Patient-specific neoantigen-human leukocyte antigen complex (NeoAg-HLA complex) (NeoAg-HLA complex)

Patient-specific neoantigen-human leukocyte antigen (HLA) complexes are the fundamental targets for personalized cancer immunotherapies, including neoantigen vaccines and T-cell receptor (TCR)-engineered T-cell therapies (NIH, 2020). These complexes consist of a mutated peptide (neoantigen) derived from tumor-specific somatic mutations, which is processed and presented on the cell surface by the patient's own HLA Class I or Class II molecules (NIH, 2024). Because these neoantigens are absent from the normal genome, they are recognized as foreign by the immune system, minimizing central tolerance and reducing the risk of autoimmune toxicity compared to shared tumor-associated antigens (NIH, 2025). The interaction between a T-cell receptor and the neoantigen-HLA complex triggers a specific immune response, leading to the expansion of cytotoxic CD8+ T cells or helper CD4+ T cells that selectively target and eliminate tumor cells (NIH, 2018). Therapeutic strategies involve identifying these unique mutations through genomic sequencing and bioinformatic prediction, followed by the delivery of the neoantigens via mRNA, DNA, or peptide-based vaccines to prime the immune system, or the infusion of TCR-T cells engineered to recognize the specific complex (Liv Hospital, 2026). The identification of these targets relies on advanced proteogenomic workflows, such as mass spectrometry-based immunopeptidomics, to validate that predicted neoantigens are indeed presented on the cell surface (NIH, 2024). Clinical outcomes are often correlated with the neoantigen load and the diversity of the induced T-cell response, which can be limited by the tumor's ability to downregulate antigen-processing machinery (NIH, 2025). However, tumors can evade these responses through mechanisms such as HLA downregulation or loss of heterozygosity, which prevents the presentation of the target complex and necessitates combination strategies with checkpoint inhibitors (NIH, 2021).

Other names

Tumor-specific neoantigen-MHC complexNeoepitope-HLA complexpMHC complexMutant peptide-HLA complexPersonalized neoantigen-MHC complex

Active immunization or adoptive cell transfer to induce or provide T cells that recognize and eliminate tumor cells presenting specific neoantigen-HLA complexes.