Tumor-associated antigens and patient-specific mutated tumor peptides presented on Major Histocompatibility Complex (TAA/Neoantigen-MHC)

Tumor-associated antigens (TAAs) and patient-specific mutated tumor peptides (neoantigens) presented on the Major Histocompatibility Complex (MHC) are the primary molecular signals that allow the adaptive immune system to distinguish malignant cells from healthy tissue (Nature Reviews Cancer, 2017). TAAs are self-derived proteins that are abnormally expressed in tumors, such as cancer-testis antigens, while neoantigens arise from somatic mutations unique to an individual's tumor genome (Nature, 2021). 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 receptor (TCR) to initiate a cytotoxic immune response (PubMed, PMID: 28459455). Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines, TCR-engineered T-cell therapies, and bispecific T-cell engagers (Science, 2017). These treatments aim to harness the high specificity of the TCR-pMHC interaction to achieve precise tumor eradication, as demonstrated by the clinical success of agents like Tebentafusp and Afamitresgene autoleucel (Nature Medicine, 2022; The Lancet, 2024). However, challenges such as the downregulation of MHC by tumor cells and the risk of lethal off-target toxicity against healthy tissues expressing similar peptides remain critical hurdles in drug development.

Other names

NeoantigensTumor-specific antigensTSACancer-testis antigensCTAPeptide-MHC complexespMHCTumor neoepitopesTumor-associated antigens

Induction of T-cell mediated cytotoxicity through the specific recognition of tumor-derived peptides presented by MHC molecules, either by stimulating endogenous T-cell expansion via vaccination or by utilizing engineered receptors like TCR-T cells and bispecific T-cell engagers (Nature Reviews Drug Discovery, 2023).