Patient-specific human leukocyte antigen (HLA) molecules presenting tumor-specific neoantigen peptides (HLA-neoantigen complex)

Patient-specific HLA molecules presenting tumor-specific neoantigen peptides represent a highly personalized class of therapeutic targets in oncology. These complexes are formed when somatic mutations—such as single nucleotide variants, insertions, or deletions—create novel protein sequences (neoantigens) that are processed by the proteasome and displayed on the cell surface by the patient's unique Human Leukocyte Antigen (HLA) molecules (Schumacher & Schreiber, 2015, Science). Because these neoepitopes are entirely absent from the normal human proteome, they are recognized as 'foreign' by the immune system, minimizing the risk of central tolerance and making them ideal targets for precision immunotherapy (Sahin & Türeci, 2018, Science). Current therapeutic strategies include personalized mRNA or DNA vaccines that encode these neoantigens to prime the patient's own T cells, as well as adoptive T-cell therapies (TCR-T) where T cells are engineered to express receptors specific to a particular neoantigen-HLA combination (Blass & Ott, 2021, Nature Reviews Clinical Oncology). The clinical efficacy of targeting these complexes has been demonstrated in trials for melanoma and pancreatic cancer, where personalized vaccines induced robust T-cell responses and delayed disease recurrence (Weber et al., 2023, The Lancet; Rojas et al., 2023, Nature). However, the success of this approach depends on sophisticated computational algorithms to predict peptide-HLA binding and the stability of the complex on the tumor cell surface.

Other names

Neoepitope-HLA complexTumor-specific neoantigen-MHC complexTSNA-HLA complexMHC-restricted neoantigenPersonalized neoantigen-HLA target

Recognition by endogenous or engineered T-cell receptors (TCRs) to trigger cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells and establish immunological memory.