Preparation and characterization of a fully human monoclonal antibody specific for human tumor necrosis factor alpha

Xinmei Liao; Hui Liang; Jian Pan; Qian Zhang; Jiaqi Niu; Cuili Xue; Jian Ni; Daxiang Cui

doi:10.1080/21655979.2021.1967710

Preparation and characterization of a fully human monoclonal antibody specific for human tumor necrosis factor alpha

Bioengineered. 2021 Dec;12(2):10821-10834. doi: 10.1080/21655979.2021.1967710.

Authors

Xinmei Liao^{1

2}, Hui Liang^{3

4}, Jian Pan⁵, Qian Zhang^{1

2}, Jiaqi Niu^{1

2}, Cuili Xue^{1

2}, Jian Ni^{1

4}, Daxiang Cui^{1

2

3}

Affiliations

¹ Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, P. R. China.
² National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai, P. R. China.
³ National Engineering Research Center for Nanotechnology, Shanghai, P. R. China.
⁴ Nuance Biotech (Shenzhen) Co. Ltd, Shenzhen, Guangdong, P. R. China.
⁵ Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.

Abstract

Tumor necrosis factor alpha (TNFα) is an important inflammatory factor. It plays a cardinal role in inflammatory synovitis and articular matrix degradation, and is, therefore, a prime target for directed immunotherapy in autoimmune diseases. In this study, we screened and isolated the B cells secreting anti-TNFα antibody from patients with rheumatoid arthritis. The heavy-chain and light-chain sequences of the antibody were cloned and used to generate a stable Chinese hamster ovary (CHO) cell line producing the antibody, which was named Haidalimumab. Haidalimumab showed a TNFα binding affinity comparable to that of the antibody Humira, which is the best TNF inhibitor on the market. Furthermore, Haidalimumab could effectively neutralize recombinant human tumor necrosis factor alpha (rhTNFα) toxicity in a C57BL/6 mouse model and showed significant therapeutic effect in a tumor necrosis factor transgenic (TNF-Tg) mouse arthritis model. In conclusion, we developed a high-affinity, fully human anti-TNFα antibody with low immunogenicity that could potentially have significant therapeutic applications in rheumatoid arthritis or other autoimmune diseases.Abbreviations: ELISAenzyme linked immunosorbent assayRArheumatoid arthritisSDS-PAGEsodium dodecyl sulfate polyacrylamide gel electrophoresisrhTNFαrecombinant human tumor necrosis factor-alphaEC₅₀concentration for 50% of maximal effectTNF-Tg micetumor necrosis factor transgenic miceAMDactinomycin DMTTmethylthiazolyldiphenyl-tetrazolium bromidePBSphosphate-buffered saline.

Keywords: Fully human monoclonal antibody; affinity; inhibitor; rheumatoid arthritis; tumor necrosis factor α.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology*
CHO Cells
Cricetulus
Female
Humans
Immunologic Factors / immunology
Mice
Mice, Inbred C57BL
Tumor Necrosis Factor-alpha / immunology*

Substances

Antibodies, Monoclonal
Immunologic Factors
Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the National Key Research and Development Program of China under Grants [No. 2017YFA0205301, No. 2017YFA0205304]; National Natural Science Foundation of China under Grants [No. 81903169, No. 82072767, No. 81770145]; Shanghai Sailing Program under Grant [No. 19YF1422300]; Natural Science Foundation of Jiangsu Province under Grant [No. BK20191175]; and Gusu Health Talents program of Soochow City under Grant [2020-104].