15 (5): 459-76. [PMID:11155818]

4. Garnache-Ottou F, Chaperot L, Biichle S, Ferrand C, Remy-Martin JP, Deconinck E, de Tailly PD, Bulabois B, Poulet J, Kuhlein E et al.. (2005) Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells. Blood, 105 (3): 1256-64. [PMID:15388576]

5. Kung Sutherland MS, Walter RB, Jeffrey SC, Burke PJ, Yu C, Kostner H, Stone I, Ryan MC, Sussman D, Lyon RP et al.. (2013) SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood, 122 (8): 1455-63. [PMID:23770776]

6. McGavin JK, Spencer CM. (2001) Gemtuzumab ozogamicin. Drugs, 61 (9): 1317-22; discussion 1323-4. [PMID:11511025]

7. van Der Velden VH, te Marvelde JG, Hoogeveen PG, Bernstein ID, Houtsmuller AB, Berger MS, van Dongen JJ. (2001) Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood, 97 (10): 3197-204. [PMID:11342449]

How to cite this page

Other immune checkpoint proteins: CD33. Last modified on 15/01/2024. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2601.