Lirentelimab

Lirentelimab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetSIGLEC8
Clinical data
Trade namesAK002
Routes of
administration		Intravenous
Identifiers
CAS Number
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6408H9884N1700O2006S46
Molar mass144308.221 g·mol−1

Lirentelimab (sold under the brand name AK002) is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis.[2] Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.[3]

Mechanism of action

In individuals with asthma, Siglec-8 expression is increased on the surface of eosinophils and mast cells in sputum.[4] Lirentelimab depletes eosinophils via antibody-dependent natural killer cell mediated cytotoxicity.

Pharmacology

Lirentelimab is a humanized, nonfucosylated IgG1 monoclonal antibody that targets Siglec-8.[5] Siglec-8 is an inhibitory receptor present on eosinophils and mast cells, with low level expression on basophils.[2][6] Interleukin-5, granulocyte-macrophage colony stimulating factor, and interleukin-33 enhance anti-Siglec-8 mediated destruction of eosinophils.[6] Lirentelimab inhibits mast cells' IgE-mediated degranulation and de novo synthesis of prostaglandin D2 in vitro.[6]

Adverse events

Mild-to-moderate infusion reactions may occur with lirentelimab, which tend to occur following the first infusion only.[3]

Research

Lirentelimab has been studied for the treatment of chronic spontaneous urticaria, indolent systemic mastocytosis, and severe allergic conjunctivitis.[5]

References

  1. ↑ "Lirentelimab". KEGG Drug Database.
  2. 1 2 Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, et al. (October 2020). "Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis". The New England Journal of Medicine. 383 (17): 1624–1634. doi:10.1056/NEJMoa2012047. PMC 7600443. PMID 33085861.
  3. 1 2 Young A (October 29, 2019). "Therapeutic antibody effective in eosinophilic gastritis". Healio. Retrieved 14 December 2020.
  4. ↑ Kerr SC, Gonzalez JR, Schanin J, Peters MC, Lambrecht BN, Brock EC, et al. (August 2020). "An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells". Clinical and Experimental Allergy. 50 (8): 904–914. doi:10.1111/cea.13681. hdl:1854/LU-8706271. PMC 7610812. PMID 32542913. S2CID 219702648.
  5. 1 2 Johal KJ, Saini SS (October 2020). "Current and emerging treatments for chronic spontaneous urticaria". Annals of Allergy, Asthma & Immunology. 125 (4): 380–387. doi:10.1016/j.anai.2019.08.465. PMC 7056515. PMID 31494233.
  6. 1 2 3 Youngblood BA, Brock EC, Leung J, Falahati R, Bryce PJ, Bright J, et al. (2019). "AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice". International Archives of Allergy and Immunology. 180 (2): 91–102. doi:10.1159/000501637. PMC 6878738. PMID 31401630.
  • "Lirentelimab". Drug Information Portal. U.S. National Library of Medicine.
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