Wilms' tumor protein 1 (126-134) peptide-HLA-A*02:01 complex (WT1-RMF-HLA-A2)

The Wilms' tumor protein 1 (WT1) 126-134 peptide epitope, specifically the RMFPNAPYL sequence, presented by the Human Leukocyte Antigen (HLA)-A*02:01 molecule, is a major target for cancer immunotherapy (PubMed: 10754337). WT1 is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation; while it is essential during embryonic development, its expression in healthy adults is restricted to specific tissues like the kidney and hematopoietic stem cells (UniProt: P19544). However, WT1 is significantly overexpressed in various cancers, including acute myeloid leukemia (AML) and several solid tumors, where it acts as an oncogene (PubMed: 22499509). The presentation of the RMFPNAPYL peptide on the cell surface via HLA-A*02:01 allows the immune system, particularly CD8+ cytotoxic T cells, to identify and destroy malignant cells. Current therapeutic strategies targeting this complex include peptide-based vaccines like Galinpepimut-S, TCR-engineered T-cell therapies (TCR-T), and bispecific T-cell engagers designed to mimic TCR specificity (ClinicalTrials.gov). Clinical challenges include potential on-target, off-tumor effects due to low-level WT1 expression in normal tissues and the requirement for patients to be HLA-A*02:01 positive.

Other names

WT1 126-134RMFPNAPYL peptideHLA-A*02:01/WT1(126-134)WT1-A2 complexWilms' tumor 1 epitopeRMF-A2

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) activation against cells presenting the WT1 peptide-MHC complex.