Design and development of a bispecific antibody targeting BAFF and IL-17 for systemic lupus erythematosus treatment.

Abstract

Background: This study aimed to develop and evaluate a bispecific single-chain variable fragment (bsscFv) targeting B-cell activating factor (BAFF) and interleukin-17 (IL-17) for the treatment of systemic lupus erythematosus (SLE).

Methods: The bsscFv was engineered by linking single-chain variable fragments (scFvs) specific for BAFF and IL-17 with a flexible peptide linker. It was expressed in E. coli BL21 and purified using affinity chromatography. Binding affinities to BAFF and IL-17 were assessed by enzyme-linked immunosorbent assay (ELISA). In vitro neutralization assays were conducted using Raji and HT-29 cell cultures. In vivo therapeutic efficacy was evaluated in an MRL/lpr mouse model of SLE, with 10 mice per group. Statistical significance was determined using a Student's t-test for comparison of two groups.

Results: The bsscFv demonstrated strong binding to both BAFF and IL-17 in ELISA. In vitro, it inhibited BAFF-induced B-cell survival, proliferation, and immunoglobulin production, as well as IL-17-induced inflammatory cytokine secretion in HT-29 cells. In the MRL/lpr mouse model, bsscFv treatment significantly reduced autoantibody levels (p < 0.05), proteinuria, renal pathology, and cytokine expression in a dose-dependent manner compared to controls.

Conclusions: The bsscFv exhibited potent neutralizing activity in vitro and therapeutic efficacy in vivo, suggesting it as a promising bispecific therapeutic agent for the treatment of SLE. Further studies are warranted to explore its clinical potential.