Peptide-major histocompatibility complex presenting patient-specific tumor antigens (pMHC)

Peptide-major histocompatibility complex (pMHC) presenting patient-specific tumor antigens, commonly referred to as neoantigens, represents a cornerstone of personalized cancer immunotherapy (Schumacher & Schreiber, 2015). These complexes consist of a mutated peptide fragment derived from tumor-specific genetic alterations bound to an MHC molecule (HLA in humans) on the surface of malignant cells (Sahin & Türeci, 2018). Unlike shared tumor-associated antigens, these neoantigens are unique to the individual patient's tumor, making them highly specific targets with a lower risk of central tolerance-related autoimmunity (Blass & Ott, 2021). The primary biological function of the pMHC is to present these non-self signals to the T-cell receptor (TCR) of CD8+ or CD4+ T cells, thereby initiating a targeted immune attack (Waldman et al., 2020). Therapeutic strategies leveraging this target include personalized neoantigen vaccines, TCR-engineered T-cell therapies (TCR-T), and soluble TCR-based bispecifics like ImmTACs. However, challenges remain regarding the accurate prediction of immunogenic neoantigens and the potential for tumor escape through the loss of HLA expression or defects in the antigen processing machinery (Yarchoan et al., 2017).

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexpHLA complexNeoepitope-MHC complexPatient-specific neoantigen-HLA complex

Engagement of the T-cell receptor (TCR) to trigger an adaptive immune response against tumor cells