HLA-A2/WT1Db126

Wilms tumor suppressor gene 1 (WT1) is one of the most important TAAs classified by the National Cancer Institute. WT1, a zinc finger transcription factor, is highly expressed in many solid cancers and leukemia cells, but not in normal tissues (including hematopoietic progenitor and stem cells). Several studies have suggested that WT1 has an essential role in leukemogenesis and tumorigenesis, and it is required to maintain the transformed phenotype/function; therefore, tumor escape from immune surveillance as a result of downregulation of WT1 expression is unlikely to occur, marking WT1 as an attractive and important target for immunotherapy. The WT1Db126 (RMFPNAPYL) peptide was identified by screening the WT1 aa sequence for 9-mer peptides that include major anchormotifs for binding to HLA-A2. In vitro immunization elicits WT1 peptide-specific CTLs that mediate lysis of WT1-expressing tumor cells, indicating that this peptide constitutes a highly immunogenic epitope. HLA-A2-WT1Db126 complex is a target of TCR-like antibodies for anti-WT1Db126 peptide CAR-T cell development.

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