Tumor-specific neoantigen-derived peptide (Neoantigen)

Tumor-specific neoantigen-derived peptides are novel protein sequences arising from somatic mutations within a tumor's genome, such as single nucleotide variants, insertions/deletions, or chromosomal rearrangements (National Cancer Institute, 2023). Unlike tumor-associated antigens, neoantigens are entirely absent from the normal human proteome, which allows them to bypass central thymic tolerance and trigger robust, highly specific T-cell responses (Schumacher & Schreiber, Science, 2015). These peptides are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they are recognized by the T-cell receptor (TCR) of CD8+ and CD4+ T cells (Nature Reviews Cancer, 2021). In the context of oncology, neoantigens serve as the primary targets for personalized immunotherapy, including cancer vaccines (mRNA, DNA, or peptide-based) and adoptive T-cell therapies (Moderna, 2024; BioNTech, 2024). By targeting these unique markers, clinicians aim to induce a durable anti-tumor immune response while minimizing the risk of off-target toxicity to healthy tissues (PubMed, PMID: 28702498). The identification of these targets typically requires high-throughput sequencing and bioinformatic prediction of MHC binding affinity to ensure the selected peptides are immunogenic (Frontiers in Immunology, 2020).

Other names

NeoantigenTumor-specific antigenTSAMutation-derived antigenPersonalized cancer antigenNeoepitope

Neoantigens act as highly specific targets for the immune system; vaccines or cell therapies targeting these peptides stimulate the expansion of neoantigen-specific cytotoxic T lymphocytes (CTLs) and helper T cells that recognize and kill tumor cells presenting these unique sequences on MHC molecules (Nature, 2017; Science, 2015).