Tumor neoantigen and tumor-associated antigen peptide-MHC complex (NeoAg/TAA-pMHC)

Tumor neoantigens and tumor-associated antigens (TAAs) are short peptide fragments derived from mutated or overexpressed proteins within cancer cells, which are subsequently presented on the cell surface by Major Histocompatibility Complex (MHC) molecules. These peptide-MHC (pMHC) complexes serve as the critical interface for the adaptive immune system, acting as the specific ligands recognized by T-cell receptors (TCRs) on CD8+ cytotoxic and CD4+ helper T cells [1, 2]. Neoantigens, resulting from somatic mutations unique to the tumor, are highly specific targets that avoid central tolerance, whereas TAAs are self-proteins with restricted or elevated expression in malignant tissues [2, 5]. Therapeutic interventions targeting these complexes include personalized cancer vaccines (e.g., mRNA-4157), TCR-engineered T-cell (TCR-T) therapies (e.g., afamitresgene autoleucel), and bispecific T-cell engagers (e.g., tebentafusp) [3, 4]. These therapies aim to induce or enhance a robust, antigen-specific immune response to selectively eliminate tumor cells while sparing healthy tissue. However, challenges such as antigen escape through MHC downregulation and potential cross-reactivity with healthy tissues remain significant hurdles in the clinical application of these targets [1, 4]. Citations: [1] Nature Reviews Cancer, "Neoantigens in cancer immunotherapy", 2017. [2] Journal of Hematology & Oncology, "Tumor-associated antigens: from discovery to clinical applications", 2023. [3] FDA, "FDA approves afamitresgene autoleucel for metastatic synovial sarcoma", 2024. [4] Cancer Discovery, "Tebentafusp: A First-in-Class ImmTAC for Metastatic Uveal Melanoma", 2022. [5] NIH National Cancer Institute, "NCI Dictionary of Cancer Terms: Neoantigen".

Other names

Tumor-specific antigen (TSA)NeoepitopeCancer-testis antigen (CTA)pMHC complexTumor-associated antigen (TAA)

Activation of antigen-specific T-cell cytotoxicity through the binding of T-cell receptors (TCRs) to peptide-MHC complexes on the tumor cell surface.