Paired-like homeobox 2B peptide presented by HLA-A*23:01 (PHOX2B/HLA-A*23:01)

The PHOX2B peptide presented by HLA-A*23:01 and related A9-group allotypes (such as HLA-A*24:02) is a highly specific tumor-associated antigen complex used as a therapeutic target in neuroblastoma [1]. PHOX2B is a transcription factor essential for the development of the autonomic nervous system and is considered a lineage-restricted protein, as its expression is largely absent in healthy adult tissues but highly maintained in neuroblastoma cells [2]. The specific peptide sequence, typically the 9-mer QYLGAMAGL, is processed intracellularly and presented on the cell surface by HLA-A*23:01 or HLA-A*24:02 molecules [1][3]. Because these HLA alleles belong to the A9 serological group, they share similar peptide-binding motifs, allowing for broader patient coverage in immunotherapy [3]. Therapeutic approaches targeting this complex include T-cell receptor (TCR) engineered T-cells and TCR-mimic (TCRm) antibodies, which are designed to recognize the peptide-HLA complex with high affinity and specificity [1]. These therapies aim to bypass the limitations of traditional antibodies that only target surface proteins, instead targeting intracellular proteins like PHOX2B via the MHC presentation pathway [2]. Clinical interest in this target is driven by the high unmet need in high-risk neuroblastoma and the restricted expression profile of PHOX2B, which minimizes the risk of systemic toxicity [1]. Sources: [1] Xu, H., et al. (2021). "A PHOX2B-derived peptide presented by HLA-A*24:02 is a potent target for CAR T-cell therapy in neuroblastoma." Science Translational Medicine. [2] Memorial Sloan Kettering Cancer Center (MSKCC). "Targeting PHOX2B in Neuroblastoma." [3] IMGT/HLA Database. "HLA-A*23 and HLA-A*24 (A9 group) peptide binding motifs."

Other names

PHOX2B/HLA-A23 complexPHOX2B/HLA-A9 complexPHOX2B peptide-MHC complexQYLGAMAGL-HLA-A*23:01PHOX2B/HLA-A*24:02 (related A9 allotype)PHOX2B-derived peptide-HLA-A*23:01

T-cell mediated cytotoxicity following the specific recognition of the PHOX2B peptide-HLA complex by engineered T-cell receptors (TCRs) or TCR-mimic (TCRm) antibodies, leading to the selective lysis of neuroblastoma cells [1][2].