Patient-specific tumor-associated and neoantigen-derived peptides presented on HLA class I and II (Neoantigen-HLA complexes)

Patient-specific tumor-associated and neoantigen-derived peptides presented on HLA class I and II represent a highly personalized class of therapeutic targets in oncology. These targets consist of short peptide fragments derived from either mutated proteins (neoantigens) or overexpressed proteins (tumor-associated antigens) that are displayed on the cell surface by Human Leukocyte Antigen (HLA) molecules (Sahin & Türeci, 2018, Science). HLA class I complexes typically activate CD8+ cytotoxic T cells, while HLA class II complexes engage CD4+ helper T cells to orchestrate a comprehensive anti-tumor immune response (Hu et al., 2021, Nature Reviews Cancer). Because neoantigens arise from somatic mutations unique to an individual's tumor, they are generally absent in healthy tissues, minimizing the risk of central tolerance and autoimmunity (Ott et al., 2017, Nature). Therapeutic strategies targeting these complexes include personalized mRNA or peptide vaccines, as well as adoptive cell therapies like TCR-engineered T cells (Xie et al., 2023, Signal Transduction and Targeted Therapy). The clinical success of these therapies depends on the accurate identification of immunogenic peptides and the patient's specific HLA alleles to ensure effective presentation and T-cell recognition (Nature Reviews Cancer, 2021). This target class is central to the development of next-generation immunotherapies that adapt to the unique mutational landscape of a patient's cancer.

Other names

Tumor neoepitopesPatient-specific tumor antigensMHC-restricted tumor peptidesTSA/TAA-HLA complexesTumor-specific antigensPersonalized tumor-associated antigens

Induction of antigen-specific T-cell mediated cytotoxicity and helper T-cell responses through the recognition of peptide-HLA complexes by T-cell receptors (TCRs).