Patient-specific cancer neoantigen (Neoantigen)

Patient-specific cancer neoantigens are unique peptides derived from non-synonymous somatic mutations—such as single-nucleotide variants (SNVs), insertions/deletions (indels), or gene fusions—that occur exclusively within a patient's tumor cells (Schumacher & Schreiber, 2015; Science). These novel sequences are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they are recognized by the host's T-cells as foreign or "non-self" (Blass & Ott, 2021; Nature Reviews Clinical Oncology). Because neoantigens are entirely absent from the normal human proteome, they bypass central thymic tolerance, making them highly immunogenic and ideal targets for precision immunotherapy (Sahin & Türeci, 2018; Science). Therapeutic strategies leveraging these targets include the development of personalized cancer vaccines (delivered via mRNA, DNA, or peptides) and adoptive cell therapies using TCR-engineered T-cells (Ott et al., 2017; Nature). By directing the immune system to specifically attack cells harboring these unique mutations, neoantigen-based therapies aim to achieve high clinical efficacy with minimal damage to healthy tissues. The identification of these targets relies on high-throughput sequencing and advanced bioinformatic algorithms to predict which mutations will result in peptides that bind effectively to the patient's specific HLA alleles (Hu et al., 2021; Nature Reviews Genetics).

Other names

Tumor-specific antigenTSANeoepitopeSomatic mutation-derived antigenPersonalized cancer antigenMutation-derived neoantigen

Induction of a de novo T-cell response or expansion of existing tumor-reactive cytotoxic T-lymphocytes (CTLs) that specifically recognize and eliminate tumor cells presenting unique mutation-derived peptides on MHC molecules (Schumacher & Schreiber, 2015).