Antigen Specificity: A Fluctuating Aspect in the Development of Clinical Antibodies?

Development of antibodies for clinical use is a complex process involving numerous aspects, with antigen specificity being the most important. Initially, polyclonal antibodies, that can recognize multiple specific and nonspecific antigens (polyreactive), were developed and were very effective in the treatments. Later on, the polyspecificity/polyreactivity of these polyclonal antibodies (binding to multiple antigens) raised concerns about therapeutic efficacy because of their nonspecific interactions and challenges, such as development of immune complexes, batch-to-batch variability. This highlighted the need for more targeted approaches. It was resolved by the marked invention of hybridoma technology in 1975 which resulted in the revolution in the antibody development field by offering monoclonal monospecific antibodies (bind single antigen). However, their limited application in complex pathologies sparked a paradigm shift, leading to the resurgence of polyspecific antibodies in the form of monoclonal polyspecific antibodies (Polybodies), which bind multiple antigens, but specifically. Till today, 14 Polybodies are approved for clinical use. This fluctuation in antigen specificity is directing the evolution of engineered antibodies that are going to drive the biopharmaceutical sector in the coming years. Through this write-up, we assert the fluctuating nature of antigen specificity during the antibody development and how it will be crucial for advancing biologics.