Tumor neoantigen (MTA) (MTA)

Mutation-derived tumor antigens (MTAs), also commonly known as tumor neoantigens, are novel peptides that arise from somatic non-synonymous mutations within a tumor's genome, such as single-nucleotide variants or frameshift insertions/deletions [8, 16]. Because these antigens are unique to the malignancy and absent from the normal human proteome, they are highly immunogenic and can bypass central immune tolerance [1, 10]. These mutated proteins are processed by the cell's machinery and presented on the cell surface by major histocompatibility complex (MHC) molecules, where they serve as targets for cytotoxic T lymphocytes (CTLs) [14, 15]. Therapeutic approaches targeting these antigens include personalized cancer vaccines (e.g., mRNA-4157, Autogene cevumeran) and adoptive cell therapies involving TCR-engineered T cells, both of which are designed to elicit or amplify a specific anti-tumor immune response [10, 16]. The clinical effectiveness of these therapies is closely linked to biomarkers such as tumor mutational burden (TMB) and microsatellite instability (MSI), which correlate with a higher probability of neoantigen formation [3, 12, 16]. Despite their promise, therapeutic challenges include the significant logistical complexity of individualized manufacturing and the risk of tumor escape through the loss of antigen presentation or clonal heterogeneity [12, 16].

Other names

Mutation-derived tumor antigenNeoantigenNeoepitopeMutated tumor antigenTumor-specific antigenTSAMutation-derived neoantigen

Stimulates a patient-specific immune response by introducing or presenting unique, non-self mutated peptide sequences to the immune system. Vaccines deliver these antigens to dendritic cells for presentation on MHC molecules, thereby priming neoantigen-specific CD8+ and CD4+ T cells. Alternatively, adoptive cell therapies utilize T cells engineered to express receptors specifically recognizing these mutation-derived epitopes, leading to the targeted lysis of tumor cells.