Neoantigen-derived peptide–Major Histocompatibility Complex (NeoAg-MHC) (NeoAg-MHC)

Neoantigen-derived peptide–Major Histocompatibility Complex (MHC) complexes are highly specific molecular targets formed when mutated proteins within a tumor are processed and presented on the cell surface by MHC molecules (Nature Reviews Cancer, 2017). These complexes are unique to cancer cells because they arise from somatic mutations—such as non-synonymous single-nucleotide variants, insertions, or deletions—that are absent in the germline and normal tissues (Frontiers in Immunology, 2020). This tumor-exclusivity makes them ideal targets for precision immunotherapy, as they bypass central thymic tolerance and minimize the risk of autoimmune damage to healthy organs. Therapeutic interventions targeting these complexes include personalized mRNA or DNA vaccines designed to prime the patient's own T cells, as well as adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize specific neoepitopes (Science, 2019). Despite their potential, the effectiveness of targeting NeoAg-MHC complexes can be limited by the heterogeneity of mutations within a tumor and the ability of cancer cells to evade detection by downregulating MHC expression or losing specific HLA alleles (Nature, 2017). Current clinical research focuses on identifying "public" neoantigens shared across patients and improving the computational prediction of peptide-MHC binding affinity to enhance vaccine efficacy.

Other names

Neoepitope-HLA complexTumor-specific neoantigen-MHCNeoantigen-HLA complexMutated peptide-MHC complexTumor-specific antigen-MHC complex

Recognition by T-cell receptors (TCRs) or TCR-like molecules, triggering T-cell mediated cytotoxicity and immune-driven tumor cell lysis.