Lung cancer-associated neoantigen

Lung cancer-associated neoantigens are unique, non-self proteins that arise from somatic mutations—such as single-nucleotide variants or frameshift mutations—within the genome of lung cancer cells (Nature Reviews Cancer, 2017). Because these antigens are not expressed in healthy tissues, they are recognized as "non-self" by the immune system, which minimizes the risk of autoimmune toxicity and central tolerance (Journal of Hematology & Oncology, 2021). In lung cancer, particularly non-small cell lung cancer (NSCLC), a high tumor mutational burden (TMB) often correlates with a greater abundance of these neoantigens, providing a broad range of targets for immunotherapy (Frontiers in Immunology, 2020). Therapeutic strategies include personalized mRNA vaccines, such as mRNA-4157, and fixed-dose peptide vaccines like Tedopi, which are designed to prime the patient's T cells to recognize and eliminate cells presenting these specific neoepitopes (The Lancet Oncology, 2022). These treatments work by enhancing the presentation of mutated peptides on Major Histocompatibility Complex (MHC) molecules to activate CD8+ cytotoxic T lymphocytes (NCI, 2023). Despite their promise, challenges such as intratumor heterogeneity and the technical difficulty of accurately predicting immunogenic neoepitopes remain significant barriers to clinical success (Cell, 2019).

Other names

Tumor-specific antigenTSANeoepitopeMutation-derived antigenCancer-specific antigen

Induction of a tumor-specific T-cell immune response through the presentation of mutated peptide fragments on MHC molecules, leading to the selective destruction of malignant cells.