Tumor-specific neoantigen peptide–human leukocyte antigen complex (Neoantigen-HLA) (Neoantigen-HLA)

Tumor-specific neoantigen peptide–human leukocyte antigen (HLA) complexes are molecular assemblies found on the surface of cancer cells, consisting of a mutated peptide fragment (neoantigen) bound to an HLA molecule [1, 2]. These neoantigens arise from somatic mutations—such as single nucleotide variants, insertions, or deletions—that are unique to the tumor and absent in normal tissues [2]. Because these complexes are not present in the thymus during T-cell development, they bypass central tolerance, allowing the immune system to recognize them as "non-self" [1, 2]. This high specificity makes them premier targets for personalized cancer immunotherapies, including neoantigen vaccines, T-cell receptor (TCR) engineered T-cells, and "TCR-like" bispecific antibodies [1, 6]. However, therapeutic challenges include the low density of these complexes on the cell surface, the potential for HLA downregulation as an immune escape mechanism, and the risk of off-target cross-reactivity with similar self-peptides [1, 5].

Other names

Neoantigen-MHC complexpHLA complexpMHC complexTumor-specific neoepitope-HLA complexTSNA-HLA complex

Targeting of the peptide-HLA complex by T-cell receptors (TCRs) or TCR-mimetic antibodies to induce cytotoxic T-cell-mediated lysis of cancer cells [1, 6].