Patient-specific tumor neoantigens and tumor-associated antigens presented on MHC class I on glioblastoma cells (GBM Neoantigens/TAAs)

Patient-specific tumor neoantigens and tumor-associated antigens (TAAs) presented on MHC class I molecules are the primary targets for personalized immunotherapy in glioblastoma (GBM). Neoantigens are derived from somatic mutations unique to the patient's tumor, providing high specificity and minimizing off-target effects, while TAAs are non-mutated proteins that are overexpressed in GBM cells. These antigens are processed into short peptides and displayed by MHC class I molecules on the cell surface, where they are recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes (Hilf et al., 2019; Keskin et al., 2019). Therapeutic interventions, such as personalized peptide or mRNA vaccines (e.g., NeoVax, GAPVAC) and adoptive T-cell therapies, aim to overcome the "cold" immune microenvironment of glioblastoma by stimulating a robust, targeted immune response (Adv Drug Deliv Rev, 2022). Despite their potential, these therapies face significant challenges, including the high intratumoral heterogeneity of GBM which leads to antigen escape, the immunosuppressive nature of the brain's microenvironment, and the physical barrier posed by the blood-brain barrier. Clinical trials have demonstrated that these personalized approaches are safe and can induce measurable T-cell infiltration into the tumor, though sustained clinical efficacy often requires combination with other modalities like checkpoint inhibitors (Nature, 2019). Monitoring efficacy involves assessing the immunopeptidome and tracking T-cell responses, while safety monitoring focuses on managing inflammation-related complications like cerebral edema (Int J Gen Med, 2021).

Other names

Personalized glioblastoma antigensGlioblastoma neoepitopesTumor-specific antigens (TSAs)Tumor-associated antigens (TAAs)MHC-I presented glioblastoma peptidesGlioblastoma immunopeptidome

Induction of a tumor-specific T-cell response through the presentation of personalized or associated peptide antigens on MHC class I molecules, leading to the activation and infiltration of cytotoxic CD8+ T cells into the glioblastoma microenvironment.