Patient-specific tumor neo-antigen peptides presented by Human Leukocyte Antigen (HLA) (Neoantigen-HLA complex)

Patient-specific tumor neo-antigen peptides presented by Human Leukocyte Antigen (HLA) are unique protein fragments derived from somatic mutations within a patient's tumor (Schumacher & Schreiber, Science 2015). These mutations, which include single-nucleotide variants and frameshifts, create novel sequences that the immune system perceives as foreign (Ott et al., Nature 2017). Once these peptides are processed and displayed by HLA molecules on the tumor cell surface, they serve as specific flags for T-cell recognition (Sahin et al., Nature 2017). Because these neoantigens are not expressed in healthy tissues, they provide a high degree of therapeutic selectivity, reducing the risk of autoimmune side effects (Hu et al., Nature Reviews Immunology 2021). Current clinical approaches involve the development of personalized vaccines, such as mRNA or peptide-based formulations, tailored to an individual's unique mutational profile (Weber et al., Lancet 2024). Additionally, adoptive cell therapies are being developed to engineer T-cells with receptors specifically targeting these neoantigen-HLA complexes (Blass & Ott, Nature Reviews Clinical Oncology 2021). Despite their potential, the effectiveness of these therapies can be limited by tumor heterogeneity and the loss of HLA expression, which allows tumors to evade immune detection (Gettinger et al., Cancer Discovery 2017). The complexity of identifying truly immunogenic neoantigens and the logistical demands of bespoke manufacturing remain significant hurdles in the field.

Other names

Tumor-specific neoantigensNeoepitopesMutation-derived antigensTumor-specific antigens (TSA)pMHC complexes

Induction of tumor-specific T-cell mediated cytotoxicity through the recognition of mutation-derived epitopes presented on MHC molecules (Schumacher & Schreiber, Science 2015).