Patient-specific tumor-associated antigen and neoantigen-derived peptide–major histocompatibility complex (pMHC)

Patient-specific tumor-associated antigens (TAAs) and neoantigen-derived peptide–major histocompatibility complex (pMHC) molecules represent a personalized class of therapeutic targets in oncology. TAAs are self-antigens that are abnormally expressed in tumor cells, while neoantigens arise from non-synonymous somatic mutations unique to an individual's tumor, making them truly tumor-specific (Schumacher & Schreiber, Science 2015). These peptides are processed and presented on the cell surface by MHC class I or II molecules, where they can be recognized by the T-cell receptors (TCRs) of cytotoxic and helper T cells (Blass & Ott, Nature Reviews Clinical Oncology 2021). In immunotherapy, these complexes are targeted using personalized cancer vaccines, such as mRNA-4157 or Autogene cevumeran, and adoptive cell therapies like TCR-engineered T cells (Sahin & Türeci, Science 2018). By focusing on neoantigens, these therapies aim to minimize off-target toxicity because the target is absent from healthy tissues. However, challenges remain regarding the identification of immunogenic neoantigens and the potential for tumor escape through the downregulation of MHC molecules or antigen loss (NIH, National Cancer Institute).

Other names

Neoantigen-MHC complexTumor-specific antigen (TSA)NeoepitopeTumor-associated antigen (TAA)Cancer-specific pMHCPersonalized tumor antigen

Induction of T-cell mediated cytotoxicity by presenting tumor-specific or tumor-associated peptides on MHC molecules for recognition by T-cell receptors (TCRs).