The making of multispecific immunoglobulins - a clinical perspective

Over the past two decades, bi- and multispecific antibodies have emerged as a rapidly advancing class of therapeutic biologics, transforming oncology and immunotherapy. By simultaneously binding two or more distinct antigens or epitopes, these molecules achieve mechanisms of action beyond those of conventional monoclonal antibodies, including immune cell redirection, dual pathway modulation, and enhanced tissue selectivity. Bispecific and multispecific antibodies exhibit considerable structural diversity, encompassing a wide range of molecular architectures covering a steady growing 'zoo' of formats. The therapeutic success and diversity of molecules and formats is reflected in the 2021 revision of the international nonproprietary name system, which introduced the suffix - mig to denote multispecific immunoglobulins. In this review, we provide an overview of multispecific antibodies in clinical development, focusing on format, molecular design, and clinical status. In total, data for 501 multispecific antibodies were compiled and analyzed, identifying 112 different formats. Overall, this analysis highlights the rapid growth, enormous format diversity, and translational potential of multispecific antibodies. It underscores their emerging role as versatile therapeutics not only in oncology, but also in non-cancer indications, reflecting a field that continues to evolve rapidly in response to both scientific innovation and clinical needs.

Antibody engineering; bispecific antibodies; clinical development; immunotherapy; multispecific antibodies; therapeutic antibodies.