Wilms' tumor 1 peptide–Human leukocyte antigen B*35 complex (WT1–HLA-B*35)

The Wilms' tumor 1 (WT1) peptide–Human leukocyte antigen B*35 (HLA-B*35) complex is a specific antigen-presenting structure found on the surface of various malignant cells, including those in acute myeloid leukemia (AML) and ovarian carcinoma. WT1 is a zinc-finger transcription factor that is highly overexpressed in many hematological and solid tumors while maintaining limited expression in normal adult tissues, making it a high-priority target for cancer immunotherapy. The complex is formed when intracellular WT1 protein is processed into specific peptides, such as TPYSSDNLY (WT1 231-239) or HAAQFPNHSF (WT1 28-37), which are then loaded onto HLA-B*35:01 molecules and presented to the immune system. Therapeutic strategies targeting this complex include T-cell receptor (TCR) engineered T-cell therapies (TCR-T), which utilize high-avidity TCRs (e.g., clones 17.2G4 and 17.2D6) to recognize and eliminate tumor cells. While promising, challenges include ensuring TCR specificity to avoid cross-reactivity with similar self-peptides and managing potential on-target off-tumor effects in tissues where WT1 is physiologically expressed.

Other names

WT1-HLA-B*35 complexWT1/HLA-B*35:01TPYSSDNLY-HLA-B*35:01 complexHAAQFPNHSF-HLA-B*35:01 complexWilms tumor protein 1 peptide presented by HLA-B*35

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted lysis of WT1-expressing tumor cells.