Patient-specific neoantigen–major histocompatibility complex (neoAg-MHC) complex (neoAg-MHC complex)

Patient-specific neoantigen–MHC complexes are unique molecular signatures found on the surface of tumor cells, resulting from somatic mutations that create novel, non-self peptides presented by the Major Histocompatibility Complex (MHC) [3, 5]. Unlike tumor-associated antigens, which are also expressed in normal tissues, neoantigens are strictly tumor-specific, making them ideal targets for precision immunotherapy with minimal risk of central tolerance or systemic toxicity [3, 6]. These complexes are recognized by the T-cell receptor (TCR) of CD8+ or CD4+ T cells, triggering a targeted immune response against the malignancy [4, 10]. Therapeutic strategies leveraging these complexes include personalized cancer vaccines (e.g., mRNA-4157), TCR-engineered T cells, and TCR-like antibodies designed to bypass the limitations of traditional treatments [3, 12]. However, challenges such as the high heterogeneity of tumors, the necessity for complex bioinformatic prediction of immunogenic epitopes, and potential tumor escape mechanisms like MHC downregulation remain significant hurdles in clinical application [6, 10, 13].

Other names

Tumor-specific neoantigen-MHCNeoepitope-HLA complexMutant peptide-MHC complexpHLA complexpMHC complex

Recognition by T-cell receptors (TCRs) on CD8+ or CD4+ T cells, leading to T-cell activation, cytokine release (e.g., IFN-gamma), and direct tumor cell lysis [3, 4, 6].