Tumor-associated antigen-HLA complex (TAA-HLA)

Tumor-associated antigen-HLA (TAA-HLA) complexes are the fundamental targets for cellular immunotherapies, consisting of intracellularly processed peptides displayed on the cell surface by Human Leukocyte Antigen (HLA) molecules (Rosenberg et al., 2015). These complexes represent a snapshot of the cell's internal proteome, allowing the immune system to distinguish between healthy and malignant cells. In the context of tumor-infiltrating lymphocyte (TIL) therapy, naturally occurring T-cells that have recognized these specific pHLA complexes are harvested, expanded, and re-infused into the patient (FDA, 2024). Similarly, TCR-engineered T-cell (TCR-T) therapies utilize synthetic receptors designed to bind specific TAA-HLA targets, such as MAGE-A4 or NY-ESO-1 (Adaptimmune, 2024). The interaction between the T-cell receptor and the TAA-HLA complex triggers a signaling cascade that leads to the release of perforins and granzymes, resulting in the targeted destruction of the cancer cell. This mechanism is highly dependent on both the presence of the specific antigen and the patient's specific HLA genotype, necessitating precise patient selection and biomarker screening (Immunocore, 2022). This target class is central to the development of personalized cancer immunotherapies for solid tumors that are otherwise resistant to checkpoint inhibition.

Other names

Peptide-HLA complexpHLATumor-specific antigen-HLA complexNeoantigen-HLA complexTumor-associated antigen

Direct recognition of the peptide-HLA complex by T-cell receptors (TCRs), triggering cytotoxic T-lymphocyte activation and subsequent lysis of the target tumor cell.