Development of potent humanized TNFα inhibitory nanobodies for therapeutic applications in TNFα-mediated diseases.

ABSTRACT: Tumor necrosis factor-alpha (TNFα) is a key pro-inflammatory cytokine implicated in the pathogenesis of numerous inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and neurodegenerative disorders such as Alzheimer's disease. Effective inhibition of TNFα is essential for mitigating disease progression and improving patient outcomes. In this study, we present the development and comprehensive characterization of potent humanized TNFα inhibitory nanobodies (TNFI-Nbs) derived from camelid single-domain antibodies. In silico analysis of the original camelid nanobodies revealed low immunogenicity, which was further reduced through machine learning-guided humanization and developability optimization. The two humanized TNFI-Nb variants we developed de

SUBMITTER: Yin T 

PROVIDER: S-EPMC12080732 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature