“Cancer Antigen WT1 Protein-Derived Peptide”-Based Treatment of Cancer -Toward the Further Development

Yoshihiro      Oka; Akihiro      Tsuboi; Fumihiro      Fujiki; Toshiaki      Shirakata; Sumiyuki      Nishida; Naoki      Hosen; Hiroko      Nakajima; Zheyu      Li; Ichiro      Kawase; Yusuke      Oji; Haruo      Sugiyama

doi:10.2174/092986708786848631

Abstract

Cancer immunotherapy targeting tumor-associated antigens is now being developed. Wilms tumor gene WT1-encoding protein is one of the promising target antigens for cancer immunotherapy, because the gene has an oncogenic function and is expressed in many kinds of malignancies. Furthermore, a series of investigations indicated that WT1 protein was highly immunogenic in cancer patients. Based on the analysis of anchor residues that were important for the interaction between peptides and HLA class I molecules, WT1 cytotoxic T lymphocyte (CTL) epitopes with the restriction of HLA-A*0201 and HLA-A*2402 were identified, and clinical trials of WT1 peptide vaccination for cancer patients with these HLA class I types were started. The vaccination-driven immunological and/or clinical responses were reported in patients with myeloid malignancies, multiple myeloma, and several solid cancers. Pediatric malignancies also may be target diseases for WT1 peptide vaccination in the future. Addition of HLA class II-restricted WT1 helper epitope peptide, chemotherapy, or molecular- target-based drug to WT1 CTL epitope peptide-based vaccination may enhance the power and usefulness of WT1 peptide vaccine. Other modalities, including gene therapy using genes encoding WT1-specific T cell receptor or DNA vaccination, are also expected to be developed.

Keywords: WT1, peptide, cancer, immunotherapy, vaccine

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