Characterization of structural and functional properties of anti-VEGF-IgG molecules under certain environmental stress conditions

Official URL: https://risc01.sabanciuniv.edu/record=b2708483_(Table of contents)

Monoclonal antibodies (mAbs) are protein-structured molecules that bind to the target molecule with high specificity and have practical biotherapeutic effects. They are produced for therapeutic purposes in the pharmaceutical industry due to their essential functions, such as antigen-dependent cell cytotoxicity (ADCC), complement-dependent cell cytotoxicity (CDC), and target molecule neutralization. However, due to the protein nature of mAbs, they can be exposed to many different environmental stress factors during and after production. In the presence of these stress factors, the structures of antibodies and, accordingly, their biological functions can be negatively affected. The mAbs are exposed to stress factors such as thermal, changing pH conditions, and oxidative environment during production and post-production processes such as shipping and storage. In the presence of these stress factors, in addition to the development of processes such as aggregation and fragmentation in the structures of antibodies, they can undergo post-translational modifications (PTMs). These modifications and degradation processes can seriously affect the therapeutic activity of antibodies. Therefore, essential authorities in drug approval, such as the Food and Drug Administration (FDA), have made it mandatory to characterize the changes in the structure of mAbs and the changes in their biological activities in the presence of these stress factors. For this purpose, a large field such as forced degradation studies has been created. Based on these studies, the antibody's characterization and biological activities can be determined quickly by imitating the stress factors that mAbs may encounter under normal environmental conditions in the laboratory environment. Within the scope of this study, both structural and functional analyzes of the antibody were performed by forming the most common stress factors such as thermal, pH change of the environment, and oxidative stress of the anti-VEGF IgG molecule in vitro. Therefore, by characterizing the PTMs and aggregation profiles that can occur, many preliminary studies will be carried out for the therapeutic use of this antibody in the pharmaceutical industry, and it will lead to studies for many industrial and therapeutic purposes.