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.

Abstract

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.