Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens

Leslie Hesnard; Catherine Thériault; Maxime Cahuzac; Chantal Durette; Krystel Vincent; Marie-Pierre Hardy; Joël Lanoix; Gabriel Ouellet Lavallée; Juliette Humeau; Pierre Thibault; Claude Perreault

doi:10.20944/preprints202404.0567.v1

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preprints.org > medicine and pharmacology > immunology and allergy > doi: 10.20944/preprints202404.0567.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens

Gabriel Ouellet Lavallée

Juliette Humeau

Pierre Thibault

Claude Perreault

Version 1 : Received: 7 April 2024 / Approved: 8 April 2024 / Online: 8 April 2024 (15:41:08 CEST)

How to cite: Hesnard, L.; Thériault, C.; Cahuzac, M.; Durette, C.; Vincent, K.; Hardy, M.; Lanoix, J.; Lavallée, G.O.; Humeau, J.; Thibault, P.; Perreault, C. Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens. Preprints 2024, 2024040567. https://doi.org/10.20944/preprints202404.0567.v1 Hesnard, L.; Thériault, C.; Cahuzac, M.; Durette, C.; Vincent, K.; Hardy, M.; Lanoix, J.; Lavallée, G.O.; Humeau, J.; Thibault, P.; Perreault, C. Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens. Preprints 2024, 2024040567. https://doi.org/10.20944/preprints202404.0567.v1

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MDPI and ACS Style

Hesnard, L.; Thériault, C.; Cahuzac, M.; Durette, C.; Vincent, K.; Hardy, M.; Lanoix, J.; Lavallée, G.O.; Humeau, J.; Thibault, P.; Perreault, C. Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens. Preprints 2024, 2024040567. https://doi.org/10.20944/preprints202404.0567.v1

APA Style

Hesnard, L., Thériault, C., Cahuzac, M., Durette, C., Vincent, K., Hardy, M., Lanoix, J., Lavallée, G.O., Humeau, J., Thibault, P., & Perreault, C. (2024). Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens. Preprints. https://doi.org/10.20944/preprints202404.0567.v1

Chicago/Turabian Style

Hesnard, L., Pierre Thibault and Claude Perreault. 2024 "Immunogenicity of Non-mutated Ovarian Cancer-Specific Antigens" Preprints. https://doi.org/10.20944/preprints202404.0567.v1

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

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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