A TROP2-targeting aptamer enables selective drug delivery and potent antitumor activity in pancreatic cancer
Year: 2026
Type: article
Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains difficult to treat, highlighting the need for strategies that selectively deliver cytotoxic agents to tumor cells. Trophoblast cell-surface antigen 2 (TROP2) has been proposed as a candidate therapeutic target in PDAC, but non-antibody-based delivery formats remain underexplored. Using protein-SELEX, we identified T17, a high-affinity aptamer that specifically binds to TROP2, and conjugated it to monomethyl auristatin E through an MC-Val-Cit-PAB linker to generate the aptamer-drug conjugate T17-M. Preclinical evaluation in cellular and animal models showed that T17-M retained TROP2-dependent binding, underwent clathrin-mediated internalization and lysosomal processing, and suppressed tumor growth in cell-line-derived and patient-derived xenografts. T17-M also reduced liver metastasis and induced calreticulin exposure, ATP release, and HMGB1 secretion, consistent with immunogenic cell death. In immunocompetent models, T17-M promoted dendritic-cell activation and CD8 + T cell infiltration, while its combination with PD-1 blockade further enhanced tumor control and prolonged survival. These findings provide preclinical proof-of-concept for T17-M as an alternative TROP2-targeted drug-delivery strategy for PDAC.
Source: Science Advances
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W7225813628