Patient-specific neoantigen–MHC complex (NeoAg-MHC)

Patient-specific neoantigen–MHC complexes are the primary molecular targets for personalized cancer immunotherapy, representing the interface between tumor-specific mutations and the adaptive immune system [1, 11]. These complexes are formed when mutated proteins (neoantigens) within a tumor are processed into peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules—Class I for recognition by CD8+ cytotoxic T cells and Class II for CD4+ helper T cells [1, 11]. Because these neoantigens arise from somatic mutations unique to the patient's tumor, they are absent from healthy tissues, making them ideal targets that minimize the risk of autoimmune cross-reactivity [3, 14]. Therapeutic strategies targeting these complexes include personalized vaccines (mRNA or peptide-based) designed to prime the patient's own T cells, and T-cell receptor (TCR) engineered therapies that provide high-affinity recognition of specific neoepitopes [2, 4]. Additionally, novel modalities like bispecific T-cell engagers are being developed to bind directly to these peptide-MHC surfaces [6]. The clinical success of targeting these complexes depends on accurate neoantigen prediction, the patient's HLA genotype, and the tumor's ability to maintain MHC expression, as downregulation of these complexes is a common mechanism of immune evasion [12, 18].

Other names

Tumor-specific antigen-MHC complexNeoepitope-HLA complexPersonalized neoantigen-MHC complexpMHC complexNeoantigen-HLA complex

Stimulation of neoantigen-specific T cells through T cell receptor (TCR) recognition of the peptide-MHC complex, leading to cytotoxic T cell activation and tumor cell lysis.