Patient-specific neoantigen and tumor-associated antigen presented on Major Histocompatibility Complex (MHC) molecule (Neoantigen/TAA-MHC)

Patient-specific neoantigens and tumor-associated antigens (TAAs) are peptide fragments derived from mutated or aberrantly expressed proteins, presented on the cell surface by Major Histocompatibility Complex (MHC) molecules [1]. Neoantigens arise from somatic mutations unique to the tumor genome, such as point mutations or frameshifts, making them highly specific targets that bypass central thymic tolerance [2]. In contrast, TAAs are self-antigens with restricted or elevated expression in malignant tissues, such as cancer-testis antigens or overexpressed lineage markers [3]. These peptide-MHC complexes are the fundamental units recognized by the T-cell receptor (TCR), which triggers a cytotoxic immune response against the cancer cell [1]. Therapeutic interventions, including personalized mRNA vaccines (e.g., mRNA-4157) and adoptive T-cell therapies, aim to enhance the recognition of these unique molecular signatures to induce selective tumor lysis [4]. The identification and selection of these targets typically involve high-throughput genomic sequencing and bioinformatic algorithms to predict peptide-MHC binding affinity and immunogenicity [5].

Other names

Tumor-specific antigen (TSA)NeoepitopePeptide-MHC complex (pMHC)HLA-restricted antigenTumor-associated antigen (TAA)Tumor-specific neoantigen

Induction of antigen-specific T-cell responses through vaccination or direct targeting via engineered T-cell receptors (TCRs) and bispecific molecules to recognize and eliminate tumor cells expressing the specific peptide-MHC complex [1, 4].