Patient-specific tumor-associated antigens and neoantigens presented on peptide-MHC complexes (pMHC-Neoantigen/TAA)

Patient-specific tumor-associated antigens (TAAs) and neoantigens presented on peptide-MHC (pMHC) complexes represent a class of highly specific therapeutic targets in oncology. Neoantigens arise from somatic mutations within the tumor genome, such as single nucleotide variants or frameshifts, which result in novel peptide sequences not found in the normal proteome (Nature Reviews Drug Discovery, 2021). These peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, where they can be recognized by the host's T-cell receptors (TCRs) to trigger an adaptive immune response (Frontiers in Immunology, 2020). Tumor-associated antigens, while also presented on MHC, are self-antigens with restricted or elevated expression in tumors compared to healthy tissues (NCI Dictionary). Modern immunotherapies, including personalized mRNA vaccines and TCR-engineered T-cell (TCR-T) therapies, aim to exploit these complexes to achieve precise tumor eradication while sparing healthy cells (Journal of Hematology & Oncology, 2021). However, the effectiveness of targeting these complexes can be limited by the heterogeneity of antigen expression and the tumor's ability to downregulate MHC molecules to evade immune detection.

Other names

Tumor-specific antigens (TSA)NeoepitopesCancer-testis antigensMutated self-antigensHLA-peptide complexesTumor-associated antigens (TAA)

Therapeutic strategies involve the induction of a polyclonal T-cell response through personalized vaccines or the use of engineered T-cell receptors (TCRs) and bispecific molecules that specifically bind the peptide-MHC complex to induce tumor cell lysis.