Tumor-associated antigen and leukemia-associated antigen presented on Human Leukocyte Antigen (HLA) molecule (TAA/LAA-HLA complex)

Tumor-associated antigens (TAAs) and leukemia-associated antigens (LAAs) represent a diverse group of proteins that are preferentially expressed in malignant cells compared to healthy tissues (National Cancer Institute, 2024). These intracellular proteins are proteolytically processed into short peptide fragments and presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, forming a peptide-HLA (pHLA) complex (Nature Reviews Cancer, 2021). This presentation allows the immune system to monitor the internal proteome of a cell, identifying transformations that would otherwise be hidden from traditional antibody-based therapies. Therapeutic strategies targeting these complexes include TCR-engineered T-cells (TCR-T), bispecific T-cell engagers, and cancer vaccines designed to induce a potent anti-tumor immune response (FDA, 2024; NEJM, 2021). A major advantage of this target class is the ability to address intracellular oncogenic drivers, such as WT1 or MAGE-A4, which are not accessible via surface receptors. However, clinical application is often restricted to patients with specific HLA alleles, and significant safety challenges exist regarding potential cross-reactivity with similar peptides in vital organs (Journal for ImmunoTherapy of Cancer, 2020).

Other names

Tumor-associated antigen (TAA)Leukemia-associated antigen (LAA)Peptide-HLA complexpHLACancer-testis antigen (CTA)Tumor-specific antigen (TSA)NeoantigenMHC-restricted antigen

Drugs targeting these complexes typically utilize engineered T-cell receptors (TCRs) or TCR-like antibodies to recognize specific peptide fragments presented by HLA molecules on the cell surface, leading to T-cell mediated lysis of the target cell (Nature Reviews Cancer, 2021; PubMed: 33536580).