Patient-specific cancer neoantigen peptide epitopes (Neoantigens)

Patient-specific cancer neoantigen peptide epitopes are unique protein fragments resulting from somatic mutations found exclusively within an individual's tumor cells (Schumacher & Schreiber, Science, 2015). These mutations, which include single nucleotide variants (SNVs) and insertions/deletions (indels), create novel amino acid sequences that the immune system perceives as foreign (Blass & Ott, Nature Reviews Clinical Oncology, 2021). The peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, specifically Human Leukocyte Antigens (HLA) in humans (Sahin et al., Nature, 2017). Because these neoantigens are absent from healthy tissues, they bypass central tolerance, allowing for the activation of high-affinity T cells without the risk of systemic autoimmunity (Ott et al., Nature, 2017). Therapeutic strategies targeting these epitopes include personalized mRNA or peptide vaccines and adoptive cell therapies like TCR-engineered T cells (Hu et al., Nature Reviews Immunology, 2021). These treatments aim to expand the patient's endogenous T-cell repertoire to specifically recognize and eliminate tumor cells (Moderna/Merck, KEYNOTE-942, 2023). The identification of these targets relies on advanced genomic sequencing and bioinformatic algorithms to predict MHC binding and immunogenicity (Gubin et al., Nature, 2014).

Other names

Tumor-specific neoantigensTSNAsNeoepitopesPersonalized neoantigensSomatic mutation-derived antigens

Personalized neoantigen therapies work by presenting unique, tumor-specific peptides to the immune system to induce or expand a population of CD4+ and CD8+ T cells that specifically recognize the mutation-MHC complex on cancer cells (Schumacher & Schreiber, Science, 2015; DOI: 10.1126/science.aaa4520).