Patient-specific tumor neoantigen presented on Major Histocompatibility Complex class I (Neoantigen-MHC-I)

Patient-specific tumor neoantigens are unique peptides derived from non-synonymous somatic mutations, such as point mutations, insertions/deletions, or gene fusions, that occur exclusively within a patient's tumor cells (Schumacher & Schreiber, 2015, Science). These neoepitopes are processed and presented on the cell surface by Major Histocompatibility Complex class I (MHC-I) molecules, where they serve as non-self signals to the immune system (Blass & Ott, 2021, Nature Reviews Genetics). Because these antigens are absent from the normal human proteome, they are highly immunogenic and less likely to be subject to central thymic tolerance, making them ideal targets for precision immunotherapy (Finn, 2017, Annals of Oncology). Therapeutic approaches include personalized mRNA or peptide vaccines, such as mRNA-4157, and adoptive T-cell therapies that utilize T-cell receptors (TCRs) specifically engineered to recognize these unique peptide-MHC complexes (Sahin & Türeci, 2018, Science). By targeting these antigens, the immune system can selectively eliminate malignant cells while sparing healthy tissue, although challenges remain regarding tumor heterogeneity and the downregulation of MHC-I by cancer cells to evade detection (Jhunjhunwala et al., 2021, Nature Reviews Cancer).

Other names

Tumor-specific antigen (TSA)NeoantigenNeoepitopeMutation-derived antigenPatient-specific antigenSomatic mutation-derived peptide

Induction of a de novo or expanded cytotoxic CD8+ T-cell response through the specific recognition of mutation-derived peptides presented by MHC-I molecules, leading to targeted lysis of tumor cells.