Recent advances in monoclonal antibody development for treatment of B-cell acute lymphoblastic leukemia.

Abstract

Monoclonal antibody (mAb)-based therapies targeting CD19, CD20, and CD22 have revolutionized B-ALL treatment, offering precision and reduced systemic toxicity by engaging immune mechanisms to eliminate leukemic cells. This review synthesizes literature from PubMed, Web of Science, and ClinicalTrials.gov (2000-2024), focusing on clinical outcomes and resistance mechanisms. Bispecific T-cell engagers (e.g. blinatumomab) and CD22-directed antibody-drug conjugates (e.g. inotuzumab ozogamicin) demonstrate robust efficacy in relapsed/refractory disease. Advances in antibody engineering, such as Fc optimization, nanobodies, and humanization, enhance tumor targeting and therapeutic safety. Persistent challenges include antigen escape, stromal-mediated resistance, and treatment-related toxicities. Combinatorial approaches integrating mAbs with CAR-T cells or checkpoint inhibitors show promise in overcoming resistance pathways. Emerging technologies like artificial intelligence and deep learning are transforming antibody design by predicting epitope binding, enabling de novo protein engineering, and streamlining affinity maturation. These innovations accelerate the development of next-generation therapies, underscoring the evolving potential of precision immunotherapy of B-ALL.