The therapeutic landscape for hematological malignancies has been fundamentally revolutionized over the last decade by the introduction of targeted antibodies. Notably, antibody–drug conjugates (ADCs) have emerged as a critical breakthrough, significantly improving the efficacy of immune-based treatment. ADCs function as highly sophisticated delivery systems: a selective monoclonal antibody recognizes a specific cell-surface target, guiding a potent toxic payload, attached via a chemical linker, directly into the cancer cell upon internalization. Intensive research has been dedicated to optimizing these components—improving antibody selectivity, enhancing linker stability, and utilizing highly effective payloads—which has resulted in a plethora of compounds that have reached patients’ bedsides and improved the clinical course of different tumors. This review provides a crucial overview of the current landscape of approved ADCs for hematological malignancies. It critically discusses their existing limitations and details the essential structural and chemical improvements that have yielded more potent and selective next-generation tools, finally presenting future strategies to generate highly effective “bullets” capable of decisively improving long-term disease prognosis.

Antibody–Drug Conjugates in Hematological Malignancies: Current Landscape and Future Perspectives

Maria Chiara Montalbano
First
;
Matilde Micillo;Silvia Deaglio
;
Tiziana Vaisitti
Last
2026-01-01

Abstract

The therapeutic landscape for hematological malignancies has been fundamentally revolutionized over the last decade by the introduction of targeted antibodies. Notably, antibody–drug conjugates (ADCs) have emerged as a critical breakthrough, significantly improving the efficacy of immune-based treatment. ADCs function as highly sophisticated delivery systems: a selective monoclonal antibody recognizes a specific cell-surface target, guiding a potent toxic payload, attached via a chemical linker, directly into the cancer cell upon internalization. Intensive research has been dedicated to optimizing these components—improving antibody selectivity, enhancing linker stability, and utilizing highly effective payloads—which has resulted in a plethora of compounds that have reached patients’ bedsides and improved the clinical course of different tumors. This review provides a crucial overview of the current landscape of approved ADCs for hematological malignancies. It critically discusses their existing limitations and details the essential structural and chemical improvements that have yielded more potent and selective next-generation tools, finally presenting future strategies to generate highly effective “bullets” capable of decisively improving long-term disease prognosis.
2026
27
2
1025
1053
https://www.mdpi.com/1422-0067/27/2/1025
antibody–drug conjugates; payload; linker; hematological malignancies; leukemia; lymphoma
Maria Chiara Montalbano, Matilde Micillo, Silvia Deaglio, Tiziana Vaisitti
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/2118100
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