Patient-specific neoantigen–Major Histocompatibility Complex (NeoAg-MHC)

Patient-specific neoantigen–Major Histocompatibility Complex (MHC) complexes are unique molecular targets formed when mutated peptides from a patient's tumor are presented on the cell surface by MHC molecules [1]. These complexes are essential for the adaptive immune system to distinguish malignant cells from healthy tissue, as neoantigens arise from somatic mutations not present in the germline [2]. Recognition of these complexes by T-cell receptors (TCRs) triggers a targeted cytotoxic immune response against the tumor [3]. Because they are unique to each individual, they are the primary targets for personalized cancer vaccines, such as mRNA-4157, and TCR-engineered T-cell therapies [4]. These therapies aim to enhance the immune system's ability to detect these specific "non-self" signals, providing a highly precise treatment modality with minimal off-target effects on normal cells [5]. However, challenges remain, including the potential for tumor immune escape through the downregulation of MHC molecules or the loss of specific neoantigens [3, 5].

Other names

Neoepitope-HLA complexTumor-specific antigen (TSA) complexPersonalized neoantigenNeoantigen-MHC class I/II complexTumor-specific neoantigen

Induction of neoantigen-specific T-cell responses through the presentation of mutated peptides by MHC molecules to T-cell receptors (TCRs) [1, 3].