Wilms' tumor 1 peptide-major histocompatibility complex (WT1-pMHC)

The Wilms' tumor 1 (WT1) peptide-major histocompatibility complex (pMHC) is a critical immunological target in oncology, representing the presentation of intracellular WT1 protein fragments on the cell surface (Source: National Cancer Institute). WT1 is a 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 (Source: PubMed, PMID: 19147505). Therapeutic strategies targeting this complex include peptide vaccines, T-cell receptor (TCR)-engineered T-cell therapies, and bispecific T-cell engagers (Source: SELLAS Life Sciences). These therapies rely on the specific recognition of the WT1 peptide (often the RMFPNAPYL sequence) bound to HLA molecules (typically HLA-A*02:01) by high-affinity T-cell receptors (Source: PubMed, PMID: 31515467). By engaging this complex, drugs can direct the immune system to selectively eliminate cancer cells expressing WT1. However, safety concerns exist regarding potential on-target off-tumor toxicity in tissues like renal podocytes where WT1 is physiologically expressed (Source: Journal of Clinical Investigation).

Other names

WT1-HLA complexHLA-A*02:01-WT1 peptide complexWilms' tumor 1 antigen-MHC complexWT1-pMHC complex

Recognition of the WT1 peptide-MHC complex by T-cell receptors (TCRs) or TCR-mimetic antibodies to trigger cytotoxic T-lymphocyte activity and targeted lysis of tumor cells (Source: PubMed, PMID: 31515467).