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

The tumor neoantigen-MHC complex is a molecular assembly consisting of a mutated peptide derived from a tumor-specific genetic alteration bound to a Major Histocompatibility Complex (MHC) molecule on the surface of a cancer cell [1]. These complexes are central to the adaptive immune system's ability to distinguish malignant cells from healthy tissue, as the mutations that generate neoantigens are absent from the normal genome [1, 3]. Recognition occurs when a T-cell receptor (TCR) binds specifically to the unique peptide-MHC (pMHC) interface, triggering T-cell activation and subsequent cytotoxic activity against the tumor [2]. Because these targets are highly patient-specific and bypass central immune tolerance, they are the focus of personalized immunotherapy strategies, including neoantigen vaccines and TCR-engineered T-cell (TCR-T) therapies [2, 3]. Vaccines like mRNA-4157 are designed to prime the patient's own immune system to recognize these complexes, while TCR-T therapies involve the infusion of T cells engineered with high-affinity receptors for a specific pMHC [3]. Despite their potential, the high degree of HLA polymorphism and the risk of antigen escape through MHC downregulation present significant therapeutic challenges [1, 2]. Accurate identification of these complexes requires advanced genomic sequencing and bioinformatic prediction of peptide-MHC binding affinity [1].

Other names

Neoantigen-HLA complexpMHC complexTumor-specific antigen-MHC complexTSA-MHCPatient-specific tumor neoantigen-MHC complex

Binding of the T-cell receptor (TCR) to the neoantigen-MHC complex triggers T-cell activation and subsequent lysis of the target tumor cell.