Neoantigen-Human Leukocyte Antigen complex (NeoAg-HLA) (NeoAg-HLA)

Neoantigen-Human Leukocyte Antigen (HLA) complexes are molecular structures on the surface of tumor cells consisting of a mutated peptide (neoantigen) bound to an HLA molecule. These complexes arise from somatic mutations—such as non-synonymous single nucleotide variants (SNVs), insertions/deletions (indels), or frameshifts—that are unique to the cancer genome and absent in healthy tissue (Nature Reviews Cancer, 2021). Because they are not subject to central thymic tolerance, neoantigen-HLA complexes are highly immunogenic and serve as ideal targets for precision immunotherapy (Science, 2017). Therapeutic approaches targeting these complexes include personalized neoantigen vaccines, which prime the patient's immune system to recognize these specific markers, and adoptive cell therapies like TCR-engineered T cells (TCR-T) that are programmed to bind the complex with high affinity (Journal of Hematology & Oncology, 2024). Despite their potential, the effectiveness of targeting these complexes can be hindered by tumor heterogeneity and the loss of HLA expression, which allows cancer cells to evade immune detection (Cell, 2019).

Other names

Neoepitope-HLA complexTumor-specific antigen-MHC complexMutant peptide-HLA complexpHLANeoantigen-MHC complex

Induction of a targeted T-cell response through the recognition of tumor-specific mutant peptides presented by HLA molecules, leading to selective destruction of malignant cells.