Tumor neoantigen-Human Leukocyte Antigen complex (NeoAg-HLA)

Tumor neoantigen-Human Leukocyte Antigen (HLA) complexes are highly specific molecular targets consisting of a mutated peptide (neoantigen) bound to an HLA molecule on the surface of cancer cells (Schumacher & Schreiber, Science 2015). These complexes arise from somatic mutations unique to an individual's tumor, such as single nucleotide variants or frameshifts, which are processed by the proteasome and transported to the cell surface (Blass & Ott, Nature Reviews Clinical Oncology 2021). Because these neoantigens are absent from the normal human proteome, they are recognized as "non-self" by the immune system, specifically by T-cell receptors (TCRs) on CD8+ and CD4+ T cells (Sahin & Türeci, Science 2018). This recognition is the cornerstone of modern personalized immunotherapy, including neoantigen-based vaccines and TCR-engineered T-cell (TCR-T) therapies. In clinical practice, these targets are identified through whole-exome sequencing and bioinformatic algorithms that predict peptide-HLA binding affinity (Yarchoan et al., Nature Reviews Cancer 2017). While they offer a high degree of tumor specificity and reduced risk of systemic autoimmunity, therapeutic efficacy can be limited by the heterogeneity of neoantigen expression and the loss of HLA expression by tumor cells as a mechanism of immune evasion (Hu et al., Nature Reviews Immunology 2021).

Other names

Neoepitope-HLA complexpHLA complexTumor-specific antigen-MHC complexPersonalized neoantigen-MHCNeoantigen-HLA complex

Targeting of the neoantigen-HLA complex via vaccine-induced T cells or adoptively transferred TCR-T cells to initiate a specific cytotoxic immune response against tumor cells (Schumacher & Schreiber, Science 2015).