Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens

Sep 21, 2026

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Epithelial ovarian cancer has not substantially benefited from immunotherapy due to insufficient actionable antigen targets. Proteogenomic analyses previously revealed 91 aberrantly expressed tumor-specific antigens arising from unmutated genomic sequences, driven by cancer-specific epigenetic changes. This study evaluates immunogenicity of 48 selected TSAs based on frequent HLA presentation and expression across a significant fraction of EOC tumors, using targeted mass spectrometry and T cell expansion assays.

LanguageEnglish

CategoryHealthcare

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Pages23

Reading Time58 min

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Abstract

Introduction

Article Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens Leslie Hesnard 1, Catherine Thériault 1, Maxime Cahuzac 1, Chantal Durette 1, Krystel Vincent 1, Marie-Pierre Hardy 1, Joël Lanoix 1, Gabriel Ouellet Lavallée 1, Juliette Humeau 1, Pierre Thibault 1,2 and Claude Perreault 1,3, * Citation: Hesnard, L.; Thériault, C.; Cahuzac, M.; Durette, C.; Vincent, K.; Hardy, M.-P.; Lanoix, J.; Lavallée, G.O.; Humeau, J.; Thibault, P.; et al. Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens. Curr. Oncol. 2024, 31, 3099–3121 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)curroncol31060236 Received: 4 April 2024 Revised: 24 May 2024 Accepted: 27 May 2024 Published: 30 May 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Institute for Research in Immunology and Cancer (IRIC), University of Montreal, Montreal, QC H3T 1J4, Canada; [leslie.hesnard@umontreal.ca](leslie.hesnard@umontreal.ca) (L.H.); catherine.theriault.4@umontreal.ca (C.T.); maxime.cahuzac@umontreal.ca (M.C.); [chantal.durette@umontreal.ca](chantal.durette@umontreal.ca) (C.D.); [krystel.vincent@umontreal.ca](krystel.vincent@umontreal.ca) (K.V.); [marie-pierre.hardy@umontreal.ca](marie-pierre.hardy@umontreal.ca) (M.-P.H.); [joel.lanoix@umontreal.ca](joel.lanoix@umontreal.ca) (J.L.); [gabriel.ouellet.lavallee@umontreal.ca](gabriel.ouellet.lavallee@umontreal.ca) (G.O.L.); [juliette.f.humeau@gmail.com](juliette.f.humeau@gmail.com) (J.H.); [pierre.thibault@umontreal.ca](pierre.thibault@umontreal.ca) (P.T.) 2 Department of Chemistry, University of Montreal, Montreal, QC H2V 0B3, Canada 3 Department of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada * Correspondence: [claude.perreault@umontreal.ca](claude.perreault@umontreal.ca) Abstract: Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy. Keywords: tumor-specific antigen; vaccine; mass spectrometry; antigen presentation; immunogenicity; dendritic cells 1. Introduction Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer death. High-grade serous ovarian carcinoma represents 70% of EOC and accounts for 90% of advanced-stage disease and mortality [1,2] . The late diagnosis is one of the main factors contributing to a low 5-year survival rate recently estimated at 50%[3] . EOC is considered a tumor type with potential immunoreactivity due to the well-documented positive correlation between the presence of tumor-infiltrating

FAQs

Why is immunotherapy less effective in epithelial ovarian cancer?

Immunotherapy has shown limited benefit mainly because well-defined actionable antigen targets are lacking for effective T cell responses.

How were the tumor-specific antigens selected for this study?

The study selected 48 TSAs based on two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors.

What experimental methods were used to assess immunogenicity?

Targeted mass spectrometry assessed antigen presentation, and naïve CD8 T cell expansion was evaluated using MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing.

Sep 21, 2026

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