Patient-specific tumor neoantigen peptides bound to MHC class I and II (Neoantigen-MHC complex)

Patient-specific tumor neoantigen peptides bound to MHC class I and II represent a highly specific class of therapeutic targets derived from non-synonymous somatic mutations unique to an individual's tumor (Nature, 2017, doi:10.1038/nature22991). These neoantigens are processed and presented on the surface of tumor cells or professional antigen-presenting cells (APCs) via Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) in humans (Science, 2015, doi:10.1126/science.aaa3820). Because these peptides are absent from the normal proteome, they are recognized as non-self by the immune system, which bypasses central thymic tolerance and reduces the risk of autoimmunity (Frontiers in Immunology, 2020, doi:10.3389/fimmu.2020.01560). Therapeutic strategies, such as personalized mRNA vaccines or adoptive T-cell therapies, aim to prime and expand neoantigen-specific CD8+ cytotoxic T cells and CD4+ helper T cells (NEJM, 2019, doi:10.1056/NEJMoa1905177). This targeted approach facilitates the selective destruction of malignant cells while sparing healthy tissue. The clinical utility of these targets is currently being explored in various solid tumors, often in combination with immune checkpoint inhibitors to overcome local immunosuppression (Cell, 2021, doi:10.1016/j.cell.2021.04.033).

Other names

Tumor-specific neoantigensNeoepitopesPersonalized cancer antigensTumor-specific antigens (TSAs)MHC-restricted neoantigensPeptide-HLA complexes (pHLA)

Induction of a de novo or expanded polyclonal T-cell response where CD8+ and CD4+ T cells recognize the specific neoepitope-MHC complex, leading to targeted lysis of tumor cells and the formation of immunological memory.