Tumor-associated antigen complexed with Human Leukocyte Antigen (TAA-HLA) (TAA-HLA)

The Tumor-associated antigen complexed with Human Leukocyte Antigen (TAA-HLA) is a molecular assembly consisting of a processed peptide fragment derived from an intracellular tumor protein bound to an HLA molecule on the cell surface [1]. This complex serves as the primary ligand for T-cell receptors (TCRs), allowing the immune system to monitor the internal proteome of cells for oncogenic transformations [2]. Unlike traditional monoclonal antibodies that target surface proteins, therapies directed at TAA-HLA complexes can target intracellular drivers of malignancy such as MAGE-A4, NY-ESO-1, or gp100 [3]. Current therapeutic modalities include TCR-engineered T-cells (TCR-T) and TCR-mimetic bispecific T-cell engagers, which are designed to recognize specific peptide-HLA combinations with high affinity [4]. These treatments are highly potent but require patients to possess specific HLA alleles, most commonly HLA-A*02:01, to ensure target recognition [5]. Clinical challenges include potential off-target toxicity if the targeted peptide sequence is shared by proteins in healthy tissues, as well as tumor resistance through the downregulation of HLA expression [6].

Other names

Peptide-MHC complexpMHCpHLATumor-specific antigen-HLA complexNeoantigen-HLA complex

Recognition of specific peptide-HLA complexes by engineered T-cell receptors (TCRs) or TCR-mimetic antibodies to induce T-cell mediated lysis of tumor cells [4].