Tumor-specific neoantigen (TSA) (TSA)

Tumor-specific neoantigens (TSAs) are unique peptides derived from somatic mutations—such as single-nucleotide variants, frame-shifts, or splice-site alterations—that occur exclusively within a patient's tumor cells (Science, 2015). These "non-self" proteins are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I and II molecules (Nature, 2017). Because these antigens are not expressed in healthy tissues, they serve as ideal targets for the immune system, as T-cells recognizing them are not eliminated by central tolerance (Frontiers in Immunology, 2020). Therapeutic interventions, such as personalized mRNA vaccines (e.g., mRNA-4157) or peptide-based vaccines, are designed to prime the patient's own immune system to recognize these specific sequences (Lancet, 2023). Once activated, neoantigen-specific CD8+ cytotoxic T-lymphocytes can selectively identify and destroy tumor cells while sparing normal tissue (Cell, 2021). This individualized approach addresses the high degree of heterogeneity found between different patients' tumors, even within the same cancer type (Science, 2018).

Other names

NeoantigenIndividualized tumor-specific antigenMutation-derived antigenPrivate neoantigenTumor-specific antigenTumor-specific mutation-derived antigen

Induction of a patient-specific, polyclonal T-cell response against unique mutation-derived peptides presented by MHC molecules on the tumor cell surface.