Shared tumor-specific epitope–HLA Class I complex (Shared pHLA-I complex)

The shared tumor-specific epitope–HLA Class I complex is a molecular assembly consisting of a tumor-derived peptide (epitope) bound within the groove of a Major Histocompatibility Complex (MHC) Class I molecule on the surface of a cancer cell (Nature Reviews Drug Discovery, 2023). These epitopes typically originate from "shared" antigens, such as public neoantigens (e.g., mutated KRAS or TP53) or cancer-testis antigens (e.g., NY-ESO-1, MAGE-A4), which are expressed across different patients with the same malignancy (Cancer Cell, 2021). This complex serves as the primary signal for recognition by the T-cell receptor (TCR) of CD8+ cytotoxic T-lymphocytes, initiating an immune-mediated destruction of the target cell (PubMed, PMID: 33024110). In drug development, these complexes are targeted by TCR-engineered T-cell therapies (TCR-T), TCR-like monoclonal antibodies, and bispecific T-cell engagers (BiTEs) (The Lancet, 2024). By targeting intracellular proteins presented via HLA, these therapies bypass the limitation of traditional CAR-T cells, which can only recognize surface-expressed proteins (NEJM, 2021). However, clinical application requires precise patient selection based on specific HLA alleles and the presence of the target antigen, while managing risks of cross-reactivity with similar peptides in healthy tissues (Frontiers in Immunology, 2022).

Other names

Shared neoantigen-HLA complexPublic neoantigen-MHC complexTumor-associated antigen-HLA complexpMHC Class I complexPeptide-HLA Class I complex

Redirection of T-cells to tumor cells via high-affinity binding to the peptide-HLA complex, leading to T-cell receptor (TCR) activation and subsequent tumor cell lysis.