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

Patient-specific neoantigen–human leukocyte antigen (HLA) complexes are unique molecular targets formed by the presentation of mutated peptide fragments on the surface of tumor cells and antigen-presenting cells (Nature, 2017). These mutations arise from somatic alterations such as single nucleotide variants, insertions/deletions, or chromosomal rearrangements that are unique to an individual's tumor and absent from the normal genome (NEJM, 2017). Because these neoantigens are not expressed in healthy tissues, they are highly immunogenic and bypass central thymic tolerance, allowing for the generation of potent, tumor-specific T-cell responses (Science, 2017). Therapeutic interventions, including personalized vaccines (e.g., mRNA-4157) and TCR-engineered T-cells, aim to exploit these complexes to achieve precise tumor destruction while sparing normal cells (Frontiers in Immunology, 2021). The identification and targeting of these complexes represent a cornerstone of precision oncology, requiring integrated genomic sequencing and computational modeling to predict which mutations will successfully form stable, immunogenic HLA complexes (PubMed, PMID: 33024320). This approach is particularly relevant in cancers with high mutational burdens, where the likelihood of generating immunogenic neoantigens is significantly increased.

Other names

Tumor-specific neoantigen-MHC complexNeoepitope-HLA complexpHLA complexPersonalized tumor antigen-HLA complexTSA-HLA complex

Induction of a de novo T-cell response or expansion of existing neoantigen-specific T-cells that recognize and lyse cells presenting the mutated peptide in the context of specific HLA alleles.