Patient-specific cancer neoantigen–Major Histocompatibility Complex (MHC) (NeoAg-MHC complex)

Patient-specific cancer neoantigen–Major Histocompatibility Complex (MHC) complexes are unique molecular structures formed when mutated proteins within a tumor cell are processed and presented on the cell surface by MHC molecules. Unlike shared tumor-associated antigens, these neoantigens arise from somatic mutations unique to an individual patient's tumor, making them highly specific targets for the immune system with minimal risk of central tolerance or autoimmunity [2, 10]. These complexes are recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, triggering a targeted immune response against the malignancy [6, 15]. Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines, which prime the immune system to recognize these specific epitopes, and adoptive cell therapies using TCR-engineered T cells [5, 12, 17]. Because they are absent in healthy tissues, neoantigen-MHC complexes represent a cornerstone of precision oncology and personalized immunotherapy [10, 13]. However, their therapeutic utility can be limited by tumor escape mechanisms, such as the downregulation of MHC expression or loss of antigen processing machinery [12, 15].

Other names

Tumor-specific antigen (TSA)-MHC complexNeoepitope-MHC complexPersonalized cancer antigen-MHCMutation-derived antigen-MHCpMHC complex

Induction or redirection of T-cell mediated cytotoxicity against tumor cells through the specific recognition of mutated peptide-MHC complexes by T-cell receptors (TCRs).