Tumor-specific neoantigen and tumor-associated antigen presented on Major Histocompatibility Complex (TSA/TAA-MHC complex)

Tumor-specific neoantigens (TSAs) and tumor-associated antigens (TAAs) presented on Major Histocompatibility Complex (MHC) molecules are central targets in personalized cancer immunotherapy. Neoantigens are derived from somatic mutations unique to an individual's tumor, making them highly specific and reducing the risk of central tolerance or autoimmune reactions against healthy tissues (Schumacher & Schreiber, Science 2015). In contrast, TAAs are self-antigens that are overexpressed or aberrantly expressed in malignant cells, such as MAGE-A4 or gp100 (Blass & Ott, Nature Reviews Clinical Oncology 2021). These antigens are processed into short peptides and displayed on the cell surface by MHC class I or II molecules, where they are recognized by the T-cell receptors (TCRs) of cytotoxic and helper T-cells. Therapeutic approaches targeting these complexes include personalized mRNA or DNA vaccines designed to prime the immune system, and TCR-engineered T-cell (TCR-T) therapies or bispecific T-cell engagers (BiTEs) that directly redirect T-cells to the tumor (Sahin & Türeci, Science 2018). While highly promising for precision medicine, the efficacy of these therapies can be limited by the heterogeneity of antigen expression and the tumor's ability to downregulate MHC molecules to evade immune detection (Rojas et al., Nature 2023).

Other names

Neoantigen-MHC complexTumor-specific antigen (TSA)Tumor-associated antigen (TAA)Peptide-HLA (pHLA) complexMHC-restricted tumor antigenPatient-specific neoantigen

Induction of antigen-specific CD8+ and CD4+ T-cell responses; redirection of T-cells to tumor cells via TCR-MHC interaction; immune system priming through vaccination.