Development of a synthetic library of humanized nanobodies for targeted IL-6 inhibition

Autor: Lei Wang, Jiayi Dong, Chenlu Wu, Chenyue Yan, Chong Bi, Chengnan Xu, Yiling Wu, Wenyun Zheng, Xingyuan Ma
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Bioengineering and Biotechnology, Vol 12 (2024)
Druh dokumentu: article
ISSN: 2296-4185
DOI: 10.3389/fbioe.2024.1440150
Popis: Interleukin-6 (IL-6) is a cytokine that can bind to IL-6 receptor and induce pleiotropic effects. It serves as a critical biomarker, involved in inflammation amplification, tumor progression, and many other disease developments. Nanobodies, featuring small structure and high affinity, are a powerful and versatile tool in medical diagnostics and therapeutics. Here, based on a scaffold optimized for humanization and stability, we developed a synthetic phage display library that rapidly generated high-affinity and humanized nanobodies, negating the need for animal immunization. Using enhanced green fluorescent protein (eGFP) as a benchmark, we demonstrated that the library produced humanized nanobodies with high function and great intracellular stability. The library was then subjected to screening against IL-6. We identified a standout nanobody, NbL3, which exhibited high affinity (22.16 nM) and stability and significantly inhibited IL-6-enhanced migration on the human breast cancer cell MCF-7 at a relatively low concentration. NbL3’s strong blocking activity provides a promising therapeutic alternative for the IL-6-targeted intervention strategy, underscoring the broader potential of our synthetic library as a versatile platform for the development of humanized nanobodies against multiple antigens.
Databáze: Directory of Open Access Journals