Abstract
Antibody therapeutics are expanding with promising clinical outcomes, and diverse formats of antibodies are further developed and available for patients of the most challenging disease areas. Bispecific antibodies (BsAbs) have several significant advantages over monospecific antibodies by engaging two antigen targets. Due to the complicated mechanism of action, diverse structural variations, and dual-target binding, developing bioassays and other types of assays to characterize BsAbs is challenging. Developing bioassays for BsAbs requires a good understanding of the mechanism of action of the molecule, principles and applications of different bioanalytical methods, and phase-appropriate considerations per regulatory guidelines. Here, we review recent advances and case studies to provide strategies and insights for bioassay development for different types of bispecific molecules.
Highlights
Genentech—A Member of the Roche Group, South San Francisco, CA 94080, USA; Abstract: Antibody therapeutics are expanding with promising clinical outcomes, and diverse formats of antibodies are further developed and available for patients of the most challenging disease areas
Case Study: Flow cytometry-based binding and blocking assays for GPC3/CD47 BsAb [92]: To develop a potential immune-modulating therapeutic to treat hepatocellular carcinoma (HCC), the authors designed a novel BsAb directed against the HCC-associated antigen Glypican-3 (GPC3) and CD47, an inhibitory innate immune checkpoint that inhibits antibody-dependent cellular phagocytosis (ADCP) by binding to SIRPa on myeloid cells
GPC3/CD47 BsAb in GPC3+/CD47+ compared to GPC3-/CD47+ cells in vitro. These results suggest that the bispecific targeting of GPC3+ and CD47 may preferentially induce killing of GPC3+ tumor cells by ADCP
Summary
The concept of the bispecific antibody (BsAb) has been around for more than 50 years, but within the last 20 years, activity and interest in the field of study has skyrocketed [1,2]. BsAbs have obtained health authority approval for use and are currently marketed as therapeutics in a number of disease areas (e.g., blinatumomab, emicizumab) around the world, highlighting the therapeutic potential of engaging two targets within a single molecule [4]. This is attributed to advanced biotechnologies, enhanced manufacturing knowledge of therapeutic antibody products, and strong scientific rationale for the development of biologics with the ability to engage more than one target [5,6]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
