Shared tumor neoantigens derived from recurrent oncogenic mutations presented on MHC class I (Shared neoantigens (sNeoAgs))

Shared tumor neoantigens (sNeoAgs) are immunogenic peptides derived from recurrent hotspot mutations in driver oncogenes, such as KRAS, TP53, and PIK3CA, which are common across different patients and tumor types (Nature Reviews Cancer, 2021). These antigens are presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, enabling recognition by the adaptive immune system, specifically CD8+ T cells (Frontiers in Immunology, 2021). Unlike personalized neoantigens that require individual sequencing and manufacturing, shared neoantigens facilitate the development of off-the-shelf therapeutic modalities, including TCR-engineered T-cell (TCR-T) therapies and fixed-composition vaccines (Journal of Hematology & Oncology, 2023). Because these mutations often drive the malignant phenotype, they are considered high-quality targets with a lower risk of loss through tumor immunoediting. However, their application is limited by MHC restriction, meaning a specific drug is only effective in patients carrying both the mutation and a compatible HLA allele, such as HLA-A*02:01 (Science, 2019). Clinical development is currently robust, with multiple trials investigating TCR-T cells and mRNA vaccines targeting common mutations like KRAS G12D and TP53 R175H in specific HLA contexts (ClinicalTrials.gov).

Other names

Public neoantigensHotspot neoantigensRecurrent neoepitopesShared neoepitopesOff-the-shelf neoantigens

Recognition of specific peptide-MHC class I complexes by T-cell receptors (TCRs) or TCR-like molecules, leading to the activation of cytotoxic T lymphocytes and subsequent lysis of tumor cells.