Neoantigen-MHC class I complex (NeoAg-MHC I)

Neoantigen-MHC class I complexes are the fundamental targets for personalized cancer immunotherapy, consisting of a mutated peptide (neoepitope) bound to a Major Histocompatibility Complex (MHC) class I molecule on the surface of tumor cells [Schumacher & Schreiber, 2015]. These complexes arise from somatic mutations unique to the tumor genome, such as single nucleotide variants or frameshifts, which are absent from the germline and thus perceived as foreign by the immune system [Xie et al., 2023]. CD8+ cytotoxic T lymphocytes (CTLs) recognize these complexes through highly specific T-cell receptors (TCRs), initiating a cascade that results in the targeted destruction of the malignant cell [Blass & Ott, 2021]. Because neoantigens are not expressed in healthy tissues, they offer a superior safety profile and higher specificity compared to traditional tumor-associated antigens, which are often subject to central tolerance. Current therapeutic strategies focus on identifying these unique complexes through genomic sequencing and bioinformatic prediction to develop personalized vaccines or TCR-engineered T-cell therapies [Xie et al., 2023].

Other names

Neoepitope-HLA complexTumor-specific antigen (TSA)-MHC complexMutated peptide-MHC complexNeoantigen-HLA-I complex

Induction of a de novo T-cell response against tumor-specific mutations via vaccination or the direct provision of engineered T-cells expressing receptors specific for the neoantigen-MHC complex, leading to perforin/granzyme-mediated apoptosis of tumor cells [Schumacher & Schreiber, 2015].