Version 1
: Received: 9 February 2019 / Approved: 13 February 2019 / Online: 13 February 2019 (15:16:44 CET)
How to cite:
Jameei, A.; Nagarajan, D.; Sarikhani, M.; Chandra, N.; Karande, A. A. Development and Characterization of a Potent Tumor Necrosis Factor-Alpha Blocking Agent. Preprints2019, 2019020117. https://doi.org/10.20944/preprints201902.0117.v1
Jameei, A.; Nagarajan, D.; Sarikhani, M.; Chandra, N.; Karande, A. A. Development and Characterization of a Potent Tumor Necrosis Factor-Alpha Blocking Agent. Preprints 2019, 2019020117. https://doi.org/10.20944/preprints201902.0117.v1
Jameei, A.; Nagarajan, D.; Sarikhani, M.; Chandra, N.; Karande, A. A. Development and Characterization of a Potent Tumor Necrosis Factor-Alpha Blocking Agent. Preprints2019, 2019020117. https://doi.org/10.20944/preprints201902.0117.v1
APA Style
Jameei, A., Nagarajan, D., Sarikhani, M., Chandra, N., & Karande, A. A. (2019). Development and Characterization of a Potent Tumor Necrosis Factor-Alpha Blocking Agent. Preprints. https://doi.org/10.20944/preprints201902.0117.v1
Chicago/Turabian Style
Jameei, A., Nagasuma Chandra and Anjali A. Karande. 2019 "Development and Characterization of a Potent Tumor Necrosis Factor-Alpha Blocking Agent" Preprints. https://doi.org/10.20944/preprints201902.0117.v1
Abstract
Tumor necrosis factor-α (TNFα), one of the major pro-inflammatory cytokines, plays a key role in an effective immune response. However, the chronic presence of TNFα can lead to several inflammatory disorders like rheumatoid arthritis, psoriasis, Crohn’s disease etc. Inhibition of TNFα by pharmacological inhibitors or antibodies has proven to be effective in palliative treatment to some extent. The aim of this study was to develop an anti-TNFα antibody which may be used as a therapeutic option to inhibit TNFα-mediated cytotoxicity. We characterized several hybridoma clones secreting monoclonal antibodies (mAbs) to human-TNFα. Four mAbs rescued L929 fibroblast cells from TNFα-triggered cell death and one of these, namely C8 was found to have the highest affinity. To gain insights into the mechanism by which mAb C8 inhibits human TNFα-mediated toxicity, the epitope corresponding to the mAb was delineated. The antigenic determinant was found to comprise of the stretch of amino acids 99-120, of which, 102-104 (QRE) form the core epitope. The observation was supported by bioinformatics analyses of an antigen-antibody complex model. In addition, the binding affinity of mAb C8 to TNFα was found to be comparable with that of Infliximab which is a commercially available anti TNFα mAb.
Keywords
Monoclonal Antibody, TNFα
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
