Monoclonal antibody
Pharmaceutical compound
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] [ 3]
Mechanism of action
In individuals with asthma, Siglec-8 expression is increased on the surface of eosinophils and mast cells in sputum.[ 4] natural killer cell mediated cytotoxicity .
Indications
As of 2023, lirentelimab has no approved indications.[ 5]
Pharmacology
Lirentelimab is a humanized, nonfucosylated IgG1 monoclonal antibody that targets Siglec-8.[ 6] eosinophils and mast cells , with low level expression on basophils .[ 2] [ 7] Interleukin-5 , granulocyte-macrophage colony stimulating factor , and interleukin-33 enhance anti-Siglec-8 mediated destruction of eosinophils.[ 7] [ 7]
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 .[ 6]
References
^ "Lirentelimab" . KEGG Drug Database .^ a b 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 . ^ a b Young A (October 29, 2019). "Therapeutic antibody effective in eosinophilic gastritis" . Healio . Retrieved 14 December 2020 . ^ 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 . ^ Dellon ES, Spergel JM (January 2023). "Biologics in eosinophilic gastrointestinal diseases" . Annals of Allergy, Asthma & Immunology . 130 (1): 21– 27. doi :10.1016/j.anai.2022.06.015 . PMC 10191215 PMID 35738437 . ^ a b 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 . ^ a b c 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 .
External links
"Lirentelimab" . Drug Information Portal . U.S. National Library of Medicine.
