Paired-like homeobox 2B (PHOX2B) peptide presented by Human Leukocyte Antigen A*24:02 (HLA-A*24:02) (PHOX2B-HLA-A24)

Paired-like homeobox 2B (PHOX2B) is a lineage-restricted transcription factor essential for the development of the autonomic nervous system, including sympathetic neurons and the adrenal medulla (UniProtKB - P50529). While its expression is normally limited to specific embryonal tissues and mature autonomic neurons, it is highly and consistently overexpressed in neuroblastoma, a common pediatric cancer (Yarmarkovich et al., Nature, 2021). Because PHOX2B is an intracellular protein, it is not accessible to conventional antibody therapies; however, its degradation products are presented as peptides on the cell surface by Human Leukocyte Antigen (HLA) class I molecules. A specific peptide, QYNPIRTTF, presented by HLA-A*24:02, has been identified as a potent immunotherapeutic target (Yarmarkovich et al., 2021). Therapeutic strategies, such as TCR-mimic (TCRm) antibodies like 10LH and CAR-T cells, are being developed to recognize this specific peptide-HLA complex to selectively eliminate neuroblastoma cells. This approach allows for the targeting of an intracellular oncogene by exploiting the antigen presentation pathway, potentially offering a new treatment modality for patients with high-risk neuroblastoma. Clinical application requires patient selection based on both PHOX2B expression and the presence of the HLA-A*24:02 allele.

Other names

PHOX2B-HLA complexPHOX2B peptide-MHCQYNPIRTTF-HLA-A*24:02PHOX2B-derived peptide presented by HLA class I

Recognition of the peptide-MHC complex by a TCR-mimic antibody or CAR-T cell, leading to T-cell activation and targeted lysis of the tumor cell.