Conclusions
The PDC examined in this study was proven to be highly efficient for NSCLC, broadening its utilization for targeted cancer therapy in EGFR overexpressed cancers.
Methods
SN38 is attached to the peptide at position 20 of the E ring's tertiary hydroxyl group via a mono-succinate linker.
Results
The developed peptide-drug conjugate (PDC) exhibited sub-micromolar anticancer activity on EGFR-positive (EGFR+) cell lines but no effect on EGFR-negative (EGFR-) cells. In vivo studies have shown that this PDC specifically accumulates in EGFR+ non-small cell lung cancer (NSCLC) xenografts and presents superior anticancer activity compared to the EGFR-specific antibody cetuximab (ErbituxTM) and free SN38. The 10 mg/kg dose of P6-SN38 in a side-by-side EGFR+/EGFR- xenograft shows eradication of the EGFR+ tumor with good tolerance, but no inhibition of tumor growth of the EGFR- counterpart. Conclusions: The PDC examined in this study was proven to be highly efficient for NSCLC, broadening its utilization for targeted cancer therapy in EGFR overexpressed cancers.