Tumor-associated human leukocyte antigen-peptide complex (Tumor-associated HLA-peptide complex)

The tumor-associated human leukocyte antigen (HLA)-peptide complex is a molecular structure formed when intracellular proteins, including mutated neoantigens or overexpressed tumor-associated antigens, are degraded into short peptides and presented on the cell surface by HLA molecules. This complex serves as the primary signal for the adaptive immune system, specifically allowing CD8+ T-cells to identify and eliminate malignant cells via their T-cell receptors (TCRs). In the context of oncology, these complexes are highly specific therapeutic targets because they represent the 'fingerprint' of a cancer cell, often presenting sequences not found on healthy tissues. Therapeutic strategies targeting these complexes include TCR-engineered T-cell therapies (TCR-T) and bispecific molecules like Immune Mobilizing Monoclonal TCRs Against Cancer (ImmTACs), which bypass the need for natural T-cell recognition to induce a potent anti-tumor response (Source: Frontiers in Immunology, 2020; PubMed: 32117311; Nature Communications, 2022; PubMed: 35915084).

Other names

pHLA complexMHC-peptide complexTumor-specific antigen-HLA complexNeoantigen-HLA complexpMHCTumor-associated antigen-MHC complex

Drugs targeting tumor-associated HLA-peptide complexes typically utilize engineered T-cell receptors (TCR-T cells) or bispecific T-cell engagers (ImmTACs) to specifically recognize and bind the peptide fragment presented within the HLA groove. This binding triggers T-cell mediated cytotoxicity, leading to the selective destruction of the tumor cell presenting the specific antigen (e.g., NY-ESO-1, MAGE-A3, or neoantigens) (Source: Nature Reviews Drug Discovery, 2021; PubMed: 33510449).