Tumor-specific neoantigen peptides presented on MHC class I and II molecules (TSNA)

Tumor-specific neoantigen peptides (TSNAs) are novel antigens arising from non-synonymous somatic mutations, such as single nucleotide variants, frameshifts, or gene fusions, that occur exclusively within a patient's tumor genome (Schumacher & Schreiber, 2015, Science). These peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I and class II molecules, where they are recognized by CD8+ cytotoxic T cells and CD4+ helper T cells, respectively (Hacohen et al., 2013, Cancer Immunology Research). Because TSNAs are absent from the normal human proteome, they bypass central thymic tolerance, making them highly immunogenic and reducing the risk of systemic autoimmunity compared to tumor-associated self-antigens (Ott et al., 2017, Nature). Therapeutic strategies targeting these neoantigens include personalized mRNA, DNA, or peptide-based vaccines and adoptive T-cell therapies using TCR-engineered cells (Sahin et al., 2017, Nature). These interventions aim to prime a precise, patient-specific immune response to eradicate malignant cells while sparing healthy tissue. However, the clinical success of targeting TSNAs depends on the accurate bioinformatic prediction of which mutations will result in immunogenic peptides and the ability to overcome tumor-mediated immunosuppression (Blass & Ott, 2021, Nature Reviews Clinical Oncology).

Other names

Tumor neoantigensNeoepitopesMutation-derived antigensPatient-specific neoantigensTumor-specific antigens (TSA)

Induction of de novo T-cell responses or expansion of existing neoantigen-specific CD8+ and CD4+ T cells to recognize and eliminate tumor cells expressing these unique mutations.