Human leukocyte antigen A2-restricted tumor neoantigen (HLA-A2-restricted tumor neoantigen) (HLA-A2 neoantigen)

Human leukocyte antigen A2-restricted tumor neoantigens are a class of highly specific cancer antigens formed by somatic mutations in the tumor genome and presented on the cell surface by the HLA-A*02:01 molecule [Schumacher & Schreiber, Science, 2015]. Because these antigens arise from mutations unique to the tumor, they are not expressed in healthy tissues, making them ideal targets for precision immunotherapy with minimal off-target effects [Blass & Ott, Nat Rev Clin Oncol, 2021]. These neoantigens are recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T cells, triggering a targeted immune response against the malignant cells [Yadav et al., Nature, 2014]. Therapeutic strategies leveraging these targets include personalized mRNA vaccines, TCR-engineered T-cell (TCR-T) therapies, and neoantigen-specific monoclonal antibodies or bispecifics [Rojas et al., Nature, 2023]. The effectiveness of these therapies often depends on the patient's HLA-A2 status and the presence of high-quality, immunogenic mutations within the tumor [Ott et al., Nature, 2017]. However, challenges such as tumor heterogeneity and the loss of HLA expression can lead to immune escape and treatment resistance [McGranahan et al., Science, 2017].

Other names

HLA-A*02:01 restricted neoantigenMHC class I-restricted tumor-specific antigenTumor-specific neoepitopeTSANeoantigen-HLA-A2 complex

Therapeutic agents target these neoantigens by either delivering the mutated peptide sequences (vaccines) or engineering T cells to express receptors (TCR-T) that specifically recognize the peptide-HLA-A2 complex, thereby inducing a cytotoxic immune response against tumor cells [Blass & Ott, Nat Rev Clin Oncol, 2021].