Towards the Application of a Label-Free Approach for Anti-CD47/PD-L1 Bispecific Antibody Discovery

Autor: Artem S. Grevtsev, Alexandra D. Azarian, Alexey K. Misorin, Daria O. Chernyshova, Pavel A. Iakovlev, Mikhail S. Karbyshev
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Biosensors, Vol 13, Iss 12, p 1022 (2023)
Druh dokumentu: article
ISSN: 13121022
2079-6374
DOI: 10.3390/bios13121022
Popis: The engineering of bispecific antibodies that exhibit optimal affinity and functional activity presents a significant scientific challenge. To tackle this, investigators employ an assortment of protein assay techniques, such as label-free interaction methodologies, which offer rapidity and convenience for the evaluation of extensive sample sets. These assays yield intricate data pertaining to the affinity towards target antigens and Fc-receptors, instrumental in predicting cellular test outcomes. Nevertheless, the fine-tuning of affinity is of paramount importance to mitigate potential adverse effects while maintaining efficient obstruction of ligand–receptor interactions. In this research, biolayer interferometry (BLI) was utilized to probe the functional characteristics of bispecific antibodies targeting cluster of differentiation 47 (CD47) and programmed death-ligand 1 (PD-L1) antigens, encompassing affinity, concurrent binding to two disparate antigens, and the inhibition of ligand–receptor interactions. The findings derived from BLI were juxtaposed with data from in vitro signal regulatory protein-α (SIRP-α)/CD47 blockade reporter bioassays for two leading bispecific antibody candidates, each demonstrating distinct affinity to CD47.
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