Patient-specific tumor-associated antigen and neoantigen (TSA/Neoantigen)

Patient-specific tumor-associated antigens (TAAs) and neoantigens represent a critical class of targets in personalized cancer immunotherapy. TAAs are self-antigens that exhibit elevated or restricted expression in malignant cells, whereas neoantigens (tumor-specific antigens) arise from somatic mutations unique to an individual's tumor, such as single nucleotide variants, indels, or chromosomal rearrangements (Schumacher & Schreiber, Science 2015). These antigens are intracellularly processed into short peptides and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) in humans (Neefjes et al., Nat Rev Immunol 2011). The resulting peptide-MHC complexes are recognized by specific T-cell receptors (TCRs), which triggers the activation and proliferation of cytotoxic T-lymphocytes capable of destroying the tumor cells. Therapeutic approaches targeting these molecules include personalized mRNA, DNA, or peptide vaccines, as well as adoptive cell therapies like TCR-engineered T-cells (TCR-T), which aim to bypass central tolerance and achieve highly specific tumor eradication with minimal damage to healthy tissues (Sahin et al., Nature 2017).

Other names

Tumor-specific antigenNeoantigenMutation-derived antigenTumor-associated antigenpMHC complexCancer-germline antigenTumor-specific neoantigen

Induction of a de novo T-cell response or expansion of existing memory T-cells specific to tumor-derived peptides presented on MHC molecules, leading to targeted lysis of malignant cells (Sahin et al., Nature 2017; Schumacher & Schreiber, Science 2015).