Development of a nano-vaccine for high-grade serous ovarian cancer†

Abstract

High-Grade Serous Carcinoma (HGSC) is characterised by aggressive malignant tumours and poor prognosis accounting for 75% of ovarian cancer. Conventional treatments often result in relapse, with a need for innovative therapeutic approaches. This study aimed to develop and evaluate a DNA vaccine targeting the preferentially expressed antigen of melanoma, PRAME, a cancer tumour antigen (CTA) overexpressed in HGSC. PRAME demonstrated the highest differential gene expression between normal fallopian tubes and HGSC tumour tissues in a range of patient datasets. The PRAME DNA was condensed by the cationic cell-penetrating peptide RALA to form nanoparticles (NPs). These self-assembling NPs exhibited a mean hydrodynamic size <150 nm and zeta potential >10 mV at N : P ratios ≥4 with ≤3% free DNA. The NPs successfully transfected NCTC-929 and DC 2.4 cells with PRAME overexpression, with negligible cytotoxicity. Vaccination with the NPs in vivo elevated CD4⁺ and CD8⁺ T-cell activation with increased expression of INF-γ and IL-2 cytokines. Vaccination also significantly improved survival rates in a PRAME-expressing tumour model in vivo. This study demonstrated the utility of a PRAME-targeted DNA vaccine for HGSC treatment which warrants further investigation.