A new CHO (Chinese hamster ovary)-derived cell line expressing anti-TNFa monoclonal antibody with biosimilar potential


Butantan affiliation
Publication type
Article
Language
English
Appears in Collections:
Metrics
Abstract
Tumor necrosis factor alpha (TNF alpha) is a pro-inflammatory cytokine that mediates the homeostasis of immune responses; its exacerbated production is associated with the pathogenesis of autoimmune and chronic inflammatory diseases. Anti-TNF alpha drugs have revolutionized the treatment of inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Currently, a worldwide race is on stage for the production of biosimilars moved by patent expiration of monoclonal antibodies (mAbs), such as anti-TNF alpha adalimumab. Our goal was to develop the first stage of an adalimumab biosimilar candidate with potential for national production, through the generation of a productive and stable cell line and assess its functionality. The robotic system ClonePix was used for screening and isolation of colonies from transfected CHO-S stable pools plated in semisolid medium. Selected clones were expanded based on growth and productivity. Purified mAbs from different clones were tested for binding and functional activity. The binding affinity of the denominated adabut clones to TNF alpha and FcR gamma did not differ statistically when compared to reference adalimumab. One functional activity assay demonstrated the antibody neutralization capacity of the cytotoxicity induced by TNF alpha in L929 murine fibroblasts. A second assay confirmed adabut as an antagonist of the TNF alpha activity by the inhibition of the cell adhesion molecule expression in HUVEC cultures. The binding and functional activity analyses performed with selected adabut clones in comparison to reference adalimumab represent an important status of "non-inferiority," part of the process required for a biosimilar development. We generated and selected high-quality adabut clones which mAbs may be further developed as the first in-house made Brazilian biosimilar, demonstrating a success case for our incipient biotechnology industry, or also modified as biobetters, thus representing an innovative strategy for the patients' welfare.
Reference
Luchese MD, Lopes dos Santos M, Garbuio A, Targino RC, Mansueli CP, Tsuruta LR, et al. A new CHO (Chinese hamster ovary)-derived cell line expressing anti-TNFa monoclonal antibody with biosimilar potential. Immunol. Res.. 2018 Jun;66(3):392-405. doi:10.1007/s12026-018-8997-4.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/2496
Journal title
Issue Date
2018


Files in This Item:

Existing users please Login
10.1007s12026-018-8997-4.pdf
Size: 4.49 MB
Format: Adobe PDF
Embargoed until January 1, 2999    Request a copy
Show full item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.