Antibody–drug conjugates (ADCs) represent an emerging class of targeted therapeutics that has attracted considerable attention in the field of precision oncology. By combining the high specificity of monoclonal antibodies with the potent cytotoxic activity of small-molecule drugs, ADCs are designed to selectively deliver highly active payloads to tumor cells avoiding healthy tissues. This targeted approach aims to broaden the therapeutic window by maximizing antitumor efficacy and minimizing systemic toxicity, overcoming some limitations associated with conventional chemotherapy. Despite the remarkable clinical success achieved by several ADCs, their therapeutic performance remains strongly dependent by payload delivery to the tumor site, as well as on the availability of robust and reliable analytical methodologies capable of accurately quantifying the released drug. Among the most promising molecular targets for ADC-based therapy is LGALS3BP, a glycosylated secreted protein that is overexpressed in a tumor progression, metastatic dissemination, and modulation of the tumor immune microenvironment, making it an attractive candidate for targeting medicine. The ADC investigated in this study is based on the humanized anti-LGALS3BP monoclonal antibody 1959, which has been rationally engineered through the substitution of selected cysteine residues with serine residues to enable precise site-specific conjugation. This strategy allows controlled attachment of the maytansinoid DM4 through a cleavable disulfide linker, resulting in a homogeneous conjugate. The accurate quantification of the cytotoxic payload released from ADCs is essential for understanding drug disposition, pharmacokinetics, and tissue biodistribution, all of which are critical parameters for preclinical and clinical development. Although mass spectrometry-based analytical techniques are widely regarded as the gold standard, their routinely use is often limited by high instrumentation costs, complex sample preparation procedures, and highly qualified staff.

AMYC- BIOMED 2026

Miryam Perrucci
;
Vincenzo De Laurenzi;
2026-01-01

Abstract

Antibody–drug conjugates (ADCs) represent an emerging class of targeted therapeutics that has attracted considerable attention in the field of precision oncology. By combining the high specificity of monoclonal antibodies with the potent cytotoxic activity of small-molecule drugs, ADCs are designed to selectively deliver highly active payloads to tumor cells avoiding healthy tissues. This targeted approach aims to broaden the therapeutic window by maximizing antitumor efficacy and minimizing systemic toxicity, overcoming some limitations associated with conventional chemotherapy. Despite the remarkable clinical success achieved by several ADCs, their therapeutic performance remains strongly dependent by payload delivery to the tumor site, as well as on the availability of robust and reliable analytical methodologies capable of accurately quantifying the released drug. Among the most promising molecular targets for ADC-based therapy is LGALS3BP, a glycosylated secreted protein that is overexpressed in a tumor progression, metastatic dissemination, and modulation of the tumor immune microenvironment, making it an attractive candidate for targeting medicine. The ADC investigated in this study is based on the humanized anti-LGALS3BP monoclonal antibody 1959, which has been rationally engineered through the substitution of selected cysteine residues with serine residues to enable precise site-specific conjugation. This strategy allows controlled attachment of the maytansinoid DM4 through a cleavable disulfide linker, resulting in a homogeneous conjugate. The accurate quantification of the cytotoxic payload released from ADCs is essential for understanding drug disposition, pharmacokinetics, and tissue biodistribution, all of which are critical parameters for preclinical and clinical development. Although mass spectrometry-based analytical techniques are widely regarded as the gold standard, their routinely use is often limited by high instrumentation costs, complex sample preparation procedures, and highly qualified staff.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11575/180181
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