Patient-specific tumor neoantigen–Major Histocompatibility Complex (neoAg-MHC)

Patient-specific tumor neoantigen–Major Histocompatibility Complex (MHC) complexes are unique molecular structures formed when mutated proteins within a tumor cell are processed into peptides and presented on the cell surface by MHC molecules (Science: 10.1126/science.aaa4971). Unlike shared tumor-associated antigens, these neoantigens arise from somatic mutations unique to an individual's tumor, making them highly specific targets that are not expressed in healthy tissues (Nature: 10.1038/nrc.2017.121). This specificity minimizes the risk of central tolerance and autoimmune toxicity, as the immune system perceives these complexes as foreign. These complexes are the primary targets for personalized cancer immunotherapies, including neoantigen vaccines, T-cell receptor (TCR) engineered T-cells, and TCR-like antibodies (Nat Rev Clin Oncol: 10.1038/s41571-020-00460-2). By leveraging the immune system's ability to recognize these "non-self" signatures, therapies aim to induce a robust and durable anti-tumor response. However, the high degree of polymorphism in HLA genes and the heterogeneity of tumor mutations necessitate a highly personalized approach to drug development and patient selection (Cell: 10.1016/j.cell.2017.10.001).

Other names

Neoantigen-HLA complexTumor-specific antigen-MHC complexNeoepitope-MHC complexMutant peptide-MHC complexTSA-MHC complex

Therapeutic agents target these complexes by either providing the neoantigen to stimulate endogenous T-cells (vaccines) or by providing engineered T-cells/antibodies that directly bind the neoantigen-MHC complex to trigger tumor cell lysis.