Patient-specific tumor neoantigen repertoire (Neoantigen repertoire)

The patient-specific tumor neoantigen repertoire consists of unique peptides derived from somatic mutations—such as single nucleotide variants, insertions, or deletions—found exclusively in a patient's tumor cells (Nature, 2020). Because these neoantigens are absent from the normal proteome, they are not subject to central thymic tolerance, allowing for the generation of high-affinity T-cell responses (Science, 2017). Therapeutic interventions targeting this repertoire involve identifying mutations via whole-exome sequencing and using bioinformatic algorithms to predict which neoepitopes will most effectively bind to the patient's specific HLA molecules (Cell, 2019). Personalized vaccines, including mRNA-based and peptide-based platforms, are then manufactured to deliver these sequences, stimulating the expansion of neoantigen-specific CD8+ cytotoxic T lymphocytes and CD4+ helper T cells (Nature Medicine, 2021). This precision medicine approach aims to provide a durable anti-tumor response while minimizing the risk of autoimmunity associated with targeting shared self-antigens (Journal of Clinical Investigation, 2018). By tailoring the treatment to the individual's genomic profile, clinicians aim to overcome the limitations of traditional therapies and address the inherent heterogeneity of human cancers (NEJM, 2019).

Other names

Personalized neoantigensTumor-specific antigens (TSAs)NeoepitopesSomatic mutation-derived antigensIndividualized tumor-specific antigens

Induction of de novo T-cell responses and expansion of pre-existing neoantigen-specific T cells to recognize and eliminate tumor cells expressing unique somatic mutations (Nature, 2017).