T cell-engaging bispecific antibodies for myeloid malignancies: Targets, formats, and clinical challenges

T cell-engaging bispecific antibodies (T-BsAbs) have revolutionized immunotherapy for hematologic malignancies, showing promise in lymphoid cancers and myeloma. However, their application in myeloid malignancies like acute myeloid leukemia (AML) faces challenges due to myelotoxicity and limited target specificity. Here, we review the current landscape of T-BsAb development for myeloid diseases, detailing target antigens, antibody engineering strategies, and clinical trial outcomes. We discuss advances in bispecific antibody formats designed to enhance efficacy and reduce toxicity, alongside emerging therapeutic combinations. Our synthesis highlights the complexity of targeting myeloid malignancies while sparing normal hematopoietic cells. These insights underscore the potential of refined T-BsAb approaches to improve treatment specificity and efficacy in AML and related disorders, informing future therapeutic strategies and clinical development.