Patient-specific tumor neoantigen peptides presented on Human Leukocyte Antigen (HLA) molecules (NeoAg-HLA complex)

Patient-specific tumor neoantigen peptides presented on Human Leukocyte Antigen (HLA) molecules are unique protein fragments derived from somatic mutations within a patient's tumor that are displayed on the cell surface for immune surveillance (Schumacher & Schreiber, 2015). These neoepitopes result from genetic alterations such as single-nucleotide variants, insertions, deletions, or gene fusions, making them entirely absent from the normal human proteome and thus highly specific targets for immunotherapy (Sahin & Türeci, 2018). The recognition of these peptide-HLA complexes by the T-cell receptor (TCR) of CD8+ and CD4+ T-cells is a critical step in the adaptive immune response against cancer (Ott et al., 2017). Therapeutic strategies, including personalized mRNA vaccines and adoptive T-cell therapies, aim to exploit this specificity to induce a potent anti-tumor response while sparing healthy tissues (Hu et al., 2021). However, the clinical success of targeting these complexes depends on the accurate identification of immunogenic mutations and the tumor's ability to maintain HLA expression to avoid immune evasion.

Other names

Tumor-specific antigensNeoepitopesHLA-presented neoantigensPersonalized neoantigensTSAsTumor-specific neoantigens

Induction of a de novo T-cell response against tumor-specific mutations through the presentation of neoepitopes on HLA molecules, leading to T-cell receptor-mediated recognition and cytotoxic killing of tumor cells.