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

Tumor-associated antigens (TAAs) presented on Human Leukocyte Antigen (HLA) molecules represent a critical class of targets for precision cancer immunotherapy, particularly for T-cell receptor (TCR) based modalities. These targets are formed when intracellular proteins, including mutated neoantigens or overexpressed self-proteins, are processed into short peptides and displayed on the cell surface by HLA class I or II molecules (Source: Nature Reviews Cancer, 2021). This mechanism provides the immune system with a window into the internal proteome of the tumor cell, allowing for the targeting of proteins that are not traditionally accessible to antibody-based therapies (Source: NIH/NCI). Drugs such as Tebentafusp and Afamitresgene autoleucel are engineered to bind these specific peptide-HLA complexes with high affinity, bypassing the natural limitations of the endogenous immune repertoire (Source: FDA, 2022; Adaptimmune, 2024). Upon binding, these therapies recruit and activate T-cells to induce a potent cytotoxic response against the malignant cell. However, the clinical application of these targets is often restricted to patients with specific HLA alleles, such as HLA-A*02:01, and faces challenges such as tumor-mediated HLA loss and potential cross-reactivity with similar peptides in vital organs (Source: Frontiers in Immunology, 2022; Journal of Hematology & Oncology, 2023).

Other names

pHLAPeptide-MHC complexTumor-specific antigen (TSA)Neoantigen-HLA complexCancer-testis antigen (CTA)Oncofetal antigenDifferentiation antigen

T-cell receptor (TCR) mediated recognition of specific peptide-HLA complexes on the tumor cell surface, leading to T-cell activation, cytokine release, and cytotoxic lysis of the target cell.