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<p>Interleukin-6 (IL-6) is a pivotal cytokine in immune regulation, inflammatory responses, and chronic inflammation. Dysregulated IL-6 signaling, which results from the interaction between IL-6 and IL-6 receptor alpha (IL-6Rα), has been implicated in the pathogenesis of numerous inflammatory diseases. Although anti-IL-6Rα monoclonal antibodies have been used to treat these diseases, their high treatment costs impose a substantial financial burden on patients. Recently, a genetically engineered strain of <i>Lactococcus lactis</i> (gmLAB) has attracted attention as a low-cost therapeutic agent. Thus, in this study, as a lower-cost alternative, a novel strategy using a gmLAB to produce a single-chain variable fragment targeting IL-6Rα (IL-6RαscFv) was developed. A recombinant strain that produces IL-6RαscFv with high binding affinity for human IL-6Rα, effectively inhibiting the interaction between IL-6 and IL-6Rα, was successfully produced. Furthermore, IL-6RαscFv significantly suppressed the expression of serum amyloid A, a biomarker of acute-phase inflammation. These findings demonstrate the potential of the recombinant strain as a promising therapeutic approach for inflammatory diseases.</p>

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Development of a Genetically Modified Lactococcus lactis Strain that Produces a Single-Chain Variable Fragment Targeting Interleukin-6 Receptor α to Suppress Serum Amyloid A

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月26日

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  • Masahiro Yoda,
  • Kaho Suzuki,
  • Shoko Yoda,
  • Kazuma Inoue,
  • Mao Kagotani,
  • Misato Kubo,
  • Aito Murakami,
  • Fu Namai,
  • Takashi Sato,
  • Takeshi Shimosato

摘要

Interleukin-6 (IL-6) is a pivotal cytokine in immune regulation, inflammatory responses, and chronic inflammation. Dysregulated IL-6 signaling, which results from the interaction between IL-6 and IL-6 receptor alpha (IL-6Rα), has been implicated in the pathogenesis of numerous inflammatory diseases. Although anti-IL-6Rα monoclonal antibodies have been used to treat these diseases, their high treatment costs impose a substantial financial burden on patients. Recently, a genetically engineered strain of Lactococcus lactis (gmLAB) has attracted attention as a low-cost therapeutic agent. Thus, in this study, as a lower-cost alternative, a novel strategy using a gmLAB to produce a single-chain variable fragment targeting IL-6Rα (IL-6RαscFv) was developed. A recombinant strain that produces IL-6RαscFv with high binding affinity for human IL-6Rα, effectively inhibiting the interaction between IL-6 and IL-6Rα, was successfully produced. Furthermore, IL-6RαscFv significantly suppressed the expression of serum amyloid A, a biomarker of acute-phase inflammation. These findings demonstrate the potential of the recombinant strain as a promising therapeutic approach for inflammatory diseases.