Tumor neoantigen-MHC complex (NeoAg-MHC) (NeoAg-MHC)

Patient-specific tumor neoantigens presented on Major Histocompatibility Complex (MHC) molecules are unique protein fragments resulting from somatic mutations in a patient's tumor cells that are not found in healthy tissue (Schumacher & Schreiber, Science 2015). These mutations, which include single nucleotide variants (SNVs), insertions/deletions (indels), and frameshifts, create novel non-self epitopes that can be recognized by the host's immune system (Blass & Ott, Nat Rev Clin Oncol 2021). The presentation of these neoepitopes by MHC class I or II molecules to autologous T-cell receptors (TCRs) is a critical step in the endogenous anti-tumor immune response and serves as the foundation for personalized immunotherapy (Rosenberg & Restifo, Science 2015). Therapeutic strategies targeting these complexes include personalized neoantigen vaccines (mRNA or peptide-based) and adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) or TCR-engineered T cells (Sahin & Türeci, Science 2018). Because neoantigens are absent from normal cells, they offer a high degree of specificity, potentially reducing the risk of off-target toxicity compared to shared tumor-associated antigens (Xie et al., Front Immunol 2023). However, the effectiveness of targeting these complexes can be limited by tumor heterogeneity, HLA downregulation, and the immunosuppressive tumor microenvironment (Schumacher & Schreiber, Science 2015).

Other names

Tumor-specific antigen (TSA)Neoepitope-HLA complexPatient-specific neoantigenpMHC complexTumor-specific neoepitope

Recognition of the specific neoepitope-MHC complex by a T-cell receptor (TCR), triggering T-cell activation, proliferation, and cytotoxic destruction of the tumor cell (Schumacher & Schreiber, Science 2015).