Tumor-specific neoantigen–Major Histocompatibility Complex (NeoAg-MHC)

Tumor-specific neoantigen–Major Histocompatibility Complex (MHC) complexes are unique molecular signatures formed when mutated peptides, derived from non-synonymous somatic mutations in cancer cells, are presented on the cell surface by MHC molecules (Zhang et al., 2021, PubMed). These complexes are critical for the immune system's ability to distinguish malignant cells from healthy tissue, as the neoantigens are not expressed in the normal proteome (Schumacher & Schreiber, 2015, Science). MHC Class I complexes are typically recognized by CD8+ cytotoxic T cells, while MHC Class II complexes are recognized by CD4+ helper T cells, both of which are essential for a coordinated anti-tumor response (Alspach et al., 2019, Nature). In therapeutic contexts, these complexes serve as the primary targets for personalized cancer vaccines and adoptive cell therapies, such as TCR-engineered T cells (TCR-T). By specifically targeting these neoepitopes, clinicians aim to trigger a potent, tumor-specific immune attack while minimizing damage to healthy organs. However, challenges remain, including the high heterogeneity of neoantigens across patients and the potential for tumors to evade detection by downregulating MHC expression (Garrido et al., 2016, Cancer Immunology, Immunotherapy).

Other names

Neoepitope-MHC complexTumor-specific antigen-MHC complexNeoantigen-HLA complexTSA-MHC complexMutant peptide-MHC complex

Induction of antigen-specific T-cell responses through the presentation of tumor-specific mutated peptides on MHC Class I (to CD8+ T cells) or MHC Class II (to CD4+ T cells) molecules, leading to targeted lysis of tumor cells (Sahin & Türeci, 2018, Science).