Patient-specific tumor-associated antigen (Neoantigen) presented on peptide–MHC complex (Neoantigen-pMHC)

Patient-specific tumor-associated antigens, commonly known as neoantigens, are novel peptides derived from non-synonymous somatic mutations, insertions/deletions, or chromosomal translocations unique to an individual's tumor (Schumacher & Schreiber, 2015). These mutated proteins are intracellularly processed and presented on the tumor cell surface by Major Histocompatibility Complex (MHC) molecules, forming a peptide-MHC (pMHC) complex (Sahin & Türeci, 2018). Unlike shared tumor-associated antigens, neoantigens are absent from the normal genome, meaning they are not subject to central thymic tolerance and can be recognized as "non-self" by the T-cell repertoire (Blass & Ott, 2021). This high specificity makes them ideal targets for precision immunotherapy, minimizing the risk of off-target toxicity against healthy tissues. Current therapeutic modalities targeting these complexes include personalized mRNA or peptide-based vaccines and adoptive T-cell therapies (TCR-T) designed to expand or introduce neoantigen-reactive T cells (Hu et al., 2021). The efficacy of these treatments often depends on the tumor's mutational burden and the efficiency of the patient's antigen presentation machinery. Furthermore, the identification of these targets requires advanced genomic sequencing and bioinformatic prediction of peptide-MHC binding affinity. Clinical success in targeting neoantigens has been observed in various solid tumors, particularly when combined with immune checkpoint inhibitors.

Other names

NeoantigenTumor-specific antigen (TSA)NeoepitopeMutation-derived antigenPatient-specific neoantigenNeoantigen-pMHC complex

Induction of neoantigen-specific T-cell responses through vaccination or adoptive transfer, leading to the recognition and cytotoxic destruction of tumor cells presenting the specific peptide-MHC complex (Sahin & Türeci, 2018).