Patient-specific tumor-associated neoantigen presented on Human Leukocyte Antigen (HLA) molecules (Neoantigen)

Patient-specific tumor-associated neoantigens (TSNAs) are unique peptides derived from non-synonymous somatic mutations occurring within a patient's tumor cells (Nature, 2017, doi:10.1038/nature22991). These mutations create novel protein sequences that are processed and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Frontiers in Immunology, 2020, doi:10.3389/fimmu.2020.01500). Unlike shared tumor-associated antigens, neoantigens are absent from healthy tissues, which minimizes the risk of autoimmune cross-reactivity and bypasses central thymic tolerance (Science, 2015, doi:10.1126/science.aaa3801). This high specificity makes them prime targets for personalized cancer immunotherapies, including mRNA-based vaccines and adoptive T-cell transfers (NCI, 2023). By training the immune system to recognize these specific neoepitopes, clinicians can induce a potent and targeted anti-tumor response tailored to the individual's unique genomic profile (Cell, 2019, doi:10.1016/j.cell.2019.04.031). Current therapeutic efforts focus on identifying these mutations through next-generation sequencing and using bioinformatics to predict which peptides will bind most effectively to the patient's specific HLA alleles (Nature Reviews Drug Discovery, 2018, doi:10.1038/nrd.2017.235).

Other names

Tumor-specific neoantigenNeoepitopeMutation-derived antigenPersonalized cancer antigenTumor-specific antigen (TSA)TSNA

Stimulation of the immune system to recognize and destroy tumor cells by presenting unique, mutation-derived peptides on HLA molecules to activate cytotoxic T lymphocytes (CTLs) and helper T cells (Nature, 2017, doi:10.1038/nature22991).