Tumor neoantigen-derived peptide–Major Histocompatibility Complex (neoAg-MHC)

Tumor neoantigen-derived peptide–Major Histocompatibility Complex (MHC) complexes are cell-surface structures composed of a mutated peptide fragment bound to an MHC molecule (HLA in humans). These complexes are central to the "non-self" recognition of cancer cells by the immune system, as the mutations (e.g., single nucleotide variants, frameshifts, or splice variants) are absent from the normal genome (Schumacher & Schreiber, 2015 [Science]). Because these neoepitopes do not undergo central tolerance, they can be recognized by high-affinity T-cell receptors (TCRs), making them ideal targets for precision immunotherapy (Blass & Ott, 2021 [Nature Reviews Clinical Oncology]). Therapeutic interventions include personalized vaccines (e.g., mRNA-4157) that prime the immune system to recognize these complexes and adoptive T-cell therapies (TCR-T) engineered to bind specific neoantigen-MHC pairs (Leidner et al., 2022 [NEJM]). Despite their high specificity, the clinical utility of these targets is often limited by the high degree of inter-patient heterogeneity and the potential for tumor immune escape through the downregulation of MHC expression (Sahin & Türeci, 2018 [Science]).

Other names

Neoantigen-HLA complexpHLA complexTumor-specific antigen-MHC complexNeoepitope-MHC complexTumor-specific neoantigen-MHC

Recognition by T-cell receptors (TCRs) or TCR-like molecules to induce a targeted cytotoxic immune response against tumor cells.