Exploiting bi-specific engagement

Bispecific antibodies (BsAbs) represent a promising class of biologics, capable of concurrently engaging two distinct antigens, thus broadening the specificity and potential clinical utility in targeting disease-associated antigen combinations. My project explores the influence of antibody affinity, concentration, and receptor expression on the avidity of bispecific interactions, aiming to identify configurations that favour bivalent over monovalent binding, thereby improving therapeutic specificity and reducing off-target effects.
Data indicate significant avid binding improvements in bispecific constructs relative to monovalent variants. Some variants outperformed monovalent constructs, albeit not entirely exceeding bivalent binding. Adjusting the affinities of each antibody arm revealed that affinity manipulation could directly influence the level of avidity, highlighting the potential to tailor bispecific constructs for enhanced selectivity.
These findings underscore the potential of bispecific antibodies to achieve highly specific targeting by leveraging avidity effects, thus offering a strategic advantage over traditional monoclonal therapies. Future research will focus on competition binding assays to validate dual-antigen engagement and imaging techniques to visualise co-localisation and confirm the selectivity of receptor interactions with bispecific antibodies.
This work demonstrates the viability of optimising bispecific antibodies for increased selectivity and binding efficacy. My results provide a framework for developing therapeutic antibodies with improved specificity for dual-expressing target cells, thereby minimising collateral damage to healthy cells and enhancing clinical outcomes. Further investigations will refine bispecific design strategies and expand their application across diverse disease contexts.