Citation: | QIU Jiwan, KONG Yong, CHEN Wei, et al. Generation and characterization of humanized monoclonal antibody against human IFNAR1[J]. J China Pharm Univ, 2024, 55(3): 404 − 411. DOI: 10.11665/j.issn.1000-5048.2024031401 |
Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Monoclonal antibody shows therapeutic potential by blocking the signaling pathway. This study used recombinant human subunit 1 of the type I interferon receptor (IFNAR1) protein to immunize New Zealand white rabbits, and applied B cell cloning technology to screen and obtain rabbit parental antibodies. After humanization modification, QX006N was obtained. In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L, and neutralize the type I interferon signaling pathway and this pathway mediated biological effects. This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.
[1] |
Ramaswamy M, Tummala R, Streicher K, et al. The pathogenesis, molecular mechanisms, and therapeutic potential of the interferon pathway in systemic lupus erythematosus and other autoimmune diseases[J]. Int J Mol Sci, 2021, 22(20): 11286. doi: 10.3390/ijms222011286
|
[2] |
Moll HP, Maier T, Zommer A, et al. The differential activity of interferon-α subtypes is consistent among distinct target genes and cell types[J]. Cytokine, 2011, 53(1): 52-59. doi: 10.1016/j.cyto.2010.09.006
|
[3] |
Peng L, Oganesyan V, Wu H, et al. Molecular basis for antagonistic activity of anifrolumab, an anti-interferon-α receptor 1 antibody[J]. MAbs, 2015, 7(2): 428-439. doi: 10.1080/19420862.2015.1007810
|
[4] |
González-Navajas JM, Lee J, David M, et al. Immunomodulatory functions of type I interferons[J]. Nat Rev Immunol, 2012, 12(2): 125-135. doi: 10.1038/nri3133
|
[5] |
Jiang J, Zhao M, Chang C, et al. Type I interferons in the pathogenesis and treatment of autoimmune diseases[J]. Clin Rev Allergy Immunol, 2020, 59(2): 248-272. doi: 10.1007/s12016-020-08798-2
|
[6] |
Rönnblom L, Leonard D. Interferon pathway in SLE: one key to unlocking the mystery of the disease[J]. Lupus Sci Med, 2019, 6(1): e000270. doi: 10.1136/lupus-2018-000270
|
[7] |
Crow MK, Olferiev M, Kirou KA. Type I interferons in autoimmune disease[J]. Annu Rev Pathol, 2019, 14: 369-393. doi: 10.1146/annurev-pathol-020117-043952
|
[8] |
Kalunian KC, Merrill JT, Maciuca R, et al. A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE)[J]. Ann Rheum Dis, 2016, 75(1): 196-202. doi: 10.1136/annrheumdis-2014-206090
|
[9] |
Anderson E, Furie R. Anifrolumab in systemic lupus erythematosus: current knowledge and future considerations[J]. Immunotherapy, 2020, 12(5): 275-286. doi: 10.2217/imt-2020-0017
|
[10] |
Khamashta M, Merrill JT, Werth VP, et al. Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study[J]. Ann Rheum Dis, 2016, 75(11): 1909-1916. doi: 10.1136/annrheumdis-2015-208562
|
[11] |
Kaplon H, Chenoweth A, Crescioli S, et al. Antibodies to watch in 2022[J]. MAbs, 2022, 14(1): 2014296. doi: 10.1080/19420862.2021.2014296
|
[12] |
Deeks ED. Anifrolumab: first approval[J]. Drugs, 2021, 81(15): 1795-1802. doi: 10.1007/s40265-021-01604-z
|
[13] |
Piehler J, Thomas C, Garcia KC, et al. Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation[J]. Immunol Rev, 2012, 250(1): 317-334. doi: 10.1111/imr.12001
|
[14] |
Weber J, Peng HY, Rader C. From rabbit antibody repertoires to rabbit monoclonal antibodies[J]. Exp Mol Med, 2017, 49(3): e305. doi: 10.1038/emm.2017.23
|
[15] |
Markham A. Brolucizumab: first approval[J]. Drugs, 2019, 79(18): 1997-2000. doi: 10.1007/s40265-019-01231-9
|
[16] |
Dhillon S. Eptinezumab: first approval[J]. Drugs, 2020, 80(7): 733-739. doi: 10.1007/s40265-020-01300-4
|