Target intelligence / Profile preview

Wilms' tumor 1 protein (WT1) peptide 126-134 presented by HLA-A*02:01 (WT1(126-134)/HLA-A*02:01)

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

Overview

The WT1 126-134 peptide (sequence: RMFPNAPYL) presented by the HLA-A*02:01 molecule is a critical target in cancer immunotherapy. Wilms' tumor 1 (WT1) is a zinc-finger transcription factor that plays a vital role in urogenital development but is highly overexpressed in various hematological malignancies and solid tumors, while maintaining restricted expression in normal adult tissues (Cheever et al., 2009). This specific peptide-MHC complex is recognized by the immune system as a foreign-like signal, making it an ideal target for T-cell-based interventions (Oka et al., 2004). Therapeutic approaches targeting this complex include peptide vaccines like galinpepimut-S, which stimulate endogenous T-cell responses, and adoptive cell therapies using engineered T-cell receptors (TCR-T) or bispecific antibodies (Maslak et al., 2018). Clinical success depends on the high specificity of the TCR or antibody to the RMFPNAPYL/HLA-A*02:01 complex to minimize damage to normal tissues such as the kidney or bone marrow where WT1 is physiologically expressed (Tawara et al., 2017).

Other names
WT1 RMF peptideRMFPNAPYL peptideWT1-A2 complexWT1-126 peptideWilms' tumor 1 antigen
02

Mechanism of action

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the surface of tumor cells, leading to T-cell activation, cytokine release, and cytotoxic lysis of the target cell.

03

Biological functions

Antigen presentationImmune responseT-cell activation
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Disease associations

Acute myeloid leukemiaMyelodysplastic syndromeSolid tumorOvarian cancerMesotheliomaCancer
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Safety considerations

On-target off-tumor toxicity (WT1 expression in kidney podocytes and hematopoietic stem cells)Cross-reactivity with similar self-peptidesCytokine release syndrome (CRS) in TCR-T therapies
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Interacting drugs

Galinpepimut-S

4 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeWT1 mRNA expressionWT1 protein expression (IHC)

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