Tumor neoantigen-MHC class I complex (NeoAg-MHC I)

Patient-specific tumor neoantigens are unique peptides derived from somatic mutations in a patient's tumor cells that are not present in healthy tissues (Schumacher & Schreiber, Science 2015). These neoantigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, where they are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (Ott et al., Nature 2017). Because these antigens are entirely tumor-specific, they represent ideal targets for immunotherapy, minimizing the risk of central tolerance and autoimmunity (Blass & Ott, Nature Reviews Clinical Oncology 2021). Therapeutic strategies targeting these complexes include personalized cancer vaccines, such as mRNA-4157, and adoptive cell therapies using TCR-engineered T-cells (Sahin & Türeci, Science 2018). The identification of these targets typically involves whole-exome sequencing and bioinformatic prediction of peptide-MHC binding affinity (Hundal et al., Nature Genetics 2016). Successful targeting leads to the selective destruction of malignant cells while sparing normal tissue. However, challenges remain regarding the heterogeneity of neoantigen expression and the potential for tumors to downregulate MHC expression to evade immune detection (Gubin et al., Nature 2014). Despite these challenges, neoantigen-based therapies represent a cornerstone of precision oncology.

Other names

NeoepitopeTumor-specific antigen (TSA)Personalized tumor antigenPeptide-MHC (pMHC) complexMutation-derived antigen

Induction of a polyclonal T-cell response against multiple patient-specific neoepitopes presented on MHC class I, leading to cytotoxic T-lymphocyte mediated lysis of tumor cells (Sahin et al., Nature 2017).