Patient-specific tumor-specific neoantigen (Neoantigen)

Patient-specific tumor-associated antigens, commonly referred to as neoantigens, are novel peptides derived from somatic mutations—such as single nucleotide variants, indels, or gene fusions—that occur exclusively within a patient's tumor cells (Sahin et al., Nature 2017). These mutated proteins are processed by the cellular machinery and presented on the cell surface bound to Major Histocompatibility Complex (MHC) molecules, allowing the immune system to distinguish malignant cells from healthy tissue. Because neoantigens are not encoded by the normal genome, they bypass central thymic tolerance, making them highly immunogenic and ideal targets for precision immunotherapy (Ott et al., Nature 2017). Therapeutic strategies targeting these antigens include personalized mRNA or peptide vaccines and adoptive cell therapies, such as Tumor-Infiltrating Lymphocytes (TILs) or TCR-engineered T cells, which are designed to elicit a robust and specific cytotoxic T-cell response against the tumor. While highly promising for reducing off-target toxicity, the clinical application of neoantigen-based therapies requires sophisticated bioinformatics for antigen prediction and rapid, individualized manufacturing processes (Blass & Ott, Nature Reviews Clinical Oncology 2021).

Other names

Tumor-specific antigenTSAMutated tumor antigenPatient-specific tumor-associated antigenNeoepitopeSomatic mutation-derived antigen

Induction of a de novo T-cell response or expansion of existing neoantigen-specific CD8+ and CD4+ T cells that recognize and lyse tumor cells presenting the specific mutated peptide-MHC complex (Schumacher & Schreiber, Science 2015).