Abstract
The authors describe the current status of immunotherapy targeting Wilms' tumor 1 (WT1) peptide for malignant gliomas, as well as other hematological and solid malignancies. WT1 is expressed in various kinds of malignancies, having an oncogenic function. WT1 antibodies at higher titers and WT1-specific cytotoxic T lymphocytes (CTLs) at higher frequencies were detected in cancer patients than in healthy donors, indicating that WT1 protein has an immunogenic function. Those findings provided us with a rationale for cancer immunotherapy targeting WT1. Clinical trials of WT1 peptide vaccination were started, and definite immunological and clinical responses were observed. Especially in recurrent glioblastomas, a disease control rate of 57.1% was achieved, with a median progression-free survival period of 20.0 weeks and a progression-free survival rate at 6 months of 33.3%. The trial showed that WT1 vaccination for malignant gliomas, which are generally believed to be an intractable disease, was safe and had a clinical response. Further clinical studies with randomization to confirm the efficacy and immunological proof of concept in patients with malignant gliomas are warranted. An enhancement of efficacy of WT1 vaccination can be expected by combined use of WT1-specific helper peptide or anti-cancer chemotherapeutic agents. WT1 vaccination as one of the multiple modalities at initial treatment or in the setting of minimal residual disease may prolong survival time of patients with malignancies.
