Harnessing T-Cell Engagement in High-Risk Leukemia: From Molecular Design to Clinical Integration
DOI:
https://doi.org/10.64784/082Keywords:
Bispecific antibodies, high-risk leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, immunotherapy, T-cell engagement, measurable residual disease, hematologic malignanciesAbstract
Bispecific antibodies have emerged as a transformative immunotherapeutic strategy in the management of high-risk leukemias, offering a mechanism-driven approach that redirects immune effector cells toward malignant targets. This review synthesizes current mechanistic, clinical, and translational evidence on bispecific antibodies, with particular emphasis on their application in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). A structured analysis of the literature reveals a progressive evolution of the field, from early engineering and proof-of-concept studies to clinically consolidated applications, especially in B-cell precursor ALL. Clinical evidence demonstrates that CD19/CD3-directed bispecific antibodies achieve meaningful disease control, including eradication of measurable residual disease and improved outcomes compared with conventional chemotherapy in advanced settings. In contrast, AML remains an area of active translational development, with CD33-directed constructs showing biological plausibility and early clinical feasibility, yet requiring further optimization. The diversification of bispecific antibody platforms, advances in safety management, and their complementary role alongside other immunotherapies, such as CAR T-cell therapy, underscore their growing relevance in modern hematologic oncology. Collectively, the evidence positions bispecific antibodies as a cornerstone of contemporary and future leukemia therapy, with significant implications for clinical practice and medical education across diverse healthcare systems.
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