Patient-specific tumor neoantigen peptide–major histocompatibility complex (neoantigen-MHC) (Neoantigen-MHC)

Patient-specific tumor neoantigen peptide–major histocompatibility complex (neoantigen-MHC) refers to the presentation of unique, mutation-derived peptides on the surface of cancer cells by MHC molecules (Schumacher & Schreiber, 2015, Science). These neoantigens arise from somatic mutations—such as single nucleotide variants or frameshifts—that are absent in healthy tissues, making them highly specific targets for the immune system (Ott et al., 2017, Nature). The recognition of these complexes by T cell receptors (TCRs) is a critical step in the adaptive immune response against cancer, triggering the activation of cytotoxic T lymphocytes (Sahin & Türeci, 2018, Science). Therapeutic strategies targeting these complexes include personalized cancer vaccines, such as mRNA-4157, and adoptive T cell therapies, which aim to prime or engineer the patient's immune system to selectively eliminate tumor cells (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Because these targets are unique to each patient's tumor, they offer a high degree of precision and a lower risk of central tolerance-related side effects compared to shared tumor-associated antigens. However, the identification and validation of these complexes require sophisticated genomic sequencing and bioinformatic prediction of MHC binding affinity (Gubin et al., 2015, Journal of Clinical Investigation).

Other names

Tumor-specific neoantigen (TSNA)Neoepitope-HLA complexMutant peptide-MHC complexPersonalized tumor antigen

Induction of antigen-specific T cell responses through the presentation of tumor-specific mutant peptides on MHC molecules, leading to the recognition and lysis of tumor cells by cytotoxic T lymphocytes.