Wilms' tumor 1-derived peptide TPYGPPHPP in complex with HLA-B*35:01 (WT1-TPY/HLA-B*35)

The target is a specific peptide-major histocompatibility complex (pMHC) consisting of a 9-amino acid fragment (TPYGPPHPP, residues 239-247) derived from the Wilms' Tumor 1 (WT1) protein, presented on the cell surface by the HLA-B*35:01 molecule. WT1 is a zinc-finger transcription factor that plays a critical role in cell growth and differentiation; while it is expressed at low levels in some normal tissues like the kidney and bone marrow, it is significantly overexpressed in various hematological malignancies and solid tumors (PubMed: 12117617). This overexpression makes the WT1-TPY/HLA-B*35 complex a highly specific target for immunotherapies, particularly in patients who carry the HLA-B*35 allele. Therapeutic interventions, such as T-cell receptor (TCR) engineered T-cells or TCR-like antibodies, are designed to recognize this specific pMHC complex to induce a targeted immune response against cancer cells (PubMed: 15155837). By binding to this complex, these therapies trigger the release of cytotoxic granules and cytokines, leading to the selective destruction of the tumor cell while sparing most healthy tissues. Clinical development of drugs targeting this complex requires patient screening for both WT1 expression and the specific HLA-B*35:01 haplotype to ensure efficacy and safety.

Other names

WT1 239-247 peptide/HLA-B*35 complexTPYGPPHPP/HLA-B*35:01WT1-B35 pMHCWilms' tumor protein 1 epitope TPYGPPHPP

T-cell receptor (TCR) mediated recognition leading to cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.