INSERM U1242 Oncogenesis Stress Signaling - SPECIAL SEMINAR

Integrative discovery of non-canonical neoantigens: emerging opportunities and challenges for cancer immunotherapy Dr. Léa PROCHASSON PharmD and molecular biologist Curie Institute - PARIS Unité « Dynamique de l’information Génétique, bases fondamentales et cancer » (UMR3244) Equipe: ARN non codant, épigénétique et fluidité des génomes Abstract The clinical success of cancer immunotherapy relies on the identification of tumour-specific antigens capable of eliciting effective T-cell responses. However, canonical mutation-derived neoantigens remain challenging targets because of their limited immunogenicity, patient specificity, and heterogeneous HLA presentation. In contrast, the non-canonical proteome, generated through the translation of alternative open reading frames (ORFs) within non-coding transcripts, represents a promising and largely unexplored source of tumour antigens. Here, we developed an integrative pipeline for the discovery and validation of shared non-canonical neoantigens in pancreatic cancer. By combining transcriptome-wide k-mer analysis, ribosome profiling, immunopeptidomics, and functional immunogenicity assays, we identified 14 non-canonical neoantigens across primary and metastatic tumors, presented by several common HLA alleles (HLA-A02:01, -A01:01 and -A24:02). Their therapeutic potential was further assessed through MHC-binding, T-cell activation, and peptide-specific T-cell receptor (TCR) screening using naïve CD8+ T cells from healthy donors.

Date
mardi 20 octobre 2026, de 11h00 à 12h00
Lieu
Centre de Lutte Contre le Cancer Eugène Marquis, Avenue de la Bataille Flandres Dunkerque, 35043 Rennes
Organisateur
UMR INSERM 1242 Oncogenesis Stress Signaling (OSS)
INSERM U1242 Oncogenesis Stress Signaling - SPECIAL SEMINAR — Rennes

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