Patient-specific tumor-associated antigens (PSTAAs) (PSTAAs)

Patient-specific tumor-associated antigens (TAAs), commonly known as neoantigens, are unique peptides arising from somatic mutations specific to an individual's tumor (Hu, Z., et al., Nature Reviews Immunology, 2021). These antigens are absent from the normal genome, making them highly specific targets that bypass central thymic tolerance and minimize the risk of systemic autoimmunity (Ott, P. A., et al., Nature, 2017). The therapeutic strategy involves identifying these mutations through next-generation sequencing and using bioinformatic tools to predict which peptides will be successfully presented on the patient's MHC Class I and Class II molecules. Once identified, these antigens are delivered via personalized vaccines—such as mRNA, DNA, or peptide platforms—to prime the immune system. This process triggers the expansion of cytotoxic CD8+ T cells and helper CD4+ T cells that specifically recognize and eliminate tumor cells (Sahin, U., et al., Nature, 2017). Because these targets are unique to each patient, they represent the pinnacle of precision oncology, though their efficacy can be limited by tumor heterogeneity and immune evasion mechanisms like HLA downregulation (Blass, E., & Ott, P. A., Nature Reviews Clinical Oncology, 2021).

Other names

NeoantigensTumor-specific antigensTSAsPersonalized tumor antigensMutanome-derived antigensTumor-specific neoantigens

Induction of a polyclonal T-cell response by delivering synthetic peptides or nucleic acids encoding patient-specific mutations, which are then presented on MHC Class I and II to activate CD8+ and CD4+ T cells, respectively (Sahin, U., et al., Nature, 2017; Hu, Z., et al., Nature Reviews Immunology, 2021).