Target intelligence / Profile preview

Wilms' tumor 1 protein (WT1) peptide 126-134 presented on HLA-A*02 (WT1(126-134)/HLA-A*02)

Target
WT1(126-134)/HLA-A*02
Molecular classification
Peptide-MHC complex, Antigen, Tumor-associated antigen (TAA)
01

Overview

The Wilms' tumor 1 (WT1) protein is a zinc-finger transcription factor that plays a crucial role in cell growth and differentiation, and is highly overexpressed in various hematological malignancies and solid tumors, while maintaining low expression in normal tissues (Source: NIH/NCI). The specific peptide sequence RMFPNAPYL, corresponding to residues 126-134 of the WT1 protein, is a well-characterized immunogenic epitope that is processed and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01 (Source: PubMed, PMID: 10667377). This peptide-MHC (pMHC) complex serves as a highly specific target for cancer immunotherapies, including T-cell receptor (TCR) engineered T-cells and TCR-mimic antibodies, which are designed to recognize intracellular antigens presented on the cell surface (Source: Journal of Hematology & Oncology). Therapeutic strategies targeting this complex, such as the peptide vaccine Galinpepimut-S and various TCR-T cell products, aim to induce a potent cytotoxic T-lymphocyte (CTL) response against WT1-expressing malignant cells (Source: Sellas Life Sciences, ClinicalTrials.gov). Because WT1 is considered one of the top-ranked cancer antigens for immunotherapy, this specific epitope-HLA combination is a focal point for treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) (Source: Leukemia & Lymphoma Society).

Other names
WT1 RMFPNAPYL peptideWT1 126-134 epitopeRMFPNAPYL/HLA-A*02:01 complexWT1-A2
02

Mechanism of action

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-mimic antibodies to induce T-cell mediated lysis of tumor cells.

03

Biological functions

Antigen presentationT-cell activationImmune surveillance
04

Disease associations

Acute myeloid leukemia (AML)Myelodysplastic syndrome (MDS)Ovarian cancerMesotheliomaGlioblastoma
05

Safety considerations

On-target off-tumor toxicity (potential impact on renal podocytes or hematopoietic stem cells)Cytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)
06

Interacting drugs

Galinpepimut-S

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeWT1 protein expressionWT1 mRNA levels

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