Patient-specific tumor neoantigen peptides presented on HLA (Neoantigen-HLA complex)

Patient-specific tumor neoantigen peptides presented on HLA (Human Leukocyte Antigen) represent a class of highly specific cancer targets derived from non-synonymous somatic mutations unique to an individual's tumor [1, 12]. These neoantigens are processed into short peptides and displayed on the cell surface by MHC Class I or II molecules, where they can be recognized by the T-cell receptor (TCR) of cytotoxic and helper T cells [2, 20]. Because these antigens are not expressed in healthy tissues, they bypass central immune tolerance, making them ideal targets for personalized immunotherapy with minimal off-target effects on normal cells [15, 18]. Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines, such as mRNA-4157 and Autogene cevumeran, as well as adoptive T-cell therapies and TCR-engineered T cells [5, 23]. The efficacy of these treatments often correlates with the tumor neoantigen burden (TNB) and the presence of clonal mutations that are shared across all tumor cells [1, 6]. However, challenges remain, including the logistical complexity of rapid personalized manufacturing, potential tumor escape through HLA downregulation or antigen loss, and the immunosuppressive nature of the tumor microenvironment [3, 7, 24].

Other names

Tumor-specific antigens (TSAs)NeoepitopesHLA-presented neoantigensPersonalized neoantigensClonal neoantigensPrivate neoantigensPeptide-MHC complex (pMHC)

Stimulation of the patient's own immune system, specifically CD8+ cytotoxic and CD4+ helper T cells, to recognize and eliminate tumor cells by presenting unique, non-self peptides derived from somatic mutations on HLA molecules.