Tumor neoantigen (NeoAg) (NeoAg)

Tumor neoantigens are unique, patient-specific peptides derived from somatic mutations, such as single nucleotide variants or frameshifts, that are presented by Major Histocompatibility Complex (MHC) molecules to T-cell receptors (TCRs) (Source: Schumacher & Schreiber, Science, 2015). Because these antigens are absent from normal tissues, they are highly specific targets for immunotherapy and can bypass central thymic tolerance, allowing for the generation of high-affinity T-cell responses (Source: Blass & Ott, Nature Reviews Clinical Oncology, 2021). Therapeutic strategies targeting neoantigens include personalized cancer vaccines (mRNA, DNA, or peptide-based) and adoptive cell therapies using neoantigen-specific TCRs (Source: Sahin et al., Nature, 2017). These treatments aim to stimulate a robust, polyclonal immune response tailored to the individual's unique tumor profile (Source: BioNTech, 2024). The clinical efficacy of neoantigen-based therapies is often linked to the tumor's mutational burden and the accuracy of computational prediction algorithms used to identify immunogenic epitopes (Source: Wells et al., Nature Biotechnology, 2020). However, challenges such as intratumoral heterogeneity and the potential for tumor escape through MHC downregulation remain significant hurdles in the field (Source: Gettinger et al., Cancer Discovery, 2017).

Other names

Tumor-specific antigen (TSA)NeoepitopeMutation-derived antigenPatient-specific tumor-associated antigen

Induction of a de novo, mutation-specific T-cell response through the presentation of patient-specific neoepitopes by MHC molecules, leading to targeted destruction of tumor cells by cytotoxic T lymphocytes (CTLs).