LAG3 (CD223) | Other immune checkpoint proteins | IUPHAR Guide to IMMUNOPHARMACOLOGY

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LAG3 (CD223)

Target id: 2932

Nomenclature: LAG3 (CD223)

Systematic Nomenclature: CD223

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

   GtoImmuPdb view: ON :     LAG3 (CD223) has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 525 12p13.31 LAG3 lymphocyte activating 3 8
Mouse - 521 6 F2 Lag3 lymphocyte-activation gene 3
Rat - 525 4q42 Lag3 lymphocyte activating 3
Gene and Protein Information Comments
The human LAG3 protein precursor is 525 amino acids including its 28 aa signal peptide. LAG3 cleavage to a soluble form is mediated by the metalloproteinases ADAM10 and ADAM17 [3,5], although the biological function of this soluble protein is not fully resolved.
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
relatlimab Hs Antagonist - - 6
[6]
General Comments
Residues in the proline-rich D1 loop of LAG3 facilitate binding to MHC class II molecules. LAG3 probably transmits inhibitory signals via its cytoplasmic domain but the precise signalling mechanism remains unknown. MHC class II expressed by melanoma cells may bind to LAG3 on melanoma-infiltrating T cells and this might facilitate their clonal exhaustion, and enhance tumour cell immune evasion. LAG3 may also interact with galectin-3, a T cell regulating lectin, and this could potentially contribute to LAG3's regulation of CD8+ cell function. A recombinant protein comprising the extracellular domain of LAG3 fused with human IgG1 Fc fragment (known as eftilagimod alfa or IMP 321) represents a soluble form of LAG3 that is being developed as an immuno-oncology therapeutic. The most advanced clinical trial (as of December 2017) evaluating IMP 321 is Phase 2 study NCT02614833 being carried out in patients with metastatic breast cancer (as an adjunct to standard chemotherapy).

References

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1. Andrews LP, Marciscano AE, Drake CG, Vignali DA. (2017) LAG3 (CD223) as a cancer immunotherapy target. Immunol. Rev., 276 (1): 80-96. [PMID:28258692]

2. Camisaschi C, De Filippo A, Beretta V, Vergani B, Villa A, Vergani E, Santinami M, Cabras AD, Arienti F, Triebel F et al.. (2014) Alternative activation of human plasmacytoid DCs in vitro and in melanoma lesions: involvement of LAG-3. J. Invest. Dermatol., 134 (7): 1893-1902. [PMID:24441096]

3. Clayton KL, Douglas-Vail MB, Nur-ur Rahman AK, Medcalf KE, Xie IY, Chew GM, Tandon R, Lanteri MC, Norris PJ, Deeks SG et al.. (2015) Soluble T cell immunoglobulin mucin domain 3 is shed from CD8+ T cells by the sheddase ADAM10, is increased in plasma during untreated HIV infection, and correlates with HIV disease progression. J. Virol., 89 (7): 3723-36. [PMID:25609823]

4. Goldberg MV, Drake CG. (2011) LAG-3 in Cancer Immunotherapy. Curr. Top. Microbiol. Immunol., 344: 269-78. [PMID:21086108]

5. Li N, Workman CJ, Martin SM, Vignali DA. (2004) Biochemical analysis of the regulatory T cell protein lymphocyte activation gene-3 (LAG-3; CD223). J. Immunol., 173 (11): 6806-12. [PMID:15557174]

6. Lonberg N, Srinivasan M. (2014) Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof. Patent number: WO2014008218. Assignee: Bristol-Myers Squibb Company. Priority date: 02/07/2012. Publication date: 09/01/2014.

7. Sharpe AH. (2017) Introduction to checkpoint inhibitors and cancer immunotherapy. Immunol. Rev., 276 (1): 5-8. [PMID:28258698]

8. Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T. (1990) LAG-3, a novel lymphocyte activation gene closely related to CD4. J. Exp. Med., 171 (5): 1393-405. [PMID:1692078]

9. Turnis ME, Andrews LP, Vignali DA. (2015) Inhibitory receptors as targets for cancer immunotherapy. Eur. J. Immunol., 45 (7): 1892-905. [PMID:26018646]

10. Zhang Q, Chikina M, Szymczak-Workman AL, Horne W, Kolls JK, Vignali KM, Normolle D, Bettini M, Workman CJ, Vignali DAA. (2017) LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes. Sci Immunol, 2 (9). [PMID:28783703]

How to cite this page

Other immune checkpoint proteins: LAG3 (CD223). Last modified on 30/07/2018. Accessed on 16/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2932.