Wilms' tumor 1 protein (WT1) 126-134 peptide-HLA-A*02:01 complex (WT1 126-134/HLA-A*02:01)

The Wilms' tumor 1 protein (WT1) 126-134 peptide-HLA-A*02:01 complex is a prominent target in cancer immunotherapy (PubMed: 10667377). WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, such as acute myeloid leukemia (AML), and several solid tumors, while maintaining low expression in normal adult tissues (PubMed: 12149211). The specific nonameric peptide sequence RMFPNAPYL (residues 126-134) is processed and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01. This complex is recognized by the T-cell receptor (TCR) of CD8+ cytotoxic T lymphocytes, making it a focal point for the development of peptide vaccines, TCR-engineered T-cell therapies (TCR-T), and TCR-like bispecific antibodies (PubMed: 23486779). Therapeutic strategies aiming at this target, such as Galinpepimut-S or TCR-T cell products like JTCR016, seek to exploit the differential expression of WT1 to selectively eliminate malignant cells while sparing healthy tissue (SELLAS Life Sciences; Juno Therapeutics).

Other names

WT1 RMFPNAPYL peptideWT1-A2 complexRMFPNAPYL/HLA-A*02:01WT1 126-134 epitope

Targeting of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated cytotoxicity against tumor cells (PubMed: 23486779).