Paired-like homeobox 2B peptide-HLA complex (PHOX2B-HLA)

The PHOX2B-derived peptide presented by HLA class I is a highly specific cell-surface target for the treatment of neuroblastoma, a common pediatric cancer. PHOX2B (Paired-like homeobox 2B) is a transcription factor essential for the development of the autonomic nervous system and is characteristically overexpressed in neuroblastoma cells while remaining largely absent in most healthy postnatal tissues. Because PHOX2B is an intracellular protein, it cannot be targeted by traditional antibodies; however, its degradation products (peptides) are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, specifically HLA-A*24:02. This peptide-MHC complex allows the immune system to 'see' the intracellular oncogenic driver. Recent therapeutic developments have focused on engineering CAR-T cells and TCR-like antibodies that specifically bind to the PHOX2B-HLA complex, offering a precision medicine approach that spares healthy cells while potentizing the immune response against the tumor. Clinical interest is high due to the restricted expression profile of PHOX2B, which minimizes the risk of systemic toxicity.

Other names

PHOX2B-derived peptide presented by HLA class IPHOX2B-HLA-A*24:02 complexPHOX2B-MHC complexQYNPIRTTF-HLA-A*24:02

The target is a specific peptide-HLA complex where a 9-amino acid sequence (QYNPIRTTF) derived from the PHOX2B protein is presented on the cell surface by HLA-A*24:02. Therapeutic agents, such as CAR-T cells or T-cell receptor-like (TCR-like) antibodies, recognize this specific complex to induce targeted lysis of neuroblastoma cells through T-cell mediated cytotoxicity or antibody-dependent mechanisms.