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ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Bioprocess Engineering
Volume 12 - 2024 |
doi: 10.3389/fbioe.2024.1440150
Development of a synthetic library of humanized nanobodies for targeted IL-6 inhibition
Provisionally accepted- 1 State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, China
- 2 Shanghai Key Lab of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China
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
Keywords: Nanobody, Humanization, stability, synthetic library, phage display, Interleukin-6, blocking antibody
Received: 29 May 2024; Accepted: 28 Jun 2024.
Copyright: © 2024 Wang, Dong, Wu, Wu, Yan, Bi, Xu, Zheng and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lei Wang, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
Jiayi Dong, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
Chenlu Wu, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
Yiling Wu, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
Chenyue Yan, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
Chong Bi, Shanghai Key Lab of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
Chengnan Xu, Shanghai Key Lab of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
Wenyun Zheng, Shanghai Key Lab of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China
Xingyuan Ma, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China
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