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The anti-Nectin-2 antibody-drug conjugate (ADC) is a preclinical therapeutic modality designed to target Nectin-2 (also known as PVRL2 or CD112), a cell adhesion molecule and immune checkpoint ligand overexpressed in various solid tumors, including ovarian, breast, and prostate cancers. These ADCs consist of a Nectin-2-specific monoclonal antibody (such as the chimeric c12G1 or the human IgG-F1) conjugated to a cytotoxic payload. Payloads investigated include maytansinoids (DM1), auristatins (MMAE), and topoisomerase I inhibitors (DXd). Upon binding to the C2 domain or other epitopes of Nectin-2, the ADC is internalized, releasing the payload to induce cell death via microtubule inhibition or DNA damage. Preclinical studies have shown significant tumor growth inhibition (up to 91% in some models) and potent cytotoxicity, supporting its potential as a targeted therapy for Nectin-2-positive malignancies.
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