Interferons (IFNs) are a kind of cytokines, which is used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. There are three types of IFNs: Type I IFN, Type II IFN, and Type III IFN. In a typical case, a virus-infected cell will release IFNs causing nearby cells to heighten their anti-viral defenses. Thus, IFNs play essential roles in inflammation, immunoregulation, tumor cell recognition, and T-cell responses.
Type I IFNs (IFNα) are polypeptides that are secreted by infected cells and have three major functions. Firstly, they induce cell-intrinsic antimicrobial states in infected and neighboring cells that limit the spread of infectious agents, particularly viral pathogens. Secondly, they modulate innate immune responses in a balanced manner. Thirdly, they activate the adaptive immune system. The predominant producers of IFNα are hematopoietic cells, particularly plasmacytoid dendritic cells. IFNα is effective in the research of several disorders, such as chronic hepatitis or malignant melanoma.
Sifalimumab (MEDI-545) is an igG1κ monoclonal antibody for IFNα subtypes.
From: Psarras A and Vital EM, et al. Nat Rev Rheumatol. 2022 Oct;18(10):575-590.
Sifalimumab is a fully human, immunoglobulin G1 κ monoclonal antibody that binds to and neutralizes the majority of IFN-α subtypes. Meanwhile, Sifalimumab suppresses abnormal immune activity by binding to multiple IFNα subtypes. In vitro, Sifalimumab attenuates lymphocyte cytotoxicity triggered by IFNα in U-87MG cells. Besides, Sifalimumab (s.c., 30 mg/kg and 3 μg/g) decreases the CpG-induced lymphocyte infiltration and the increase of CD45 in mice. Also, Sifalimumab can decrease the IFNα signature within days by 90% (protein and gene expression) and decrease skin lesions. Therefore, Sifalimumab is effective in the research of systemic lupus erythematosus (SLE) dermatomyositis, and polymyositis.
All in all, Sifalimumab (MEDI-545) is an anti-IFNα monoclonal antibody. Sifalimumab suppresses abnormal immune activity by binding to multiple IFNα subtypes.
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