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oai:figshare.com:article/32639622 2026-10-01T16:38:30Z portal_1172 item_type_8 month_year_10_2026

Design and development of a DNA vaccine for high grade serous ovarian cancer Chayanika Saha (20764301) PUREID: 590286508 ovarian cancer cancer vaccine nucleic acid delivery immunotherapy high grade serous ovarian cancer peptide nanoparticles nanoparticles Ovarian Cancer (OC) is a highly lethal gynaecological cancer with a ≤30% 5-year overall survival rate. High-grade serous carcinoma(HGSC) accounts for 75% of OC cases and is characterized by aggressive growth, asymptomatic progression, and suboptimal detection. Conventional treatments like chemotherapy and surgery often lead to high relapse rates, underscoring the need for alternative therapies. This study explores the potential of using differential antigen expression levels for early detection and vaccination strategies in OC. Specifically, the cancer-testis antigen PRAME, which is overexpressed in OC but minimally expressed in normal tissues (except the testis), was identified as a promising target. Analysis of patient gene expression datasets and online platforms confirmed PRAME's significant differential expression in HGSC. Furthermore, PRAME overexpression correlated with lower metastasis-free survival and was prevalent in platinum-resistant HGSC. A DNA vaccine encoding PRAME was developed using the cationic cell-penetrating peptide RALA to encapsulate and deliver the plasmid DNA (pDNA). The RALA/pPRAME nanoparticles (NPs) were characterized, showing a mean size of <150 nm and a zeta potential >10 at N:P ratios above 4, which is optimal for cellular uptake. Gel retardation and PicoGreen assays demonstrated effective pDNA condensation and encapsulation efficiency >80% at N:P ratios of 6 and above. In vitro transfection of NCTC 929 and DC 2.4 cell lines confirmed the functionality of the NPs, with observed PRAME overexpression and minimal cytotoxicity (cell viability >80% at N:P ratio 4 and above). Lyophilisation of the RALA/pPRAME NPs with 10% trehalose preserved their characteristics and functionality. In vivo studies in mice showed an enhanced immune response, with elevated CD4+ and CD8+ T-cell activity, reduced tumor growth, and improved survival rates in vaccinated mice compared to controls. These findings suggest that the RALA/pPRAME vaccine holds promise for treating platinum resistant HGSC and warrants further investigation.<br><br><i>Thesis is embargoed until 31 July 2029</i>.<br><br><br> 2026-10-01T16:38:30Z Text Thesis 10.17034/32639622.v1 https://figshare.com/articles/thesis/Design_and_development_of_a_DNA_vaccine_for_high_grade_serous_ovarian_cancer/32639622 All Rights Reserved Open Access after 2029-07-31