Patient-specific tumor neoantigen (TSNA) (TSNA)

Patient-specific tumor neoantigens are unique peptides derived from non-synonymous somatic mutations, such as single nucleotide variants, insertions, or deletions, that occur exclusively within a patient's tumor cells (Schumacher & Schreiber, Science 2015). These neoantigens are processed by the proteasome and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they serve as targets for recognition by the T-cell receptor (TCR) of CD8+ and CD4+ T cells (Xie et al., Signal Transduction and Targeted Therapy 2023). Because these antigens are absent from the normal human genome, they are not subject to central thymic tolerance, allowing the immune system to mount high-affinity responses against them with minimal risk of attacking healthy tissues (Ott et al., Nature 2017). Therapeutic strategies targeting these neoantigens include personalized cancer vaccines—delivered via mRNA, DNA, or synthetic peptides—and adoptive T-cell therapies designed to prime or amplify the patient's own immune response (Sahin et al., Nature 2017). While highly specific, the clinical efficacy of targeting neoantigens can be challenged by the high degree of intratumoral heterogeneity and the potential for tumors to evade detection by downregulating antigen presentation machinery (Blass & Ott, Nature Reviews Clinical Oncology 2021).

Other names

NeoepitopeMutation-derived antigenPersonalized neoantigenTumor-specific neoantigenTumor-specific antigen (TSA)Private neoantigen

Active immunization to induce de novo neoantigen-specific T-cell responses or expand existing memory T-cell populations; Adoptive transfer of autologous or engineered T-cells targeting specific neoepitopes.