Human leukocyte antigen (HLA) complex presenting tumor neoantigens (HLA-neoantigen complex)

The Human leukocyte antigen (HLA) complex presenting tumor neoantigens is a personalized molecular target essential for the immune system's ability to identify and eliminate malignant cells. Neoantigens are novel peptides generated from tumor-specific genetic mutations, such as non-synonymous point mutations or frameshifts, which are not found in normal tissues (Schumacher & Schreiber, 2015, Nature). These peptides are loaded onto patient-specific HLA Class I or Class II molecules and displayed on the cell surface for recognition by T-cell receptors (TCRs) (Janeway et al., 2001, Immunobiology). This interaction is the fundamental basis for several precision immunotherapies, including personalized neoantigen vaccines and TCR-engineered T-cell (TCR-T) therapies (Sahin et al., 2017, Nature; Hu et al., 2021, Nature Reviews Immunology). By targeting these unique HLA-peptide complexes, therapies can achieve high specificity, potentially reducing the risk of systemic toxicity compared to traditional treatments. However, the high degree of HLA polymorphism and the unique nature of most neoantigens require sophisticated genomic sequencing and computational modeling for each patient (Gubin et al., 2015, Journal of Clinical Investigation). Challenges to this approach include tumor-mediated HLA downregulation and the potential for off-target toxicity if the neoantigen resembles a self-peptide (Ott et al., 2017, Nature).

Other names

MHC-restricted neoantigensTumor-specific antigens (TSAs)NeoepitopespHLA complexPatient-specific neoantigens

Induction of antigen-specific T-cell responses through the recognition of the HLA-peptide complex by T-cell receptors (TCRs), leading to targeted lysis of tumor cells.