Clinical Development of Bispecific Antibodies: Review, Advances, and Challenges in Hematological Malignancies

Precision therapies such as monoclonal antibodies (mAbs), immune-checkpoint inhibitors (ICIs), and chimeric antigen receptor T (CAR T)-cell therapies have revolutionized the treatment of cancer. Of these, bispecific antibodies (bsAbs) are gaining attention for their ability to simultaneously target two distinct molecular antigens, aimed at engaging T cells to circumvent cancer immune evasion mechanisms, resulting in tumor cytolysis. Several bsAbs have now been approved in the United States, Europe, and Japan for the treatment of hematological malignancies, most of which are CD3-redirecting bsAbs, although other immune-activating mechanisms are also being explored. This chapter reviews bsAbs in clinical development for hematological malignancies, their basic structure and mechanism of action, and efficacy and safety results of the most advanced bsAbs under clinical investigation.