Patient-specific tumor-associated antigen peptides presented by HLA class I molecules (Neoantigen)

Patient-specific tumor-associated antigen peptides, frequently termed neoantigens, are unique protein sequences arising from somatic mutations—such as single nucleotide variants or frameshifts—within a patient's tumor cells (Schumacher & Schreiber, 2015). These mutated proteins are processed intracellularly and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, serving as non-self signals to the immune system (Finn, 2017). Because these antigens are entirely absent from the normal human proteome, they are highly specific targets that allow the immune system to selectively destroy malignant cells while sparing healthy tissue (Sahin & Türeci, 2018). Therapeutic approaches targeting these peptides include personalized mRNA or peptide vaccines, which aim to expand the population of neoantigen-specific CD8+ T cells (Blass & Ott, 2021). Additionally, adoptive cell therapies, such as TCR-engineered T cells, are being developed to recognize these specific peptide-HLA complexes with high affinity. The identification of these targets typically involves genomic sequencing of the tumor followed by bioinformatic prediction of peptide binding to the patient's specific HLA alleles. Despite their therapeutic potential, challenges include the high degree of tumor heterogeneity and the ability of tumors to downregulate HLA expression to evade immune detection (Schumacher & Schreiber, 2015).

Other names

NeoantigensTumor-specific antigensNeoepitopespHLA complexesMHC-I restricted tumor peptidesTSAs

Stimulation of cytotoxic T-lymphocyte (CTL) responses through the recognition of mutation-derived peptides presented by HLA class I molecules.