Tumor-specific neoantigen peptide–MHC class I complex (NeoAg-MHC-I)

Tumor-specific neoantigen peptide–MHC class I complexes are molecular assemblies presented on the surface of cancer cells, comprising a mutated peptide fragment derived from somatic mutations and a Major Histocompatibility Complex (MHC) class I molecule [1]. These complexes are critical for the "non-self" recognition of tumors by the immune system, as the neoantigens they present are not found in the normal human proteome [2]. In a therapeutic context, these complexes are targeted by personalized cancer vaccines, such as mRNA-4157 and BNT122, which aim to expand the population of endogenous T-cells capable of recognizing these specific markers [3]. They are also the primary targets for adoptive cell therapies, including TCR-engineered T-cells (TCR-T), which are modified to express receptors with high affinity for a specific neoantigen-MHC pair [4]. Because these targets are highly specific to the tumor, they offer a wider therapeutic window compared to traditional tumor-associated antigens, although their high degree of patient specificity necessitates personalized manufacturing approaches [5]. However, tumor evolution can lead to the loss of these complexes through HLA downregulation or antigen loss, presenting a significant challenge to sustained therapeutic efficacy [6].

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexpHLA complexNeoantigen-MHC-I complexMutated peptide-MHC complex

Induction of neoantigen-specific T-cell responses via vaccination or direct targeting by engineered T-cell receptors (TCRs) to facilitate selective lysis of tumor cells.