Table 2_TGF-β-induced epithelial to mesenchymal transition drives proteoglycan binding specificity of HPV-based drug conjugates for cancer cells.xlsx

Similarly modified PGs are also found on cancer cells, which enables HPV with tumor-selective binding properties and highlights the potential development of HPV capsid-based anti-cancer therapies. In this study, we sought to investigate cancer-specific gene signatures and genetic factors that give rise to selective binding by HPV capsids.</p>Methods<p>Using belzupacap sarotalocan (bel-sar; AU-011), an HPV virus-like drug conjugate (HPV-VDC) currently in clinical trials, we performed a cell binding screen using 115 cancer cell lines from which we performed gene expressions analysis.

We developed drug resistant lines to investigate the developmental factors involved in tumor targeting.</p>Results<p>We identified a strong association between drug binding and pathways involved in TGF-β-induced epithelial to mesenchymal transition (EMT). Furthermore, dose escalation treatments leading to selection of bel-sar resistant HeLa cells resulted in a marked reduction in TGF-β signaling and reversal of EMT, which was associated with a reduction in the synthesis and expression of heparan- and chondroitin sulfate proteoglycans.</p>Conclusion<p>Overall, these data suggest that bel-sar binding is strongly dependent on the differential expression and modification of PGs that occurs during the EMT process.