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]
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | SIGLEC8 |
| Clinical data | |
| Trade names | AK002 |
| Routes of administration | Intravenous |
| Identifiers | |
| CAS Number | |
| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6408H9884N1700O2006S46 |
| Molar mass | 144310.21 g·mol−1 |
Mechanism of action
editIn 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.
Indications
editAs of 2023, lirentelimab has no approved indications.[5]
Pharmacology
editLirentelimab is a humanized, nonfucosylated IgG1 monoclonal antibody that targets Siglec-8.[6] Siglec-8 is an inhibitory receptor present on 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] Lirentelimab inhibits mast cells' IgE-mediated degranulation and de novo synthesis of prostaglandin D2 in vitro.[7]
Adverse events
editMild-to-moderate infusion reactions may occur with lirentelimab, which tend to occur following the first infusion only.[3]
Research
editLirentelimab has been studied for the treatment of chronic spontaneous urticaria, indolent systemic mastocytosis, and severe allergic conjunctivitis.[6]
References
edit- ^ "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
edit- "Lirentelimab". Drug Information Portal. U.S. National Library of Medicine.
