Patient-specific neoantigen peptides presented on MHC molecules (Neoantigen-MHC)

Patient-specific neoantigen peptides presented on Major Histocompatibility Complex (MHC) molecules are unique protein fragments derived from somatic mutations within a patient's tumor cells (Schumacher & Schreiber, 2015, Science). These mutations—such as single-nucleotide variants, frameshifts, or chromosomal translocations—create novel amino acid sequences that are absent from the normal human proteome, making them ideal targets for highly specific immunotherapy (Ott et al., 2017, Nature). Once these mutated proteins are processed by the proteasome, the resulting peptides are loaded onto MHC Class I or Class II molecules and displayed on the cell surface for recognition by T-cell receptors (TCRs). This presentation acts as a "non-self" signal, allowing the immune system to selectively identify and destroy malignant cells while sparing healthy tissue (Sahin et al., 2017, Nature). Therapeutic strategies leveraging these targets include personalized mRNA or peptide vaccines and adoptive TCR-engineered T-cell therapies, which aim to amplify the patient's endogenous anti-tumor immune response (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Because these neoantigens are restricted to the individual's tumor, they offer a high degree of precision and a lower risk of systemic autoimmunity compared to traditional shared tumor antigens.

Other names

Tumor-specific antigensNeoepitopesMHC-restricted neoantigensSomatic mutation-derived antigensTSAsPersonalized neoantigens

Induction of a de novo or expanded T-cell response (CD8+ and CD4+) against unique tumor-specific epitopes presented on MHC molecules to mediate selective tumor cell lysis.