Tumor-specific neoantigen-major histocompatibility complex (NeoAg-MHC)

Patient-specific tumor antigens, commonly known as neoantigens, are unique peptides derived from somatic mutations within a patient's tumor that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Nature Reviews Cancer, 2021). Unlike tumor-associated antigens, neoantigens are not expressed in normal tissues, which minimizes the risk of central tolerance and off-target autoimmune toxicity (Science, 2015). These complexes serve as the primary targets for personalized immunotherapy, including neoantigen vaccines and adoptive T-cell therapies (NEJM, 2017). By sequencing a patient's tumor exome and identifying these unique mutations, clinicians can design therapies that specifically prime or engineer the immune system to recognize and destroy cells displaying these specific neoantigen-MHC complexes (Nature, 2017). The clinical utility of these targets is highly dependent on the tumor's mutational burden and the efficiency of the cellular antigen processing machinery (Cell, 2019). Despite their potential, challenges remain regarding the identification of truly immunogenic neoepitopes and the potential for tumor escape through the loss of MHC expression or antigen presentation components.

Other names

NeoantigenTumor-specific antigenTSANeoepitopeSomatic mutation-derived antigenPersonalized tumor antigenPatient-specific neoantigen

Induction of neoantigen-specific T-cell responses through vaccination or direct targeting via engineered T-cell receptors (TCRs) that recognize the peptide-MHC complex.