Patient-specific tumor neoantigen peptides (TSNA) (TSNA)

Patient-specific tumor neoantigen peptides are unique protein fragments resulting from somatic mutations—such as single nucleotide variants, insertions, or deletions—within a patient's tumor genome (Schumacher & Schreiber, 2015). Unlike tumor-associated antigens, neoantigens are entirely absent from the normal human proteome, which allows the immune system to recognize them as foreign (non-self) without the constraints of central tolerance (Blass & Ott, 2021). These peptides are presented on the surface of cancer cells by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T cells and CD4+ helper T cells (Hacohen et al., 2013). Therapeutic approaches, including personalized mRNA or peptide vaccines and adoptive cell transfer, aim to amplify the patient's immune response against these specific targets (Sahin & Türeci, 2018). This precision medicine approach minimizes "off-target" damage to healthy tissues, although its efficacy is often limited by the tumor's ability to downregulate MHC expression or the immunosuppressive nature of the tumor microenvironment (Jhunjhunwala et al., 2021).

Other names

NeoantigensTumor-specific antigensTSAsMutation-derived antigensPersonalized neoantigens

Induction of a de novo T-cell response against tumor-specific mutations through MHC-restricted antigen presentation, leading to the selective destruction of malignant cells (Sahin & Türeci, 2018).