Prezalumab, formerly known as AMG557, is a human monoclonal antibody direct against human inducible costimulator ligand (ICOSL). This drug was developed by Amgen combined with AstraZeneca subsidiary MedImmune and has been investigated in the treatment of sjogren's syndrome cutaneous lupus erythematosus, psoriasis, and systemic lupus erythematosus (SLE). At the same time, the safety, tolerance, pharmacokinetics and pharmacodynamics of prezalumab in the treatment of systemic lupus erythematosus and psoriasis were also evaluated. In 2018, prezalumab's phase I study for systemic lupus erythematosus has been terminated in a number of places, such as France, Malaysia, Canada and USA. In addition, prezalumab's treatment studies on cutaneous lupus erythematosus and psoriasis were terminated. However, in 2018, MedImmune completes a phase II trial in primary sjogren's syndrome in USA, United Kingdom, France and Sweden.
Inducible costimulator ligand (ICOSL), the target molecular of prezalumab, also known as B7-related protein-1 (B7RP-1) in mouse. ICOSL belongs to the B7 family and is widely expressed in non-lymphoid tissue and lymphoid tissue of the body. ICOSL was mainly expressed in B cells and monocytes in lymphoid tissue, and also expressed in macrophages and dendritic cells. ICOSL is also expressed in non-lymphoid tissues, such as melanoma cells and glioma cells. The signal produced by the binding of ICOSL to ICOS plays an important role in the activation of T cell-dependent B cells, which promotes the synthesis of antibodies and the secretion of IL10 by B cells. This signal is involved in regulating the differentiation of Th cells, enhancing the Th2 response and inhibiting the Th1 response. Because ICOS/ICOSL signaling pathway plays an important role in the immune process of the body, blocking this pathway may be an effective method to treat systemic lupus erythematosus (SLE) and other autoimmune diseases. Prezalumab is an IgG2 type monoclonal antibody designed to bind to ICOSL, inhibiting the interaction between ICOSL and ICOS and reducing the body's autoimmune response.
Fig.1 Mechanism of Action of Prezalumab