Bispecific antibodies: The next generation of targeted inflammatory bowel disease therapies

Targeting various disease pathways using monoclonal antibodies (mAbs) has transformed the treatment paradigm for inflammatory bowel disease (IBD), with these agents exhibiting improved efficacy over corticosteroids or immunosuppressive therapies. Antibodies targeting tumor necrosis factor α (TNF-α) were the first approved biologics for IBD, followed by the more recent approval of antibodies targeting the α4β7 integrin heterodimer and ustekinumab, which targets the p40 subunit of interleukin-23. Current efforts are focused on the development of additional biologics targeting these known and other newly discovered pathways. Still significant unmet needs remain, as a large proportion of patients either fail to achieve remission or fail to respond altogether. Both Crohn's disease and ulcerative colitis are complex and heterogeneous diseases with several molecular pathways involved in disease pathophysiology. We propose an additional therapeutic approach to the treatment of IBD, bispecific antibodies (BsAbs), which combine two distinct binding specificities within a single biologic to allow the simultaneous targeting of multiple disease-causing cytokines or pathways. Although primarily used in oncology thus far, the unique combinatorial mechanism of action of BsAbs may provide new therapeutic options for a broad range of clinical applications, including autoimmune and inflammatory diseases. This review will discuss the current status of BsAb development in general and potentially therapeutic application in IBD.