التفاصيل البيبلوغرافية
العنوان: |
Chimeric ScFv Monoclonal Antibody Composed of Tocilizumab-Light Chain, Heavy Chain, and Bacterial Flagellin for the Treatment of Autoimmune Disorder: Insilco Design and Cytotoxicity Study. |
المؤلفون: |
Rajaganapathy, K., Masilamani, K., Senthilnathan, B., M., Vasanth Kumar, P., Suthakaran, P., Panneerselvam, M., Vigneshwar, C. N., Prashantha |
المصدر: |
Journal of Pharmaceutical Negative Results; 2022 Special Issue, Vol. 13, p644-659, 16p |
مصطلحات موضوعية: |
FLAGELLIN, AUTOIMMUNE diseases, MONOCLONAL antibodies, CHIMERIC proteins, RHEUMATOID arthritis, IMMUNE system, IMMUNE response |
مستخلص: |
Introduction: The Tocilizumab (TCZ), a recombinant humanised anti-interleukin-6 receptor (IL-6R) monoclonal antibody, is primarily used to treat various autoimmune disorders specifically, rheumatoid arthritis. The usage of tocilizumab injection may reduce our capacity to combat infections brought on by bacteria, viruses, and fungi and raise our risk of developing a serious or potentially fatal illness that may spread throughout the body. To overcome these obstacles, the current work was concentrate on the Designing of a Chimeric Flagellin-mediated Tocilizumab Monoclonal Antibody for Autoimmune Disorders. The flagellum, a whip-like appendage that facilitates bacterial mobility, has a component protein called flagellin which has now been discovered to be a potent immune activator that shapes both the innate and adaptive immune systems in response to microbial infections. Methods: In this study, we were developed an In-silico, methods to design Chimeric-ScFv Monoclonal antibody which was based on speciallized linker to connect bacterial flagellin to Tocilizumab, between the heavy and light chains, yielding a chimeric antibody. Further the preliminary In-vitro cytotoxicity study attempt was on carried out on the MTT Viability assay of Chondrocytes and Fibroblasts in RA co-cultures with TCZ, Flagelline and TCZ+Flagelline Coadminstration. Results: Our findings suggest that the Flagelline mediated Tocilizumab monoclonal antibody, which was created by in-silico methods using chimeric ScFv, has good solubility, stability, and agonist and antagonist effects on TLR-5 and IL-6 respectivelly, based on binding and activation. The preliminary cytotoxicity study indicating the most active inhibition effects on fibroblast and chondrocytes with Co-adminstration of TCZ+Flagelline. Conclusion: Under this Proof of concept, the focus of future work will be based on the development, cloning, protein purification, characterization, and assessment of Chimeric flagelline mediated Tocilizumab monoclonal antibody for the treatment autoimmune disorders. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |