Tumor-specific neoantigen-Major Histocompatibility Complex (Neoantigen-MHC) (NeoAg-MHC)

Tumor-specific neoantigen-MHC complexes are unique molecular targets formed when mutated proteins within a cancer cell are processed into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Schumacher & Schreiber, Science, 2015). Unlike tumor-associated antigens, neoantigens arise from somatic mutations such as single nucleotide variants, insertions, deletions, or frameshifts and are entirely absent from healthy tissues (Blass & Ott, Nature Reviews Clinical Oncology, 2021). This high degree of specificity minimizes the risk of central tolerance and off-target autoimmune toxicity. These complexes are primarily recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T cells, which then execute the destruction of the malignant cell (Sahin et al., Nature, 2017). Therapeutic interventions leveraging these targets include personalized cancer vaccines, such as mRNA-4157, and adoptive cell therapies using neoantigen-specific TCR-engineered T cells (Ott et al., Nature, 2017). The efficacy of these treatments often correlates with the tumor mutational burden and the efficiency of the cellular antigen presentation machinery. However, tumors can develop resistance by downregulating MHC expression or through the loss of the specific genomic segments encoding the neoantigen (Zaretsky et al., NEJM, 2016). Overall, neoantigen-MHC complexes represent a critical frontier in personalized immunotherapy, offering a path toward highly selective and potent cancer eradication.

Other names

Neoepitope-HLA complexTumor-specific antigen (TSA)Mutation-derived neoantigenpMHC complexNeoantigen-HLA complex

Induction of antigen-specific CD8+ and CD4+ T-cell responses through the recognition of mutation-derived peptides presented by MHC molecules, leading to the selective destruction of tumor cells (Schumacher & Schreiber, Science, 2015; Sahin et al., Nature, 2017).