Tumor-associated antigen and neoantigen peptide-MHC complex (pMHC)

Tumor-associated antigens (TAAs) and neoantigens presented on peptide-major histocompatibility complexes (pMHC) are the primary targets for personalized cancer immunotherapies. TAAs are proteins with elevated expression in tumors compared to normal tissues, whereas neoantigens are derived from non-synonymous somatic mutations unique to an individual's malignancy (PubMed: 29735922). These peptides are processed intracellularly and displayed on the cell surface by MHC Class I or II molecules, where they are recognized by the T-cell receptors (TCRs) of circulating lymphocytes (NIH: PMC7347117). Therapeutic modalities such as personalized mRNA vaccines, TCR-engineered T-cell therapies (TCR-T), and bispecific T-cell engagers (BiTEs) are designed to specifically bind these pMHC complexes to induce a potent anti-tumor immune response. Because neoantigens are absent from the normal proteome, they provide a high degree of specificity, potentially minimizing the risk of off-target autoimmune reactions. However, the clinical success of targeting these complexes is often challenged by tumor-mediated downregulation of MHC molecules and the high degree of intratumoral heterogeneity (Nature Reviews Cancer: 10.1038/s41568-019-0135-y).

Other names

Tumor-specific antigen (TSA)NeoantigenTumor-associated antigen (TAA)Cancer-specific peptide-MHC complexNeoepitope

Induction of antigen-specific T-cell responses and direct T-cell mediated lysis of tumor cells through T-cell receptor (TCR) binding to specific peptide-MHC complexes.