Patient-specific tumor-associated antigen and neoantigen peptide-MHC complex (pMHC)

Patient-specific tumor-associated antigens (TAAs) and neoantigens presented as peptide-MHC (pMHC) complexes serve as the fundamental recognition units for the adaptive immune system to identify and eliminate malignant cells (Schumacher & Schreiber, 2015). Neoantigens are derived from somatic mutations—such as non-synonymous single nucleotide variants (SNVs), insertions/deletions (indels), or frameshifts—that are unique to the patient's tumor genome and are not found in normal tissues (Blass & Ott, 2021). These mutated proteins are processed intracellularly into short peptides and loaded onto Major Histocompatibility Complex (MHC) molecules, also known as Human Leukocyte Antigens (HLA) in humans, for presentation on the cell surface. T-cell receptors (TCRs) on circulating T cells specifically bind to these pMHC complexes, triggering a signaling cascade that leads to T-cell activation, proliferation, and the subsequent lysis of the tumor cell (Sahin & Türeci, 2018). Therapeutic interventions targeting these complexes include personalized neoantigen vaccines (mRNA, DNA, or peptide-based) and adoptive cell therapies using TCR-engineered T cells (TCR-T) or tumor-infiltrating lymphocytes (TILs). Because neoantigens are absent from the healthy proteome, they are highly attractive targets for precision oncology, offering the potential for high specificity and reduced off-target toxicity compared to traditional therapies (Yarchoan et al., 2017).

Other names

Neoantigen-MHC complexTumor-specific antigen (TSA) complexNeoepitope-HLA complexpMHC complexTumor-associated antigen (TAA) complex

Personalized vaccines and TCR-T therapies target these complexes to induce or provide T-cell mediated cytotoxicity. Vaccines prime the immune system to recognize specific pMHC neoepitopes, while TCR-T cells are engineered to express receptors with high affinity for these complexes, both resulting in the targeted destruction of tumor cells (Sahin & Türeci, 2018; Blass & Ott, 2021).