Patient-specific tumor neoantigen–peptide–major histocompatibility complex (Neoantigen-pMHC)

Patient-specific tumor neoantigen–peptide–major histocompatibility complex (neoantigen-pMHC) represents a class of highly specific therapeutic targets formed by the presentation of mutated protein fragments (neoepitopes) on the surface of cancer cells via HLA molecules (Nature Reviews Cancer, 2017). These complexes are unique to an individual's tumor and are absent from healthy tissues, making them ideal targets for precision immunotherapy with minimal off-tumor toxicity (Science, 2019). The biological function of these complexes is to signal the presence of intracellular mutations to the adaptive immune system, specifically to T-cell receptors (TCRs). Therapeutic interventions targeting neoantigen-pMHCs include personalized mRNA or peptide vaccines designed to expand endogenous neoantigen-specific T cells, as well as adoptive cell therapies using TCR-engineered T cells (Frontiers in Immunology, 2020). While highly promising, the efficacy of targeting these complexes can be limited by tumor heterogeneity, the loss of HLA expression, or the presence of an immunosuppressive tumor microenvironment.

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexNeoantigen-peptide-HLA complexTSA-pMHCNeoantigen-pMHC complex

Recognition by T-cell receptors (TCRs) on CD8+ or CD4+ T cells, triggering an adaptive immune response that leads to the selective destruction of tumor cells presenting the specific neoepitope (Nature Reviews Cancer, 2017).