Patient-specific neoantigen–Major Histocompatibility Complex (neoAg-MHC) (neoAg-MHC)

Patient-specific neoantigen–Major Histocompatibility Complex (MHC) complexes are unique molecular signatures formed when mutated proteins in cancer cells are processed and presented on the cell surface by MHC molecules (Nature, 2017, doi:10.1038/nature22991). Unlike shared tumor-associated antigens, neoantigens arise from somatic mutations unique to an individual's tumor, making them highly specific targets that bypass central thymic tolerance (Science, 2015, doi:10.1126/science.aaa3801). These complexes are recognized by the T-cell receptor (TCR) of CD8+ and CD4+ T-cells, triggering a potent and specific immune response against the tumor (NEJM, 2017, doi:10.1056/NEJMoa1706223). Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines, such as mRNA-4157, which prime the immune system to recognize these unique markers, and adoptive cell therapies using TCR-engineered T-cells (Moderna, 2024). Because these antigens are absent in healthy tissues, they offer a high therapeutic index with reduced risk of autoimmunity compared to traditional therapies. However, their clinical application is challenged by the need for sophisticated bioinformatic prediction of immunogenic epitopes and the potential for tumor escape through MHC downregulation or loss of heterozygosity (Frontiers in Immunology, 2020, doi:10.3389/fimmu.2020.01100).

Other names

Tumor-specific neoantigenNeoepitope-HLA complexMutant peptide-MHC complexTSA-MHC complexNeoantigen-MHC complex

Induction of de novo T-cell responses and expansion of neoantigen-specific CD8+ and CD4+ T-cells to recognize and lyse tumor cells presenting the specific neoepitope-MHC complex (Nature, 2017).