Patient-specific tumor neoantigen–Major Histocompatibility Complex (MHC) (NeoAg-MHC)

Patient-specific tumor neoantigen–Major Histocompatibility Complex (MHC) complexes are unique molecular targets formed when somatic mutations in a patient's tumor lead to the production of non-self proteins (Schumacher & Schreiber, 2015, Science). These mutant proteins are processed into peptides and presented on the cell surface by MHC molecules, where they can be specifically recognized by T-cell receptors (TCRs) (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Because these neoantigens are absent from healthy tissues, they represent highly specific targets for personalized immunotherapy, minimizing the risk of autoimmune cross-reactivity (Rosenberg & Restifo, 2015, Science). Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines designed to prime the immune system, as well as adoptive cell therapies using TCR-engineered T-cells (TCR-T) (Sahin & Türeci, 2018, Science). The identification of these complexes typically requires high-throughput sequencing and computational algorithms to predict which mutations will result in immunogenic neoepitopes (Ott et al., 2017, Nature). Despite their potential, challenges remain regarding tumor heterogeneity and the mechanisms by which tumors may downregulate MHC expression to evade immune detection (Gettinger et al., 2017, Cancer Discovery).

Other names

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

T-cell receptor (TCR) binding to the peptide-MHC complex leading to the activation of cytotoxic T-lymphocytes and subsequent tumor cell lysis.