Wilms tumor 1 peptide-MHC complex (WT1-MHC complex)

The Wilms tumor 1 (WT1) peptide-MHC complex is a molecular target consisting of a processed peptide from the WT1 protein presented by Major Histocompatibility Complex (MHC) molecules, such as HLA-A*02:01 (Cheever et al., 2009, Clinical Cancer Research). WT1 is a zinc-finger transcription factor that is highly overexpressed in various hematological malignancies, including acute myeloid leukemia (AML), and several solid tumors, while maintaining limited expression in normal adult tissues (Van Driessche et al., 2005, Leukemia). This differential expression makes the WT1-MHC complex an ideal target for immunotherapies like dendritic cell (DC) vaccines and T-cell receptor (TCR) engineered T cells (Sugiyama, 2010, Japanese Journal of Clinical Oncology). In specific clinical applications, autologous cord blood-derived dendritic cells are used to present these WT1 peptides to the patient's immune system to stimulate a robust cytotoxic T lymphocyte (CTL) response (MD Anderson Cancer Center, NCT01734785). These CTLs are then able to recognize and eliminate WT1-positive malignant cells by binding to the WT1-MHC complexes on the tumor surface (Oka et al., 2004, Scientific World Journal). The use of cord blood-derived DCs is particularly relevant in the post-transplant setting, where they can be used to prevent relapse by boosting the graft-versus-leukemia effect (Trivedi et al., 2017, Blood). Therapeutic success depends on the correct processing and presentation of the WT1 peptide within the MHC groove to ensure high-affinity binding with the TCR (Yasukawa et al., 2002, Blood).

Other names

WT1-HLA complexWilms tumor protein 1 peptide-MHC complexWT1 antigen-MHC complexWT1 peptide-HLA-A*02:01 complexWT1 peptide–MHC complexes on autologous cord blood-derived dendritic cells

Induction of antigen-specific cytotoxic T lymphocyte (CTL) responses through the presentation of WT1 peptides by MHC molecules to T-cell receptors (TCRs).