Modern medicine still lacks a radical cure for this disease, but intervention therapy can be implemented according to the patient’s symptoms, disease severity, and complications to improve the condition, ensure long-term survival, prevent organ damage, and avoid other adverse reactions. Since the specific pathogenesis of lupus erythematosus remains unclear, clinically, patients with mild disease are generally treated with drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) and antimalarial drugs for disease control. However, for patients with poor treatment response or organ-threatening disease, immunosuppressants, glucocorticoids, or even high-dose intravenous immunoglobulin (IVIG) may be required.
The current main treatment methods still pose significant adverse consequences, such as osteoporosis, increased susceptibility to infection, obesity, and even severe liver and kidney damage.
Nowadays, the global research and development of biological agents for this disease may open a new door for treatment strategies.
As early as August 2015, Ablynx initiated the research and development project of Vobarilizumab, a therapeutic drug for systemic lupus erythematosus (SLE). This is a nanobody monoclonal antibody composed of an anti-IL-6R domain and an anti-human serum albumin domain, which can be used in the research of inflammatory autoimmune diseases. However, after three years of research and development experiments, Ablynx announced the failure of the project in the Phase II clinical stage. The main reason was that the drug failed to show a dose-response relationship in clinical practice. Nevertheless, the drug still exhibited good tolerability in all tested dose groups, demonstrating its favorable safety profile.
In 2023, the clinical trial application for Relmacabtagene autoleucel, a CD19-targeted CAR-T product developed by JW Therapeutics for the treatment of moderate-to-severe refractory systemic lupus erythematosus (SLE), was approved. Subsequently, the IND application for GenScript ProBio’s CD19/BCMA dual-target autologous FasTCAR-T cell therapy was also approved by the FDA. This year, the research results of Naxicabtagene autoleucel, developed by Allogene Biotherapeutics, for the treatment of immune thrombocytopenia in systemic lupus erythematosus were published in the New England Journal of Medicine. The research paper demonstrated that Naxicabtagene autoleucel exhibits good and durable efficacy as well as unique safety in the treatment of this disease.
Figure 1: Correlation between serum anti-β 2GPI and immune function
Figure 2: Correlation between serum FSTL1 and immune function
Figure 3: Correlation between serum PD-1 and immune function
To summarize, biological agents hold great potential for the development of drugs for the treatment of systemic lupus erythematosus. In addition, more therapeutic targets for autoimmune diseases are gradually being discovered. Recently, an article published by Puyang People’s Hospital in the Journal of Rare and Uncommon Diseases pointed out that the high expression of serum anti-β2-glycoprotein I (anti-β2GPI), follistatin-like protein 1 (FSTL1), and programmed death 1 (PD-1) may be involved in the occurrence of cellular immune dysfunction and exacerbation of disease activity in SLE patients.This discovery now provides new ideas for pharmaceutical researchers. From Ablynx’s Vobarilizumab R&D project, the stability, targeting ability, and extremely low immunogenicity of nanobodies may become a drug development strategy for systemic lupus erythematosus (SLE) in the future.
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