Major Histocompatibility Complex-presented tumor-associated antigens and neoantigens (MHC-TAA/Neoantigen)

Major Histocompatibility Complex (MHC)-presented tumor-associated antigens (TAAs) and neoantigens are short peptide fragments derived from intracellular proteins that are displayed on the cell surface by MHC molecules (PubMed: 31015575). TAAs are self-antigens that are overexpressed or aberrantly expressed in cancer cells, such as cancer-testis antigens (e.g., MAGE-A4, NY-ESO-1), while neoantigens arise from somatic mutations unique to the tumor genome (Frontiers in Immunology, 2020, 11:1560). These peptide-MHC complexes are the primary targets for advanced immunotherapies, including T-cell receptor (TCR) engineered T-cells, tumor-infiltrating lymphocytes (TILs), and therapeutic cancer vaccines (NIH National Cancer Institute). By targeting these specific complexes, the immune system can distinguish malignant cells from healthy tissue based on internal protein expression, which is inaccessible to traditional antibody-based therapies (Science, 2021, 371:eabc0718). However, therapeutic efficacy is often challenged by the heterogeneity of antigen expression and the risk of on-target, off-tumor toxicity if the antigen is present in vital organs (Journal of Clinical Oncology, 2015, 33:16). Additionally, tumors may evade detection through the downregulation of MHC molecules or other components of the antigen-processing machinery (Nature Reviews Cancer, 2019, 19:334-352).

Other names

Tumor-specific antigensTSATumor-associated antigensTAANeoantigensHLA-presented peptidesCancer-testis antigenspMHC complexes

Recognition of peptide-MHC complexes by T-cell receptors (TCRs) or TCR-mimetic antibodies, triggering cytotoxic T-lymphocyte mediated apoptosis of the tumor cell.