Patient-specific tumor neoantigen (Neoantigen)

Patient-specific tumor neoantigens are novel peptides derived from somatic mutations unique to an individual's tumor cells, such as single nucleotide variants, insertions/deletions, or chromosomal translocations (Schumacher & Schreiber, Nature Reviews Cancer, 2017). These mutated proteins are processed by the cellular machinery and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Jiang et al., Frontiers in Immunology, 2020). Once presented, they are recognized as non-self by the host's T-cell receptors (TCRs), triggering a targeted immune response (Rizvi et al., Science, 2015). Because these antigens are absent from healthy tissues, they provide a high degree of tumor specificity, minimizing the risk of autoimmune damage to normal organs (Sahin & Türeci, NEJM, 2018). Therapeutic strategies targeting these neoantigens include personalized cancer vaccines and adoptive T-cell therapies, such as TCR-engineered T-cells (TCR-T) or tumor-infiltrating lymphocytes (TILs) (Nature, 2021). These treatments aim to expand and activate neoantigen-specific CD8+ and CD4+ T-cells to selectively eliminate malignant cells. The identification of these targets typically requires whole-exome sequencing (WES) and RNA sequencing of the tumor compared to healthy tissue, followed by computational algorithms to predict MHC binding affinity and TCR recognition.

Other names

Tumor-specific antigenTSANeoepitopeMutation-derived antigenPrivate neoantigenTumor-specific neoantigen

Induction of a de novo or expanded T-cell response against unique tumor mutations through active vaccination (mRNA, DNA, or peptide) or adoptive transfer of TCR-engineered T-cells to recognize specific peptide-MHC complexes.