Chemico-physical and biological properties of two monoclonal antibodies, Bevacizumab (Avastin®) and Durvalumab (Imfinzi®) under real-life light doses

INTRODUCTION. Monoclonal antibodies (mAbs) have recently gained prominence as protein drugs in the treatment of different kinds of cancer. Because of their protein nature, they can be unstable to some stressors during manufacturing, transportation, storage, handling/dilution, and administration [1]. Light can induce chemico-physical changes which can be relevant when amino acids are in the CDRs, as efficacy and safety could be compromised [2,3]. AIMS. Chemico-physical stability of Bevacizumab-Avastin® and Durvalumab- Imfinzi®, and their biological activity were evaluated under light doses close to the exposure of mAbs in their real-life. RESULTS. Exposure of the diluted mAbs to a dose of sunlight experienced in their real life did not affect their conformation. On the other hand, light was able to induce mAb aggregation, at a higher extent in Bevacizumab than in Durvalumab. The chemical modifications detected on both mAbs revealed low oxidative damage plus deamidations. Chemico-physical modifications on both Bevacizumab and Durvalumab had little effect on their target recognition (VEGF and PDL1, respectively). Furthermore, immunogenic potential in dendritic cells from differentiated monocytes seems absent. CONCLUSIONS. The chemico-physical changes induced by real-life doses of light on the tested mAbs are not crucial for the overall protein structure and very low chemical modifications involve amino acids located in the CDRs. Consequently, in vitro target recognition barely decreases. Moreover, the detected aggregation does not seem to induce immunogenicity but to have a role on the decrease of the biological activity. AKNOWLEDGEMENTS This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement N° 101007939 (RealHOPE). References: [1] Fayek R, Soleyman M, Jiskoot W, Crul M. Evaluation of post-production handling practices of monoclonal antibodies throughout the world. European Journal of Oncology Pharmacy 2021;4:e031. [2] Laptoš T, Omersel J. The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies (Review). Experimental and Therapeutic Medicine, 2018. [3] Hipper E, Blech M, Hinderberger D, Garidel P, Kaiser W. Photo-Oxidation of Therapeutic Protein Formulations: From Radical Formation to Analytical Techniques. Pharmaceutics, 14:72, 2021