Paired-like homeobox 2B peptide–HLA-A*24:02 complex (PHOX2B-HLA-A24)

Paired-like homeobox 2B (PHOX2B) is a master regulator transcription factor essential for the development of the peripheral autonomic nervous system (Yarmarkovich et al., 2021). In the context of oncology, PHOX2B is a highly specific marker for neuroblastoma, as its expression is largely restricted to the embryonal sympathetic nervous system and is absent in most healthy postnatal tissues (Maris, 2010). While PHOX2B is an intracellular protein and thus inaccessible to conventional antibody-based therapies, its degradation products are presented on the cell surface as peptides bound to Human Leukocyte Antigen (HLA) molecules. Specifically, the PHOX2B-derived peptide QYLGAMSSV presented by HLA-A*24:02 has been identified as a potent immunotherapeutic target (Yarmarkovich et al., 2021). Therapeutic strategies, including peptide-centric chimeric antigen receptor (PC-CAR) T cells and TCR-mimic antibodies, have been developed to recognize this complex. These therapies aim to induce targeted lysis of neuroblastoma cells while sparing normal tissues that lack PHOX2B expression or the specific HLA presentation. This approach bypasses the "undruggable" nature of intracellular transcription factors and provides a high degree of tumor specificity.

Other names

PHOX2B-HLA complexPHOX2B-MHC complexQYLGAMSSV-HLA-A*24:02PHOX2B-derived peptide–HLA complexes

Targeted T-cell mediated cytotoxicity via recognition of peptide-MHC complexes