Tumor-associated antigen presented on Human Leukocyte Antigen (HLA) molecules (TAA-HLA complex)

Tumor-associated antigens (TAAs) presented on Human Leukocyte Antigen (HLA) molecules represent a critical class of targets for cancer immunotherapy, particularly for T-cell receptor (TCR) based platforms. These targets consist of short peptide fragments derived from intracellular proteins that are processed by the proteasome and displayed on the cell surface by HLA class I or II molecules [1]. Unlike traditional antibody targets that must be surface-expressed proteins, the TAA-HLA complex allows the immune system to monitor the internal proteome of a cell, enabling the targeting of mutated proteins (neoantigens), overexpressed self-proteins, or proteins with restricted expression patterns like cancer-testis antigens [2]. Current therapeutic strategies include TCR-engineered T-cells (TCR-T), soluble TCR-based bispecific engagers, and personalized cancer vaccines [3]. Because these therapies are restricted to specific HLA alleles, such as HLA-A*02:01, patient selection requires both HLA typing and confirmation of antigen expression in the tumor [4]. While highly specific, the primary challenge remains the risk of cross-reactivity with similar peptides in healthy tissues, which can lead to severe off-target toxicities [5].

Other names

Peptide-HLA complexpHLApMHCMHC-restricted tumor antigenNeoantigen-HLA complexCancer-testis antigen-HLA complex

T-cell receptor (TCR) mediated recognition of specific peptide-HLA complexes on the surface of tumor cells, leading to the formation of an immunological synapse, T-cell activation, and subsequent cytotoxic lysis of the target cell [1, 4].