Wilms' tumor 1 peptide presented by HLA-A*02:01 (WT1/HLA-A*02:01)

The Wilms' tumor 1 (WT1) peptide presented by the HLA-A*02:01 complex is a highly prioritized tumor-associated antigen (TAA) target for cancer immunotherapy. WT1 is a zinc-finger transcription factor that is overexpressed in a wide range of hematological malignancies, such as acute myeloid leukemia (AML), and various solid tumors, while having limited expression in normal adult tissues (Source: Cheever et al., 2009, Clinical Cancer Research). The specific 9-amino acid peptide, typically RMFPNAPYL, is processed and presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (Source: Dao et al., 2013, Science Translational Medicine). This peptide-MHC (pMHC) complex is recognized by specific T-cell receptors (TCRs), making it a focal point for the development of TCR-engineered T-cell therapies, vaccines, and TCR-mimic antibodies (Source: Chapuis et al., 2013, Science Translational Medicine). Targeting this complex allows the immune system to selectively identify and eliminate malignant cells expressing the intracellular WT1 protein. Clinical trials are currently evaluating several modalities, including the vaccine Galinpepimut-S and various TCR-T cell products, to treat patients with WT1-positive malignancies who carry the HLA-A*02:01 allele (Source: ClinicalTrials.gov).

Other names

WT1-A2 complexWT1 peptide-MHC complexRMFPNAPYL/HLA-A*02:01Wilms tumor protein 1/HLA-A*02:01 complex

Recognition by engineered T-cell receptors (TCRs) or TCR-mimic antibodies leading to T-cell mediated cytotoxicity