Patient-specific neoantigen-derived peptide-MHC complex (NeoAg-MHC)

Patient-specific neoantigen-derived peptide-MHC complexes are unique molecular targets formed when somatic mutations in a tumor's genome result in novel protein sequences not found in healthy tissue. These neoantigens are processed intracellularly and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) in humans (Schumacher & Schreiber, 2015, Science). Because these complexes are absent from the normal proteome, they are highly immunogenic and bypass central thymic tolerance, making them ideal targets for precision immunotherapy (Blass & Ott, 2021, Nature Reviews Clinical Oncology). Therapeutic strategies targeting these complexes include personalized cancer vaccines—utilizing mRNA, DNA, or peptides—and adoptive T-cell therapies using engineered T-cell receptors (TCR-T) (Sahin & Türeci, 2018, Science). These interventions aim to prime or provide T-cells that can specifically recognize the mutation-bearing cells, thereby inducing a potent and selective anti-tumor immune response. However, the clinical efficacy of targeting these complexes depends heavily on the accuracy of neoantigen prediction algorithms and the tumor's ability to maintain antigen presentation machinery (Hu et al., 2021, Nature Medicine).

Other names

Tumor-specific neoantigen (TSNA)Neoepitope-HLA complexMutation-derived antigenPersonalized neoantigenTumor-specific antigen (TSA)

Induction of a de novo or expanded cytotoxic T-lymphocyte (CTL) response where T-cell receptors (TCRs) specifically recognize and bind the neoantigen-MHC complex, leading to targeted tumor cell lysis.