Tumor neoantigen presented on MHC (Neoantigen)

Patient-specific tumor antigens, commonly known as neoantigens, are unique peptides derived from somatic mutations within a patient's tumor that are not found in healthy tissues [1.1.5, 1.5.3]. These mutated proteins are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I or Class II molecules [1.1.4, 1.4.1]. Because neoantigens are entirely absent from the normal genome, they are not subject to central tolerance, allowing the immune system to recognize them as foreign and mount a potent T-cell response [1.1.5, 1.2.5]. This high specificity makes them ideal targets for personalized cancer immunotherapies, such as mRNA-based vaccines (e.g., mRNA-4157) and adoptive T-cell receptor (TCR) therapies, which aim to expand the pool of neoantigen-reactive T cells [1.3.3, 1.5.2]. However, the effectiveness of these therapies can be limited by tumor-mediated immune evasion, such as the downregulation of MHC molecules or the presence of subclonal mutations that do not exist in all tumor cells [1.2.2, 1.5.4].

Other names

Patient-specific tumor antigenTumor-specific antigenTSAMHC-bound neoepitopeMutant peptide-MHC complexTumor neoantigen

Induction or enhancement of a T-cell mediated immune response against tumor cells by presenting non-self peptides on MHC molecules, leading to the activation of cytotoxic T lymphocytes (CTLs) and helper T cells that selectively recognize and eliminate malignant cells.