Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers

Bispecific antibodies (BsAbs) and multispecific antibodies (MsAbs) represent a transformative class of immunotherapeutics in oncology. These engineered molecules possess the unique ability to simultaneously target two or more distinct antigens, thereby facilitating precise immune cell engagement and disrupting multiple signaling pathways. This comprehensive review focuses on their pivotal role in redirecting both innate (natural killer cells, phagocytes) and adaptive (T cells) immunity, with a particular emphasis on their application against hematologic cancers. Significant clinical successes, exemplified by the FDA approval of agents such as blinatumomab, underscore the profound impact these therapies have had on patient outcomes. Despite their promise, inherent challenges persist, including managing treatment-related toxicities, overcoming tumor resistance mechanisms, and optimizing pharmacokinetic profiles. Ongoing research, however, continues to drive innovative strategies to address these hurdles, highlighting the immense potential of immune engagers to deliver more personalized, scalable, and highly effective cancer treatments in the future.