Mutated neoantigen (Neoantigen)

Mutated neoantigens are novel, tumor-specific proteins that arise from non-synonymous somatic mutations, such as single nucleotide variants, insertions, or deletions, within a cancer cell's genome (Nature Reviews Cancer, 2017). Because these antigens are entirely absent from the normal human proteome, they are not subject to central thymic tolerance, making them highly immunogenic and ideal targets for precision immunotherapy (Frontiers in Immunology, 2020). These peptides are processed by the cellular machinery and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T-cells and CD4+ helper T-cells (NIH National Cancer Institute). Therapeutic strategies targeting neoantigens include personalized mRNA or peptide vaccines, such as mRNA-4157, designed to stimulate a de novo immune response, as well as adoptive cell therapies using TCR-engineered T-cells (Moderna, 2024; BioNTech, 2023). By focusing the immune system on these unique markers, clinicians aim to achieve potent anti-tumor activity with minimal off-target toxicity to healthy tissues. However, challenges remain regarding the heterogeneity of neoantigen expression within a tumor and the potential for "immunoediting," where tumors lose the targeted antigen to evade detection (Journal of Hematology & Oncology, 2021). Additionally, the identification of these targets requires complex bioinformatic pipelines to predict which mutations will result in peptides that bind effectively to a patient's specific HLA alleles (Nature, 2023).

Other names

Tumor-specific antigenTSANeoepitopeSomatic mutation-derived antigenTumor-specific neoantigen

Mutated neoantigens serve as highly specific targets for the immune system; drugs such as personalized vaccines or TCR-engineered T-cells work by priming or directing the patient's own T-lymphocytes to recognize these unique peptide-MHC complexes, leading to the selective destruction of tumor cells while sparing healthy tissue (Nature, 2023; Science, 2019).