Neoantigen peptide-Major Histocompatibility Complex (neoAg-MHC)

Patient-specific neoantigen peptide-Major Histocompatibility Complex (neoAg-MHC) complexes are unique molecular structures formed when mutated proteins within a tumor are processed and presented on the cell surface by MHC molecules (Schumacher & Schreiber, Science, 2015). These complexes are central to the cancer-immunity cycle as they allow the immune system to distinguish malignant cells from healthy ones. Because neoantigens arise from somatic mutations unique to an individual's tumor, they are not present in normal tissues, making them highly specific targets for immunotherapy with minimal risk of central tolerance (Sahin & Türeci, Science, 2018). Therapeutic strategies targeting these complexes include personalized cancer vaccines (mRNA, DNA, or peptide-based) and adoptive T-cell therapies, such as TCR-engineered T cells (TCR-T) (Blass & Ott, Nature Reviews Clinical Oncology, 2021). By binding to these complexes, T-cell receptors (TCRs) on CD8+ and CD4+ T cells trigger cytotoxic activity and cytokine release, leading to targeted tumor destruction. Despite their promise, challenges include the high heterogeneity of neoantigen expression and the potential for tumors to downregulate MHC expression to evade immune detection.

Other names

Neoepitope-MHC complexTumor-specific neoantigen-HLA complexpHLA (peptide-HLA) complexMutation-derived antigen-MHC complex

Presentation of tumor-specific mutant peptides to T-cell receptors (TCRs) to induce a targeted cytotoxic and helper T-cell immune response against malignant cells.