[Immunotherapy targeting the Wilms' tumor 1 gene product for patients with malignant brain tumors].
In this paper, we review the current status of immunotherapy targeting Wilms' tumor 1 (WT1) peptide in malignant brain tumors as well as in other hematological and solid malignancies. WT1 is expressed in various kinds of malignancies, and is involved in oncogenesis. The titers of antibodies against WT1 and the frequency of WT1-specific cytotoxic T lymphocytes (CTLs) were higher in cancer patients than in healthy donors, indicating that WT1 protein has immunogenic function. These findings provided us with a rationale for developing cancer immunotherapy that targets the WT1 peptide. Clinical trials of the WT1 peptide vaccination were initiated, and definite immunological and clinical responses were observed. The disease control rate of 57.1% was obtained especially in the case of recurrent glioblastomas, with a median progression-free survival period of 20.0 weeks and progression-free survival rate at 6 months of 33.3%. The trial showed that WT1 vaccination for malignant gliomas, which is generally believed to be an intractable disease, was safe and elicited a favorable clinical response. Further clinical studies of WT1 vaccination in patients with malignant gliomas as well as other cancers are warranted. An enhancement of the efficacy of WT1 vaccination can be expected with a combined treatment using the WT1-specific helper peptide or anti-cancer chemotherapeutic agents. Administration of WT1 vaccination along with other therapeutic modalities during initial treatment or in the case showing minimal residual disease may prolong the survival time of the cancer patients.
Hashimoto
Naoya
N
Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Tsuboi
Akihiro
A
Chiba
Yasuyoshi
Y
Izumoto
Shuichi
S
Oka
Yoshihiro
Y
Yoshimine
Toshiki
T
Sugiyama
Haruo
H
D000912:Antibodies, Neoplasm; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000627:therapeutic use; D025721:WT1 Proteins / Q000276:immunology*
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D025721:WT1 Proteins