Patient-specific tumor neoantigens presented on MHC class I molecules (NeoAg-MHC-I)

Patient-specific tumor neoantigens presented on MHC class I molecules are a class of highly specific therapeutic targets derived from somatic mutations unique to an individual's tumor. These neoantigens are processed into short peptides and displayed on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, where they serve as the primary signal for immune recognition by CD8+ cytotoxic T lymphocytes. Because these antigens are absent in healthy tissues, they are not subject to central immune tolerance, allowing for the induction of potent and selective anti-tumor responses with minimal risk of autoimmunity. Therapeutic interventions targeting these complexes include personalized mRNA or peptide vaccines designed to prime the immune system, as well as adoptive cell therapies using T-cell receptors (TCRs) engineered to recognize specific neoantigen-MHC combinations. While highly promising for precision oncology, the effectiveness of these therapies can be limited by tumor heterogeneity, low antigen density, and mechanisms of immune evasion such as the loss of antigen presentation machinery.

Other names

Tumor-specific antigens (TSAs)NeoepitopesMHC-I restricted neoantigensPersonalized tumor antigensMutant peptide-MHC complexespMHC-I complexes

Induction of a de novo, patient-specific T-cell response by presenting tumor-unique mutant peptides to CD8+ T cells via MHC class I molecules, leading to selective lysis of cancer cells.