Patient-specific tumor-associated neoantigen (TSNA)

Patient-specific tumor-associated neoantigens are novel, immunogenic peptides derived from non-synonymous somatic mutations, such as point mutations, insertions/deletions, or chromosomal translocations, occurring exclusively within a patient's tumor cells (Blass & Ott, Nature Reviews Clinical Oncology 2021). These antigens are processed by the intracellular proteasome and presented on the cell surface by human leukocyte antigen (HLA) molecules, serving as 'non-self' signals to the adaptive immune system (Schumacher & Schreiber, Science 2015). Unlike traditional tumor-associated self-antigens, neoantigens bypass central thymic tolerance, allowing for the activation of high-affinity T cells without the risk of systemic autoimmunity (Sahin et al., Nature 2017). Therapeutic strategies targeting these neoantigens include personalized cancer vaccines (mRNA, DNA, or peptide-based) and adoptive T-cell therapies, which aim to prime or enhance the patient's own immune system to selectively destroy malignant cells (Ott et al., Nature 2017). The identification of these targets relies on comparative whole-exome sequencing of tumor and healthy tissue combined with predictive algorithms for MHC binding affinity and immunogenicity (NCI, 2023).

Other names

NeoantigenTumor-specific antigenNeoepitopeSomatic mutation-derived antigenPrivate neoantigenMutanome-derived antigen

Induction of a de novo T-cell response or expansion of pre-existing neoantigen-specific CD4+ and CD8+ T cells to recognize and eliminate tumor cells expressing the specific mutated peptide-MHC complex (Schumacher & Schreiber, Science 2015).